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HOST DEFENSE & PATHOGENICITY OF MICROBES

(With special reference to bacterial infection)

Host defense mechanisms related to:-

1. Bacterial Structure2. Mechanisms of pathogenicity

(Hence related to susceptibility of bacteria to appropriate to appropriate immunologicalmechanisms)

Bacterial Structure

4 main types of cell walls

1. Gram positive2. Gram negative3. Mycobacterium4. Spirochaetes

G

ram positiveG

ram negativeM

ycoacterium Spirochaetes1. 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. LipoarabinoMannan - - + -

* 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 entryb. Chemicals

2. Second line of defense Mediated via recognition of common bacterial components Innate ImmunityThe following cause the attraction of the complement system:

Lipoproteins Lipoteichoic acids Lipoarabinomannan LPS

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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 permeabilityb. 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-)

MHC Expression Activates monocytes

= Delayed Type HS effect

4. Adjuvant Effect (Adjuvant = to help) Stronger B& T cell response

Outer membrane ofGram 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 activitiesbut 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, ClostridiumTetani)

ii. Invasion without toxicity (e.g, Mycobacterium Tuberculosis, Mycobacterium Leprae)ButMOST bacteria are in between (eg, Staphylococcus Aureus)

Ultimately most bacteria are killed by phagocytosis

Bacterium that induce HS Type IV:

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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 ofGram negative outer membranec. Block transport mechanism and receptors

Fe chelating compoundsd. Avoidance of phagocytosis

Anti M and anti capsule -> Opsonization -> PhagocytosisSuperantigens

Bacterial components

Bind directly (unprocessed) to T-Cell Receptor (V) Cross-link to MHC Activate all T-cells bearing V gene products

E.g; S. Aureus& Epidermolytic toxins A&B, Streptococci, Mycoplasma

Massive cytokine/lymphokine releaseE.g; S. Aureus and toxic shock syndrome