1.2 HOST vs.

MICROBES
Dr. Teresa S. Ludovice-Yap June 19, 2012

DEFENSE MECHANISMS OF THE B. Penetration into host

BODY  Structures & components
 Pluripotent stem cells with the ability for unlimited self  Enzymes
renewal colonize various sites of haemopoiesis: bone  Intracellular existence
marrow, spleen, liver C. Mechanism of Damaging Host cells
 Progenitor cells with irreversible commitment to cell 1. Direct Damage
lineage 2. Production of Toxins
 Specialized cells: myeloid, lymphoid,erythroid 3. Producing Hypersensitivity Reactions

Notes: Bursa of Fabricius (bird) BACTERIAL TOXINS

Man – Bone marrow Exotoxins Endotoxins
Primary B organ – GALT, MALT  Produced inside the cell  Part of outer portion of
Secondary lymphoid tissues – lymph nodes  Mostly from Gram (+) cell wall (LPS)
 Released into medium  Gram (-)
 Proteins  Released with cell death
MICROBIAL EXPOSURE  Highly specific effects  Lipid A
 Usually, exposure to various organisms starts when the cytotoxin, neurotoxin  Same SSx for all
baby first breaths air after birth. organisms - DIC
 Unfortunately for some, exposure starts prenatally.
 Initially, microbes are dealt with by maternal antibodies. 1. Exotoxins
 Produced inside the cell
Note: The neonate’s antibodies increase as the maternal antibodies  Mostly from Gram (+) organisms (do not need to die
decrease eventually leading to a larger amount of antibodies in the in order to release toxins)
neonate after approximately 6 months  Released into medium; usually proteins (viable)
 Highly specific effects: destroy particular parts of
host cells or inhibit certain metabolic function
CLONAL SELECTION HYPOTHESIS Examples:
 Every individual contains numerous clonally derived  Corynebacterium diphteriae found in the
lymphocytes, each clone having arisen from a single throatforms a pseudomembrane
precursor and being capable of recognizing and  Tetanus exotoxin targets nerves
responding to a distinct antigenic determinant to which he  Grouped into three types based on mode of action:
has been exposed previously.  Cytotoxins- kill host cells or affect their functions
 Antigen selects a specific pre-existing clone and activates  Neurotoxins- interfere with normal nerve
it, leading to its proliferation and its differentiation into impulse transmission
effector and memory cells.  Enterotoxins- affects cells lining the
gastrointestinal tract
Notes:  Antibodies called antitoxins are produced
CLASSES OF INFECTIOUS AGENTS by the body that provide immunity to
exotoxins
Five Groups
 Toxoids: exotoxins inactivated by heat or
1. Extracellular bacteria
by formaldehyde, iodine or other
2. Intracellular bacteria
chemicals; can stimulate the body to
3. Viruses
produce antitoxins but are non-infectious
4. Parasites
2. Endotoxins
5. Fungi
 Systemic, almost the same for all Gram (-) bacteria
 Part of the outer portion of cell wall (LPS)
Three Groups according to location
Lipopolysaccharide portion
1. Extracellular
 For Gram (-) organismsantibiotics are
2. Intracellular within a phagosome
givenorganism dies endotoxins are released
3. Intracellular but not within a vacuole
systemic effect
 Released with cell death; Lipid A
BACTERIA  Same symptoms for all organisms
A. Entry into host cells o Chills, fever, weakness, generalized aches and
 Portals of entry in some cases, shock and even death --> septic
 Number of invading organisms shock
 Adherence  DIC (Disseminated Intravascular Coagulation)

