Lecture 2

What is a microorganism?

Organism invisible to the naked eye

Structure of a bacterial cell

Plasma membrane
● Lipid bilayer
● Selectively permeable
● Molecular transport, secretion, energy
generation
● Important role in sensing environmental signals
to modulate gene regulation eg. to switch on
virulence-related genes

Cell wall
● Major component peptidoglycan - polymer of N-acetylglucosamine (NAG) and N-
acetylmuramic acid (NAM)
● Peptidoglycan maintain structure. Due to osmotic pressure bacteria have a high internal
pressure and need the peptidoglycan to maintain a rigid structure to stop them from
bursting open.
● Thick gram positive = 15-80 nm; thin gram negative ~ 10 nm

Outer membrane (unique to gram membrane)

● Distinct from other biological membranes (NOT LIPID BILAYER) ; lipopolysaccharide
LPS on outermost surface, phospholipid inner layer; LPS is an endotoxin and can be
toxic to animals; LPS can trigger inflammation response in its hosts; contains O-specific
polysaccharides which can be used as adhesions which can help bacteria attach to tissues
- helps bacteria establish infection;
● Valuable to microbe but problem to host = antibiotic resistance as larger compounds
from drug compounds cannot penetrate the outer membrane and cannot reach target
inside the cell of the drug compound eg. gram negative cell with thin peptidoglycan layer
could be less susceptible to a peptidoglycan targeting antimicrobial because even though
it has a peptidoglycan layer, it cannot be reached because the drug cannot pass through
the outer membrane
● Can exclude large antibiotic (Ab) molecules = gram negative higher Ab resistance

Capsule (glycocalyx)
● Few microorganisms have a capsule
● Very effective virulence mechanism; helps cells evade phagocytosis
● Extracellular polysaccharide
● Helps evade host immune system and avoid phagocytosis
 Image:

Bacteria capsule

White area around the darker cells = polysaccharides;

capsule that protects the cell in the center.

Outside of the capsule is coated with proteins from the host;

hides cells to make it appear it belongs to the host and to
prevent recognition by immune cells

Types of Microorganism Overview

Cellular - smallest unit of living organism; includes, cell membrane, nucleic acid aka RNA/DNA,
cellular constituents to help make protein
● Eukaryotes (membrane-bound organelles)
○ Fungi eg. yeasts, mold
○ Protist eg. algae, protozoa, slime molds
● Prokaryotes (generally lack membrane-bound organelles)
○ Bacteria eg. escherichia coli
○ Archaea eg. methanogens; has special membrane different from eukaryotes and
prokaryotes; does not cause disease to human (not adapted to humans)

Acellular - missing one or more components listed above of a cellular microorganism eg. cell
membrane; non-living
● Virus
○ Composed of protein and nucleic acid
● Viroids
○ Composed of RNA
● Satellites
○ Composed of nucleic acid enclosed in a protein shell
● Prions
○ Composed of protein

NOTE:
Satellites rely on virus to replicate → virus rely on host to replicate; satellites are a parasite to
virus
Prions are proteins bent out of shape; small size enables them to cross the blood brain
barrier; bends other proteins our brains out of shape = causes disease
 Microorganism Characteristics Summary

Fungi Protist Bacteria Archaea

unicellular/multicellular Unicellular/ Unicellular

multicellular
Shape

Size (uM) <10

Cell wall makeup Chitin Peptidoglycan

Cellular

Prokaryotes/eukaryote Prokaryote; absent

(Membrane bound membrane bound
organelles) organelles

Size order 1
(smallest) 1 2 3 4 (largest)

Examples Unicellular:
Yeast
Multicellular:
filamentous
fungi
Penicillium spp.

Filamentous Yes

Penetration level Deep

Normal flora or Opportunistic Pathogenic

commensal/opportunistic/
pathogenic

Biomass (animals = 1 2 3
lightest; plants = heaviest)
(Lightest) 1 2 3 (Heaviest )

Bacteria

Pathogenicity
 Bacteria can generally be categorised into gram negative and gram positive according to
its cell membrane
Gram positive: thick proteoglycan wall followed by a thin plasma membrane inside
Gram negative: two layers of thin membrane - outer and inner proteoglycan membrane;
Distinguish a bacteria’s gram status: Gram positive cells have a thicker proteoglycan wall
and so stain a darker purple while gram negative will remain lighter purple or pink
pigment

Fungi

Can be either unicellular (yeasts) or larger multicellular (moulds)

Moulds
● Has a canal between each cell to share nutrients and transport in/out of cell
● Example: filamentous fungi. Grows when they are next to each other with a nucleus in
the middle.
 ● Example: penicillium spp. Antibiotics.

Majority of fungi are opportunistic; not good at invading the human immune system; large size
enables the immune system to detect fungi early and activate defence mechanisms.

Immunocompromised individuals are very susceptible to fungi as they are very filamentous and
can penetrate deep tissue. All human cells exposed to fungi must be removed as they are very
persistent and rooted deep in the human cells.

Fungi related diseases are hard to treat because:

Chitinous cell walls of fungi are more resistant to harsher environments and harder to
penetrate
Filamentous characteristic of fungi means some can go deep into the human tissue,
unless human tissue is destroyed as well.

Although fungal diseases are mild, the long duration of its treatment means high costs.

Protists

General category to place organisms that do not fit into the other three categories. Protists are
eukaryotes that are not plants, animals nor fungi.

Algae (plant-like eukaryotes)

● Photosynthetic
● Produces ~75% of the Earth’s oxygen
 ● Can be pathogenic

Protozoa (animal-like aka mobile eukaryotes)

● Unicellular
● Heterotroph
● Eg. plasmodium spp. causes malaria

Slime moulds (fungi-like eukaryotes)

● Behave like both protozoa and fungi across lifestyle (mobile and non-mobile stage during
lifetime, respectively)

Biomass of Life on Earth

Microorganisms and the One Health Concept

Microorganisms are ubiquitous

Essential roles in the human body and the environment

Vast majority of microbes are not pathogens

Directly improve human life eg. therapeutic drugs, food products, beverages

The “One Health” concept holds that all aspects of global health, including human, animal,
plant, marine, environmental and microbial health are intertwined.

The Normal Human Microbiota

Normal human microbiota- resident microbes associated with healthy individuals

Normal Human Microbiome

 Common Human Microbe Characteristics

Bacteria Normal human Function Preferred

microbiota location environment

Coagulase-negative Mouth Air exposed

staphylococci Oropharynx environments
Outer ear
Conjunctiva
Nose
Skin
Urethra

Lactobacillus spp. Small intestine Sufficient amount

(helps digest) will produce
vitamin B

Bacteroides spp. Small intestine Sufficient amount

(helps digest) will produce
vitamin K

Firmicutes (Genus) Mouth, gut, Help make

oesophagus, skin, bacteria, digest
vagina food
 Colonises multiple
areas of body
which keeps out
the bad bacteria
(fighting for space)
Symbiosis

Symbiosis = living together of organisms

Spectrum or host/microbe associations

One organism lives in/on body of another

Symbiotic relationships
● Parasitism: + +
● Mutualism: + o
● Commensalism: + -

Benefits of the Human Microbiota

Compete with pathogens for attachment sites, nutrients

Produce antimicrobial compounds = toxic to invaders, pathogens

Aid digestion

Supply essential growth requirements

Stimulate immune system

NOTE: human microbes can be commensal (transient bacteria when touching hand) or mutual
(normal human microbiota that colonises urethra and prevent invasion of pathogenic bacteria)

Human Microbiota becomes Pathogenic

Some normal microbiota may become pathogens if the “opportunity” arises; human microbiota
are not always friendly.

Criteria when microflora can become pathogenic:

● Microflora travels to a part of the body it normally does not inhabit
● Massive imbalance of microflora (eg. imbalance between fungi and bacteria microflora)
Examples of endogenous pathogens:
● Coagulase-negative (typically non-pathogenic) Staphylococcus can become pathogenic if
it invades deep skin tissue layers or into the blood; can break down blood cells and get
nutrients from it. Friendly in skin; pathogenic when access to blood
● Candida albicans can cause infection if the balance of microbiome is changed by use of
antibacterials (less competition for nutrients/attachment sites etc.); strong dose of
antibiotics shifts the balance of yeast fungi and bacteria
● 20-40% of the population have staphylococcus aureus in the nose normally and also in
the upper respiratory tract. However, if it gets into the deeper skin tissues, pustules and
infections can occur

Opportunities make Pathogens

Often infections/diseases occur when a microorganism is able to take advantage of an

“opportunity” eg. altered immune status

“Always” a pathogen - exogenous (and endogenous)

Pathogens are mostly always exogenous but sometimes can be endogenous; immune system can
almost always strike a balance with endogenous pathogens.

Exogenous pathogens: Smallpox (eradicated), herpes, Ebola

What makes a Pathogen?

