Download Bacterial Infection and Immunity

Bacterial Infection and Immunity
Xiao-Kui GUO
Symbioses

Commensalism: one
partner benefits and the
other is neither harmed
nor benefited.
 Mutualism: both
partners benefit.
 Parasitism: one partner
benefits at the expense of
the other.
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 crossreactive antibodies.

Hospital acquired infection: Infections acquired during hospital stays.

Pathgen: A microorganism capable of causing sisease.

Nonpathogen:

Opportunistic pathogen:

Pathogenicity: The ability of an infectious agent to cause disease

Virulence: The quantitative ability of an agent to cause disease. Virulent agents cause disease
.
A microorganism that does not cause disease; may be part of the normal flora
An agent capable of causing disease only when the host’s
resistance is impaired (ie, when the patient is “immunocompromised”).
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 LD .
ID50: The number of pathogens required to cause disease (or, at least, infection) in half of
50
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 of disease.
Koch's postulates
Koch’s Postulates
 Molecular Koch’s
Postulates
 Molecular Guidelines for
Establishing Microbial
Disease Causation


Isolated
– diseased not healthy
people

Growth
– pure culture

Induce disease
– susceptible animals

Re-isolated
– susceptible animals
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 number of organisms in the
initial exposure.
Source of infection
Exogenous infection : patient, carrier, diseased
animal or animal carrier.
 Endogenous condition : most are normal flora,
cause infection under abnormal condition.

Transmission
• Airborne droplets
• Food
• Water
• Sexual contact
Routes of
infection
Respiratory
 Gastroenteric
 Genitourinary tract
 closely contact
 insect bitting
 blood transfusion
 Parenteral route
 Mucous membranes

According to
infectious state
According to
infectious sites


1.
2.
3.
4.
5.
Local infection
Generalized or systemic
infection
Toxemia : is the presence of
exotoxins in the blood.
Endotoxemia : is the presence
of endotoxins in the blood.
Bacteremia : is an invasion of
the bloodstream by bacteria.
Septicemia : illness that occurs
when poisonous substances
(toxins) produced by certain
bacteria enter the bloodstream.
Pyemia : is caused by pyogenic
microorganisms in the blood.




Inapparent or subclinical
infection
Latent infection
Apparent infection : cause
apparent clinic syndrome
Carrier state: carrier
BACTERIAL VIRULENCE FACTORS
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
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
interacting with the bacterial glycocalyx (capsule)
receptor
Adhesion
BACTERIUM
adhesin
Type 1
EPITHELIUM
P
mannose
galactose
– glycolipids
– glycoproteins
E. coli fimbriae
lipoteichoic acid
F-protein
fibronectin
2. Invasion of host cells & tissues
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.
Active Binding

Antibodies (anti-toxins)
neutralize
– vaccination
Cell surface
A
B
Endotoxins










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

Non-specific inflammation.
 Cytokine release
 Complement activation
 B cell mitogens

Polyclonal B cell activators

Adjuvants
Peptidoglycan of Grampositive bacteria

May yield many of the same biologic
activities as LPS.
4. Enzymes

Tissue-degrading
enzymes
 IgA1 proteases:
split IgA1, an
important secretory
antibody on
mucosal surfaces,
and inactivate its
antibody activity.
1. H. influenzae
2. S. pneumoniae
3. N. gonorrhoeae
4. N. meningitidis
5. Antiphagocytic
factors

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.
Antiphagocytic Substances

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 Pseudomonas
aeruginosa

4. O polysaccharide associated with LPS of E. coli
 5. K antigen (acidic polysaccharides) of E. coli or the analogous Vi
antigen of Salmonella typhi
 6. Cell-bound or soluble Protein A produced by Staphylococcus aureus. Protein A
attaches to the Fc region of IgG and blocks the cytophilic (cell-binding) domain of the Ab.
Thus, the ability of IgG to act as an opsonic factor is inhibited, and opsonin-mediated
ingestion of the bacteria is blocked.
Protein A inhibits phagocytosis
PHAGOCYTE
Fc receptor
immunoglobulin
Protein A
BACTERIUM
M protein inhibits phagocytosis
Complement
fibrinogen
M protein
r
peptidoglycan
r
r
6. Intracellular
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 phagosomelysosome fusion and living
within the phagosome, or
being resistant to lysosomal
enzymes and surviving
within the phagolysosome.
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
antigenic form of their surface structures in vitro
and presumably in vivo, allowing the bacteria to
evade the host’s immune system.
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
assimilation systems.
Bacterial siderophores compete effectively for
Fe3+ bound to lactoferrin and transferrin.
Development of the Immune
System
ery pl
neu
mφ
CD8+
nk
CTL
CD4+
TH1
thy
TH2
mye
lym
Components of the Immune
System
Nonspecific
Humoral
complement,
interferon,
TNF etc.
Cellular
macrophages,
neutrophils
Specific
Humoral
antibodies
Cellular
T cells; other
effectors cells
Balance between Infection and
Immunity
infection
immunity
Disease =
Bolus of infection x virulence
immunity
Response to Infection
infection
Innate
immunity
x
disease
no
disease
adaptive
immunity
Significance of the Immune System


Beneficial:

Protection from Invaders

Elimination of Altered Self
Detrimental:

Discomfort (inflammation)

Damage to self (autoimmunity)
Components of Innate and Adaptive
Immunity
Innate Immunity
Adaptive Immunity
physical barriers
skin, gut Villi, lung cilia,etc
none
soluble factors
many protein and
non-protein secretions
cells
phagocytes, NK cell
eosinophils, K cells
Immunoglobulins
(antibody)
T and B lymphocytes
Macrophage Attacking E.coli (SEM x8,800)
Chemotactic response to inflammatory stimulus
Adaptive Immunity
Characteristics of Innate and
Adaptive Immunity
Innate Immunity
Adaptive Immunity
Antigen independent
Antigen dependent
No time lag
A lag period
Not antigen specific
Antigen specific
No Immunologic
memory
Development
of memory

Immunity of extracellular bacterial infection:
antibodies (IgG, IgM, SIgA); phagocytes
(neutrophils); complement; humoral immunity
mainly.
 Immunity of intracellular bacterial infection:
cell-mediated
immunity
(delayed-type
hypersensitivity, DTH response (DTH) involving
TH1and macrophages) mainly.
INADEQUATE IMMUNE RESPONSES
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
antigenic shift and antigenic drift that creat new antigenic
phenotypes which evade the host’s current immunity and
allow reinfection with the virus.