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Host-Microorganism Interactions

National Institutes of Health initiated a The Encounter Between Host


Project (2007) - Human Microbiome Project
and Microorganism
Human microbiome - consists of microorganisms that The Human Host’s Perspective
are present in and on the human body at any given ➢ Because microorganisms are found
time without causing harm. everywhere, human encounters are
inevitable, but the means of encounter vary
The initial development of the microbiome project Widely.
focused on four major goals: Example: acquiring salmonellosis because one fails to
(1) determining whether a core cook the holiday turkey thoroughly is avoidable,
human microbiome exists. whereas contracting tuberculosis as a consequence of
(2) determining whether changes in the human living in conditions of extreme poverty and
microbiome correlate with health and disease overcrowding may be unavoidable
(3) developing new technology and bioinformatic
tools to manage the project data. Microbial Reservoirs and Transmission
(4) addressing the ethical, legal, and social ➢ Humans encounter microorganisms when
implications associated with the microbiome they enter or are exposed to the same
project. environment in which the microbial agents
live or when the infectious agents are brought
to the human host by indirect means.
• Reservoir- the environment, or place of
origin, of the infecting agent
• Mode of transmission - the means by
which etiologic agents are brought in
contact with the human host (e.g.,
infected blood, contaminated water,
insect bite).
• Vector - the agents of transmission that
bring the microorganism from the
reservoir to the host may be a living
entity, such as an insect.
• Vehicle/fomite - nonliving entity
Microbial reservoirs
a. humans
b. animals
c. water
Stages of interaction d. food
(1) the physical encounter between the e. air
host and microorganism f. soil
(2) colonization or survival of the microorganism on
an internal (gastrointestinal, respiratory, or
genitourinary tract) or external (skin) surface of the
host
(3) microbial entry, invasion, and dissemination to
deeper tissues and organs of the human body
(4) resolution or outcome.
Human and Microbe Interactions Microorganism Colonization
➢ Humans play a substantial role as microbial
of Host Surfaces
reservoirs.
The Host’s Perspective
• Direct transmission - acquiring a
Once a microbe attains contact with a human
microorganism from another human serving
host, the outcome of the encounter depends on
as the reservoir.
what happens during each step of the interaction
example: passage of a neonate from the
beginning with colonization.
sterile environment of the mother’s womb through
Surfaces that microorganisms will initially come in
the birth canal, which is heavily colonized with various
contact with the human host:
microbial agents.
• Indirect transmission - can occur when 1. Skin (including the conjunctival epithelium
microorganisms from one individual covering the eye)
contaminate a vehicle of transmission. 2. Mucous membranes lining the mouth or oral
Example: water (cholera) cavity, the respiratory tract, the
• Nosocomial infections - Infection for which the
gastrointestinal tract, and the genitourinary
etiologic agent was acquired in a hospital or
tract.
long-term health care center or facility.
Example: exposure in a variety of settings that are Nonspecific defense mechanisms includes:
not confined to in-patient care within a traditional *skin, mucous membranes, secretions, excretions,
health care institution. enzymes, inflammatory responses, genetic
factors, hormonal responses, nutritional status,
Animals as Microbial Reservoirs behavior patterns, and the presence of other
➢ Infectious agents from animal reservoirs can diseases.
be transmitted directly to humans through an Skin and Skin Structures
animal bite (e.g., rabies) or indirectly through - Skin serves as a physical and chemical barrier
the bite of insect vectors that feed on both to microorganisms.
animals and humans (e.g., Lyme disease and - The acellular, outermost layer of the skin,
Rocky Mountain spotted fever). along with the tightly packed cellular layers
• Zoonotic infection - an infectious disease that underneath, provides an impenetrable
is transmitted between species from animals physical barrier to all microorganisms, unless
to humans (or from humans to animals). damaged.
- these layers continuously shed, thus
Insects as Vectors dislodging bacteria that have attached to the
➢ The most common role of insects (arthropods) outer layers.
in the transmission of infectious disease is as • The follicles and glands of the skin produce
vectors rather than as reservoirs. various natural antibacterial substances,
Example: Malaria (mosquito bite through vector including sebum and sweat.
Female Anopheles mosquito) • Skin colonizers – microorganisms that can
• Ectoparasites - they are able to survive survive the conditions of the skin.
on the skin of the host without gaining
access to internal tissues.

