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Plasma proteins etc

Organisation of the Body

QuestionAnswer
Physiological challenges Do not harm when all is normal Provide pathogen specific ligands Provide immune memory Recruit leukocytes to sites of infection Deliver a coup de grace to pathogens Transport insoluble and reactive nutrients
Plasma proteins Albumin Alpha 1 - orosomucoid and lipoproteins Alpha 2 - plasminogen, prothrombin, haptoglobin, ceruloplasmin macroglobulin Beta - lipoproteins, transferrin Gamma - immunoglobulins
Albumin and lipoproteins Carriers of fatty acids, cholesterol and triglycerides Albumin 4% HSA complex with 5x myristic acid - binds lipids
Effector functions of antibodies Neutralisation of virus infectivity Opsonization of phagocytic uptake and killing of bacteria Antibody dependant cytotoxicity Mast cell responses Complement activation
Antibody neutralising SARS-CoV-2 Binds to plasma membrane in order to inject genetic material for replication Antibodies bine to the virus and prevent this docking
Broadly neutralizing antibody Best correlate for antiviral immunity More effective with acute than chronic infections Strong selection pressure for neutralisation escape HIV particularly variable VRC01 example Potential as a theraputic
Prototypic antibody 2 light chains 2 heavy chains Fab and Fc regions Made of Ig domains
Hypervariable complementary determining regions These confer antigen specificity 6 total regions per antibody
B lymphocyte antigen receptor Secreted by b lymphocyte derived plasma cells A membrane bound splice variant of antibody Generated by alternative specificity Antigen binding - signalling - activation - proliferation, differentiation
Immunoglobin fold Light chain central control region - 7 beta strands connected by disulphide bonds Loops can be altered without affecting structure - occurs in light chain
Antibody classes IgG IgM IgD IgA IgE
Multimeric forms of Ig IgM in plasma - pentameric IgA in mucosal secretions - dimeric Corresponding BCRs - monomeric Joining chain connects multiple Igs
Avidity The massive reduction in dissociation rate due to multiple binding sites Occurs in multimeric Ig Once one antigen binds it is easier for another to bind
Antibody dependent opsonization Antibody Fab binds antigen on pathogen Antibody Fc binds low affinity Fc receptor on phagocyte Zipper mechanism Closure by plasma membrane fusion Actin dependant phagolysosome fusion Lysosome mediated digestion
Antibody dependent cytotoxicity Antibodies bind antigens on the surface of target cells NK cell CD16 Fc receptors recognise cell bound antibodies Cross linking of CD16 triggers degranulation into a lytic synapse Tumour cells die by apoptosis
Antibody dependent mast cell responses Helpful - defend against helminth infection, defend against snake venom, trigger acute inflammation Harmful - drive immunopathology in asthma and atopic allergy, systemic mast cell degranulation kills people in anaphylaxis
Complement Antibacterial activity of plasma - heat stable fraction (IgG) and heat liable fraction (complement) Major functions ; direct lysis by membrane attack complex, indirect killing by opsonization for phagocytes vasodilation and chemotaxis
Complement cascade 2 major and 1 minor pathway Amplifying loop - produces a serine protease C9 complement - introduces a hole in the membrane
Complement cascade pathways Alternative - activated by C3 itself binding to membrane and auto cleaving Classical - C1 binding to IgG antibody Lectin - Activated by MBL recognising mannose on surface of membrane All produce C3 convertase
Effector functions of complement cascade Opsonization Strong attracter for leukocytes C5 convertase starts complement reactions - inserts MAC leading to holes and lysis
Transferrin Plasma glycoprotein at 2.5mg/mL Made in liver Reversibly binds Fe3+ at nanomolar conc Most cells acquire iron from transferrin via RME Reduces free iron, inhibiting growth of free living bacteria Transports iron from duodenum to liver
Alpha 1 antitrypsin Most abundant serpin in plasma Deficiency - genetic disease AATD predisposes to lung disease and susceptibility to cigarette smoke, dust, fumes and chemicals Risk factor for COPD
Haptoglobin Synthesised in liver during inflammation Binds haemoglobin released from damaged erythrocytes Complex removed by liver macrophages Prevents Fe3+ kidney damage Important in malaria and SCD
Ceruloplasmin Synthesised in the liver Major copper carrying plasma protein Ferroxidase aids iron binding by transferrin very rare genetic deficiency Aceruloplasminemia leads to neurological disorders - iron accumulation in brain Elevated seen in copper poisoning
Hepcidin and Iron homeostasis Elevated iron induces hepcidin synthesis in liver Hepcidin inhibits iron transport by ferroportin into blood from gut and macrophages Iron levels are decreased
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