Virulence is the outcome of a specific host-pathogen interaction

The host and the wider ecological context (holobiont) play a role in determining whether an
organism is pathogenic

The immune response can sometimes do more harm than the invading agents, or at least active
takes part in the harm caused

Pathogens lack structures unique to them that would set them apart from commensals
unambiguously
 The Human Body as an Ecosystem

Skin: air exposed, dry

Gut: food, low acidity

Body systems as environmental niches

● The genitourinary system
● The respiratory system
● The gastrointestinal system
● The skin system

Human Body Environment

Genitourinary system Includes: urinary, reproductive system

Female vs. male: length varies according to gender. Urethra is close to vagina
and anus. Urethra is far from anus in men. Thus, there are differences in
amount and types of microorganisms in the two reproductive systems
Female microbiota: bacteria and fungi that feed on discharges and break it
down. Produces lactic acid in the metabolic process. Majority is lactobacillus
spp. which produces lactic acid.
Respiratory system Upper respiratory: includes nasal cavity, nasopharynx, oropharynx; microbe
dense, more available nutrients, lower temperature (ambient), humidity and pH

Lower respiratory: trachea, lungs; nutrient poor, higher temperature (37

degrees celsius), humidity and pH

Upper respiratory tract is generally more microbe-dense than lower respiratory

tract

Larger particles cannot travel

deep into the body; obstructed in
upper RT

Diagram: wider width = greater

variable (eg. pH, temperature)

Gastrointestinal tract Moist, constant 37 degrees celsius, nutrient rich, large variation in pH, very
diverse microbiome

pH is low in stomach but slowly start to rise going through small and large
intestine

Oxygen is abundant in the start. At the end of the large intestine oxygen is very
low, not many microbes can survive;

Less diversity of microbes in the large intestine but more fungi. Fungi is
resilient, and can break down fiber which bacterias cannot.
Small intestine: bacterias = bacteroides, clostridium, streptococcus; fungi =
candida, saccharomyces

Gut: gram negative bacteria is good at surviving the gut due to their lipid
bilayer. Colinises the GI tract commonly.
Skin Can be dry (forearm, most (axilla) or oily (forehead)

Variable temperature, depends upon body location and ambient temperature

Transient microbes

Secretions from sweat and oil glands which have antimicrobial properties

Gram positive is more likely to survive on skin than negative due to its thicker
cell wall which makes it more resilient against, dehydration, UV exposure

Lecture 3
Properties of Viruses

Non-living: as they are incapable of arising directly prom a

preexisting virus; incapable of reproducing (lacks protein
synthesis machinery)
Not made of cells
Can not reproduce on their own
Do not undergo division
Lack machinery for protein synthesis: no nucleus, mitochondria, ER, golgi, ribosomes; cannot
independently undergo the process of turning mRNA → amino acid → protein; must hijack the host
cell’s machinery to act as a reaction vessel for reproduction. Will die without a host cell.
Has a nucleic acid genome of DNA or RNA (eg. corona, influenza)
Viral genome encodes the genetic information to make virus copies
Nucleic acid surrounded by a capsid (protective protein coat)
In some viruses, an outer membranous layer, called an envelope, made of lipid and protein,
surrounds the capsid

Routes of virus entry

Skin, respiratory tract, gastrointestinal tract, genitourinary tract, conjunctiva

Virus must travel to the specific human cell it can infect and replicate in
~ 21 different virus families infect humans
Virus must breach host barriers to infect
Some viruses can infect/breach multiple portals of entry listen above (eg. skin)
Respiratory tract is the most common portal as it is always open/accessible (in order for
breathing)
Mechanical trauma can break skin barrier (eg. bug) and allow access to viruses

Types of Viral Infection

Localised infection
● Replication at primary site of infection
● Spread to adjacent cells or within a single organ system
● Many viruses multiply in epithelial cells at site of entry; produce a spreading infection,
then shed directly to exterior
● Respiratory infections - influenza, rhinoviruses
● Gastrointestinal infections - rotaviruses
● Skin infections - papillomaviruses
Disseminated infection
● Must breech physical and immunological barriers
● Extends beyond primary site of infection
● Eg. chicken pox enter through respiratory tract but
spreads to skin and causes lesions
● Some viruses infect via circulatory system: organ
invasion from viruses migrating from blood vessels;
directly through capillaries via bite or puncture; HIV
infects via lymphocytes, monocytes; EBV via B
lymphocytes; measles via monocytes; VZV infects
via T lymphocytes
● Some viruses infect via nervous system: enter
sensory/motor nerve ending; via sensory (dorsal
root ganglia), motor (motor neurons); eg. rabies
(causes motor deficits), poliovirus (causes motor
deficits), HSC (Herpes Simplex Virus), VZV
(varicella-zoster virus reacts to cause the shingles)

Systemic infection
● Many organs affected
● Viruses that can spread
● Viruses that cause systemic infection have a higher mortality rate
● Affects mostly individuals with underdeveloped or suppresses immune system;
opportunistic virus acts on it

Viruses need to move to target organ/tissue or preferred site of replication. Correct viral protein
needed to bind to its human receptor; prevents plant viruses from infecting humans;
coronavirus infects only some cells in the human body as not all cells possess the cellular
receptors for the viral protein.

Virus Entry Target Cell System Infection Effect

transport Type

HIV Damages
immune
system

EBV

Measles

VZV
(varicella-
 zoster virus)

Rabies

Poliovirus

Herpes
Simplex
Virus (HSC)

Innate and Adaptive Immunity

Innate immunity
● First line of defense (passive barriers. Immediately effective)
○ Skin
○ Mucous membranes
○ Gastric juice
● Second line of defense (activation required, effective in less than 24h)
○ Natural killer cells
○ Macrophages
○ Eosinophils
○ Cytokines (eg. interferons)
● Adaptive immunity
○ Third line of defense

Adaptive immunity (effective after a few days)

● Third line of defense
○ T-cells (cell killing, cytokines)
○ B-cells (antibody production)
Types of Infection

Acute infection
● Rapid production of infectious virus
● Rapid resolution and elimination of infection
● Typical course for viruses such as rhinovirus, rotavirus, influenza virus
● Infections usually brief in immunocompetent hosts
● Virions and infected cells are completely cleared by the immune response
● Commonly localised infection but can also be disseminated infection
Persistent infection
● Unlike acute infection, persistent infection is not cleared effectively by the immune
response
● Virus particles or products continue to be produced for long periods
● Two types of persistent infection (i) slow/chronic and (ii) latent
● Slow/chronic infection
○ Long periods of time with low virus production or infectious genome spread
(Measles subacute sclerosing panencephalitis)
○ Eg. HIV; kills CD4 positive T cells slowly until little count → HIV starts replicating
at higher levels; antiretroviral therapy can suppress HIV long enough that you die of
old age

● Persistent latent infection

○ After initial acute infection, infectious virus is completely cleared by the immune
response
○ Viral genome persists without any detectable infectious virus production
○ Periodically virus can “re-awaken” from latency by a process called reactivation
○ Reactivation leads to new infectious virus with/without disease
○ Herpesviruses characterised by their capacity to establish latent infection
○ Eg. herpes simplex goes into sensory neurons of nervous system and sets up
lifelong latent infection
○ Once infected, the virus will always be in the but in a non-infectious, non-
replicative form with the capacity to reactivate
○ Eg. shingles is the reactivation of the chicken pox virus
○ DISTINCTIVE FEATURE OF PERSISTENT LATENT INFECTION: genome
present, infectious virus absent
Viral Shedding: Release of Infectious Virus from Host

Transmission via aerosols

● Some of the most medically important viruses are spread via aerosol droplets (sneezing
and coughing)
● Eg. influenza virus, coronavirus, rhinovirus, adenovirus

Faecal-0ral transmission
● High virus shed in watery diarrhea and vomiting associated with viral gastroenteritis;
but also through:
○ Shellfish - when harvested in contaminated sewage waters
○ When people have contact with objects or surfaces which are contaminated
○ Through infected people who may be preparing foods for others
○ When water used is contaminated with sewage
● Viruses spread via the fecal-oral route include: poliovirus, Hep A and Hep E, rotavirus,
norovirus

Transmission via skin lesions

● Herpes Simplex Virus presenting as cold sores or genital herpes will be shed in the lesion
and thus can be transmitted to uninfected individuals

Transmission via blood and body fluids

● Blood - west nile virus, dengue virus, hepatitis C, HIV
● Blood transmission via biting insects, sexual activity, childbirth, exposure to
contaminated blood
● Semen- HIV, CMV, hepatitis B
● Breast milk- CMV
● Urine- hantaviruses

Note: Successful transmission depends on

● Number of virus particles shed; more viral particles spread = more chance virus will
survive long enough to be exposed to someone else to make them sick
● Number of virus particles required to infect a new host
● Stability of virus in environment; eg. longer lifespan of virus = more chance of infecting
host
Routes of Transmission

Horizontal transmission
● Respiratory tract, cough, sneeze, saliva, blood
● Faecal-oral
● Sexual contact

Vertical transmission (generally mother to child)

● Prenatal - transplacental
○ HIV, rubella, CMV
● Perinatal - infected birth canal
○ Hepatitis B
○ HSV
● Postnatal - milk or direct contact
○ CMV, hepatitis B

Zooness - transmission from animals

● Biting arthropods or vertebrate reservoirs
● VIRUSES THAT ONE TRANSMIT ANIMAL-PERSON NOT PERSON-PERSON
● Eg. insect/animals infected by an infected person → virus replicates and amplifies in
insect/animal → insect/animal infects new person; eg. dengue
Fate of Host - What causes the symptoms?

Damage to cells due to direct effect of virus infection

● Cell death by rupture of cell during virus release

● Infected cell loses function
● Infected cell transformed by virus - tumors

Damage due to the host response to infection

● Antibodies and immune cells destroy infected cells - can damage tissue
● Symptoms of immune cells infiltrating the area where virus infection has occurred
(swelling, rash etc.)

Lecture 4
Lecture Objectives
 ● Describe the role of the immune response
● Discuss what comprises the immune system
● Identify features and cells of the innate immune response
● Identify feature and cells of the adaptive immune response
● Compare and contrast the main features of the innate and adaptive immune systems

What is the immune system?

A collection of:
● Molecules (eg. cytokines, chemokines, complement proteins)
● Leukocytes aka white blood cells
● Specialised tissue (eg. spleen, lymph nodes, bone marrow, skin, blood, intestines, liver,
lungs

Immune System Aim

To maintain homeostasis throughout body; once compromised from

infection, disease etc. the immune system activates

Roles of the Immune System

Principal function = host defense against pathogens

Detection of malignant cells and repair damaged tissue
Responds to foreign agents

What Compromises the Immune System?

