Flashcards in L25: Perturbations super system Deck (10):
What's so special about a super antigen?
Some bacteria and viruses CIRCUMVENT the multiple safeguards and fail/safe immune reaction regulatory mechanisms characterized by agonist/antagonist cytokines relationships....
Superantigens differ in at least 3 major ways from conventional peptide antigens:
1. Superantigens can react with MHC Class II determinants in UNPROCESSED form.
2. Superantigens bind to the ‘side’ of the mononuclear MHC Class II TCR complex, not the peptide binding groove
3. They elicit a massive immediate primary polyclonal response in T cells.
Bacterial pathogens that cause shock syndromes usually do so by producing toxins that act as superantigens. The rapid activation of T cells leads to ‘cytokine storm’ that causes massive release of vasoactive and pro- inflammatory cytokines. These, in turn, cause severe perturbations in organ function, especially of the liver and kidney, manifested as severe clinical diseases and the toxic shock syndrome. The intensity of the response is strongly dependent on the polymorphism of the host’s MHC class II and (probably) the TNF gene complex also. The importance of polymorphism became evident when it was discovered that the same bacterial strain might cause death in some patients and hardly any clinical disease in others. The individual’s MHC binding characteristics dictated the magnitude of T cell activation.
The classic example is that of toxic shock caused by
Streptococcus/ Staphylococci (Mg2+ tampons)
Bacteria and viruses can downregulate TLRs-remember the Toll receptors and innate immunity?
Interfering in the methods by which Class I MHC transports antigen to the surface so it can be sampled by CD8 cells. By doing so, viral antigens remain camouflaged or hidden within the cell and cannot be deleted by antigen specific CD8 cytotoxic T-cells.
Piracy of the genes that produce inhibitor signals for NK cells. The latter can recognize an altered MHC-I but can’t do anything about it.
Preventing cytokine up-regulation of MHC Class I and II antigens.
Stealing genes that produce inhibitory cytokines-IL 10 or other IL
12 inhibitors-or induce genes that produce products that antagonize
the effects of pro-inflammatory cytokines.