The complement system

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The complement system
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???????Pfeiffer ?? heat labile serum factor
?.?.2437 Pillemer ?? Alternate pathway ?.?.
2497 Ihara, I. ?? Lectin pathway ?.?. 2525
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??????????????????????????????????????????????????
????????????????????????????? gt34 ????
?????????????????????????????????????? 3
??????1. ????????????????? (cell lysis)2.
????????? opsonization3. ??????????????????
??????? cell activation
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????????????????????????1. ?????????????
inactive form2. ?????????????????????????????????
???? (cascade)3. ????????????????????????????????
???????? (biological active intermediate
products) ????????????????????????????4.
??????????????????????????????????????????????????
?????
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????????? complement component1. Protein ???
glycoprotein ?????????????? 5 ??? serum
protein2. ???????? ??? ??? macrophage ?????????
???????????? ??????????????????? fibroblast,
monocyte ??????????3. ????????????
????????????????????????? 6-8 wk4. ???????? half
life ?????? 24 ??.5.????????? (heat labile)
??????????? 56 ? 30 ????6. ?????????????
inactive form7. ????????????????????????????
immunize
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?????????????????????????????

• complement component ??????????? C
  ????????????????????????? ???? C1, C2, C3...C9
• Properdin(P), factor B (B), factor D (D)
• complement component ???????? ????????????????????
  ????????????? ??????????????????????????????????
  ???? C2 ?????????? C2a ??????? C2b ???????
  ??????????????????????????????????????????????????
  ??????????????????????????????????? C1r ????
  C4b2a ???????

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3 complement pathways
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Classical pathway

• ?????????? antigen antibody complex, aggregated
  immunoglobulin, protein A, C-reative protein,
  trypsin like enzymes

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?????????????????

• 1. Recognition step ??????? C1qrs ??? Fc ??? Ab
  ?????????? Ag ???? C1 esterase
• 2.Activation step ???? C4, C2 ???? C3 convertase,
  C5 convertase
• 3. Attack step C5b ???????????????? C6,7,8,9

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Alternative pathway

• ?????????? yeast cell wall, bacterial cell wall,
  endotoxin, ????????? , inulin
• ??????????????? C3 ??? ??????????? C1, C4, C2
• C3b ?????????????????????????????????????????
  ????????????? ?????????????????????? factor H ???
  factor I
• C3b ??????? factor B m??????????? Factor D ?????
  Properdin (P) ??????? stabilize ??? C3 convertase
  ??? C5 convertase ??? alternative pathway ????

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Lectin complement pathway (Mannan Binding Lectin
Pathway)

• ???? pathway????????????????????? ??.1982
  ???????????????????????? Ihara I.
• ???????1990 ????????????????????????????
  complement ?? pathway ?????? Ohta, S.

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?????????? lectin pathway

• ?????????????????????????????????????
  ??????????????????????? MBL (mannan binding
  lectin) ?????????????????? C1q ????????????? Ca
  ???????? classic pathway ????????????????????? 2
  ???????????? serine protease  ??? MASP-1???
  MASP-2 (MBL-associated plasma proteins)
• MASP-1 ?????????????? C1r ??????????????? C2, C3
  ??? C4 
• MASP-2 ?????????????? C1s ???????????? C4
• ?????????? lectin pathway ??????? factor D ???
  factor B ??????????????

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• MBL ???? acute phase protein ????????? inate
  immunity ?????????????????????????????????? MBL
  ????  ????????? MBL ????????????????? opsonin
  ??????????????????????????? phagocyte
  ??????????????   ????????????????????? MBL
  ??????????????????????????????????????????????????
  ?????????????????? HIV ????????????

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CONTROL OF THE COMPLEMENT SYSTEM

• ???????? C3b ??????? amplification loop
  ??????????????????????? alternate pathway,
  ??????? complement component ????? ??????
  activate complement ??????????????? attack
  complex ???????????????????????????
  (????????????????) ???????????????????????????????
  ????????????????????????????????????? host cell
  ??? ????????????????????????????????? complement
  ??????????????????????????????????? component
  ????? ???????????????????????complement???????????
  ???????????????????????????????????
  ????????????????? ???????????????????

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C1 inhibitor

• ??????????????? glycoprotein ????????????????? C1
  inhibitor ???????????????? C1s ??? plasmin
  ???????????????????? catabolic site
  ??????????????????????????????????????????????
  complement ??????????? ????????????? C1 inhibitor
  ??? inhibit kinin, fibrinolytic ??? coagulation
  system (kallikrein, Hageman factor, plasmin)
  ???????????????????? C1 inhibitor
  ??????????????????? ???????????????? larynx
  ??????????? airway obstruciton ?????????
  ????????????????????? hereditary angioedema
  ???????????????????? kinin-like C2 fragment
  ???????????? C1s ???? C2 ?????????????????????????
  ???????????????????

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• Factor I ????????? C3b ??????????????????????
  classical pathway ??? alternate pathway
  ?????????????????????? peptidase
  ????????????????? Factor I ???????????????????????
  ?? C3b ???????????????????????????? solution
  ????????????????? C4b23b ???? C3bBb ??? C4b
  ??????????????????? peptidase ????????????????????
  ????????????????? factor I ???????

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• Factor H ??????????????????????????????
  ????????????????? C3b ????????????????????????????
  ? complement 3 ???????? 1. ??????? factor B
  ????????? C3b 2. ??????? factor Bb ?????? ctive
  C3 convertase ?? alternate pathway 3.
  ?????????????????????????????????????? factor I
  ??? membrane-bound C3b ??? 30 ???????????

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• C4 binding protein ??????????????????????????
  C4b ???????????????????????????? C4b
  ?????????????
• Decay accerelating factor (DAF)
  ?????????????????????????????????????
  ??????????????????? ?????????????
  ??????????????????????????????????? C3 convertase
  Complement receptor-1 (CR-1) receptor
  ????????????????????????????????????????????????
  C3b ????????????????????? amplification loop
  ???????????????????????????? C3b ??? factor I
  (?????? factorH)
• Anaphylatoxin inactivator ???? alpha globulin
  ???????????????? inactivate C3a C4a C5a
  ?????????? COOH-terminal Arginine ?????????????
  component ????????????????????

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• S protein ?????????????????????????? C5b67
  complex ???? Sc5b67 ??????????????????????????????
  ???, S protein ??????????????????? attack step

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The acute laryngeal edema seen here that killed
the patient was due to an anaphylactic reaction
to penicillin. Such an allergy is a form of type
I hypersensitivity reaction in which there is
preformed IgE antibody on mast cells that
quickly reacts with an antigen. The mast cells
release histamine and other mediators that lead
to the edema.
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