Dysfunctional immune system can lead to allergy, autoimmune

disease or chronic inflammation

Origin of Immune Cells

Derived from hematopoietic stem cells in the bone marrow

Hematopoietic stem cell → multipotent progenitor → early progenitor with

myeloid potential → dendritic cell, monocyte, neutrophil, eosinophil, basophil,
mast cell, platelets, megakaryocyte, erythrocyte

Hematopoietic stem cell → multipotent progenitor → common lymphoid

progenitor → T-cell, B-cell, NK cell
Where is the Immune System?
Tissue resident immune cells are throughout the body, waiting to detect any threat; recruits
more immune cells if foreign agents are detected to eradicate pathogen urgently

Cytokines

Small soluble proteins

Secreted in response to a stimulus: cytokine binds to specific receptors on the outside of cellular
membrane of host cells → induces signaling cascade within cell and then induces that cell to activate
gene transcription and translation (to turn on antiviral proteins, drive production of different
cytokines etc.); eg. pathogen binding to pattern recognition receptor

Key families: interleukins (IL), tumor necrosis factor (TNF), chemokines (chemoattractant
cytokines), interferons (IFN)

Producer cells: innate immune cells such as dendritic cells, macrophages, mast cells can
produce in large quantities; lymphocytes, non-immune epithelial cells

Mediate immune and inflammatory reactions

Some are anti-inflammatory: important for regulatory control (eg. dampening when no longer
needed)

Cellular communication system: allows immune system cells to communicate + cross-talk

between immune and non-immune cells

Examples of cytokine roles:

● Local inflammation:
○ Act on endothelial cells to increase
permeability allowing cells to migrate out of
the bloodstream and into the tissue as well as
complement proteins
○ Can act on leukocytes, causing them to
produce different cytokines of chemokines in
response
● Systemic protective effects:
○ Large quantities of cytokines can act on
brain to induce fever response, on liver to
increase production of acute phase proteins
(includes complement proteins)
○ Act on bone marrow to increase leukocyte
production
● Systemic pathologic effects
○ Large quantities can have pathological effects eg. decreasing heart output
Chemoattraction
● Chemokines (chemoattractant cytokines)
● Vital role in cell migration
● Cells follow a chemokine gradient (from decreasing to increasing
concentrations); cells migrate out of bloodstream into the tissue
towards chemokine production site where infection would be
● To do above, cell must express a complimentary chemokine receptor
eg. CXCL10 (L= ligand ie. chemokine) binds to CXCR3 (R=receptor)

Complement

30+ enzymes produced in the liver

Circulate in the blood, inactive

Called complement because when they were initially discovered, they were found to complement
the killing of microbes by antibodies; but now found three activation methods

Activated in directly in the presence of microbes or by antibodies binding to microbes

Three complement system activation ways:

● Alternate pathway: microbe directly bound by components of the complement pathway
● Classical pathway: microbes bound by antibodies to activate the classical pathway
● Lectin pathway: microbes bound by mannose binding lectin to activate lectin pathway

Activated in one of the three ways above → proteolytic cascade begins

All three pathways converge at a common point at the formation of C3 and C5 convertases; three
outcomes can occur from this:
● Inflammation; driven by some complement proteins being cleaved
● Microbe can be oxidised; microbe coated in complement proteins which signals
phagocytosis of microbe
● Microbe can be lysed by products of the complement system when the membrane attacks
complex forms on the plasma membrane of the microbe; essentially punched holes in the
microbe causing it to lyse.

Explanation

Classical pathway: antibodies bind on to the antigens in the pathogen’s surface. C1

(complex 1 protein) binds to the antigen-antibody complex and activates + C2, C4 splits
into two; this begins the cascade - once it starts it will not stop until completion. One
fragment of C2 and C4 combine to form C3 convertase. C3 convertase splits to form C3a
 and C3b. The smaller C3a fragment diffuses out and attracts more phagocytes. The larger
C3b binds to the pathogen’s surface for destruction and causes C5 to split into two - C5a
and C5b. C5b binds with C6, C7, C8, C9 to form the membrane attack complex. This
complex attaches to the pathogen’s membrane and makes a hole. Water rushes inside
pathogens to kill it.

Alternative pathway: same as classical pathway but skips the antigen binding + C1, C2,
C4; starts with C3. C3 gets activated by binding directly to the pathogen itself. C3 then
interacts with other proteins - eg. factors P, B, D. This causes C3 to split into C3a and
C3b. The above classical pathway steps continue.

Phagocytosis

Key players: neutrophils, monocytes, macrophages, dendritic cells

Phagocytes ingest microbes

● Triggered by binding to pattern recognition receptors (PRRs) or phagocytosis receptors
● Once phagocyte is bound, the plasma membrane closes around the microbe and brings
the microbe into the cell in a phagosome
● Phagosome fuses with lysosome = phagolysosome; contains reactive oxygen species
(ROS), nitric oxide (NO) and lysosomal enzymes kill the microbe
● Some phagocytes - particularly dendritic cells - picks up parts of microbe and travel to
lymph nodes to activate adaptive immune response

Summary of Acute Inflammation

Acute inflammation is the process of recruiting immune cells and plasma proteins to the site of
infection. This will typically result in heat, redness and swelling at the site because of the
increase in cells, plasma and liquid in the tissue. This activates an immune response.

1) Microbe breaks physical barrier (eg. skin)

2) Sentinel tissue resident cells senses microbe and secrete cytokine + chemokines in
response
3) Cytokines + chemokines (inflammatory mediators) increases permeability of endothelial
cells (vasculature) to allow complement proteins and innate immune cells to come out of
the bloodstream and into the tissue
4) The complement, antibodies and anti-microbial proteins bring phagocytic cells
(neutrophils, monocytes, dendritic cells)into the tissue to kill microbes. Initiated by
adhesion molecules and chemokine receptors that cause leukocyte migration into the
tissue.
5) Antigen presenting cells (eg. dendritic cell) captures pathogen and process it for antigen
presentation to activate adaptive immune response

The Innate and Adaptive Immunity

 Collaborative and interdependent systems: Innate immune response initiates the adaptive
response; Adaptive immune response can enhance the innate immune response

Innate Immune Response Adaptive Immune Response

Who has it? All healthy individuals; natural Acquired immunity; not born with but
immunity learned

Recognition type Global recognition system (pattern
recognition receptors)
Highly specific recognition; binding
between B-cell or T-cell receptor is
highly specific because it recognises
distinct parts of molecules - antigens,
epitopes

Specificity Non-specifc Specific

Occurrence time Minutes to hours of a pathogen Days to give first response

infection

Rapid response due to the high

expression of pattern recognition
receptors on innate immune cells; ready
to go

Barriers Physical and chemical

Molecules Cytokines
Plasma proteins eg. complement

Cells Phagocytes: neutrophils, macrophages,

dendritic cells; these scavenge and
engulf microbes

Innate lymphocytes: natural killer (NK)

 cells (directly kills infected cells)
Exocytes: mast cells, basophils,
eosinophils; these actively release
mediators to destroy pathogens + drive
inflammatory response
Process Microbe breach physical barrier → tissue
resident cells senses pathogen through
pattern recognition receptors (search for
conserved products on pathogen that are
not present on healthy tissue) → pathogen
binded to pattern recognition receptor
triggers cytokines release; cytokines act
on endothelial cells + induce cells to
migrate from bloodstream into tissue +
complement proteins follow → activation
and recruitment of more cells,
complement proteins + inflammation →
removal of infectious agent + pathogen
parts used to activate adaptive immune
response if required
Components of adaptive immune
response = humoral, cell-mediated
Humoral immunity; provided by B
lymphocyte (B cell)
● B lymphocytes provide
protection against extracellular
microbes
● Secretes antibodies -
immunoglobulins: IgA, IgG,
IgM, IgE; antigen receptor B cell
uses is an antibody that is
initially bound to surface of B
cell but
● IgA antibodies are typically
found in mucosal surfaces (eg. in
respiratory tract and
gastrointestinal tract)
● IgM, IgE and IgG antibodies are
typically found in the serum or
blood
Cell-mediated immunity; provided by T
lymphocyte (‘T cell’)
● T cells only act on other cells
● T-cell:
1) Pathogen in periphery is picked
up by dendritic cell
2) Dendritic cell phagocytoses
pathogen and travel to draining
lymph node
3) Dendritic cell breaks down
pathogen + processes and
presents pathogen antigens
(parts of pathogens) to a T cell
4) T cell recognises pathogen and
gains effector function it
requires to activate and leaves
lymph node to the site of
 infection to control it

● Two types: cytotoxic (expresses

co-receptor CD8+) t cells and
helper (expresses co-receptor
CD4+) t cells
● Cytotoxic t cells function: after
gaining effector function to
become cytotoxic, they are good
at dealing with intracellular
microbes, particularly viruses.
Viruses replicate inside host
cells. Cytotoxic t-cells are good
at identifying virally infected
cells.
● Effector mechanism of cytotoxic
t-cells: directly kills the
pathogen which eliminates any
reservoirs of infection and
hopefully end the viral infection

● Helper t cells come in the

subsets Th1, Th2, Th17. The
CD4+ helper t cells help
macrophages deal with
phagocytosed microbes.
Intracellular bacteria (eg.
mycobacterium tuberculosis)
are good at surviving the
phagocytosis process and can go
on and live within a
macrophage. CD4+ t cells can
help macrophage to aid in killing
any cells that survived the
phagocytosis process. Summary:
CD4 t cells eliminate
phagocytosed microbes +
secrete cytokines to help b-cells
and t-cells
● Effector mechanisms of helper t
cells: secrete cytokines →
cytokines activate macrophage +
increase macrophage’s production
 of reactive oxygen, species and
nitric oxide to ensure engulfed
bacteria is killed

Both T and B cells undergo clonal

expansion to increase frequency of
antibodies that can recognise the
particular pathogen

Repetitive Yes. Does not learn from pathogen No. Secondary infection is swifter and
interaction = same response every time larger than primary.

Reaction to self No. Once a cell becomes damaged (cell No

starts to burst) and its contents start to
spill, it is recognised by innate
immunity and triggers a response. But
does not react to self.

Clonal expansion No Yes. T and B cells can undergo clonal

expansion.

