1. Many of the components are enzymes that become activated when cleaved into two peptides.

2. one peptide binds to the immune complex and becomes a functional part of it

3. the other peptide diffuses away and can become an inflammatory mediator (binds to a receptor)

1. Lysis: complement attaches to target cell which induces lysis

2. Opsonization: uptake of particulate antigens with a bacteria by a phagocyte that induces phagocytosis

3. Activation of Inflammatory responses: complement receptor that attaches to a phagocyte with rolling and extravasion

4. Clearance of immune complexes: Ag-ab complex that bind to the phagocyte and will clear it out.

by Jules Bordet "hemolysis"; Paul Ehrlich "complement"

1. enzymes synthesized primarily by liver hepatocytes

2. designated by numbers, letters and random names.

3. most circulate as inactive proenzymes or zymogens until cleaved.

4. clevage and the generation of small and large complement fragments.

1. classical pathway

2. lectin pathway

3. alternativa pathway.

1. Activated by

   a. formation of Ag-Ab complex

   b. binding of Ab (IgM, IgG1,2,3) to Ag on a target cell

2. Ab-Ab complex induces conformation change in Ab exposing binding sites for C1 

3. C1 = C1q, 2 C1r, and 2 C1s

 a. C1qr2s2 stabilize by Ca2+

 - C1q -> C1r cleaves C1s

4. C1s (binds Ag complex) hydrolyzes C4 -> C4a + C4b

    and C2 - > C2a + C2b

  - C4b + C2a -> C3 convertase

5. C3 convertase hydrolyzes C3 -> C3a + C3b

    - C3b + c46C2a (c3 convertase) -> c5 convertase

6. C5 convertase cleaves C5 -> C5a and C5b

   - C5a diffuses -> anaphylatoxin

   - C5b binds c6 --> MAC

7. C5a binds C6, 7 and 8

8. C5b6,7,8 binds to poly C=9 -> forms pore lysis

1. C3b can diffuse and coat immune complexes by recognizing free hydroxyl or amino groups

- will allow for phagocytosis during

opsonization found on phagocytes.

2. joins C4b2a => C5 convertase.

- Does not require Ag-Ab complex formation

- Produces activate C3 and C5 convertase

- includes 4 serum proteins

- initiated by foriegn cell surface proteins

- activate c3 is generated spontaneously.

1. C3 binds to foreign surface antigen on bacteria

2. then hydrolyze into C3a and C3b to factor B which exposes site cleaved by factor D.

3. Clevage generates active C3bBb (c3 convertase) that is bound by properdin

4. C3bBb (c3 convertase) hydrolyzes C3 (a 2nd molecule) into C3a and C3b to amplify response.

5. C3bBb3b is a c5 convertase that hydrolyzes C5 and leads to MAC formation.

1. Activated by mannose-binding lectin to mannose residues on foreign surface

2. binding activates MASP-1 and MASP-2 that cleave and activate c4 and C2

3. cleaves C4 and C2 generate C3 convertase like classical pathway.

5. then continues to MAC

When does regulation of complement pathways occur?

Give an example

1. before convertase activity

2. after c3 convertase activation

3. during MAC formation

Example. c1 inhibitor restricts activation of C4 and C2, RCA proteins (C4bBP, Cr1, MCP) of classical pathway

1. CR1 MCP and factor H in the alteranative pathway to bind C3b and prevent C3b association with factor B to form C3bBb

Describe the regulation of the complement sytem

before the assemby of convertase activity.

1. c1 inhibitor (C1Inh) binds c1r2s2, causing dissociation from c1q.

2. ASsociation of C4b and C2a is blocked by binding c4b-binding protein (c4bBP), complement receptor type I (Cr1) or membrane cofactor protein (MCP). Inhibitor bound C4b is cleaved by factor I.

4. In alternative pathway, CR1, MCP, or factor H prevents binding of C3b and factor B.

5. Inhibitor bound C3b is cleaved by factor I.

Describe the regulation of complement sytem

after the assembly of convertase.

1. C3 convertases are dissociated by C4bBp, CR2, factor H, and decay-accelerating factor (DAF)

1. S protein prevents insertion of C5b67 MAC component into the membrane

2. Homologous restriction factor (HRF) or membrane inhibitor of reactive lyss (MIRL or CD59) bind c5bB678, preventing assemply of poly-c9 and blocking formation of MAC.

Inflammatory response, opsonization of particulate antigens, viral neutralization and solubilization and clearance of immune complexes.

- depends on the binding complement to complement receptors

- binding often generates breka down products with specific functional roles.

- gram positive bacteria: some microbes produce inactivating enzymes

- nucleated cells are harder to lyse

- not paticularly effective against tumor cells (they can endocytose MAC and repair damage)

C3a, C4a and C5a lead to inflammation.

   - regulated by serum protease carboxypeptidase N

   - bind receptors on mast cells and blood basophils

   - induce granulation, release histamines, and

   inflammatory mediators, induce smooth muscle

   contraction and increase vascular permeability

   - C3a, C5a, C5b67 induce monocytes and neutrophils

    to migrate to site of complement activation.

1. C3b- primary opsonin, also c4b and ic3b

2. c3b coats immune complexes or antigen

3. bound by complement receptor (cr1, cr3, cr4) on phagocytes

4. receptors expression is upregulated by c5a anaphylatoxin.

1. formation of larger viral aggregates

2. coating of virus with antibody and/or complement

3. increased binding of viral particle or Fc or type I complement receptors of immune cells.

4. direct lysis of enveloped virus.

1. C1, C2, C4, CR1 solubilize and clear immune complexes from the blood.

2. C3b coats, CR1 on erthrocytes bind C3b

3. Erythroctes carry the complex to the liver and spleen where it is phagocytosed.

due to recurrent severe bacterial infections

1. MAC deficiencies- recurrent Neisseria infections no immune complex disease

2. Regulatory protein deficiencies

a. edema

b. RBC lysis