HOST DEFENSE & PATHOGENICITY OF MICROBES

(With special reference to bacterial infection)

Host defense mechanisms related to:-
1. Bacterial Structure
2. Mechanisms of pathogenicity
(Hence related to susceptibility of bacteria to appropriate to appropriate immunological
mechanisms)

Bacterial Structure
4 main types of cell walls
1. Gram positive
2. Gram negative
3. Mycobacterium
4. Spirochaetes

Gram positive Gram negative Mycoacterium Spirochaetes

1. Capsule*/Microcapsule*/Envelope* +/- +/- +/- +/-
2. Fimbriae*/Flagella* +/- +/- - +/-
3. Outer membrane# - + + +
a. LPS* - + - -
b. Glycolipid & Mycolic Acid* - - + -
c. Arabinogalactan - - + -
d. Lipoprotein - + - +
4. Peptidoglycan (Murein/Mucopeptide) + + + +
5. Cytoplasmic membrane + + + +
a. Lipoteichoic Acid + - - -
b. Lipoarabino Mannan - - + -
* Structures with adjuvant properties (lead to immune response)
# Susceptible to lysis (complement and cytotoxic cells)

IMMUNITY TO BACTERIAL INFECTIONS

1. First line of defense
● Antibacterial mechanisms that do not depend on antigen recognition.
● INNATE IMMUNITY
a. Barrier / Prevention of entry
b. Chemicals
2. Second line of defense
● Mediated via recognition of common bacterial components
● Innate Immunity
The following cause the attraction of the complement system:
● Lipoproteins
● Lipoteichoic acids
● Lipoarabinomannan
● LPS
● Formyl peptides
 ● Muramyl peptides
● Peptidoglycan
● CKP
● Mannose binding lectin

Consequences
1. Complement activation through Alternative / Lectin pathway
● Lysis
● Mast cell degranulation
● Vasoactive amine release leads to:
a. Increased vascular permeability
b. Smooth muscle contraction
= Anaphylaxis

2. Release of cytokines from macrophage

● IL-1
● TNF
= These 2 cytokines lead to activation of phagocytes and increase adhesion to
endothelium

3. Release of cytokines from NK Cells

● IFN (especially IFN-γ)
● MHC Expression 
● Activates monocytes
= Delayed Type HS effect

4. Adjuvant Effect (Adjuvant = to help)

● Stronger B & T cell response

● Outer membrane of Gram negative bacteria

= Susceptivle to lysis by complement components and cytotoxic cells
● Other bacteria = Mainly gotten rid of by phagocytosis
- Fimbriae, flagella & capsule on outer surface of bacteria protects bacteria from
phagocytosis and complement activities…but they are TARGETS from Antibody response (i.e,
they are IMMUNOGENIC!)

HOST IMMUNITY RELATED TO PATHOGENICITY

2 Extremes of bacterial pathogenicity
i. Toxicity without invasion (e.g, Corynebacterium Diptheriae, Vibrio Cholerae, Clostridium
Tetani)
ii. Invasion without toxicity (e.g, Mycobacterium Tuberculosis, Mycobacterium Leprae)
But MOST bacteria are in between (eg, Staphylococcus Aureus)
Ultimately most bacteria are killed by phagocytosis
Bacterium that induce HS Type IV:
● Listeria monocytogenes
 ● Mycobacterium Tuberculosis
● Mycobacterium Leprae
● Salmonella Spp.

SHOCK SYNDROME
(Antigen non-specific immune mechanisms)
If cytokine release is sudden & massive -> Severe and acute tissue damage -> Shock syndromes
which are potentially fatal

ANTIGEN SPECIFIC IMMUNITY

Depends on mechanism of pathogenicity
- Bacterial toxin ---leads to---> Specific anti-toxin that neutralizes the toxin
e.g, Diptheria toxin neutralized by blocking attachment of binding portion to target cell
- Mucosal secretory IgA prevents the attachment of specific bacteria to epithelium
E.g, Anti-M protein of S. Pyogenes
Role of specific antibodies in pathogenesis of bacterial infection
a. Attachment to:
● Fimbriae
● Lipoteichoic Acid
● Capsules
b. Triggers complement mediated lysis of Gram negative outer membrane
c. Block transport mechanism and receptors
● Fe chelating compounds
d. Avoidance of phagocytosis
● Anti M and anti capsule -> Opsonization -> Phagocytosis

Superantigens
Bacterial components
● Bind directly (unprocessed) to T-Cell Receptor (Vβ)
● Cross-link to MHC
● Activate all T-cells bearing Vβ gene products
E.g; S. Aureus& Epidermolytic toxins A&B, Streptococci, Mycoplasma
● Massive cytokine/lymphokine release
E.g; S. Aureus and toxic shock syndrome