Interactive response Yes

Naive Lymphocytes require Activation

Naive Lymphocytes = Naive T and B cells

Naive lymphocytes require activation to perform effector

functions; cannot contain microbe without activation

Need antigen recognition and other signals - costimulation

(given by innate immune cells) - to proliferate and become
effector cells

Both T and B cells are in a naive state until it recognises

antigens and given costimulatory signals; they then undergo
proliferation and gain effector functions; they can also
convert into memory cells which can react + proliferate
faster than a naive lymphocyte

T cell activation
5) Pathogen in periphery is picked up by dendritic cell
6) Dendritic cell phagocytoses pathogen and travel to
draining lymph node
 7) Dendritic cell breaks down pathogen + processes and presents pathogen antigens (parts
of pathogens) to a T cell
8) T cell recognises pathogen and gains effector function it requires to activate and leaves
lymph node to the site of infection to control it

Components of Adaptive Immune System

Humoral immunity
● Provided by B lymphocyte (B cell)
○ B lymphocytes provide protection against extracellular microbes
○ Secretes antibodies - immunoglobulins: IgA, IgG, IgM, IgE; antigen receptor B
cell uses is an antibody that is initially bound to surface of B cell but
○ IgA antibodies are typically found in mucosal surfaces (eg. in respiratory tract
and gastrointestinal tract)
○ IgM, IgE and IgG antibodies are typically found in the serum or blood

Cell-mediated immunity
● Provided by T lymphocyte (‘T cell’)
○ T cells only act on other cells
○ Two types: cytotoxic (expresses co-receptor CD8+) t cells and helper (expresses
co-receptor CD4+) t cells
○ Cytotoxic t cells function: after gaining effector function to become cytotoxic, they
are good at dealing with intracellular microbes, particularly viruses. Viruses
replicate inside host cells. Cytotoxic t-cells are good at identifying virally infected
cells.
○ Effector mechanism of cytotoxic t-cells: directly kills the pathogen which
eliminates any reservoirs of infection and hopefully end the viral infection
○ Helper t cells come in the subsets Th1, Th2, Th17. The CD4+ helper t cells help
macrophages deal with phagocytosed microbes. Intracellular bacteria (eg.
mycobacterium tuberculosis) are good at surviving the phagocytosis process and
can go on and live within a macrophage. CD4+ t cells can help macrophage to aid
in killing any cells that survived the phagocytosis process. Summary: CD4 t cells
eliminate phagocytosed microbes + secrete cytokines to help b-cells and t-cells
○ Effector mechanisms of helper t cells: secrete cytokines → cytokines activate
macrophage + increase macrophage’s production of reactive oxygen, species and
nitric oxide to ensure engulfed bacteria is killed

Note: Serology is the study of antibodies in blood; serotype is a subset of a species that can be
recognised by the same antibody (eg. there are three different serotypes of the poliovirus, they
are all poliovirus but the proteins expressed on the outer capsule of polio 1 vs polio 2 are slightly
different, some antibodies for serotype 1 will bind to the poliovirus variant whereas a different
antibody will bind to poliovirus 2 so that the two can be distinguished)
Antigen, epitope, peptides
Antigen: derived from “antibody generator” but now we refer to antigens as anything that a B
cell or T cell receptor binds to. T and B cell receptors recognises and bind to proteins. Only B cell
receptors recognise and bind to lipids and polysaccharides as well.

Epitope is the specific region of the antigen that the lymphocyte receptor recognises; epitope is
the region of an antigen that an antibody recognises.

Adaptive immune response has a property of specificity. Binding between an antibody (T-cell or
B-cel) to an antigen is highly specific. A huge variety of different T-cell and B-cell receptors must
be encoded to distinguish between the millions of antigens. Changing a single amino acid in the
epitope of an antigen protein, the antigen-antibody binding can be abolished.

Note: T-cell can only recognise/bind to protein antigens. T cell epitopes are peptides; T cells
recognise the short chains of amino acids that form the part of the protein that T cells recognise.

Cognate T and B cells recognise the same antigen. Does not have to be recognising the same
specific part of antigen but the same antigen.

Clonal Selection and Immunological Memory

A vast supply of T and B cells are maintained; each with unique antigen recognition receptors;
this ensures potential to respond to any type of pathogen the body encounters

When the body encounters a pathogen, only those T and B cells that recognise the pathogen are
triggered to respond - multiply in number → clonal expansion. That particular antibody undergoes
clonal expansion to multiply in number. All the daughter cells can encode the same antigen receptor
as the original cell to deal with the particular antigen. Fate of daughter cells of an antibody is either
1. become plasma cells and secrete antibodies that bind to the particular antigen 2. become memory
cells

Prior to infection, the frequency of the antibody for a particular antigen is low. Once clonal
expansion occurs after the infection, the particular antibody frequency increases.

Some convert to memory cells- poised to attack if we re-encounter the pathogen

Secondary response is much larger and quicker than primary; this is the basis for vaccination.
Summary of Adaptive Immune System

Takes days to mount primary response (must undergo activation and proliferation first)

Highly specific recognition (recognises distinct parts of a molecule - antigens, epitopes)

Huge diversity of B and T cells (ensures response to any type of pathogen)

B and T cells can undergo clonal expansion

Memory cells can be generated after primary infection to ensure much swifter response to a
second encounter with pathogen

The Immune system vs the Pathogen

Pathogen is not passive and will fight back to the immune system by encoding
immunomodulatory mechanisms to evade the host’s immune response
Lecture 5
 ● Identify features and cells of the innate immune response
● Identify feature and cells of the adaptive immune response
● Compare and contrast the main features of the innate and adaptive immune systems
● Outline how immune cells are recruited into sites of infection and lymph nodes
● Discuss the role of lymph nodes in the immune response
*Textbook chapters: 1 and 2 (Abbas, Basic Immunology)

How do Immune Cells Traffic to the Site of Infection - travel from blood to infected
cell?

Cells follow from a low to high gradient

Images below:
● Left: uninfected in lungs. Many white spaces for gas exchange to occur.
● Right: active infection in lungs.

Recruitment of cells

● Leukocytes need to actively leave the blood to migrate to sites of infection; otherwise
they continue traveling in the blood fast
● Step wise process

1. Infection is sensed and resident cells respond by producing cytokines and chemokines
2. Cytokines increase adhesion molecules - selectins (E- and P-selectin), on endothelial
cells (eg. edges of vessels). Active key and lock mechanism slows down the cells -
otherwise they continue traveling fast in the blood.
3. Leukocytes express a selectin ligand that recognises the selectin on epithelial surface.
Leads to initial interaction between leukocyte and endothelial cell.
4. Flow of blood leads to rolling; cells roll along the edge of the blood vessel instead of
flowing at a fast pace in blood.

Recruitment of cells to sites of interaction

1. Chemokines displayed on endothelial cells by proteoglycans (proteins with glycans and
sugar residues)
 2. Leukocytes express chemokine receptors which bind the chemokines
3. Induce integrins (LFA-1 and VFA-4 - REMEMBER NAMES) to change from a low to high
affinity state; makes leukocytes stop completely instead of only rolling.
4. Integrin ligands (ICAM-1 and VCAM-1) are also upregulated on the endothelial cells.
This strengthens the interaction between the leukocyte and endothelial cell, leading to
arrest

Image below:
● I = cells actively interact with endothelial cells
● II = cell spreads along to squeeze through junction between two endothelial cells after
detecting chemokine gradient. Cells migrate towards chemokine gradients and
complement fragments in the tissue.
The Adaptive Immune Response requires Activation

Naive = lymphocytes that have not encountered their antigen

Naive T and B cells responses to foreign antigens are initiated and develop in secondary
lymphoid tissue

Strengths and Limitations of the Immune Systems

Innate Adaptive

Strengths Huge diversity due to clonal

expansion = very dynamic

Limitations Must be well controlled due

to activation requirement and
to prevent self reaction

Time consuming to maintain

huge diversity
Lymphoid Tissue

Primary
● Provide growth signals and educate
lymphocytes
○ Bone marrow (B cells
mature)
○ Thymus (T cells mature)

Secondary
● Lymph nodes
● Spleen
● Mucosal and cutaneous associated
lymphoid tissue

The Lymphatic System

Lymphatics: specialised vessels, drain fluid from tissues into lymph nodes

Essential for tissue fluid homeostasis and the immune response.

Antigen presenting cells such as dendritic cells capture antigens and travel via
lymphatics to lymph nodes

Free antigens can also drain to lymph nodes in fluid; picked up by macrophages
and dendritic cells in the lymph node

Lymph Nodes

Specific B and T cell zones

Lymph fluid and migrating dendritic cells enter via afferent
lymphatic vessels (ONE DIRECTION)
Naive lymphocytes enter via high endothelial venules and migrate
to their zones

Naive Lymphocytes

Naive lymphocytes circulate through secondary lymphoid tissue

 Naive T-cell
trafficking

● Naive T
cells enter
lymph
node via high endothelial venules (HEV) - T cell zone
○ HEV express selectin ligands, ICAM-1 and chemokines
○ Naive T-cells express L-selectin, LFA-1 and CCR7
● T cells leave via efferent lymphatic vessel
● View table below
 Cell/Fluid Entry into lymphatic vessel

Migrating Dendritic Afferent lymphatic vessel

cell

T-cell High endothelial venules to T cell zone

Lymph Fluid Afferent lymphatic vessel

MHC-I and CD8 T-cells

CD8 T-cells recognise peptides presented on MHC-I

● MHC-I derived peptides come from inside the cell

Activated CD8 T-cells are cytotoxic T-cells (granular)

● Destroy infected cells
● MHC-I is expressed on all nucleated cells

MHC-II and CD4 T-cells

CD4 T-cells recognise peptides on MHC-II
● MHC-II derived peptides come from outside the cell, following phagocytosis

CD4 T-cells provide help to other cells eg. macrophages and B-cells
● MHC-II is expressed on dendritic cells, macrophages and B-cells
NOTE: difference between MHC-I and MHC-II: MHC-I is derived from peptides INSIDE the cell
and presented on all cells whereas MHC-II is derived from peptides OUTSIDE the cell and
presented on dendritic cells, macrophages and B-cells

APC provide signals to T-cells to activate them

Naive T-cells can’t perform effector functions

Activated by mature antigen presenting cells in secondary

lymphoid tissue (eg. lymph node)
● MHC recognition
● Co-stimulatory signals (to verify a true and valid
activation)

Drives proliferation and gain of effector function

Antigen specificity unchanged

 B-cell vs T-cell

B-cell T-cell

Recognition of antigen Recognises folded, 3-D structure Recognises linear epitope of small peptide
chain of protein

Recognises interwoven in a major

histocompatibility complex with the
foreign peptide.

Identification of T-cells look for a complex on a cell surface

antigens (major histocompatibility complex aka
MHC + foreign peptide)

T-cells work with other host cells because

they must find the antigen peptide
presented on an MHC molecule.

Directly kills infected/or damaged cells

(CD8+) or provides ‘help’ (CD4+)
 Lecture 6

● Distinguish the various causative agents of disease

● Explain the links in the infectious disease chain and appreciate how they interrelate to
increase the incidence of disease
● Explain how breaking any link will control an epidemic outbreak
● Compare differences in the occurrence of disease: terms in the science of epidemiology
● Understand how epidemiologists recognise epidemics
● Explain how the spread of disease can be controlled

Evolution of Microbial Disease Concepts

“Miasma theory” (Hippocrates, 4th century BC) suggested contagious diseases caused by a
miasma, a noxious form of “bad air” from rotting organic matter.

