Immunology- 2011
Lesson Outline
Infectious disease
2. Pathogenicity
3. How does host and pathogen interact?
4. Microbial Virulence Factors
Antiphagocytic factors

Exotoxins

Endotoxins
1.
Infectious disease
 occurs as the result of interaction between pathogen
and the host
 Infections begin at some surface of the host- skin,
conjunctiva, internal surface of the mucous membrane
of respiratory tract, intestine etc.
 Many pathogens can selectively attach to particular
host surface.
 pathogenic organism penetrates the body surface and
gain access to the internal tissues
 Infections of microorganism becomes localized,
growing near its point of entry into the body.
 Some pathogens cause generalized infection and
microorganisms become widely distributed and grows
through out the body.
 Pathogen capable of growth within the cell of the host
disrupts the normal physiological process.
What damages the body cells?
 Toxins by microorganisms.
 Virulence factors - combat various defense
mechanisms of the host.
what is pathogenicity?
 Is the capability of a microbial species to cause
disease.
 various strains of a pathogenic species may differ with
regard to their degree of pathogenicity and with
regard to their virulence.
highly virulent - only a few bacterial cells
2. less virulent - larger numbers of cells
3. avirulent - incapable of causing the disease even
when large numbers.
1.
what are attenuated strains?
 When virulent strains of many pathogens are repeatedly
cultured on laboratory media or grown in vivo in hosts
other than their normal hosts , they lose their virulence.
 widely used as vaccines to elicit immunity to various
diseases.
How to measure the virulence of an organism?
 By determining its LD50 dose for a laboratory animal.
 LD50 - defined as that number of organism which
when administered to number of laboratory animals,
kills 50 percent of them.
 LD100
Infection
 Represents the most intimate way in which a
microorganism may cause disease.
 Host is invaded and multiply in close association with
host’s tissue.
 Note: not all diseased caused by microorganisms are
infections.
Process of infection
Pathogen must accomplish the following:
 It must enter the host
 It must metabolize and multiply on or in the host
tissue
 It must resist host defenses
 It must damage the host.
Process of Host pathogen interaction
1.
Microbial adherence
2.
Penetration/ entrance into the body
3.
Events of infection following penetration
4.
microbial virulence
Microbial adherence
 first step in initiation of infection is by adherence of
pathogens to some surface of the hosts.
 Attachment is selective.
 various pathogens attaches to certain tissues.
 Mode of attachment is not yet understood, for pathogenic
fungi & protozoa.
For bacteria:
 Neisseria gonorrhea - epithelial layer of human cervixpili.
 E. coli - mucosal lining of the intestine- pili.
 Streptococcus pyrogenes- epithelial cells by means of cell
wall protein called M-protein.
Virus:
 Influenza virus particle is studded with haemagglutinin
spikes- to specific mucoprotein receptors on the surface of
the host cell.
 Polio virus - to lipid and glycoprotein containing
receptors on host cells.
Penetration/entrance of pathogen
 Microorganism may merely multiply on the epithelial
surface & cause damage without penetration into the body.
Example:
V. cholerae, causative agent of the severe diarrheal
disease known as cholera,
multiply on the epithelial layer of the small intestine
where it produces a toxin that cause the loss of fluid from
the epithelial cells and kills the cells.
 Penetration may be achieved not only actively but also
passively .
 Actively - by the adherence and penetration mechanism of
the pathogens itself.
 Passively - by mechanisms having nothing to do with the
properties of the microorganism.
 portals of entry are the respiratory tract and
gastrointestinal tract
 Any mechanically caused breach on the body surface can
introduce pathogen directly .
Events in Infection following penetration
 the microorganism multiplies
 resist the defense mechanism of the host,
 and begin to cause the tissue damage.
 may simply grow in the tissue in which it find itself,
causing a localized infection
Types of Infections:
 Example: Staphylococcous aureus
infection where characteristic lesion is an abscess .
 a walled off cavity is formed in the tissue containing
staphylococci and numerous blood cells (that
collectively form a pasty mass called pus), and dead,
disintegrating tissue cells that have been killed by the
toxins elaborated from the staphylococci.
the organism may not remain localized but may spread
through the tissues.
 Example: An anaerobic bacterium C. perfringens causes
the wound infection gas gangrene.
 As it grows, it elaborate toxins that kills some of the
surrounding healthy tissues.
 dead tissues becomes anaerobic can support the growth of
most Clostridia, which in turn elaborate more toxins.
 kills more tissues and allow the organism to spread
further.
 Other Factor is the production of large amounts of
hydrogen gas by the bacteria
 Hydrogen gas separates connective tissue sheaths from
muscle tissue forming a space
 rapidly get filled in by Clostridia containing fluid.
 Bacteria invade the entire length of muscles.
 Amputation of affected limbs is often the only way to
stop the spread of C. perfingens to the rest of the body
Infection of lymphatic system
 microorganisms can spread form the initial site of
infection to the lymphatic system.
 carried by lymphatic vessel to lymph nodes.
 channel within a node is lined with cells called
Macrophages,
 can engulf and destroy the bacteria that enter the lymph
node (Phagocytosis).
 lymph nodes removes nearly all of the bacteria that enter
it,
 and it may become inflamed enlarged sore when infected
called a bubo.
 In bubonic plague, such swollen lymph nodes are
particularly prominent- exhudate filled with plague bacilli.
Infection of blood
 by passive or active means, a pathogenic microorganism
 enter a blood capillary or venule
 there by gain direct access to the blood vascular system,
cause in a Bacteremia ( presence of bacteria in the blood).
 carried to various parts of the body and cause localized
infections.
 bacteria may actively multiply in the blood stream and
produce toxic products and a condition known as
septicemia.
 Septicemia infections range from chronic to acute.
Example:
 anthrax a disease of animals and sometimes humans
 number of Bacillus anthracis organism may often exceed
the number of erythrocytes in the blood.
Microbial Virulence Factors: Antiphagocytic
factors
 Virulence: degree of pathogenicity exhibited by a
strain of microorganism.
 The virulence of many pathogenic bacteria is
influenced by the presence or absence of a non-toxic
polysaccharides material composing the capsules
surrounding the cells.
 capsules can prevent the engulfment and destruction
of the bacteria by the phagocytic defense .
 Capsular polysaccharides can be isolated in pure
form.
 capsular polysaccharides of pneumococcal are injected
into humans,
 stimulate the productions of antibodies
 protect against the type of Pneumococcus from which they
were obtained.
 Some antiphagocytic factors made by pathogenic bacteria
are not capsules
 but like capsules that are located on the outer surface of
the bacterial cell wall is called M-protein
Eg. M protein of S. pyogenes
Toxins