The Environment as a Microbial Reservoir


➢ The soil and natural environmental debris are
reservoirs for countless types of
microorganisms.
Example: San Joaquin Valley fever (acquired by
inhalation of soil and dust particles containing
microorganisms).

The Microorganism’s Perspective


➢ Microorganisms are also driven by survival,
and the environment of the reservoirs they
occupy must allow their metabolic and
genetic needs to be fulfilled.
damage that promotes microbial invasion, and
contains specific chemical (i.e., antibodies) and
nonspecific antibacterial substances.
*Mucosa-associated lymphoid tissue (MALT) -
initiates immune responses to specific antigens
encountered along all mucosal surfaces.

Specific Protective Characteristics


• Mouth/oral cavity - protected by the flow of
saliva that physically carries microorganisms
away from cell surfaces and also contains
antibacterial substances, such as antibodies
(IgA) and lysozyme that participate in the
destruction of bacterial cells.
• Gastrointestinal tract - low pH and
proteolytic (protein-digesting) enzymes of the
stomach prevent the growth of many
microorganisms.
• Small intestine - protection is provided
through the presence of bile salts, which
disrupt bacterial membranes, and by
peristaltic movement and the fast flow of
intestinal contents, which hinder microbial
attachment to mucosal cells.
• Upper respiratory tract - nasal hairs keep
out large airborne particles that may contain
microorganisms.
Cilia - hairlike cellular projections

General Protective Characteristics The Microorganism’s Perspective


• Mucus – major protective component of the • Transient colonizers - they are able to
membranes. survive, but do not multiply, on the surface
✓ This substance serves to trap bacteria before and are frequently shed with the host cells.
they can reach the outer surface of the cells.
✓ Lubricates the cells to prevent
• Resident microbiota -microorganisms that Disruption of Surface Barriers
survive, thrive and multiply; their presence is
more persistent.

Microbial Colonization
➢ Colonization may be the last step in the
establishment of a long-lasting, mutually
beneficial (i.e., commensal) or harmless
relationship between a colonizer and the
human host.
➢ Alternatively, colonization may be the first
step in the process for the development of
infection and disease.
❖ Whether colonization results in a
harmless or damaging infection depends
on the characteristics of the host and the
microorganism.
➢ Besides surviving the host’s physical and
chemical conditions, colonization also
requires that microorganisms attach and
adhere to host surfaces.
Responses to Microbial Invasion of Deeper
Tissues:
✓ Once surface barriers have been bypassed,
the host responds to a microbial presence in
the underlying tissue in various ways.
Some of these responses are:
1. Nonspecific – they occur regardless of the
type of invading organism.
2. More specific - involve the host’s immune
system.
➢ Both nonspecific and specific host responses
are critical if the host is to survive.
➢ Without them, microorganisms would
multiply and invade vital tissues and organs,
resulting in severe damage to the host.

