Lesson Outline 1. Infectious disease 2. Pathogenicity 3. How
does host and pathogen interact? 4.Microbial Virulence Factors
Antiphagocytic factors Exotoxins Endotoxins
Slide 3
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
Slide 4
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.
Slide 5
What damages the body cells? Toxins by microorganisms.
Virulence factors - combat various defense mechanisms of the
host.
Slide 6
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. 1. 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.
Slide 7
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.
Slide 8
How to measure the virulence of an organism? By determining its
LD 50 dose for a laboratory animal. LD 50 - defined as that number
of organism which when administered to number of laboratory
animals, kills 50 percent of them. LD 100
Slide 9
Infection Represents the most intimate way in which a
microorganism may cause disease. Host is invaded and multiply in
close association with hosts tissue. Note: not all diseased caused
by microorganisms are infections.
Slide 10
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.
Slide 11
Process of Host pathogen interaction 1. Microbial adherence 2.
Penetration/ entrance into the body 3. Events of infection
following penetration 4. microbial virulence
Slide 12
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 cervix- pili. E. coli - mucosal lining of the intestine-
pili.
Slide 13
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.
Slide 14
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.
Slide 15
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.
Slide 16
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
Slide 17
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.
Slide 18
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
Slide 19
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
Slide 20
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).
Slide 21
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.
Slide 22
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.
Slide 23
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.
Slide 24
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.
Slide 25
capsular polysaccharides of pneumococcal are injected into
humans, stimulate the productions of antibodies protect against the
type of Pneumococcus from which they were obtained.
Slide 26
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
Slide 27
Toxins produce poisonous substances known as toxins. potency
can be expressed in most precise terms of : A. LD 50 -kills 50% of
test animals that are injected with toxins. B. MLD minimum lethal
dose or LD 100 dose-kills 100% of test animals. Toxins are of two
types: 1. exotoxins and 2. endotoxins.
Slide 28
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 1g
gives rise to severe nausea and vomiting (Staphylococcus food
poisoning).
Slide 29
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.
Slide 30
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.
Slide 31
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.
Slide 32
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: 1.
pyrogenicity 2. blood change and 3. shock
Slide 33
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.
Slide 34
Blood changes: 1. endotoxin damage blood platelets
(thrombocytes) 2. 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.
Slide 35
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.
Slide 36
Other Virulence factor: 1.Coagulase Staphylococcus aureus
produce an enzyme commonly called coagulase. reacts with an
activator in plasma to cause clotting.
Slide 37
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.
Slide 38
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.
Slide 39
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 H 2 O 2 and NH 3. Accumulate locally to high
concentration thereby damaging the epithelial cells.
Slide 40
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.
Slide 41
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.
Slide 42
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.