Download Microbial Pathogenesis and infection

College of Medicine
Microbiology(Bacteriology)
Dr. Bara H. Hadi
----------------------------------------------------------------------------------------Microbial Pathogenesis and infection
Infection is presence and multiplication of pathogenic microbe within human body,
and cause symptoms of infection. The infection differs from other diseases is that
caused by living microbial pathogens.
Infection (or not) is determined by balance between number and virulence of microbe
and competency of that host defense. If microbes are overcome, the disease
results.Outcome of most host-parasite relationship is dependent on three main factors
;
a. Number of pathogenic microorganism infecting the host(dose).
b. Degree of pathogenicity of organism(virulence).
c. Degree of host defense (resistance).
The infectious disease equation:
Number of organisms(dose) x Virulence
= Infectious Disease
Host resistance
The infection does not arise in vacuum. It results from interaction of several factors
include mainly three factors:
a. Virulent microbe.
b. Susceptible host.
c. Environmental factors
Stages of microbial pathogenesis:
1. Encounter of microbe with susceptible host.
2. Entry and adhere to susceptible host tissues.
3. Multiply and spread to adjacent cells or to specific cells.
4. Evade host defense mechanism.
5. Damage the host tissues and disease symptoms.
6. Progression or resolution of the disease.
7. Shedding of microbial pathogen into environment.
Sources of infection:
1. Human : is common source of infection from patients or carriers. The
carrier is person recovered from disease but harboring pathogenic organism in
his body. Fomites are inanimate objects of patients that may be contaminated
and serves as source of pathogenic organisms.
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The infectious agent is transmitted from person to person by various ways
such as direct contact, kissing, inhalation of aerosols, faecal-oral, venereal
contact, blood transfusion and insect bite.
Animals ; are important source of pathogenic organisms that infect human.
The animals can be serve either the source (reservoir )or made transmission
(vector)of certain organism.
The organisms can be transmitted from infected animals to human when
direct contact with animals, and handling or consumption of their products ,
also transmitted indirectly by bite of vectors.
Food: the foods are most important media for surviving and transporting the
infection eg. food poisoning. Transmission of organisms from food to human
during feeding or food handling.
Water: many pathogenic microbes are found in water. The infectious agents
are transmitted to human by consumption of water or when swimming in it.
Soil: it serves as source of infection for many pathogenic organisms or spores
of some bacteria and fungi. The infectious disease agents are transmitted to
human through direct work with soil that contain infectious agents or
inhalation of dust .
Portals of entry(routes of infection) :
Major:
1. Respiratory tract(nose).
2. Elementary tract(mouth).
3. Skin, non-intact.
4.Genital tract(vagina).
Minor :
1. Eye.
2. Anus
3. Ear canal
4. Urethral canal.
Mode of transmission:
Horizontal transmission:
 Inhalation: the pathogenic agents may be transmitted by inhalation of
respiratory secretions of infected patients, or by inhalation of contaminated
dust with pathogenic bacteria .
 Ingestion: the infectious agents can be transmitted by consumption of
contaminated water or food. Also the infection may acquire during handling
food, swimming in water or inhalation of water aerosols.
 Skin : any small break, abrasion, and wound in skin that permit initial entry.
The transmission may occur through direct contact(such as handshaking,
kissing)with infected person , infected animal or during handling of fomites of
patients, or the organism is transmitted indirectly by vector bite .
 Blood transfusion: some pathogenic microorganisms can be transmitted by
blood transfusion. Injection of needles during intravenous drug use or
indwelling catheter, have role in transmission.
 Sexual intercourse: certain pathogenic microorganisms can be transmitted by
sexual contact in homosexual or heterosexual persons.
Vertical transmission:
The pathogen can transmitted from infected mother to her fetus ;
 Across the placenta (prenatal) ,or
 At time of delivery from birth canal (perinatal), or
 During breast feeding (postnatal) .
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Adherence of microbe to host cell:
 The microbes tend to exhibit cell and organ specificities dependent on :
1. Presence of specific cellular receptors on cell surface which interact with
microbe.
2. Environmental factors such as physical barriers, local temperature, pH,
oxygen tension and others are very important in initial infection.
 The presence of cellular receptors and environmental factors as well as initial
location and other conditions on tissue can determine which part of human
body is infected .
Multiplication of pathogen:
 The microbes can be multiplied by growing at site of adherence and form
colonization. Colonization means establishment of a site of microbial
multiplication in the host.
