BISC 307L 1st Edition Lecture 31 Current Lecture Immunoglobulins o o If you take serum proteins they are pretty much all globular proteins so called globulins 5 classes 1st class A albumin not called a protein though A1 A2 B Gamma are the other four which are classified by molecular weight gamma ones are antibodies also known as immunoglobulins Ig There are 5 classes of Ig All secretions of activated B lymphocytes 1 Most abundant in plasma is IgG 4 parts 2 identical light chains and 2 identical heavy chains y shape constant C and variable V regions Fab when you digest Ig with enzyme called papain it is cleaved into antigen binding fragment Fc The other part it is cleaved into is crystallizable fragment 2 IgD structure has a pink transmembrane region B cell receptor 3 IgM first Ig secreted by B cells Large molecule Cannot leak out of capillaries even inflamed ones Action is in the blood After a month of secreting this it undergoes class switching the constant region is switched from IgM IgG not in the antigen binding region The IgG has the same identical antigen binding specificity as IgM which will have the same specificity as IgD therefore this cell will only make antibodies that have this particular specificity 4 IgG smaller molecule and leaks out during inflammation only maternal antibody that can cross the placenta helps confer passively some of the mothers immunity onto the fetus some plasma cells when they switch from IgM IgG they may switch to IgE instead This is abnormal TRIGGERS ALLERGIES 5 IgE allergies abnormality parasitic worm infections 6 IgA most abundant form for mucus secretions milk tears mucus Transcytosis of IgA o o Single epithelium cells Secretion of IgA antibodies is coming from plasma cells in the tissue below the basolateral membrane of the epithelium When the cell is activated it will secrete IgM and them switch to IgA IgA consists of two subunits and a joining chain and it binds to a poly Ig receptor and this triggers endocytosis of the Ig complex and is transported in a vesicle by transcytosis Rearrangement of Immunoglobulin Genes o o What s the problem with diversity If every Ig has a different variable region how different are they Antibody reservoir is about 100 billion There cannot be one gene for each protein because we have a lot of proteins Solution mechanism of recombination of the genes for Ig Left side gene for a light chain in an immature b lymphocyte with variable region There are multiple versions of these regions At random there is somatic recombination and the intron between the variable region and the joining region will be deleted Piece of RNA ligated to form mRNA and translated into light chain Heavy chain variable region of the heavy region made up of 3 regions V J D All joined together Diversity of Immunoglobulin Genes o o Normally there are enzymes that correct errors but these are suppressed in the variable region of the B cell o In the box you can see two different types of errors that are allowed to persist mutations are allowed in the variable region o These errors multiplied times the 2 million gets you into billions of combinations Allergic Responses o o Immediate and delayed allergic responses Most things people are allergic too are immediate allergies due to inappropriate B cell responses Delayed reactions to poison oak or ivy and skin reactions to jewelry due to inappropriate T cell responses o Pollen provoke immune response allergens phagocytized by macrophages and dendritic cells and internalized but fragments of the allergen are processed and presented on the surface of the phagocyte and presented for the benefit of the helper T lymphocyte has T cell receptors on its surface that are highly variable and diverse that are presented to by antigen presenting cells helper T cell will release cytokines to activate specific B cell that is capable of creating antibodies to bind to antigen helper T cells will only activate B cells that themselves can bind directly to the antigen and must be stimulated by cytokines Response is B cell becomes activated produce memory B cells and clonal cells that secrete antibodies IgM IgG THIS IS NORMAL RESPONSE OF B CELL o First time you are exposed to this pollen you get a very mild reaction Then you become sensitized If instead secretes IgE than IgG it binds to Fc receptors of on the surface of mast cells and basophils IgE antibody with complex of antigen bound it becomes a mast cell or basophil receptor Later presentation of the allergen evokes a response of the mast cell or basophil to degranulate and cause inflammation o If this happens deep in the lungs you can get bronchorestriction and makes it hard to breath and excess mucus secretion Anaphylaxis o o Extreme allergic reaction o Widespread release of histamine you get too much bronchoconstriction and too much muscus and vasodilation and increase in capillary permeability Edema in tissues but decrease in blood pressure and volume and this leads to shock brain starts dying o Treatment injection with epinephrine causes vasodilation in the bronchiolar smooth muscle Major Histocompatibility Complex MHC o o Substantial of the genome codes for cell surface glycoproteins the set of genes that code for these are th major histocompatibility complex In humans these are called HLA In mice they are called H 2 But for the most part we will call them MHC genes o 2 major classes I II Within each of these classes there are dozens of different types of proteins and for each type there is a lot of variability across the human population adds up for a lot of variability Very diverse set on the surface of cells and each one is a particular allele that is different from everyone else Function 1 Identify cells in your body as being self cells 2 Present antigens to lymphocytes