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Immuno Antibody-effector TB Notes.docx

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McMaster University
Health Sciences
Jonathan Bramson

Antibody-Effector Function  Neutralization, opsonization, mediates NK cell killing (ADCC) and classical complement activation  ADCC= antibody dependent cytotoxicity= NK cells  Ab= can also activate your mast cells crosslinks  mast cells release your granules etc.. Recall: The isotypes  Human= IgM, IgD, IgG (IgG1,2,3,4), IgA (IgA1,2)  Mouse= IgM, IgD, IgG (IgG1,2a,2b,3), IgA  Human IgG1,IgG3= induced by interferon gamma  Human IgG4= IL-4 induced  Mouse IgG1= IL-4 induced  Mouse IgG2a,3= IFN gamma induced Antibody response  Naïve B-cell will enter the LN from the blood  In the LN it will encounter its antigen= has two choices (1) becomes a primary focus (i.e. plasma cell in the medullary cords) or (2) will go to germinal center and get somatic hypermutation and isotype switching  becomes a plasma cell  can go to the medullary cords  exits via the efferent lymph vessel  Can go back to the bone marrow Three differences to remember about antibodies 1. Isotypic differences= i.e. IgG vs. IgA 2. Allotypic differences= based on a polymorphism in the constant region 3. Idiotypic differences= differences in the epitope binding Isotype Properties  IgM= easiest to produce, no isotype switching, good at classical complement activation, can also do a little bit of opsonization and neutralization  IgD= marker of B-cell maturity  IgG= highest circulating Ab, neutralization, opsonization, ADCC, can activate complement  IgA= very good at neutralization, found in mucosal sites (i.e. in the GI tract), minor functions= can opsonize and activate complement  IgE= allergy association (mast cell sensitization/activation), parasitic infections—mast cells are helpful Isotype Distribution  Blood= IgG and IgM (note: IgG can pass the placenta)  Extracellular space= IgG and IgA (note: IgA can cross the epithelium)  Below epithelium (Mast cells)= IgE Neutralization  Ab can bind with toxins, viruses, bacteria  all require receptors on the cell surface  Therefore, binding prevents access to receptors/ entry into the cell  Recall: IgM, IgG, IgA Classical complement activation  MAC formation, increase inflammation, opsonization (i.e. C3b) Classical Complement= Clearance of Immune Complexes  Antigen:antibody complexes coated by C3b  RBC have CR1 (complement receptor) and bind with CR3  Get carried to spleen= high amounts of macrophages= phagocytosis Fc Receptors  Fc Gamma= IgG  Fc epsilon= IgE  Fc alpha= IgA  Consequences of Fc ligation? o Fc gamma receptor= increase uptake, increase killing, increase granule release (eosinophils), inhibition of ITAMS o Fc gamma receptor FC epsilon receptor III= induces NK cell killing o FC epsilon receptor= target mast cell and basophils= granules released o Fc alpha receptor- uptake killing  On macrophage membrane get crosslinking of the receptors== leads to receptors  Uptake killing= macrophages uptake Ab coated particle, get lysosomal fusion and degration= lysosome has many weapons ADCC  Ab binds the target cell  FCgR NK recognizes antibody  Crosslinking occurs (brings the FC receptors together) and leads to signaling  Signal to kill  NK cells kill (via perforin and granzyme= need both)  Apoptosis Eosinophils  Release their granules and cytokines Mast Cells  Have high amounts of histamine (i.e. high amounts of IgE)  Crosslinking of the epsilon receptors= leads to granule release= histamine release  Get smooth muscle contraction  Also, in GI tract= have vomiting and diharrea  Airways, nasal passages, eyes= get blockage and over production of mucus  Blood vessel= increase permeability and vascular leakage Antibody Applications Benefits  High specificity and high affinity  Easy to generate  Very stable (i.e. can stay at 37 deg Celsius)  Can manipulate its biochemical properties  Can use for diagnosis, experimental research and therapeutic methods  Note: Affinity vs. avidity o Affinity= the interaction between single epitope to a single binding site (i.e. Ab:Ag complex) o Avidity= the total strength of your binding interactions (i.e. involvement of multiple binding sites)= i.e. an antibody binding two epitopes look at
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