TNF Family

The IL-1 family is also called the immunoglobulin superfamily. The IL-IR family includes both transmembrane and soluble proteins withan immunoglobuhn-like structure. There are four primary members of the IL-1 family IL-la, IL-1 [3, IL-18, and IL-lRa. IL-1 ligands (IL-la and IL-1[3, collectively referred to as IL-1) are potent pro-inflammatory cytokines that induce genes associated with inflammation and autoimmune disease. IL-lRa, on the other hand, is the specific receptor antagonist for IL-la and IL-1 [3 but not for IL-18. 

The designation of five cytokine families based upon receptor structural homology is rather vague. Cytokines within each structural family have further diversity in function hence. 

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TNF family TNF-a, TNF-p, CD40 ligand, CD95 ligand, TRAIL... 

The Fas ligand or FasL is a type II transmembrane protein that belongs to the tumor necrosis factor (TNF) family. The binding of Fas ligand with its receptor induces apoptosis. 

It is well established that caspases participate in the final stages of apoptosis (Fig. 32-4), but what initiates the process There appear to be many ways in which apoptosis can be triggered. If every cell has a proper location in the body, which is determined by signals from adjacent cells, what will happen if the cell becomes detached There is evidence that such detachment with the loss of survival signals causes apoptosis.53a 152b Cell damage is also a major trigger. In other cases the cell is "instructed" to die. An example is the death of unneeded lymphocytes, one of many cellular processes induced by cytokines of the tumor necrosis factor (TNF) family. To allow for this process cells have surface receptors of the TNF... 

We have already alluded to the fact that the NGF-activated p75 4TR receptor is a potential death receptor, like other members of the TNF family of receptors. Evidence is now becoming available that NGF-dependent activation of p75 s can initiate ceU death and apoptosis, whereas NGF and neurotrophin-binding to TRKs (growth-factor tyrosine-kinase-type receptors) has the opposite effect and prevents cell death. Thus, early in development, endogenous NGF causes the death of neurons that express p75 4TR whereas cells that express TRK receptors are not affected and survive. Thus, the fate of developing neurons depends on the type of the receptor e3q>ressed.55 This points to the central role of programmed ceU death in the development of the nervous system.5 ... 

List five members of TNF family of cytokine and their effects in CNS inflaimnation. 

Liu Y, Xu L, Opalka N, Kappler J, Shu HB, Zhang G Crystal structure of sTALL-1 reveals a vims-like assembly of TNF family ligands. Cell 2002 108 383-394. 

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