Bacterial Infection and
Bacterial Infection and
Immunity
Immunity
Symbioses
Symbioses
Commensalism: one
partner benefits and the other is neither harmed nor benefited.
Mutualism: both
partners benefit.
Parasitism: one partner
Role of the resident flora
Role of the resident flora
• Members of the resident flora in the intestinal tract
synthesize vitamin K and aid in the absorption of nutrients.
• Members of the resident flora on mucous membranes
and skin may prevent colonization by pathogens and possible disease through “bacterial interference”.
• The normal flora may antagonize other bacteria
through the production of substances which inhibit or kill nonindigenous species.
• The normal flora stimulates the development of certain
tissues, i.e., the caecum and certain lymphatic tissues (Peyer's patches) in the GI tract
• The normal flora stimulate the production of
Hospital acquired infection: Infections acquired during hospital stays.
Pathgen: A microorganism capable of causing sisease.
Nonpathogen: A microorganism that does not cause disease; may be part of the normal flora.
Opportunistic pathogen: An agent capable of causing disease only when the host’s
resistance is impaired (ie, when the patient is “immunocompromised”).
Pathogenicity: The ability of an infectious agent to cause disease
Virulence: The quantitative ability of an agent to cause disease. Virulent agents cause disease when
introduced into the host in small numbers. Virulence involves invasion and toxigenicity. LD 50 (age /sex /health /route of entry, etc )
LD50: The number of pathogens required to cause lethal disease in half of the exposed hosts is called an LD50.
ID50: The number of pathogens required to cause disease (or, at least, infection) in half of
the exposed hosts is called the ID50
Adherence(adhesion, attachment): the process by which bacteria stick to the surfaces of host cells.
Once bacteria have entered the body, adherence is a major initial step in the infection process. The terms adherence, adhesion, and attachment are often used interchangeably.
Invasion: The process whereby bacteria, animal parasites, fungi, and viruses enter host cells or
tissues and spread in the body.
Toxigenicity: The ability of a microorganism to produce a toxin that contributes to the development
Koch’s Postulates
Molecular Koch’s
Postulates
Molecular Guidelines for
Establishing Microbial Disease Causation
Koch's postulates
IIsolated solated
– diseased not healthy diseased not healthy
people people GGrowthrowth
– pure culturepure culture
IInduce disease nduce disease
– susceptible animalssusceptible animals
RRe-isolated e-isolated
Pathogenesis
Pathogenesis
Pathogenesis is a multi-factorial
process which depends on the
immune status
of the host, the
nature of
the species or strain
(
virulence factors
) and
the
Source of
Source of
infection
infection
Exogenous infection : patient, carrier, diseased
animal or animal carrier.
Endogenous condition : most are normal flora,
cause infection under abnormal condition.
•
A
A
irborne droplets
irborne droplets
•
F
F
ood
ood
•
W
W
ater
ater
•
S
S
exual contact
exual contact
Transmission
Transmission
Respiratory Gastroenteric Genitourinary tract closely contact
insect bitting blood transfusion
Parenteral route Mucous membranes
Routes of
Routes of
infection
According to
According to
infectious sites
infectious sites
Local infection
Generalized or systemic
infection
1. Toxemia : is the presence of exotoxins in the blood.
2. Endotoxemia : is the presence of endotoxins in the blood.
3. Bacteremia : is an invasion of the bloodstream by bacteria. 4. Septicemia : illness that occurs
when poisonous substances (toxins) produced by certain bacteria enter the bloodstream. 5. Pyemia : is caused by pyogenic
microorganisms in the blood.