‘Germ theory of disease’ 1800’s:

● Fungus (Phytophthora infestans) cause of Irish potato blight, fungal

infection of cereal crops etc.
● Louis Pasteur: work around fermentations (wine, bread) and
pastuerisation (applying high heat in short time to reduce bacterial
load but denatures protein) recognised microbial relationship
● Joseph Lister: antiseptic surgery (introduced antiseptic spray on
surgical equipment to reduce contamination and infection)

Microbial Disease Concepts

Casual relationship between microbe and a specific disease:

 ● 1890 - Robert Koch “Koch’s postulates”; Helped establish relationship between pathogen
and disease

1) It must be found in all cases of the disease

2) It must be isolated from the host and grown in pure culture
3) It must reproduce the original disease when introduced into a susceptible host
4) It must be found present in the experimental host so infected

● 1988 - Stanley Falkow developed “Molecular Koch’s postulates”

○ discovered only some bacteria cause disease despite being part of the same
species
○ eg. benign and pathogenic E.coli
○ Falkow hypothesised some pathogenic E.coli must have a unique feature
○ Pathogenic E.coli does have a capsule-like pillai that makes it easier to attach to a
patient's tissue.
○ Pathogenic bacteria have a gene that codes for a virulence factor which helps
establish disease; the gene causes disease not the bacteria itself
○ Experiment: pathogenic E.coli is placed in model organism = animal is infected.
The pillai making the E.coli pathogenic is removed and put back into animal
model = animal is not infected. Thus, the pillai is the disease causative agent.

Limitations of the two models:

● Some microorganisms cannot be grown in pure culture in the lab (some ned other
bacterias or host tissue to be cultured
● Viruses need host cells to be cultured
● No animal model of infection for some microorganisms
● Not all hosts react the same way to every infectious agent
● Variability in presentation of symptoms
● What about co-infections?
● Where does asymptomatic carriage fit?
● Sometimes the causative organism is gone by the time the symptoms appear

Infectious Diseases Chain Principle

INFECTIOUS DISEASE IS CIRCULAR. Infectious disease

requires a cyclical mechanism where it exits the reservoir to
enter another host and cause infection. The links below must be
prevented to control infectious diseases. Non-circular disease are
not infectious eg. diabetes, cancer do not have a portal of
transmission.
Reservoirs - where the pathogen can be used to replicate (pathogens cannot replicate in
fomites); humans are the reservoirs in human disease = pathogens that live and replicate in
humans. Can be symptomatic or asymptomatic (carrier)
● Inanimate objects eg. food, water, cups, towels
● Contagious humans
○ Symptomatic with active disease
○ Eg. temperature, cough, sore throat, vomiting, diarrhea etc.
● Human carriers
○ Asymptomatic
○ Acute: incubation stage
○ Chronic: recovered from disease, possibly shed > infective for years
● Animals (zoonoses)
○ Eg. cow with TB via milk, rabies via bite
Transmission
Direct
● Contact: skin to skin (horizontal)
○ Shaking hands (staphylococci)
○ Kissing (streptococcal sore throat)
○ STI’s (chlamydia, gonorrhea, syphilis, HIV-AIDS, trichomoniasis, HSV)
○ Polymicrobial (multiple organisms all causing an immune response and
staphylococcal infections
● Air-borne: Aerosols (horizontal)
○ Coughing
○ Talking
○ Sneezing
○ Bacterial pathogen stay aerolised for a shooter time than viral aerosolised
comparison
○ eg. flu, chicken pox, mumps, measles, SARS Cov-19 etc.
● Mother to baby in utero (vertical): microcephaly (Zika virus causing
microcephaly), AIDS (HIV)
● Trauma: tattoo, burn, bite, injury (polymicrobial/staphylococci)
Indirect
● Vehicles: contaminated food/water: cholera, food poisoning (salmonella, listeria
etc.), polio
● Fomites: inanimate objects that carry pathogenic microorganisms and thus can
transfer disease to a new host, serving as a source of infection. Microorganisms
survive on fomites for minutes or hours. Common hospital sources = Dust, linen,
dry shed skin, hair, clothing; hospitals = nosocomial infection (staphylococci);
fomites are used as a transportation device, replication does not occur in fomites.
Any infection acquired from another patient, staff or visitor. Hospital cleaning is
crucial to reduce the impact of fomites.
Vectors (transmission via non-human organisms - animal, insect etc.)
● Insect: mosquito (malaria), tsetse fly (trypanosomiasis sleeping sickness), flea
(plague)
● Anopheles mosquito → malaria (fevers, anaemia)
 ● Malaria is not spread person to person but only through mosquitos; Key method
to control malaria is controlling mosquito bites through pesticide programmes,
mosquito netting or abolishing standing water where mosquitoes can replicate
● Tsetse fly → trypanosomiasis = sleeping sickness; penetrates and shuts down nervous
system

Control
Transmission

● People
○ Physical barriers: wear mask (COVID-19, 1918 Spanish flu), condoms (STI’s)
○ Physical distancing (COVID-19)
○ Isolation/quarantine = isolation of cases/carriers/contacts (cholera, plague,
rabies, smallpox, yellow fever, SARS, HPAIH, viral haemorrhagic fevers, ebola,
COVID-19 in some countries)
● Animals
○ Control disease in animals - zoonoses: rodent fleas = plague; dogs/canines
(unvaccinated) = rabies; cattle = brucellosis, mad cow disease
● Water
○ Treat sewage to reduce water contamination (vibrio cholerae = cholera;
roundworm = ascariasis; giardia lamblia = giardiasis)
○ Provide safe drinking water: chlorination, filtration; eliminate water-borne
pathogens
○ Water especially bad for GI tract related diseases
● Food
○ Safe food practices: manufacturing, manage food poisoning risks eg. pasteurise
milk; food handling; food storage
● Eliminate vectors
○ Eg. mosquito: malaria
 ● Use therapeutics
○ Eg. antibiotics: penicillin: syphilis, yaws
● Infection control practices in hospitals

Note: Control of Transmission = masks, social distancing, quarantine

Epidemiology

Epidemiological investigation involves

● What caused the disease?

● Where did it came from?
● How it got into the population?
● Why it became a problem?

● Goals: 1) control transmission/speed of spread

2) eliminate pathogen from population

Important terminologies: incidence aka morbidity,

prevalence/morbidity rate, death/mortality rate

● Amount of water in the bathtub = prevalence =

current number of sick people
● Aim = reduce amount of water in bathtub = reduce
current number of people sick
● Incidence = water dripping from tap = new disease
introduced
● Higher the incidence = higher the prevalence
 ● Two ways people can be removed from prevalence pool = recovery (evaporation of bath
water) and death/mortality (drain from bottom tube)
Patterns of Diseases

● Epidemiologists use data of expected prevalence and actual prevalence to evaluate the
status of a disease
Expected Prevalence Actual Prevalence

Sporadic Disease Low Low

Eg. Salmonella food
poisoning

Outbreak Low High

Eg. Hendra virus Qld 2012 &
2013, Ebola in Congo

Endemic High High

Eg. common cold, TB,
malaria

Epidemic Low High

Eg. seasonal influenza

Pandemic Low High

Eg. SARS CoV-2

Differences: Outbreak = disease occurs in a single spot; Epidemic = disease occurs in a greater
radius around a single spot; Pandemic = disease occurs around the globe

Endemic- disease is constantly present in a population. at low frequency

Epidemic- disease suddenly increases in a population

Pandemic- disease increases within large widespread populations usu. worldwide

Herd Immunity

Threshold density- rate of people

getting sick will reduce

Instead of looking at only a single

point, observing the chronological
pattern of a disease helps determine
the causative agent of a disease.
Common-source epidemic: if a
disease has a sharp rise and decline of
prevalence, it can be caused by a
common source, eg. guests get food
poisoned from the same dish.
Propagated epidemic: diseases
transferred between people = slower
pattern (blue) eg. strep throat,
COVID-19, influenza). To determine a
propagated status, a month or year
long data is required.
Emerging and re-emerging Infectious Disease
 Lecture 7

● Critically comment on what causes the shift to parasitic relationships in the symbiosis
spectrum
● Distinguish commensals from pathogens
● Build on Lecture 6 outcomes to explain the links in the infectious disease chain and
appreciate how they interrelate to increase the incidence and spread of disease
● Explain how breaking any link will control an epidemic outbreak
● Understand how microbial strategies and/or products allow them to: colonise, invade, evade
the immune response, and damage the host
● Understand the role of the host immune system in responding to infection

What makes a disease easier to eradicate?

● Less prone to mutation

● Low modes of transmission

What made the eradication of smallpox successful?

● Worldwide vaccination program

● Symptoms obvious
● Quarantine effective
● No other host

The symbiosis spectrum

Mutualism to parasitism

● E.coli in the gut helps its human host. However, if the host becomes
immunocompromised or the E.coli mutates, it can cause an issue.

Pathogen and host relationship is dynamic; can change status of mutualism, commensalism or
parasitism.
Constant Battle between Host and Microbe (Parasitism Relationship)

Eg. trypanosomiasis (African Sleeping Sickness).

Vector: Tse-tse fly
Causative pathogen = protozoan trypanosomes
Two steps to infection: 1) Tse-tse fly has a blood meal and the trypanosomes will reside
in the human’s lymph nodes. 2) Neurological phase: trypanosome produces a type of
protease that helps them breach the blood-brain-barrier.
Symptoms: extreme fatigue - sleepy to the point they cannot get up to eat and die of
starvation in their sleep

Infectious Disease as Product of One Health

Human, animal and environment are always interplaying with each other
Eg. transmission of the sleeping disease relies on Tsetse fly abundance deceased from its
original habitat
Tsetse fly is abundant in Zimbabwe's Mana pool. The temperature increased in the pool
and the lake started drying up making it inhabitable for the tsetse fly - tsetse fly
abundance decreased in original habitat.
The Tsetse fly moved to higher altitude in the north.