Nonspecific Responses
Some nonspecific responses are:
1. Biochemical - factors that remove essential
Microorganism Entry, Invasion, nutrients, such as iron, from tissues so that it
and Dissemination is unavailable for use by invading
microorganisms.
The Host’s Perspective - In most instances, to
2. Cellular – responses that are central to tissue
establish infection, microorganisms must penetrate or
and organ defenses, and the cells involved are
circumvent the host’s physical barriers (i.e., skin or
known as phagocytes.
mucosal surfaces); overcoming these defensive
barriers depends on both host and microbial factors.
✓ When these barriers are broken, numerous Phagocytes
other host defensive strategies are activated. ➢ are cells that ingest and destroy bacteria and
other foreign particles.
➢ Phagocytes ingest bacteria by a process
known as endocytosis and engulf them in a
membrane-lined structure called a
phagosome.
the immune system or as a result of the
presence of invading microorganisms.
• Cytokines - chemical substances, or proteins
secreted by a cell, that have effects on the
Types of phagocytes: activities of other cells.
a. Polymorphonuclear leukocytes (neutrophil’s - draw more phagocytes toward the infection
PMN’s) and activate the maturation of monocytes to
b. Macrophages macrophages.
c. Dendritic cells

• Phagolysosome - a cytoplasmic body formed


by the fusion of a phagosome with a lysosome
in a process that occurs during phagocytosis.
The two major phagocytes, PMNs and macrophages,
differ in viability and anatomic distribution.
✓ PMNs develop in the bone marrow and spend
their short lives (usually a day or less)
circulating in blood and tissues.
• PMNs usually are the first cells on the scene
of bacterial invasion.
✓ Macrophages also develop in the bone
marrow. Macrophages circulating in the
bloodstream are called monocytes.
• When deposited in tissue or at a site of The manifestations of inflammation are
infection, monocytes transform into mature readily evident and are familiar to most
macrophages. adults; they include the following:
a. Swelling—caused by an increased flow of
Inflammation fluid and cells to the affected body site.
- inflammatory response plays an extremely b. Redness—results from vasodilation of blood
important role as a primary mechanism vessels and increased blood flow at the
against microbial survival and proliferation in infection site.
tissues and organs. c. Heat—results from increased cellular
➢ has both cellular and biochemical components metabolism and energy production in the
that interact in various complex ways (Table affected area.
3-3). d. Pain—caused by tissue damage and pressure
➢ Complement system - composed of a on nerve endings from an increased flow of
coordinated group of proteins activated by fluid and cells.
Three major types of cells immune response:
1. B Lymphocytes - originate from stem cells
and develop into B cells in the bone marrow
before being widely distributed to lymphoid
tissues throughout the body.
✓ primarily function as antibody producers
(plasma cells)
2. T lymphocytes - also originate from bone
marrow stem cells, but they mature in the
thymus and either directly destroy infected
cells (cytotoxic T cells) or work with B cells
(helper T cells) to regulate antibody
production.
3. Natural killer cells - are a subset of T cells.
Specific Responses—The Immune System
Types of natural killer cells but most prevalent is:
➢ The immune system provides the human host • Invariant natural killer T (NKT) cells - most
with the ability to mount a specific protective prevalent natural killer cells
response to the presence of the invading ➢ Develop in the thymus from the same
microorganism. precursor cells as other T lymphocytes
➢ Have a limited repertoire of T cell receptors
Components of the Immune System that respond to synthetic, bacterial and fungal
➢ The central molecule of the immune response glycolipids.
is the antibody. ➢ Activated by the release of cytokines during
• Antibodies, also referred to as viral infections.
immunoglobulins, are specific glycoproteins
produced by plasma cells (activated B cells) in Two Branches of the Immune System
response to the presence of a molecule
1. Antibody-mediated immunity/humoral
recognized as foreign to the host (referred to
immunity - centered on the activities of B
as an antigen).
cells and the production of antibodies.
Five major classes of antibody have been identified: 2. Cell-mediated immunity/cellular
1. IgG - production of the most abundant immunity – typically comes into play at body
antibody. sites where cells are infected by a virus,
2. IgA - secreted in various body fluids (e.g., bacteria, or fungi (intracellular invaders).
saliva and tears) and primarily protects body
surfaces lined with mucous membranes.
3. IgM - largest and first antibody produced
when an invading microorganism is initially
encountered.
4. IgD - is attached to the surface of specific
immune system cells and is involved in the
regulation of antibody production.
5. IgE – increased IgE is associated with parasitic
infections and allergies.
Antibodies protect the host in a number of ways:
• Helping phagocytes to ingest and kill
microorganisms through a coating mechanism,
referred to as opsonization.
• Neutralizing microbial toxins that are detrimental to
host cells and tissues.
• Promoting bacterial clumping (agglutination) that
facilitates clearing from the infection site.
• Inhibiting bacterial motility.
• Viral neutralization; blocking the virus from
entering the host cell.
• Combining with microorganisms to activate the
complement system and inflammatory response.

