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BIOL 2050U
Peter Cheung

IMMUNOLOGY EFFECTOR FUNCTIONS OF ANTIBODY -gene rearrangement and somatic mutation of variable region regionsdiverse Ab -rearrnged variable region can be associated w/different constant regions (class switching) -Variable region = antigen specificity Effector Function=heavy chain constant regions Ig’s in body fluids: IgG – internal IgA – external (on mucosal surfaces) IgM – first one made in reponse to antigen -NO hypermutation  low overall affinity -Pentamaric= 10 binding sites  high AVIDITY IgG – 4 subclasses (varying hinge region flexibility, glycosylation sites) -some respond to T-INDEPENDENT antigens (LPS) - IgG2, IgG4 -otherwise, predominant reponse is T dependent from IgG1 -only Ig class to cross the placenta IgA – monomer in serum; active as a DIMER on mucosal surfaces -held together by J-CHAIN and SECRETORY Component -make a lot daily, since a lot is secreted IgE – heavily glycosylated; mediates allergic reactions and fights against parasites -binds specific receptors on basophils and mast cells Males carrying xid gene on X chromosome cant make antibody to pneumococcal antigen. Very low LD50 -“slippery capsule prevents antigen from being ingested! Isotype Dependent Effector Functions (depends on Hc) - Transport o IgA- mucosal o IgG – placenta - Non-inflammatory o all but IgE (neutralization of virus/toxins and blocking adherence of bacteria) (especially IgA) - Inflammatory o IgG – phagocytosis/opsonization o IgM/IgG – complement activation (especially IgM) o IgE – mast cell activation (allergy) o IgG –antibody-dependent, cell mediated cytotoxicity MUCOSAL TRANSPORT – 3g of IgA made daily; very little enters systemic transport -local production of Ab is independent from systemic production of Ab so termed mucosal immune system -adhesion molecules on mucosal cells directs IgA secreting B cells and T cells to tissues (GALT/BALT) Secreted dimeric IgA made by plasma cells in the lamina propria then transported across mucosol surface -M cells=monocytes like epithelial cells that pinocytosis to present antigen in lumen to lymphocytes -B cells in center of lymphoid tissue and T cells around edge no capsule, sits under mucosa Roles of IgA in host Defense 1. Barrier to exclude foreigners from bodyprevents binding of pathogens to body neutralization (block infectivity even with attachment) 2. Barier to environmental antigenscomplexes with food and complex is destroyed or excreted (before IgE) PRODUCTION OF IgA submucosal LYMPHOID FOLLICLE secretes IgA (trachea, for example) GERMINAL CENTER = core consisting of identical B cells epithelial M CELLS phagocytose/pinocytose foreign particles in lumen transport digested antigens into follicle and stim. antibody production *mucosal immunity is not the same as serum immunity – “parallel systems” nasally administered poliovirus increases IgA in mucosal secretionNO CHANGE in serum IgA, IgM levels* -IgA receptor made by and expressed on basolateral surface of mucosal epithelial cells SC1 domain recognizes complex of J chain and alpha chain dimerization: J-Chain: -made in B cells!! connected to IgA Cα3 by disulphide bonds -essential in binding of SC SC (secretory component) – produced by MUCOSAL EPITHELIUM “pIG” 5 globular domains: SC1 – non-covalently binds Cα3 of dimeric IgA (or IgM) SC5 – disulphide bonds to Cα2 cytoplasmic tail – targeting STEPS FOR TRANSPORT OF IgA 1) secreted on basolateral surface of epithelium 2) binds dimeric IgA 3)endocytosis 4)transcytosis to apical surface; cytoplasmic tail cleaved 5)secretion (SC still bound) ***SC necessary for IgA secretion, stability*** (prevents against digestion) IgG and Placental Transport -ACTIVE trans. of IgG (preference for IgG1 and IgG3) across placenta; 6 mos. of protection for baby Mediated by Brambell Receptor (FcRB or FcRn) -made of two chains homologous to MHC I -α1 and α2 domains bind the Fc region of IgG (2 molecules of FcRB bind one IgG molecule) -receptor caries IgG across endothelium and into extracellular spaces -selectively recycles endocytosed IgG from cellular endosomes back to extracellular fluid (after the antigen dissociated from the Ab and was degraded) prolongs the serum half-life of IgG!!!! NON INFLAMMATORY ACTIVITIES 1. Virus Neutralization Ex: Influenz ssRNA viruses with HA and NA glycoproteins extending from the envelope HA/NA (1)easily mutated (2)interact with host segm
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