produce poisonous substances known as toxins.
 potency can be expressed in most precise terms of :
A. LD50 -kills 50% of test animals that are injected
with toxins.
B. MLD minimum lethal dose or LD100 dose-kills
100% of test animals.

Toxins are of two types:
1. exotoxins and
2. endotoxins.
Exotoxin
 Toxic proteins that are secreted by living
microorganisms
 have extraordinarily high potency with minute
amounts being needed to kill animals.
 Not all exotoxins are lethal and merely cause
unpleasant effects.
 Example:
S. aureus produces toxin which when ingested by a
human in quantities as little as 1μg gives rise to severe
nausea and vomiting (Staphylococcus food
poisoning).
Types of Exotoxins
Toxoids
 Exotoxin lose their toxicity when treated with
formaldehyde but antigenic properties are retained .
 In this form they have the ability to stimulate the
production of antitoxins (antibodies that react with
toxins and neutralize them) in the body of a host
animal- – called Toxoids.
 important in protection of susceptible host from
disease caused by bacteria that produce exotoxin.
 Example:
Toxoids are widely used as vaccines for immunization
against tetanus and diphtheria.
 The ability of the bacteria to produce such exotoxin
(toxigenicity) is due to a Chromosomal gene.
Mechanism of action of Exotoxin
Botulism Toxin
 In botulism toxin binds to the axon near the neuro
muscular junction
 prevents the secretion of acetylcholine;
 thus the muscle cannot contract.
 If this paralysis extends to the muscles of the chest and
diaphragm, death by respiratory may result.
Endotoxins
 are lipopolysaccharides located in the outer membrane of
the cell wall of many Gram Negative bacteria.
 All endotoxins exhibit similar pharmacologic effects.
 They are:
pyrogenicity
2. blood change and
3. shock
1.
1. Pyrogenecity:
Is the ability to cause change in the body temperature.
 In human it cause an increase in body temperature
(i.e a fever response).

Indirect effect: chemical agent endogenous
pyrogen released from the blood leukocytes under
the influence of endotoxins that causes the
temperature change.

pyrogen affects the hypothalamus for the brain
which regulates body temperature.
Blood changes:
1.
2.


endotoxin damage blood platelets (thrombocytes)
cause an increase in the permeability of blood
capillaries
causing them to leak the fluid portion of the blood .
sometimes even whole blood (Hemorrhage) and these
effect can cause serious change in the circulation and
blood pressure.
Shock
 When gram negative bacteria are present in large numbers
or when endotoxin is injected intravenously, severe shock
may occur as evidenced by:
 decreased blood pressure
 Feeble rapid pulse
 Decreased respiration and sometime unconsciousness.
 High dose can result in circulatory collapse and death.
Other Virulence factor: 1.Coagulase
 Staphylococcus aureus produce an enzyme commonly
called coagulase .
 reacts with an activator in plasma to cause clotting.
2. Deoxyribonuclease (DNase)
 an enzyme produced by S. pyogenes, S. aureus, C.
perfringens and other pathogens.
 Its ability to destroy DNA would seem to indicate that it
is a formidable cytotoxin.
3. Protein A
 Present on the cell wall of S. aureus
 has the ability to bind the antibodies regardless of their
specificity.
 The antibody molecules are distorted so that their binding
site for complement ( C) is exposed.
4. Hydrogen peroxide and Ammonia
 Bacteria of genera Mycoplasma and Ureaplasma
adhere firmly to the epithelial tissue of the respiratory
or urogenital tract.
 They secrete toxic by product of their metabolism
H2O2 and NH3.
 Accumulate locally to high concentration thereby
damaging the epithelial cells.
5 Microbial iron chelators
 aerobic microbial pathogens which has the ability to
compete with a host for available iron has
considerable bearing on microbial virulence.
 Aerobic or aero tolerant organisms are continually
faced with the difficulty of obtaining enough iron for
growth,
 required for biosynthesis of iron-containing enzymes
such as cytochromes and catalase.
 Most of the iron that is available for aerobic or aero
tolerant organisms is present in the oxidized ferric form,
which is extremely insoluble.
 Aerobic organism have had to evolve ferric iron-binding
compounds in order to solubilized and take up ferric iron.
 The iron-binding compound formed by microorganisms is
termed siderophores.
 These generally belong to two major classes the
phenolates and the hydroxalates.
 The role of microbial siderophores in virulence is to
compete with the host for available iron.
 The host, being aerobic, also possesses iron-binding
compounds, proteins known as Lactoferrin and
transferrin,
 which can limit the amount of iron available to an
invading pathogen.