 If pathogen successful in colonization in human body ,The pathogen must
multiply to sufficient number in host tissues to cause the symptoms of disease.
The number of microbe present in patient body must exceed a given threshold
to cause disease. If the number is below that threshold, no signs and symptoms
of disease will be apparent.
 The period between entry pathogenic organism and beginning of symptoms
known as incubation period.
Invasion of host tissues:
The invasiveness is ability of microorganism to spread into host tissues. Some
bacteria are non invasive, but multiply at site of adherence. Bacteria secrete
several invasive factors (spreading factors) that result in degrading tissue and
facilitate the pathogen spreading through human body.
Evasion of host defense:
Generally, Some mechanisms that play important role in resistance of pathogenic
organism to host defenses:
 Certain bacteria have capsule that prevent the phagocytosis.
 Certain pathogens able to survive and grow intracellular because have able to
inhibit the fusion of phagosome with lysosome.
 Certain bacteria secrete enzymes(eg.IgA protease)that destroy antibody IgA.
 Certain bacteria produce toxin(such as leucocidin) that lead to destroy the
immunity cells.
 Change in genetic materials lead to antigenic variation.
Pathogenesis (mechanism of damage and death of cell):
In general, the pathogenic microbes cause damage of tissue by two main mechanisms
of pathogenesis:
1. Production of toxins and enzymes.
2. Immunopathological reactions .
Toxin production(toxigenicity):the ability of pathogen to produces toxin that damage
the host tissue and produce disease. Bacterial pathogens produce two types of toxins;
exotoxin and endotoxin.
Exotoxin is produced by Gram positive and Gram negative bacteria . In contrast,
endotoxin is produced by only Gram negative bacteria.
Exotoxins produce various effects by different mechanisms in host body. For
example, Diphtheria toxin cause cell death by inhibition of protein synthesis.
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Enterotoxins cause watery or bloody diarrhea by stimulation of adenylatecyclase.
Tetanus toxin cause paralysis by effect on neurotransmitters, and so on.
Endotoxins less potent than exotoxins and produce similar effects on host such as
fever ,hypertension, DIC and shock.
Endotoxin does not cause effects directly. It in blood stream is bound to circulating
proteins, which then interact with receptors on macrophage and monocytes and other
cells of reticuloendothelial system. IL-1, TNF and other cytokines are released, and
the complement and coagulation cascades are activated.
Immunopathological reaction :
 Microbial pathogens may stimulate the immune system to attack the host
tissue because it carries antigens that resembled those of host. It may be
appears as autoimmune response(the immune system fails to distinguish
between self and non-self, and attacks part of the body) or as cross-reaction
between antigens of pathogenic microbes and antigenic components of human
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body. Some diseases also might be due to hypersensitivity reaction (the
immune response that damages the body's own tissues). Tuberculosis is a good
example of involvement of hypersensitivity reaction in disease.
Mechanical effectcauses of disease:
 Mechanical obstruction results from pathogen such as many Ascariscan
occlusion of intestine lumen. A single worm may migrate to bile duct and
obstruct the passage of bile.
 Mechanical obstruction results not from microbe but from response of
inflammatory host such as infection of prostate can obstruct flow of urine from
bladder; inflammation of epiglottis may impede the passage of air.
Outcome of infection:
 If microbial pathogens overcome the defenses of infected individual, the
disease resulted and may cause death of infected host, while the host defenses
overcome in first step, the disease is not occurring.
 If the host defenses overcome the virulent microbe after infection, this lead to
repair and healing, and recovery from infection.
 If the host defense is failure to eliminate the microbe from the body, the
infection may become chronic(persistent infection), which mean the microbes
may continue to multiple and produce significant symptoms of disease for
long period.
Persistence of infection:
It mean the microbes may continue to multiply and able to infect other hosts.
Persistent infections represent a failure of host defenses to eliminate the microbe
from the body.
Three types of persistent microbial infections:
1. Chronic infections: some patients who have infected with some microbes
continue to produce significant symptoms of disease and significant amount of
microbes for long period.
2. Latent infection: some patients recover from initial infection and microbe
production stops. However, the patients harboring the microbe in their bodies
(remain as carriers).
3. Slow microbial infections: some infections require to long period between
initial infection and onset of disease, which are usually measured in years
(such as Kuru disease, and HIV, TB, and Rabies).
Microbes shedding:
 The last stage in pathogenesis is the shedding of infectious microbes. The
microbial pathogens leave the host and shed back into environment or return
to reservoir or enter a new host.
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