Colonization and Infection


➢ Many human body surfaces are colonized
with a wide variety of microorganisms or
microbiota without apparent detriment.
• Infection - involves the growth and
multiplication of microorganisms that result in
damage to the host.
• Disease - results when the infection
produces notable changes in human physiology
associated with damage or loss of function to one
or more of the body’s organ systems.

Pathogens and Virulence


• Pathogens - microorganisms that cause
infections or disease.
• Virulence factors - the characteristics that
enable them to cause disease.
• Pathogenicity - specifically refers to the
Major histocompatibility complex (MHC)- group of organism’s ability to cause disease.
genes that code for proteins found on the surfaces of • Virulence - refers to the measure or degree
cells that help the immune system recognize foreign of pathogenicity of an organism.
substances. ✓ An organism of high pathogenicity is very
Two primary classes of major histocompatibility likely to cause disease, whereas an organism
molecules: of low pathogenicity is much less likely to
1. MHC I - molecules are located on every cause infection.
nucleated cell in the body and are • Opportunistic pathogens - organisms that
predominantly responsible for the recognition cause infection when one or more of the
of endogenous proteins expressed from host’s defense mechanisms are disrupted or
within the cell. malfunction.
2. MHC II – molecules are located on ✓ These are type of pathogens in which they are
specialized cell types, including macrophages, the normal floras in our body then if maabot
dendritic cells, and B cells, for the sila sa lain part sa ato body nga dili jud ilaang
presentation of extracellular molecules or specific location they can cause infection or
exogenous proteins. disease.
Example: Staphylococcus aureus, Pseudomonas
aeruginosa, Staphylococcus epidermidis
• Opportunistic infections - infections
That is caused by opportunistic pathogens.

Microbial Virulence Factors


➢ Virulence factors provide microorganisms
with the capacity to avoid host defenses and
damage host cells, tissues, and organs in a
number of ways.
• Attachment - Whether humans encounter
microorganisms in the air, through ingestion,
or by direct contact, the first step of infection
and disease development is microbial
attachment to a surface.
• Intoxication - common mechanism of food
• Invasion - Once surface attachment has
poisoning involves ingestion of preformed
been secured, microbial invasion into
bacterial toxins (present in the food at the
subsurface tissues and organs (i.e., infection)
time of ingestion).
is accomplished by disruption of the skin and
two general types of bacterial toxins
mucosal surfaces by several mechanisms or by
1. Endotoxin - is a component of the cellular
the direct action of an organism’s virulence
structure of gram-negative bacteria and can
factors.
have devastating effects on the body’s
• Survival Against Inflammation - if a
metabolism, the most serious being endotoxic
pathogen is to survive, the action of
shock, which often results in death.
phagocytes and the complement components
2. Exotoxin - produced by gram-positive
of inflammation must be avoided or
bacteria tend to be more limited and specific
controlled.
than the effects of gram-negative endotoxin.