Inapparent or subclinical
infection
Latent infection
Apparent infection : cause
apparent clinic syndrome
Carrier state: carrier
According to
According to
infectious state
Environmental signals often control the expression of the virulence genes. Common signals include:Temperrature/Iron availability : C diphtheriae /low ion/Osmolality /Growth phase/pH/Specific ions
BACTERIAL VIRULENCE FACTORS
1. Adherence Factors
1. Adherence Factors
1. Tissue tropism:
2. Species specificity:
3. Genetic specificity within a species:
Hydrophobic interactions Electrostatic attractions
Atomic and molecular vibrations resulting from
fluctuating dipoles of similar frequencies
Brownian movement
Recruitment and trapping by biofilm polymers
Adhesion
Adhesion
adhesin adhesin EPITHELIUM EPITHELIUM receptor receptor BACTERIUM BACTERIUM fibronectin fibronectin lipoteichoic acid lipoteichoic acid F-protein F-protein mannose mannose Type 1 Type 1 galactose galactose– glycolipids glycolipids – glycoproteins glycoproteins
P
P
E. coli
2. Invasion of host cells & tissues
3. Toxins
3. Toxins
Exotoxins
Endotoxins
Exotoxins
Produce in vitro cause food poisoning:
botulin, staphylococcal enterotoxin, etc.
Produce in vivo:
Systematic toxic effects : e.g. diphtheria, tetanus, and streptococcal erythrogenic toxins.
Local toxic effects : e.g. cholera, and toxigenic E. coli enterotoxins. ActiveActive BindingBinding
A A Cell surface Cell surface B B
Antibodies (anti-toxins) Antibodies (anti-toxins)
neutralize
E
E
ndotoxins
ndotoxins
LPS Lipopolysaccharide:
core or backbone of CHO
side chains of CHO: "O" antigen Lipid A
Cell wall lysis required
formaldehyde and heat resistant poor antigen as free molecule Endotoxin effects
Fever-pyrogen 1 microgram/ kg
Leukopenia and leukocytosis necrosis Shwartzman phenomenon and
disseminated intravascular coagulation (DIC).
Endotoxemia and shock
Lethal 1 milligram/ kg Identification:
Limulcyte assay
NNon-specific inflammation. on-specific inflammation CCytokine releaseytokine release
CComplement activationomplement activation B cell mitogensB cell mitogens
Peptidoglycan of Gram-
Peptidoglycan of
Gram-positive bacteria
positive bacteria
May yield many of the same biologic
4.
4.
Enzymes
Enzymes
Tissue-degrading
enzymes
IgA1 proteases:
split IgA1, an
important secretory antibody on
mucosal surfaces, and inactivate its antibody activity.
1.
1. H. influenzaeH. influenzae
2.
2. S. pneumoniaeS. pneumoniae
3.
3. N. gonorrhoeaeN. gonorrhoeae
4.
4. N. meningitidisN. meningitidis
Some pathogens evade
phagocytosis or leukocyte microbicidal mechanisms by adsorbing normal host
components to their surfaces. A few bacteria produce
soluble factors or toxins that inhibit chemotaxis by
leukocytes and thus evade phagocytosis.
5. Antiphagocytic
5. Antiphagocytic
factors
A
A
ntiphagocytic
ntiphagocytic
S
S
ubstances
ubstances
1.
Polysaccharide capsules
of S. pneumoniae, Haemophilus influenzae,Treponema pallidum ; B. anthracis and Klebsiella pneumoniae.
2.
M protein
and
fimbriae
of Group A streptococci
3.
Surface slime
(
polysaccharide) produced as a biofilm by Pseudomonasaeruginosa
4.
O polysaccharide
associated with LPS of E. coli
5.
K antigen
(acidic polysaccharides) of E. coli or the analogousVi
antigen
of Salmonella typhi
6.