Host/Microbe (Parasite/Pathogen) Interaction

Image above:

● First decrease in the number of parasites is due to immune response; although some
parasites are killed by the immune system, some are still replicating and creating new
versions of themselves.
● Parasite changes outer coat protein (antigenic variation/) to evade immune response
>>> pathogen load increase

Image above:

● Host response to antigenic variation

● First wave: green pathogen has been controlled by immune system = pathogen numbers
declined because the green antibodies that the immune system has created has identified
the antigen’s epitopes
● The pathogen has evolved into the purple version; the green antibodies cannot recognise
the new antigen
● ‘Antigenic stress’
● Antigenic variation is not specific to parasites; can be applied to bacteria, viruses
● Microbes have a quicker replicative cycle than humans
● Are viruses more prone to antigenic shifts than bacteria? Yes because viruses have a
smaller genome and more mobile genetic elements, shifting the genetic elements
between viruses does not kill them. However, mutations in bacteria can kill them.

Factors Governing Symbioses

Virulence - severity or harmfulness of a microorganism; increased virulence = shift to parasitism

Host susceptibility: increased immunecompetence = shift to paristitism

Load of microorganism: the number and type of microorganisms contaminating an object or
organism; increased load (eg. poor hygiene habits, chemotherapeutic agents) = shift to
parasitism
Microbial virulence - degree or intensity of pathogenicity of a microbe (pathogenicity = the
ability to cause disease; increased virulence = increased likelihood to cause harm = parasitism;
indicated by: fatality rates, ability to invade host tissues and cause disease symptoms

Virulence factors

Microbial strategy/trait that contributes to virulence = virulence mechanism

Clear connection between virulence and infection
Virulence is influenced by microbial traits (ie. genes) that mainly fall in four categories:
1) Those that affect the ability of the pathogen to replicate/colonise (eg. mutation that
speeds by the microbe’s replicating cycle)
2) Those that affect host defense mechanisms (i.e. immune-evasion mechanisms); eg.
microbe can actively produce a protein to downregulate MHC molecules on host cells,
microbes can be undetectable by immune system to prevent triggering inflammatory
cytokine release
3) Those that affect tropism, spread throughout the host and transmissibility
4) Those that encode products that directly damage host cells

Can include “housekeeping” functions ie. deriving nutrients/energy for survival in host

Virulence Factors:

● Aid colonisation: capsule, pili/fimbriae, OMP’s etc.

○ Attachment/adhesion virulence factor
■ Non-specific (size wise): biofilms (slimy layer of bacteria stack),
glycocalyces (slimy polysaccharide layer that helps bacteria stick to the
tissue)
■ Specific (size wise)

○ Adhesins/ligands virulence factor: bind to receptors on host cells

■ Specific to host receptors (eg. spike proteins)
■ Fimbriae (pili) - specific to bacteria
■ Outer membrane proteins

● Allow penetration of host tissue: invasins

○ Hyaluronidase - breaks down hyaluronic acid; hyaluronic acid acts as glue to
protect between epithelial cells; bacteria penetrates hyaluronic acid to reach the
deeper underlying tissue
○ Collagenase - breaks down collagen; collagen accounts for 30% of body’s protein
○ Hemolysis - bacteria breaks down red blood cells to get the iron for nutrition
 ○ Invasins: bacterial surface proteins - promote ingestion; invasins bait microfold
cells aka M cells; microfold cells see epithelial cells that is responsible for
sampling the antibody
○ Endocytosis: non-phagocytic cells > exocytosis: actin tail propulsion
○ Phagocytosis
○ Transcytosis

● Prevent/reduce host response: evade immune system

○ Evade phagocytosis and immune clearance
○ Capsules: mask antigenic sites, protective ie. anti-phagocytic; eg. gram-negative
bacteria - only encapsulated E.coli is pathogenic; most bacteria become 100X
more virulent if encapsulated; capsules effective because: slimy = helps with
attachment, protects from immune response
○ Antigen change: antigenic variation/phase variation, protein mimicry (bacteria
decorated with good proteins to fool immune system)
○ Microbe produces antibody proteases: destroy immunoglobulins (IgA)
○ Intracellular survival
○ Affect phagocytosis
■ Destroy phagocyte
■ Inhibit phagocytosis:
● Prevent chemotaxis
● Inhibit phagosome/lysosome fusion
● Resist lysosomal enzymes

● Cause direct damage to host

○ Toxic membrane end products: acid, gas
○ Proteins: cytotoxins, degradative enzymes
○ Exotoxins: A-B, membrane disrupting, superantigens
○ endotoxins: gram negative = LPS; gram positive = peptidoglycan, LTA, TA;
endotoxins cause fever - when gram negative bacteria is phagocytosed and gets
disintegrated, the lipids inside their membrane gets picked up by interleukin and
the signal goes to the brain causing the prostaglandin level to increase = fever. If
this continues, more cytokines are activated which lowers blood pressure to a
point where the organ goes into shock = fatal.
■ Induce inflammation

● Pathogenicity islands
○ Large segments (10-200 kb) of DNA (chromosomal or plasmid)
■ Mobile elements
■ Encode major virulence factors
○ Increase microbial virulence
■ Absent in non-pathogenic strains
○ Pathogens may have multiple PI
○ Acquired via horizontal gene transfer
○ Confer antimicrobial resistance
○ The islands harbours genetic elements that encode for a lot of the virulence
factors.
○ Different names for different microorganisms and they code for different things;
superantigens elicit strong, powerful information response
○ MEMORISE TABLE
Host Susceptibility

Impacted by:
● Host factors- age, socio-economic status, occupation, sex and inherited factors, naivety
of immune system (if immune system has been exposed to the pathogen before)
● Non-specific host defences and barriers to infection - physical, chemical, biological eg.
break in skin, mucosal membrane, cytokine, hormones
● Immune status - immunocompromised eg. vaccination, if under immunosuppressant
drugs

Infectious Dose (Load)

Successful infection results from: initial inoculum or virulence of microbe or host susceptibility

Infectious dose: ID50 = number of microbes required to cause disease in 50% inoculated hosts
eg. <10 cells: mycobacterium tuberculosis, shigella dysenteriae, histoplasma, hepatitis B
~ 1 x 10^5 salmonella, legionella pneumophila
10^6 - 10^11 vibrio cholerae
High numbers in dental plaque > dental caries: polymicrobial

Limitations of our Knowledge of the Host-Pathogen Relationship

Cohort selection - what happens in a caucasian male (or a mouse model) is nto always relevant
other races or sexes…
Ethcial considerations
The integrated aspect of health and our world - multifactorial
● The One Health concept
● Understanding holobionts (holobiont = the network formed by a host and the many
other species living in or around it, which together form a discrete ecological niche.
 Week 8 - The Genitourinary System - Structure,
Microorganisms and Diseases
● Describe the structure of the genitourinary system
● Compare the differences between the male and female reproductive tracts and the impact on
type and rate of infection
● Understand the importance of the normal microbiota in this system
● Recall some of the major sexually transmitted pathogens that infect the reproductive tract
and describe the diseases they cause
● Discuss the pathogenesis of Herpes simplex virus-1/2
● Describe how genital herpes is transmitted
● Discuss prevention, control and treatment strategies for some of the major sexually
transmitted pathogens

Overview of the Genitourinary System

What factor affects how easy and far bacteria can spread?
Length of the urethra tract.The urethra tract is shorter in females than male. It is easier
for bacteria to travel up in females.
Proximity of the openings. In females the urethral, vaginal and anal opening is close
together.

Microbe of the Genitourinary Tract

Male genitourinary tract

● Bladder and urethra continuously flushed by urine

● Very low number
● Male genitourinary tract is more simplistic compared
to females in terms of infection
● In healthy individuals, microbiota consists of resident
microbes found on the skin eg. Staphylococcus
● Why is there a low diversity and quantity of
microbiota in male genitourinary tract compared to
females? Skin microbiota can enter the genitourinary
tract through the urethra but the continuous urine
flushes it out easily
Female genitourinary tract

● Complex and dynamic normal microbiota

● Lower reproductive tract dominated by Lactobacillus species. They feed on the glycogen
supply of the lower genitourinary tract and produce lactic acid. This lowers pH to ~ 3.9
which inhibits growth of other bacteria. Lactobacillus also fights off other bacterial
colonisation
● Major role in non-specific defence against infection eg. low pH (lactic acid), hydrogen
peroxide, bacteriocins, competition for nutrients and binding sites.
● Why is there a greater diversity and quantity of microbes in females genitourinary tract
than males?
○ Moist
○ Nutritious: contains glycogen in vaginal area + menstrual blood can be broken
down by some bacterias
 Sexually Transmitted Infections (STI)

30 known bacterial, viruses and parasites are known to be transmitted between humans via
sexual contact

Causative Neisseria gonorrhoeae Treponema pallidum Trichomonas vaginalis Chlamydia trachomatis

Microorganisms

Pathogen Type Gram-negative Gram-negative Unicellular Protozoan Gram-negative bacteria

diplococci bacteria parasite

Description Spiral cell shape, motile

(spiral shape helps move
through viscous fluid eg.
blood)

Disease Syphilis

Obligate Human Obligate human Obligate intracellular

Pathogen or pathogen = avoid detection by
obligate immune system
intracellular

Infection Area Urethra

Cervix
Throat
Anus
Eyes

Transmission Horizontal: Horizontal: Horizontal: Horizontal:

Penis STI ST, genital touching STI
Vagina
Anus Vertical: Vertical:
Mouth Mother-child in Vaginal Mother-child in Vaginal
childbirth (congenital childbirth
Vertical: syphilis)
Mother-child in
Vaginal childbirth

Virulence Type IV pili - adhesion, Shape of the bacteria: AP65, AP51, AP33 - Type III secretion
Factors immune evasion entry and movement adherence, immune system (syringe) - ejects
(antigenic/phase (burrow into host tissue evasion (mimicry); AP = effector protein in cell
 variation), natural + move around adherence protein
transformation (eg. TARP - host cell
incorporates exogenous TprK - surface protein, CP65 - cysteine protease, remodelling for
DNA in genome = great attachment, immune tissue damage pathogen survival
variability = easier evasion (antigenic
antimicrobial variation) Dysbiosis - phagocytosis Pgp3 - immune evasion
resistance) of protective normal (suppression)
Outer membrane sheath microbiota Lactobacillus
PorinB (channel)- - immune evasion
outer membrane (masking); minimal
protein into periplasm, protein exposed in
immune evasion antibody for immune
(suppression) system

IgA protease - Immune

evasion (direct damage
to immunoglobulin),
tissue invasion

Symptomatic No - 70-80% Face melt (physical No - 70% infection in

disfigurement) Blood in your vaginal women asymptomatic
Can include: discharge.
Penile discharge, Neurological &
irritation or pain when psychological impact 0
urinating, anal impacts CNS Itching and irritation in
discharge or and around your vagina.
discomfort,
conjunctivitis and eye Swelling around your
inflammation genitals.

