Complement system and diseases.pptx for medicine and paediatrics

Complement system and the related diseases

1. COMPLEMENT SYSTEM

2. named “complement system” because it was first identified as a heat-labile component of serum that “complemented or augment” antibodies in the killing of bacteria Consists of serum and cell surface proteins . involved in defense against pathogens and tissue damage mediated by antibodies Plays major role in both innate and adaptive immunity. Most of these proteins are found in serum or on cell surfaces. Synthesized in liver as inactive precursors and are activated by Proteolysis Also produced by blood monocytes, tissue macrophages and epithelial cells of the gastrointestinal and genitourinary tract.

3. Are glycoproteins. Are synthesized rapidly in inflammatory responses – hence are called acute phase proteins. Heat labile and lost activity at 56⁰ C for 30 mins and inactivated. Immunoglobulins are not inactivated at this temperature. Binds with Fc portion of immunoglobulins

4. Three main effects of complement are: Lysis of cells (bacteria, allografts, tumor cells) Generation of mediators of inflammation Opsonization – enhancement of phagocytosis

5. COMPLEMENT PATHWAYS Three pathway of complement activation Classical pathway:- antibody dependent pathway. triggered by formation of antigen-antibody complex Alternative pathway:- antibody independent pathway stimulated by antigen directly Lectin Pathway:- Also antibody independent but resembles classical pathway.

6. STAGES OF COMPLEMENT ACTIVATION Three main stages in the activation of complement by any pathway are Formation of C3 convertase Formation C5 convertase Formation of membrane attack complex(MAC)

7. COMPLEMENT ACTIVATION C3b- the central molecule of the complement cascade All three pathways lead to the production of C3b, the central molecule of the complement cascade C 3b has two important functions: It combines with other complement components to generate C5 convertase , the enzyme that leads to the production of the membrane attack complex and opsonized bacteria because phagocytes have receptors for C3b on their surface.

8. MASP-1 (mannan-binding lectin-associated serine protease-1)

9. Clinical Aspects of complement Deficiency of C5-C8 & Mannan-binding lectin ,Predispose to severe Neisseria bacteraemia Deficiency of C3 Severe, recurrent pyogenic sinus & resp. tract infections Deficiency of C1 esterase inhibitor Angioedema -inc. capillary permeability and edema Deficiency of DAF Paroxysmal nocturnal haemoglobinuria- Increased complement-mediated hemolysis -

10. Transfusion mismatches Activation of complement → generate→ large amounts of anaphylatoxins & MAC → red cell hemolysis Autoimmune diseases immune complexes bind complement → low complement levels + activate inflammation → tissue damage Severe liver disease Deficient complement proteins predispose to infection with pyogenic bacteria Factor I deficiency Haemolytic Uremic Syndrome- Mutations in factor I gene

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