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 o Blood-clotting proteins are activated and blood
clots form causing blockage of capillaries,
IMMUNE EVASION
leading to ischemia Strategy of the microorganism to escape the immune system
 Pyrogenic response
o Macrophages are induced to produce EXTRACELLULAR BACTERIA
interleukin-1 (IL-1), which induces the Bacteria’s virulence factor will depend
hypothalamus to release prostaglandins that I. ANTI – INFLAMMATORY ACTIVITY AND
cause resetting of the thermostat in the PREVENTION OF CHEMOTAXIS
hypothalamus to a higher temperature.  E.g., Pseudomonas aeruginosa (Gram negative) elastase
 Septic shock destroys c3a and c5a
o Phagocytosed G(-) bacteria cause phagocytes Note: c3a and c5a function as anaphylatoxin /chemoattractants and
to release tumor necrosis factor (TNF) which release histamine for the inflammatory process. Without them,
damages blood capillaries, increasing their movement of inflammatory cells to site of infection would be
permeability and thereby leading to loss of compromised.
large amounts of fluid drop in blood
pressure. II. RESISTANCE TO PHAGOCYTIC ATTACHMENT
 Allow bacteria to cross blood-brain barrier  Production of capsule (difficult to phagocytose)
 E.g. Streptococcus pneumoniae (pneumonia)
Note: Aspirin and Acetaminophen reduce fever by inhibiting Neiserria meningitides (meningitis)
prostaglandin synthesis. Klebsiella pneumoniae (pneumonia)
Bacteroides fragilis (intestinal tract infection)
Note: an easier way to remember- EXotoxin is to G (+); ENdotoxin Pseudomonas aeruginosa (hospital-acquired infection)
is to Gram (-)
III. PROTEIN A
Table 9–4. Characteristics of Exotoxins and Endotoxins  Binds to Fc fragment og IgG1, IgG2, IgG4 and PMN’s
(Lipopolysaccharides). -Jawetz interfering with opsonisation
Exotoxins Endotoxins  Anticomplimentary
 Elicits platelet injury
Excreted by living cell; high Integral part of the cell wall of gram-
 E.g., Staphylococcus aureus
concentrations in liquid negative bacteria. Released on
medium. bacterial death and in part during
growth. May not need to be released IV. HYALURONIC ACID
to have biologic activity.  Similar to human connective tissue
Produced by both gram- Found only in gram-negative
positive and gram-negative bacteria. V. M PROTEIN
bacteria.  Inhibits alternative C’ pathway activation
 E.g., Streptococcus pyogenes
Polypeptides with a molecular Lipopolysaccharide complexes.
weight of 10,000–900,000. Lipid A portion probably
responsible for toxicity. VI. PILI
 Retards ingestion by phagocytes
Relatively unstable; toxicity Relatively stable; withstand heating
 Utilized for attachment of cells
often destroyed rapidly by at temperatures above 60°C for
heating at temperatures above hours without loss of toxicity.
 E.g., Neisseria gonorrhoea
60°C.
VII. SYNTHESIS OF PROTEIN
Highly antigenic; stimulate Weakly immunogenic; antibodies
 Induce dissociation or prevent formation of the C3
formation of high-titer are antitoxic and protective.
antitoxin. Antitoxin Relationship between antibody titers
convertase
neutralizes toxin. and protection from disease is less  Serve as co-factors for Factor I mediated cleavage of
clear than with exotoxins. C3b and C4b
 Bind C3 so it can’t cleave
Converted to antigenic, Not converted to toxoids.
nontoxic toxoids by formalin,  Use C’ receptors to establish infection
acid, heat, etc. Toxoids are
used to immunize (eg, tetanus Host Defenses Against Extracellular Microbes
toxoid). PRIMARY RESPONSE
Highly toxic; fatal to animals Moderately toxic; fatal for animals in  Phagocytes (macrophages, monocytes, PMN’s)
in microgram quantities or tens to hundreds of micrograms.  Alternative C’ pathway
less.  Antigen presenting cells (APC’s) – through T-cell
Usually bind to specific Specific receptors not found on cells. receptors, ADCC, NK cells
receptors on cells.
ANTIGEN PRESENTATION
Usually do not produce fever Usually produce fever in the host by
in the host. release of interleukin-1 and other  Antigen fragment-MHC Class II presented on APC
mediators. surfaces
 Activation of Th1 and Th2 to induce cytokine production
Frequently controlled by Synthesis directed by chromosomal
 Predominance of Th2 for B cell activation
extrachromosomal genes (eg, genes.
plasmids).
Note: many cell responses require both Th1 and Th2 cytokines

