By Dr J. Stalin RoyProf K.S. Chenthil’s Unit

(IMCU)STANLEY MEDICAL COLLEGE

INNATE IMMUNE RESPONSE TO INVADING BACTERIA The innate immune system is able to detect

pathogens via Pattern Recognizing Receptors (PRR)

PRR are able to recognize conserved motifs expressed by pathogens known as Pathogen Associated Molecular Pattern (PAMP)

Examples of PAMP are LPS, Lipotechoic acid, peptidoglycans, lipopeptides, flagellin, bacterial DNA

PRR and PAMP

LTA

LPS

Various PAMP, PRR and pathogens

Bactericidal/permeability increasing protein-BPI BPI is another important endotoxin binding

protein produced by neutrophils. Similar in structure to LBP but has distinctly

antagonistic function i.e. it inhibits the LPS delivery to CD14 (endogenous antiendotoxin).

Hence the relative concentration of these two determine the net effect of LPS release.

In human plasma the concentration of LBP is 2-3 times that of BPL whereas in abscess cavities BPL is much higher.

Bacterial superantigens

These are protein based exotoxins produced by staphylococci, streptococci and other pathogens that share unusual immunologic property.

They have the capacity to activate a large number of CD4+ T cells bypassing the usual process of antigen processing and presentation

Normal antigen

Antigen presenting cell

(APC) Phagocytose

invading bacteria

The CD4+ T cell gets activated

and proliferates clonally

Broken down bacterial antigens are processed and expressed on the surface of MHC II

Each processed antigen is

recognized by specific T cell

receptor (TCR)

Super antigen

Super antigen binds directly to

MHC II (non antigen binding

domain)

It is then able to bind to non

matching TCR

Leads on to activation of

more than 10% of the circulating lymphocytes

Massive release of inflammatory

mediators

TSST -1 superantigen

TLR/NOD –> NFKB –> T cell activation

Gram positive and fungal causative organisms

Summary