Males - unusual vaginal

discharge, irregular Pain during sex.
vaginal bleeding, pain
when urinating, pelvic
pain especially during
sex, anal discharge or
discomfort,
conjunctivitis and eye
inflammation

Long-term Ectopic pregnancy Can cause pregnancy

effects complication eg. preterm
Disrupt microbiome delivery, low birth
 weight
Fatal if untreated

Culture with Yes eg. ceftriaxone,

antibiotics? azithromycin

Antimicrobial High Not common but

Resistance increasing
Why? Naturally capable
of taking variation eg.
incorporates exogenous
DNA in genome

Antibiotic Penicillin, ciprofloxacin Not common but Not common but No.
Resistance are mainly ineffective increasing increasing

Treatment Antibiotics eg. One dose of Cured with

benzathine metronidazole; inhibits azithromycin,
benzylpenicillin protein synthesis by doxycycline,
interacting with DNA, erythromycin (all
causes a loss of helical inhibit protein
DNA structure and synthesis, binds 50S or
strand breakage 30S ribosomal subunit)

Global Patients 82 million (2020) 7.1 million (2020) 156 million (2020) 129 million (2020)
Aus: ~20,000/year

Notes 4 stages of disease - Cluster around human Nonreplicating

primary, secondary, cell and apply pressure -
latent, tertiary squeeze so hard they kill Noninfectious reticulate
the cell and can also eat body inside mucosal
cell; phagocytosis, cells
clustering
Image Comes in pairs

Major Viral Pathogen of the Genitourinary System

Human immunodeficiency virus - HIV

● Disease = Acquired immunodeficiency (AIDS); substantial decrease in CD4 t cells
● Associated with respiratory disease

Human papillomavirus (200+ strains, 40 responsible for STIs) - HPV

● Disease = Genital warts or cervical cancer (also vaginal, anal, vulvar and penile cancers)
● Vaccine available to protect against strains 6, 11, 16 and 18 - the most likely of causing
cervical cancer

Herpes Simplex Virus type-1 and -2

● Genital herpes

Herpes Simplex Virus

Herpesviridae family
Alphaherpesvirus subfamily
● Herpes simplex virus type 1 (HSV-1)
● Herpes simplex virus type 2 (HSV-2)
 ● Varicella Zoster virus (VZV); causes Chicken pox (note: each cell will look similar to cold
sore - presented as lesion on lips of genitourinary area)

HSV-1 and HSV-2

Double-stranded DNA viruses (all herpes viruses are double-stranded DNA)

Viral genome replication occurs in the host cell nucleus

These viruses attach and enter into target host cells - typically epithelial cells - and its double-
stranded DNA genome is transported into the host cell’s nucleus. In the nucleus, the DNA is a
template for transcription; transcribed into mRNA → exported to cytoplasm of the cell → viral
protein produced. The double-stranded DNA genome also gets replicated = many copies from the
virus. These can be packaged int0 new viral capsids within the nucleus, using the viral proteins
translated by the host cell. An assembly of new virus particles begin in the nucleus and transit
through the cell and leave the cell. Herpes viruses leave cell in great quantities which causes the death
of the host cell.

HSV-1 and 2 share a high degree of genome sequence homology

HSV-1 more commonly associated with cold sores
HSV-2 more commonly associated with genital infections
However, both can cause frequent and painful genital lesions
Can be distinguished serologically (by antibodies)
~22% of Australians seropositive to HSV-2
As serology tests for antibodies, can’t distinguish between an infection which causes cold sores
or genital lesions

HSV Pathogenesis

Primary infection:
● Break in the skin, virus accesses the mucosa, infection established in epithelial cells
● Virus replication in oral or genital mucosa
● Newly made virus particles released from infected cells access sensory nerve endings

Latent infection:
● Viral genome is sequestered in a non-replicating state in primary sensory neurons
● No virus proteins or particles being made
● Hidden from the immune system
● The epithelium includes sensory neuron ending collections known as ganglia. This is part
of the PNS. When HSV replicates in the epithelial cells and is released from the infected
cells, it gets into the ends of the sensory nerve ending and travels through retrograde
transport, up those sensory neurons to their actual cell bodies in the ganglia. The virus
shuts down into latency after it arrives. When latency occurs, the viral DNA genome is
sequestered in a non-replicating state within the cell body of those sensory neurons; the
virus does not produce any proteins or new viral particles = hidden from the immune
system. Cold sore on lip suggests virus has gotten up into the sensory nerve endings; the cold
sore disappears and body appears healthy but the virus is still inside the body →
RECURRENT INFECTION (INFO BELOW).

Recurrent Infection
● Viral genomes reactivate from the latent state
● Enter replication cycle again
● New infectious virus particles made
● Trigger/s for reactivation unclear, immune suppression plays a role
● Virus reactivates week/month/year from state of latency. Virus accesses epithelial cells
again of the oral mucosa or the genital mucosa depending on where the infection is
established. Infects this area again and causes a new lesion. New viral particles are made
which gives viruses a new opportunity to spread to a new host.

NEVER cleared from sensory neurons - always carried.

 HSV establishes latency in the ganglia
that innervates the site of primary
infection. It will then reactivate from
that same ganglia, meaning that if you
get cold sores the virus cannot suddenly
travel and cause genital lesions; DOES
NOT SPREAD THROUGH BODY UNLESS EXTREMELY IMMUNOCOMPROMISED

Genital herpes: transmission and symptoms

Transmitted during sexual intercourse, oral-genital

More common in females- suggests female genital tract more permissive to infection
Only 10-25% of infected people are aware of the infection
Blisters visible 4-7 days after transmission
Associated with pain, itching and burning sensations
Asymptomatic shedding of the virus can occur, this is a large driver of transmission
Genital lesions increase the chance of HIV transmission
Prevention and control of pathogens of the genitourinary system - STIs

Best to prevent initial infection ;

● Comprehensive education about STI
● Counseling and support particularly for at risk populations
● Promotion of barrier protection – use of condoms
● Development of vaccines – currently no vaccine for any bacterial or protozoan STIs

Easy to control these pathogens after infection, however;

● MUST have de-stigmatization of STIs
● Education about symptoms and importance of early diagnosis & control of spread to
sexual partners
● Access to health care and timely and effective treatment
Week 9 - The Immune Response to HSV
● Discuss the mechanisms and cell types involved in the response to viral infections
● Discuss how the host recognizes an infection and initiates an immune response
● Describe the role of type I interferons in viral infections
● Describe the role of NK cells in viral infections and how NK cells are activated
● Describe the role of immune memory in controlling HSV infections
● Outline the immune response to bacterial STIs

Immune Response in Genitourinary Tract

Skin
Type II Mucosa
Type I Mucosa

Immune Response in the Female Reproductive Tract

Hormone fluctuations occur
Tissue remodeling, cyclic shedding and regeneration
Balance between tolerance to infection and immunity to infection
During pregnancy the mother must tolerate foreign antigens

Typical Immune Response to a Viral Infection

Interferons (IFN) and proinflammatory cytokines produced
● By local immune cells e.g. tissue resident dendritic cells, as well as keratinocytes and
epithelial cells
NK cells
CD8+ T cells
B cells and CD4+ T cells

Immunopathology of herpes lesions

HSV replication in mucosa/skin causes cell death, leads
to blisters containing cellular debris, immune cells and
virus particles
Generally the primary infection is most severe
● Lack of adaptive immune response
Secondary lesions heal faster
 ● Memory T cells quick to act to to control

Image:
● Light pink = lesion = concentrated with viral particles

Starting the Immune Response

Before the immune response can begin, we first need a way to detect the pathogen
Distinguish: self from non-self, danger from harmless
Need receptors at all possible sites where pathogens could enter eg. skin, epithelial layers,
mucosal layers are loaded with tissue resident memory cells (express receptors at high levels) -
other cells can also detect pathogen.

How do Host Cells Initially Recognise a Pathogen

Pattern Recognition Receptors (PRRs) recognise pathogen associated molecular patterns

(PAMPs); aka looks for things that are broadly unique to pathogens and not typically in normal
healthy cells
Pattern Recognition Receptors

Expressed by virtually all cells

● But not all cells express all the receptors, each different cell type express a certain subset
High levels on resident and innate immune cells such as macrophages
PRRs found on the cell surface, in endosomes and in the cytoplasm and nucleus
Five major families of PRRs:
● Toll-like receptors (TLRs)
● C-type lectin receptors (CLRs)
● Nod-like receptors (NLRs)
● RIG-like receptors (RLRs)
● Cytosolic DNA sensors (CDSs) - senses DNA is cytoplasm as in normal healthy cells DNA
is in the nucleus

Pathogen Associated Molecular Patterns (PAMPs)

PAMPs (pathogen associated molecular patterns)
● Structures common to many different pathogens which are not present in healthy cells
○ Components of bacteria, fungi or viruses which are generally essential e.g. nucleic
acids, cell wall lipids, carbohydrates and proteins
○ Note: Pattern Recognition Receptors look for these broadly conserved patterns
(listed above), it cannot specifically identify pathogen eg. distinguish between the
different E.coli strains as they look for example polysaccharides which are in
multiple bacterias
DAMPs (damage associated molecular patterns)
● Released from damaged/dying cells in the wrong place at the wrong time
PAMPS vs antigen

PAMPS:
Common structures shared by different microbes e.g. LPS
Recognised by innate receptors- germline encoded

Antigen:
Features unique to each individual pathogen
Recognised by specific adaptive immune cell receptors- arise through gene recombination
unique

PRRs Trigger Inflammation and Antiviral Defence

Engagement of PRR → Signaling cascade —> Drives:

● Production of proinflammatory cytokines (e.g. TNF, interleukins IL-6, IL-1B)
● Production of type I interferon
 ● Programmed cell death (virus replication is dependent on cell machinery - cell death =
virus dies)
● Stimulation of adaptive immunity Kick starts the immune response

What do the receptors sense during a viral infection?

