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USC BISC 307L - Mechanisms of Acquired Immunity
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ImmunoglobulinsIf 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 lymphocytes1. Most abundant in plasma is IgG4 parts (2 identical light chains and 2 identical heavy chainsy shapeconstant C and variable V regionsFab= when you digest Ig with enzyme called papain it is cleaved into antigen binding fragmentFc= The other part it is cleaved into is crystallizable fragment2. IgD- structure has a pink transmembrane region. B cell receptor.3. IgM- first Ig secreted by B cells.Large moleculeCannot leak out of capillaries (even inflamed ones)Action is in the bloodAfter a month of secreting this it undergoes class switching (the constant region is switched from IgM  IgG) not in the antigen binding regionThe 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 specificity4. IgGsmaller molecule and leaks out during inflammationonly maternal antibody that can cross the placentahelps confer passively some of the mothers immunity onto the fetussome plasma cells when they switch from IgMIgG they may switch to IgE instead. This is abnormal: TRIGGERS ALLERGIES5. IgEallergiesabnormalityparasitic worm infections6. IgAmost abundant form for mucus secretions (milk tears, mucus)Transcytosis of IgASingle epithelium cellsSecretion of IgA antibodies is coming from plasma cells in the tissue below the basolateral membrane of the epitheliumWhen the cell is activated it will secrete IgM and them switch to IgAIgA 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 transcytosisRearrangement of Immunoglobulin GenesWhat’s the problem with diversity?If every Ig has a different variable region how different are they?Antibody reservoir is about 100 billionThere cannot be one gene for each protein because we have a lot of proteinsSolution: mechanism of recombination of the genes for IgLeft side: gene for a light chain in an immature b lymphocyte with variable region. There are multiple versions of these regionsAt 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 chainHeavy chain: variable region of the heavy region made up of 3 regions (V,J,D)All joined togetherDiversity of Immunoglobulin GenesNormally there are enzymes that correct errors but these are suppressed in the variable region of the B cellIn the box you can see two different types of errors that are allowed to persist- mutations are allowed in the variable regionThese errors multiplied times the 2 million gets you into billions of combinationsAllergic ResponsesImmediate and delayed allergic responsesMost things people are allergic too are immediate allergies due to inappropriate B cell responsesDelayed: reactions to poison oak or ivy and skin reactions to jewelry due to inappropriate T cell responsesPollen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 CELLFirst 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 inflammationIf this happens deep in the lungs you can get bronchorestriction and makes it hard to breath and excess mucus secretionAnaphylaxisExtreme allergic reactionWidespread 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)Treatment: injection with epinephrine- causes vasodilation in the bronchiolar smooth muscleMajor Histocompatibility Complex (MHC)Substantial of the genome codes for cell surface glycoproteins- the set of genes that code for these are th major histocompatibility complexIn humans these are called HLAIn mice they are called H-2But for the most part we will call them MHC genes2 major classesIIIWithin 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 variabilityVery diverse set on the surface of cells and each one is a particular allele that is different from everyone elseFunction:1.Identify cells in your body as being self cells2. Present antigens to lymphocytesBISC 307L 1st Edition Lecture 31 Current Lecture- Immunoglobulins oo If you take serum proteins they are pretty much all globular proteins so calledglobulins (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 iscleaved into antigen binding fragment- Fc= The other part it is cleaved into is crystallizable fragment 2.


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