T-independent antigen vs. Super-antigen vs. Toxic shock vs. IL-1, IL-2, IL-6, TNF-alpha, ING-gamma

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Foot Fetish

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For the love of God, can someone please set these topics straight for me once and for all?

  • What is the difference between a super antigen vs. a T-independent antigen?
  • Which one causes the release of what? (IL-1, IL-2, IL-6, TNF-alpha, ING-gamma...)
  • Which one is caused by endotoxin (Gram-negative LPS) versus exotoxins?


    Title should be IFN-gamma >_< D'Oh!

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What is the difference between a super antigen vs. a T-independent antigen?
Which one causes the release of what? (IL-1, IL-2, IL-6, TNF-alpha, ING-gamma...)

Superantigen is one that causes constitutive activation between TCR and MHC. Since it is foreign there is also binding of B7 and CD28 allowing for the secondary activation of the T-cell. This T cell then release IFN-Y which activates the presenting cell (the macrophage) to release TNF-alpha, IL-1, IL-6.

T-independent antigen from what I recall describes two separate methods of B-cell activation. This type of antigen is usually a bacterial polysaccharide and will bind to receptors on B-cells upon which can induce antibody production. Because there is no T-cell interaction the overall efficacy of the antibody isn't that great (remember that you need T cell activation to induce isotope switching from B cells). This also means no memory B cells are produced.
Which one is caused by endotoxin (Gram-negative LPS) versus exotoxins?
Superantigen is derived from exotoxin: Staphylococcal and streptococcal superantigen exotoxins. - PubMed - NCBI
I am not too sure if you can classify T-independent antigen as exo or endo-toxin derived.
 
For the love of God, can someone please set these topics straight for me once and for all?

  • What is the difference between a super antigen vs. a T-independent antigen?
  • Which one causes the release of what? (IL-1, IL-2, IL-6, TNF-alpha, ING-gamma...)
  • Which one is caused by endotoxin (Gram-negative LPS) versus exotoxins?


    Title should be IFN-gamma >_< D'Oh!

"What is the difference between a super antigen vs. a T-independent antigen?":

I basically think of them as the exceptions to naive T-cell and to naive B-cell activation. Just a refresher, naive T-cells are CD4+ and CD8+ T-cells that come fresh from T-cell development in the thymus, thus a primary lymphoid organ, to secondary lymphoid organs. Naive B-cells likewise come fresh from the bone marrow.

In any event, normal activation of naive T/B-cells requires 2 signals (TCR binding to MHC + costimulatory 2nd signal B7/IL-1, and BCR aka antibody binding to MHC + costimulatory 2nd signal IL-4) and the subsequent memory and effector cells (TH1/TH2 for activated T-cells and antibody-secreting plasma cells for B-cells) have different functions.

So the exceptions. Naive T-cells can be activated by a single signal aka a super antigen (TSST/TSLS) which bind the MHC part of antigen-presenting cells and the TCR of the naive T-cell (beta chain part) thus causing nonspecific activation of naive T-cells. So the key here is that super antigens are the exception to normal 2-signal activation.

Meanwhile, naive B-cell activation also has an exception to activation and is also a 1-signal activation mechanism. This is T-cell independent antigen, named because normally B-cells act as antigen-presenting cells in that they process and present antigen with MHC-I/II to naive T-cells, which can then activate naive B-cells since TH2 effector cells release IL-4 to help activate those naive B-cells. So the normally route of B-cell activation is T-cell dependent since the activation pathway involves T-cells. T-cell independent antigens (like bacterial polysaccharides), however, can nonspecifically activate naive B-cells by cross-linking neighboring IgM on the surface of naive B-cells, which allows them to be activated by a single signal. So no T-cell involvement here thus they are called T-cell independent antigens. This is a problem since single signal activation means no class-switching cytokines released from TH2 cells.

So to recap, 1-signal activation exception to naive T-cells = super antigen while 1 signal activation exception to naive B-cells = T-cell independent antigen.

"Which one causes the release of what? (IL-1, IL-2, IL-6, TNF-alpha, ING-gamma...)":

First, only the effector T-cells (aka activated naive CD4+ T-cells) release cytokines between the 2 lymphocytes of adaptive immunity. Macrophages of innate immunity are the other big secretor of cytokines. So macrophages = innate cytokines, TH1/TH2 = adaptive cytokines.

TH1 effector CD4+ T-cells are formed in the presence of specific cytokines [IL-12, IFN-gamma, TGF-beta, if you are interested], and release the "inflammatory cytokine profile" aka IL-2, IFN-gamma, TNF-beta which are basically the same cytokines required to make them go from naive T-cells to TH1 effectors in the first cell with the exception of IL-2. IL-2 activates NK cells and can act as the alternate 2nd signal of activation for naive CD8+ T-cells in the periphery, IFN-gamma/TNF-beta generally activate macrophages.

TH2 effector cells on the other hand generate IL-4 (most important), 3/5/6/13 (so 3-6 + 13. IL-4 is most important here because as we said it's the second signal required for activation of naive B-cells from the bone marrow.

Finally, macrophages are secreting IL-1 (inflammatory, from the FA mnemonic Hot T-Bone stEAK, and also 2nd signal of naive T-cell activation as we said) and IL-6 + TNF-alpha.

Which one is caused by endotoxin (Gram-negative LPS) versus exotoxins?

Exotoxins like TSST (toxic-shock-syndrome toxin from Staph aureus) and TSLS (from Strep pyogenes) are the only super antigens I can think of.

Not to sure about LPS endotoxin, since as far as I know the T-cell independent antigens tend to be bacterial polysaccharides or whatever can cross-link the surface IgM on naive B-cells.
 
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