Viruses replicate using host cells

● Limited targets for PRRs

Viral PAMPs:
● Viral RNA (e.g. double-stranded RNA)
● Viral DNA
● Viral glycoproteins

Major response to PRR recognition of viral PAMPs: Type 1 Interferon production

Secondary response: cytokines e.g. TNF, IL-12, IL-1b

HSV PAMPS

Different PRRs trigger different responses

Pathogens trigger multiple PRRs

HSV-1 PAMPS:
● Viral glycoproteins
● DNA genome
● Viral RNA

Typical Immune Response to a Viral Infection

Type I Interferon (IFN) and proinflammatory cytokines produced

● By local immune cells e.g. tissue resident dendritic cells, as well
as keratinocytes and epithelial cells
Type I Interferon establish an ‘antiviral state’ and recruit immune cells
Interferon (IFN)

3 types of IFNs:
● Type I interferon: alpha and beta (both use same
receptor, does similar work)
● Type II interferon: gamma
● Type III: gamma

Main sources of IFNs:

● IFN-a: produced by dendritic cells and
macrophages (innate cells)
● IFN-b: produced by fibroblasts
● IFN-g: produced NK cells, T cells

Note: all cells can produce type I interferons as all cells with a nucleus can be infected by viruses

Type I Interferon function

Type I IFN (a and b) can be secreted from virally infected cells and induce an ‘antiviral’ state in
surrounding uninfected cells
● Induce Interferon stimulated genes
○ Anti-viral enzymes
○ Shut down host cell metabolism

IFNs increase MHC-I expression- increases chance of CD8 T cells detecting infected cells; MHC-
I present antigen to CD8 T cells to increase chance of cytotoxic T-cell coming and killing infected
cell

HSV lesions and interferon production

Infected keratinocytes, epithelial cells, tissue resident immune cells, dendritic cells and
macrophages can all produce type 1 interferon in response to HSV infection

(Lymphocytes can produce type II interferon/IFN-g )

Note: human fibroblasts cannot produce type I interferon; type I interferon is crucial in limiting
initial viral spread

HSV Evasion of Type I IFN Responses

HSV encodes numerous gene products that inhibit the induction of type 1 IFN and IFN signaling
Natural Killer Cells
Innate lymphocyte
Circulate in the blood
Recruited to sites of infection by chemokines
Found in HSV lesions
People who lack NK cells are extremely susceptible to
severe HSV infections

Express a mosaic of activating and inhibitory

receptors
Can recognise and lyse virally infected cell
Decision to Kill:
● Summation of +ve & -ve signals; activating and inhibiting signal
Use same cytotoxic mechanisms as CD8+ T cells to induce cell death
If activating signals higher: release cytokines- IFN-gamma, helps adaptive immune response,
and macrophages

Cell stress (e.g. infection) drives expression of activatory ligands

Some viruses cause a downregulation of MHC-I - “Missing self hypothesis”; viruses stop MHC-I
on cell surface to prevent detection by CD8 T-cell NK. However, the Natural Killer cells are
inhibited by MHC-I on cell surfaces on normal healthy cells. Activating signal on cell surface +
lack of inhibitory signals = NK cell degranulates, kills the cell

If the activation signal is engaged and the inhibitory receptor is not, this leads to NK cell
activation
Adaptive Immunity-Requires Recognition of Antigens

T cells are crucial in controlling viral infections

Need innate response to activate the adaptive response

Activated effector CD8+ T cells then recognise and directly kill virally infected cells and CD4+ T
cells produce cytokines and provide help to B cells to generate antibody responses

Antibody response are important, particularly for preventing reinfection with viruses

We will address T cell activation in the TB/respiratory module- please be aware that T cell
activation and the T cell response is important for viral infections such as HSV also!

We will cover how B cells generate specific antibody responses in the Polio/gastrointestinal
modules and look at the role of antibodies in controlling and preventing viral infections

Immunological Memory and HSV

Primary lesions are the worst because adaptive immune response does not occur

HSV infection always re-occurs in the same spot

Infection/virus travels up the sensory neurons to the dorsal root ganglia or sensory root ganglia.
The virus has to use the same neuronal pathway to come back down for the recurrence eg. cold
sore or genital lesion to reoccur. The sensory root ganglia only innervates a specific area of the
body eg. a particular patch of skin.

If a person has a recurrent cold sore on the left hand side of their face, a section of the lesioned
area can be stained by using antibodies to identify neuronal axons in order to find T-cells. T-
cells typically associate along the ends of the sensory neuronal endings as they are ready to
attack the virus when it comes back again as the body has learned the area most likely to be
infected. More tissue resident, adaptive immune cells inhabit that area to quickly shut down the
infection. Thus secondary lesions are quicker to be maintained.
Immune response to Bacterial STIs

Chlamydia trachomatis
● Infects epithelial cells and replicates within them
● Can cause mucopurulent cervicitis, pelvic inflammatory disease and non-gonococcal
urethritis
● Immune response largely responsible for symptoms

Neisseria gonorrhea:
● Very strong immune response leads to symptoms- pus/discharge, and potentially
scarring of tissue, can lead to infertility
● Neutrophils recruited to phagocytose bacteria but this bacteria can survive inside
neutrophil, may facilitate transmission; the discharge has neutrophils with live bacterias
which can infect another human
Treponema pallidum:
● Chancre contains replicating spirochetes surrounded by immune cells (T cells, plasma
cells, macrophages).
● Immune response can clear local infection- macrophage phagocytosis bacteria, but T.
pallidum spreads systemically, antigenic escape

Trichomonas vaginalis:
● Triggers inflammation (in women can cause scarring, infertility), can be broken down
and killed by neutrophils

Images
 Bacteria capsule

White area around the darker cells =

polysaccharides; capsule that protects the cell
in the center.

Outside of the capsule is coated with proteins

from the host; hides cells to make it appear it
belongs to the host and to prevent recognition
by immune cells

Definitions

Pathogenicity- ability of an organism to cause disease

Questions

How do you distinguish a bacteria’s gram status? Gram positive cells have a thicker proteoglycan wall and
so will stain a darker purple while gram negative will
remain lighter purple or pink pigment

Note: this is a colony not a cell
Sometimes bacteria and fungi look alike. What can be
a distinctive feature?
Are there more gram positive or negative bacteria on
hands?
Why can dye in gram negative be washed off more by
alcohol than positive.
Can plant diseases infect humans? Can coronavirus
infect all the cells in the body?
When are cytokines secreted?
Explain the process of the innate immune system
B; B is more opaque and is less likely for light to
penetrate the cell. A is more translucent = thinner cell
wall.
Bacteria = peptidoglycan cell wall
Fungi = chitin cell wall
Gram positive. Gram positive is more likely to survive
on skin than negative due to its thicker cell wall which
makes it more resilient against, dehydration, UV
exposure
The dye is trapped by the thick proteoglycan cell wall of
gram positive while the dye can easily escape the two
thin cell walls of the gram negative, when washed with
alcohol.
Correct viral protein needed to bind to its human
receptor; prevents plant viruses from infecting humans;
coronavirus infects only some cells in the human body
as not all cells possess the cellular receptors for the viral
protein.
Secreted in response to a stimulus (e.g pathogen binding
to pattern recognition receptor)
Microbe breach physical barrier → tissue resident cells
 senses pathogen through pattern recognition receptors
(search for conserved products on pathogen that are not
present on healthy tissue) → pathogen binded to pattern
recognition receptor triggers cytokines release → activation
and recruitment of more cells, complement proteins +
inflammation → removal of infectious agent + pathogen
parts used to activate adaptive immune response if required

What distinguishes the innate from the adaptive

immune response?

What are the strengths and weaknesses of the innate

and adaptive immune systems?

How do we generate all that receptor diversity in

adaptive immunity?

Why the need for CD8 vs CD4 T cells?

How do we ensure the right cell responds in a

particular scenario in adaptive immune responses?

Why does the adaptive immune system bother helping

the innate system; why can it not do everything itself?

How do free antigens drain to lymph nodes in fluid? Free antigens are picked up by macrophages and
dendritic cells in the lymph node

Where do lymph fluid and migrating dendritic cells The afferent lymphatic vessels
enter the lymph nodes?
Why is complement-mediated lysis most effective
against gram negative rather than gram positive
bacteria?

Why does the adaptive immune response require

activation; why is it tightly controlled?

How do we ensure we have T and B lymphocytes that

can recognise every potential pathogen?

3 types of cellular pathogens that can cause infectious Bacteria, protozoa and fungi (virus is acellular and
diseases in humans? Bacteria, protozoa and fungi archaea does not cause disease)

Is contaminated water considered a vehicle or yes

reservoir depending on the pathogen ?

Is a toy considered a fomite? Yes. It is an inanimate object that a virus can travel on.

People who have a subclinical case of a disease are Yes

frequently carriers of a particular disease?

Endemic (high expected prevalence + high actual

prevalence): every region except Asutralia
Sporadic (low expected prevalence + low actual
prevalence): Australia.

Status of the disease in North America is best an outbreak.

described as…
 Expected prevalence = 5-10 yearly across US = low
Actual prevalence = high

Outbreak

Anopheles gambiae is a mosquito

that only exist in sub-Saharan
Africa
 Not contaminated food or water ruled = NOT vehicle
Not person-person = NOT direct contact
NOT vector

Answer = fomite

Common source; most likely medical equipment was

contaminated.

Are viruses more prone to antigenic shifts than Yes because viruses have a smaller genome and more
bacteria? mobile genetic elements, shifting the genetic elements
between viruses does not kill them. However, mutations
in bacteria can kill them.

What is the absolute requirement for a pathogen to

cause disease? ANSWERS ARE NOT: invade host tissues (eg. E.coli
does not invade but produces toxins which causes harm)
nor adhering to host tissue nor producing exotoxins

What would be the first sign of infection

 Adhesin eg. pili

Clues given: adhesin is specific to host receptors.

Can HSV be transmitted during latent state? Cannot transmit during true latent state where no viral
particles are being produced.