Cell-bound or solubleProtein A
produced by Staphylococcus aureus. Protein AProtein A inhibits phagocytosis
Protein A inhibits phagocytosis
immunoglobulin
immunoglobulin Protein AProtein A
Fc receptor Fc receptor BACTERIUM BACTERIUM PHAGOCYTE PHAGOCYTE r r r peptidoglycan peptidoglycan Complement
Complement fibrinogenfibrinogen
M protein M protein
M protein inhibits phagocytosis
6. Intracellular
6. Intracellular
pathogenicity
pathogenicity
Some bacteria live and grow within
polymorphonuclear cells, macrophages, or
monocytes by avoiding
entry into phagolysosomes and living within the
cytosol of the phagocyte, preventing
phagosome-lysosome fusion and living within the phagosome, or being resistant to lysosomal enzymes and surviving
7. Antigenic heterogeneity
7. Antigenic heterogeneity
Antigenic type of bacteria may be a marker for
virulence, related to the clonal nature of pathogens, though it may not actually be the virulence factor.
Some bacteria may make frequent shifts in the
Bacterial siderophores compete effectively for Fe3+ bound to lactoferrin and transferrin.
8. The requirement for iron
8. The requirement for iron
For the host, the iron
metabolism denies
pathogenic bacteria an
adequate source of iron for growth.
For the bacteria, they have
developed several methods to obtain sufficient iron for essential metabolism, e.g., the low-affinity iron
assimilation system or the high-affinity iron
Development of the Immune
Development of the Immune
System
System
Development of the Immune
Development of the Immune
Components of the Immune
System
Components of the Immune
System
Humoral
Cellular
Humoral
Cellular
Specific
Nonspecific
complement, interferon,
TNF etc.
macrophages, neutrophils
Balance between Infection and
Balance between Infection and
Immunity
Immunity
Balance between Infection and
Balance between Infection and
Immunity
Immunity
infection immunity
Bolus of infection x virulence immunity
Response to Infection
Response to Infection
Response to Infection
Response to Infection
infection
x
disease
Innate
immunity no disease
recov ery
adaptive immunity
re-inf ectio
n no
disease
Beneficial:
Protection from Invaders
Elimination of Altered Self
Detrimental:
Discomfort (inflammation)
Damage to self (autoimmunity)
Beneficial:
Protection from Invaders
Elimination of Altered Self
Detrimental:
Discomfort (inflammation)
Damage to self (autoimmunity)
Significance of the Immune System
Significance of the Immune System
Significance of the Immune System
Innate Immunity Adaptive Immunity
Components
Components
of Innate and Adaptive
of Innate and Adaptive
Immunity
Immunity
Components
Components
of Innate and Adaptive
of Innate and Adaptive
Immunity
Immunity
skin, gut Villi, lung cilia,etc
many protein and
non-protein secretions
phagocytes, NK cell eosinophils, K cells
physical barriers soluble factors cells none Immunoglobulins (antibody)
Chemotactic response to inflammatory stimulus Macrophage Attacking E.coli
Adaptive Immunity
Innate Immunity Adaptive Immunity
Characteristics
Characteristics
of Innate and
of Innate and
Adaptive Immunity
Adaptive Immunity
Characteristics
Characteristics
of Innate and
of Innate and
Adaptive Immunity
Adaptive Immunity
No Immunologic memory
Antigen independent
No time lag
Not antigen specific
Antigen dependent
A lag period
Antigen specific
Immunity of extracellular bacterial infection: antibodies (IgG, IgM, SIgA); phagocytes (neutrophils); complement; humoral immunity mainly.
Immunity of intracellular bacterial infection:
INADEQUATE IMMUNE RESPONSES
INADEQUATE IMMUNE RESPONSES
TO INFECTIOUS AGENTS
TO INFECTIOUS AGENTS
Causes immune suppression—an example is infection with
HIV, which alters T cell immunity and allows further infection with opportunistic pathogens.
Release toxins that function as superantigens, initially
stimulating large numbers of T cells to proliferate but, because of the release of cytokines from T cells, ultimately suppressing the immune response and allowing the pathogen to multilply.
Evade the immune defenses by altering their antigenic
structure—an example is that influenza virus undergoes antigenic variation by two mutational mechanisms called