Mechanisms of Acquired Immunity Part II

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Mechanisms of Acquired Immunity Part II

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University of Southern California
Bisc 307l - General Physiology
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BISC 307L 2nd Edition Lecture 33 Current Lecture Major Histocompatability Complex (MHC) Recap: All cells produce at least one of the types of MHC molecules. There are several dozen proteins – hundreds of different alleles on the population, people are heterozygous for – that means each nucleated cell is labeled with a large complement of unique cell surface glycoproteins. Nonnucleated cells don’t have this, for example, RBC’s don’t have MHC molecules. They only have two/three cell surface glycoproteins that they use for recognition, and they are called A and B. There are four blood types, so crossmatching blood or tissue matching blood for transfusions, and blood is a fluid tissue so it is a tissue transplant, is one thing that MHC molecules do. Another thing they do is present antigens to lymphocytes. Classes of MHC Proteins Class I – expressed in all cells w/nuclei. Works by presenting antigens to T cells. There are two important types of T cells – cytotoxic and helper. They will recognize antigens by virtue of the fact that antigens will bind to T-cell receptors, which have a different structure than the B cell receptor. But they are similar in that they have a lot of variability in the antigen b inding site. Variability arises by gene recombination, as it does for the B- lymph receptors. But this is a dimer, not a tetramer, and it is a heterodimer with an alpha chain and beta chain. And a given T cell during its differentiation will commit itself by gene rearrangement to producing only one type of alpha chain and one type of beta chain that will combine to produce a receptor with one type of antigen binding specificity. The T cell receptor binds to the antigen, so here is a cytotoxic T cell receptor in purple binding to an antigen (the blue triangle) but T cell receptors do not bind to naked antigens like B cell receptors do. The antigen has to be part of a multidimensional binding event, that is, the T cell receptor has to bind the antigen but also the class I MHC presenting the antigen. And this complex between the antigen, the MHC molecule, and the receptor, has to be stabilized by binding of a cytotoxic T cell binding protein called CD8, a specific protein for a specific marker of cytotoxic T cells. So there are two t-cell receptors binding to two things being presented by the antigen presenting cell. And all of this multiple binding has to happen in order for the T cell to be activated. The antigen is presented by the cell, and this is a class I MHC so every cell in your body except RBC’s produces this. And when the MHC class I molecule is made inside the cell, it picks up peptide fragments being synthesized in the cell and carries them and displays them on the surface. So the message displayed by every cell in your body except RBC’s is to present to cytotoxic T cells ...

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