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Complement

Complement pathways: Classical pathway Alternative pathway Lectin pathway. Complement proteins. Classical pathway C1q C1r C1s C4 C2Alternative pathway D C3 BLectin pathway MBL MASP-1 MASP-2Membrane attack complex(MA

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Complement

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    3. Complement proteins Classical pathway C1q C1r C1s C4 C2 Alternative pathway D C3 B Lectin pathway MBL MASP-1 MASP-2 Membrane attack complex(MAC) C5 C6 C7 C8 C9 Membrane regulatory proteins CD55 CD46 CD59

    4. Soluble regulatory proteins Positive regulation Properdin Negative regulation C1-INH C4-bp Factor H Factor I Carboxypeptidase S protein Clusterin

    5. Comparison of the classical and alternative complement pathways

    8. Complement pathway activators Classical pathway IgM-containing immune complexes IgG-containing immune complexes Mannose-binding lectin(MBL) C-reactive protein(CRP) Serum amyloid P(SAP) Myocardial damage products Membranes of apoptotic cells C4 nephritic factor (C4Nef) Myelin

    9. Alternative pathway Tickover Amplification from classical pathway C3b fixation Repeating polysaccharides Endotoxin Virally infected cells(measles,influenza,Epstein-Barr virus) IgA-containing immune complexes Some Ig light Chains C3 nephritic factor(C3Nef) Cobra venom factor(CVF) Zymosan(yeast cell wall) Lectin pathway Repeating simple sugars

    10. Complement-fixing potential of antibodies Classical pathway: IgM>IgG3>IgG1>IgG2>>IgG4 IgA can activate the alternative pathway IgE will activate complement only in unusual circumstances

    11. Structural and functional homologs in activation pathways C2 and factor B C1q and mannose-binding lectin(MBL) C1r/C1s and MASP-1/MASP-2 C3/C4/C5 C6/C7/C8/C9

    12. Complement regulatory proteins and primary locations Fluid phase C1-INH Factor I Factor H C4b-binding protein (C4-bp) S protein(vitronectin) SP-40,40(clusterin) Carboxypeptidase

    13. Cell membrane Decay-accelerating factor(DAF,CD55) Membrane cofactor protein(MCP,CD46) CD59 Membrane C3-proteinases Matrix Decorin

    14. Complement pathway regulatory mechanisms and examples of each Protease inhibitors C1r:C1-INH C1s:C1INH

    15. Complement pathway regulatory mechanisms and examples of each Proteases C4a C3a Carboxypeptidase Inactivated C5a

    16. Complement pathway regulatory mechanisms and examples of each Decay-acceleration DAF,C4-bp,CR1 C2a C4b2a C4b DAF,H,CR1 Bb C3bBb C3b

    17. Complement pathway regulatory mechanisms and examples of each Cofactor activity Factor I C3b C3bi MCP,H,CR1 FactorI C4b C4bi MCP,C4-bp,CR1

    18. Complement pathway regulatory mechanisms and examples of each Inhibition of assembly C1:Decorin C5b-C7:S protein C5b-C7:SP-40,40 C5b-C9:CD59 C9polymerization:CD59

    19. Complement receptors C1q receptor Complement receptor 1(CR1) Complement receptor 2(CR2) Complement receptor 3(CR3) Complement receptor 4(CR4) C5a,C3a and C4a receptors

    20. Anaphylatoxins and disease Target Smooth muscle Mast cells Blood capillary wall Vascular endothelium Leukocytes Platelets Immune response Effect Contraction Histamine release Increase in vascular permeability Increased adhesiveness for leukocytes Adhesion,aggregation,chemotaxis,release of lysosomal enzymes,generation of oxygen radicals Aggregation,release of serotonin C3a:suppression C5a:enhancement

    21. Complement as an effector pathway in disease

    22. Vasculitis and immune complex diseases Polyarteritis nodosa(PAN) Hypersensitivity vasculitis Henoch-Schonlein purpura(HSP) Rheumatoid vasculitis Systemic lupus erythematosus(SLE)

    23. Rheumatologic disease

    24. Pulmonary disease Acute respiratory distress syndrome SLE

    25. Platelet diseases Idiopathic thrombocytopenic purpura (ITP)

    26. Hemolytic disease Paroxysmal nocturnal hemoglobinuria (PNH) Hemolytic-uremic syndrome (HUS)

    27. Myocardial disease Unstable angina Myocardial infarction Reperfusion injury

    28. Renal disease(Glomerulonephritis)

    29. Atherosclerosis

    30. Cutaneous disease SLE Phototoxic reactions Autoimmune bullos diseases Acne Psoriasis

    31. Systemic lupus erythematosus

    32. Reproduction and pregnancy

    33. Myositis Dermatomyositis

    34. Neurologic disease Multiple sclerosis SLE Guillian-Barre syndrome Alzheimer’s disease

    35. Xenotransplant rejection

    36. Diseases in which complement inhibitors will probably be effective Some forms of vasculitis Rheumatoid arthritis ARDS SLE Many types of renal diseases ITP Hemolytic anemia Myocardial infarction Neurologic disease Ischemia-reperfusion injury Antiphospholipid syndrome Recurrent immune-mediated fetal loss Ab-mediated cutaneous disease Xenotransplant rejection

    37. Complement deficiencies

    38. Clinical presentation of complement deficiencies Infection Autoimmune disease

    39. Summary of complement deficiency states

    40. Summary of complement deficiency states

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