Genetics of Virulence: Pathogenicity Islands


• Pathogenicity islands (PAIs) – These are
mobile genetic elements that contribute to
the change and spread of virulence factors
among bacterial populations of a variety of
species.
➢ PAIs are widely disseminated among
medically important bacteria.
PAIs have been identified as playing a role in virulence
for each of the following organisms:
Helicobacter pylori
Pseudomonas aeruginosa
Shigella spp.
Yersinia spp.
Vibrio cholerae
Salmonella spp.
Escherichia coli (enteropathogenic,
enterohemorrhagic
• Survival Against the Immune System - a or serotoxigenic, verotoxigenic, uropathogenic,
pathogen can use more than one strategy to enterotoxigenic, enteroinvasive, enteroaggregative,
avoid immune-mediated defenses, and meningitissepsis associated; Chapter 19)
microbial survival does not necessarily require Neisseria spp.
devastation of the immune system. Bacteroides fragilis
Listeria monocytogenes
• Microbial Toxins Staphylococcus aureus
Toxins - are biochemically active substances Streptococcus spp.
Enterococcus faecalis
released by microorganisms
Clostridium difficile
that have a particular effect on host cells.
Outcome and Prevention of Infectious
Diseases
Outcome of Infectious Diseases
➢ Basically, outcome depends on the state of
the host’s health, the virulence of the
pathogen, and whether the host can clear the
pathogen before infection and disease cause
irreparable harm or death.
✓ The time from exposure to an infectious agent
Biofilm Formation and the development of a disease or infection
depends on host and microbial factors.
➢ Microorganisms typically exist as a group or
• Acute infections - Infectious processes that
community of organisms capable of adhering
develop quickly.
to each other or to other surfaces.
• Chronic infections – develop and progress
➢ Once the initial biofilm has developed, a
slowly, sometimes over a period of years.
process which takes approximately 4 to 6
hours, depending on the growth rate of the • Latent - Some pathogens, particularly certain
microorganism, maturation of the biofilm viruses, can be clinically silent inside the body
occurs. without any noticeable effect on the host
before suddenly causing severe and acute
Microorganisms that are capable of infection.
forming biofilms: Medical intervention can help the host fight the
infection but usually is not instituted until after
• S. aureus, P. aeruginosa, and Candida albicans the host is aware that an infectious process is
➢ Persister cells - dormant cells that form underway.
spontaneously within a biofilm that are highly • Signs - are measurable indications or physical
recalcitrant to antimicrobial challenge. observations, such as an increase in body temperature
(fever) or the development of a rash or swelling.
• Symptoms - are indictors as described by the
patient, such as headache, aches, fatigue, and
nausea.
Whether medical procedures contribute to controlling
or clearing an infection depends on key factors,
including:
• The severity of the infection, which is determined by
the host and microbial interactions already discussed
• Accuracy in diagnosing the pathogen or pathogens
causing the infection
• Whether the patient receives appropriate treatment
for the infection (which depends on accurate
diagnosis).
Prevention of Infectious Diseases
➢ The treatment of an infection is often difficult
and not Two basic approaches to immunization
always successful. Because much of the damage may 1. Active immunization - modified antigens
already have been done before appropriate medical from pathogenic microorganisms are
intervention is provided, the microorganisms gain too introduced into the body and cause an
much of a “head start.” immune response
✓ Another strategy for combating infectious 2. Passive immunization - antibodies against a
diseases is to stop infections before they start particular pathogen that have been produced
(i.e., disease prevention). in one host are transferred to a second host,
where they provide temporary protection.
❖ The passage of maternal antibodies to the
newborn is a key example of natural
passive immunization.
Successful immunization has proven effective
against many infectious diseases, including
diphtheria, whooping cough (pertussis),
tetanus, influenza, polio, smallpox, measles,
hepatitis, and certain Streptococcus
pneumoniae and Haemophilus influenzae
infections.
Epidemiology
➢ is the science that characterizes these
aspects of infectious diseases and
monitors the effect diseases have on
public health.
Epidemiologic investigations cannot proceed
unless researchers first know the etiologic or
causative agents.

Immunization
➢ Most effective method in preventing disease
to occur.
➢ Medical strategies exist for minimizing the risk
of disease development when exposure to
infectious agents occurs.

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