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 5.) Antigenic variation - Antigenic shift or drift
 Changes its coat
 Antigenic shift: major changes in viral structure
 Antigenic drift: minor changes in viral structure
 Example: Influenza virus

The Host
 Extracellular viruses (Viremic phase – bloodstream /
circulation)
 Destruction by phagocytes
 Neutralization by antibodies
 Intracellular viruses
 Attack by: NK cells or CD8+ T-lymphocytes (Tc)

Host Defenses Against Intracellular

INTRACELLULAR MICROBES WITHIN Organisms In The Cytoplasm
PHAGOSOMES  NATURAL KILLER CELLS (NK)
I. PREVENTION OF FUSION WITH PHAGOSOME  Mechanism is ADCC (Type II Hypersensitivity)
 E.g. Mycobacterium tuberculosis - (can escape fusion)  NK target cells with bound Immunoglobulins
Toxoplasma gandii  Interaction with infected cells release perforin
Chlamydia trachomatis  Osmotic lysis of target cell

Mycobacterium tuberculosis Processing And Presentation Of Endogenous Antigens

AGENT HOST
Prevention of fusion Within macrophages: superoxides, nitric acid
of phagosomes due to action
sulfatides Tubercle formation
Reactive O2 intermediates result in low level
degradation of bacteria
Antigen fragment recognition MHC Class II
by Th1
Th1 cytokines act on NADPH and nitric
oxide synthase

Chlamydia trachomatis
AGENT HOST
Infective stage: elementary body Type 1 cytokines (IFNϒ, TNF)
Evasive stage: reticulate body Chemokines
 Viral proteins enter the cell.
Antibodies: IgM, IgG, IgA
 Endoplasmic reticulum contains MHC Class I and TAP, a
transporting protein. It proceeds to the Golgi apparatus
II. RESISTANCE TO DIGESTION
and its buds.
 E.g., Leishmania, Mycobacterium leprae (protozoa;
 Viral proteins undergo degradation by fusion with
relative of tuberculosis)
proteasomes. On the surface of the cell, it is then presented
as viral peptides together with MHC Class I.
III. ESACPE FROM PHAGOSOME IN THE CYTOPLASM
 MHC Class I, when fused with a viral peptide, acts as
 After fusing, they detach themselves
signal for CD8+ T-lymphocytes (Tc) to directly eliminate
 E.g., Trypanosomes, Rickettsia, Chlamydia
infected cell.
Note: MHC Class I can fuse with viral peptide because it came from
Host Defenses Against Intracellular
inside the cell. Antigen is endogenous / within cell
Microbes Within Phagosomes
 Macrophages act as APC’s GOAL: Destruction Of Infected Cell Antigen Presentation
 Antigenic peptides – MHC Class II complex presented on
 Antigen fragment-MHC Class I complex on APC surfaces
APC surface
 Recognized by Tc cells which had been primed by IL2
 Induces Th1 cytokine Type 1 production

(Type 1 cytokine)
 Enhances activity of NADPH oxidase and production of
 Release of perforin by Tc cells inducing osmotic lysis in
nitric oxide synthase

target cells
 Nitric oxide crosses membrane into phagosome

HEPATITIS B (DNA virus)

VIRUSES AGENT HOST
 Enter the cell without invitation Cytopathic effect Neutralizing anti-viral IgM&IgG
 Attacks DNA / RNA of cell Anti - complementary activity Viral proteins degraded into
particularly in chronic cases peptides by proteasome in cytosol
Tissue damage due to host-virus MHC I-Ag complex recognized by
1.) Intracellular Existence

interaction Tc
2.) Adherence to Host Cells

3.) Cytopathic Effects
 - moderate / modify cell
4.) Cytocidal Effects or Non-Cytocidal Effects
 Cytocidal effects – result in cell death
 Non-cytocidal effects – result in cell damage but

not cell death

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 Influenza Malaria
AGENT HOST AGENT HOST
Hemagglutinin (HA) Extracellular (Antibodies);  Extracellular  CD4+ T cell help for
CD4+  Fast entry into RBCs cells with antibody
Neuraminidase (NA) Intracellular CD8+ T cells, NK  Differing antigenic formation (IgG, IgM)
Mutations in HA (attachment) & NA epitopes (sporozoite and  Phagocytes
(virus release into cells) ==drift or merozoite)
shift  Intracellular
Antigenic variation  Anatomic inaccessibility  Balance between Type
in RBCs 1 and Type 2
 Immunosuppression cytokines
FUNGI  Antigenic variation  CD8+ T cells
A. Superficial *Emphases on these topics are still for 2nd Semester, but read through
B. Systemic it just in case 
1. Structures: capsule protects the microorganism
(anti phagocytic structure) *In Endemic Areas With “Stable” Malaria
Cryptococcus neoformans (very thick capsule,  Mostly affected are on the younger age group; have the
seen by india ink stain) highest parasitemia
2. Allergic responses  Antibodies from mother transmitted to newborn
3. Toxins onlyuntil 6 months
Aflatoxin from Aspergillus (opportunistic;  Highest parasitemia in children 6 months- 5 years (at 6
seen in immunocompromised individuals) months, immunity disappears and becomes susceptible)
 As they grow older, they become immune
Host Defenses Against Fungi  Adolescents and adults low parasitemia
 Phagocytes as first line of defense  Antiparasitic immunity directed against asexual stages
 Cytotoxic function enhanced by Th1 cytokines in blood acquired later in life
 B cell production of antibodies
*In Endemic Areas With “Unstable” Malaria
PARASITES  All ages susceptible to clinical malaria and epidemics
I. DAMAGE TO HOST TISSUE DIRECTLY OR BY may occur
METABOLIC WASTE PRODUCTS  Erratic epidemiology
 Entamoeba  Parasitemia can be in any age groups
 Balantidium
*Innate Resistance
II. ANTIGENIC VARIATION *there are certain blood groups that are innate, so they don’t get
 Plasmodium infected with Malarial Infection.
 Trypanosomes  Hemoglobin structure
 Thalassemia
III. ABSORPTION OF NUTRIENTS  G6PD deficiency
 Ascaris  ATP levels within RBC
 Taenias
VACCINATION
IV. INTRACELLULAR EXISTENCE
 Plasmodium  Stimulation of adaptive immunity
 Leishmania  Specificity
 Memory
Host Defenses Against Parasites
 Humoral response when parasites invade the bloodstream VACCINES
 Cell-mediated immunity for tissue parasites  Attenuated Virus (live but w/ no virulence factor)
 Hypersensitivity Type I  must replicate to be effective
 immune response similar to natural infection
Schistosomes  usually effective on a single dose
AGENT HOST  severe reactions possible
Cercariae Immediate and Delayed  unstable
Hypersensitivity  Examples:
Schistosomulae ADCC  Measles
Schistosomes/eggs Ag-Ab complexes  Mumps
Eggs Delayed hypersensitivity
 Rubella
 Chickenpox
 Polio
Intestinal Lumen Dwelling Helminths
 Killed (Inactivated)
AGENT HOST
 not lived, cannot replicate
Competition for nutrients in the host IgE levels increased
 general not as effective as live vaccines
Anaphylactic hypersensitivity
 requires 3-5 doses
 immune response mostly humoral
 antibody titer falls over time
 Examples:
 Influenza
 Rabies
 Hepatitis A

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  Polio (Salk)
 Pertussis

 Antigenic Fragments
 Hepatitis B (recombinant)
 Pertussis (acellular)
 Pneumococcal polysaccharide
 Meningococcal polysaccharide
 H. influenza polysaccharide

 Toxoid (inactivated toxins)

 Diphtheria
 Tetanus

HERD IMMUNITY

significant portion of the population provides a measure of protection

for individuals who have not developed immunity.

SUMMARY
 World wars may end but the war raging in the human
body is far from over.
 Microorganisms persistently try to establish themselves
in the host. When they are successful, disease occurs.
 But the immune system is always on the look-out for the
enemy. When it is vigilant, the host is healthy.
 Thus, a battle for supremacy occurs continuously in man’s
body.

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