Complement.ppt

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ComplementComplement

ComplementComplement Definition :Definition : series of heat-labile serum proteins series of heat-labile serum proteins

Site :Site : serum and all tissue fluids except urine and CSF serum and all tissue fluids except urine and CSF

Synthesis :Synthesis : in liver – appear in fetal circulation during 1 in liver – appear in fetal circulation during 1stst 13 W 13 W

Function :Function : Responsible for certain aspects of Responsible for certain aspects of

immune response and inflammatory responseimmune response and inflammatory response

Activation :Activation : antigen-antibody complex or endotoxin, capsule antigen-antibody complex or endotoxin, capsule

series of proteins activated sequentiallyseries of proteins activated sequentially

Inactivation:Inactivation: inhibitors in plasma (short lived) inhibitors in plasma (short lived)

Biological effects:Biological effects: either beneficial or harmful to host either beneficial or harmful to host

Complement pathwayComplement pathway

A) Classical pathway:A) Classical pathway:

- - ComplementComplement is is activatedactivated by antigen –antibody by antigen –antibody

complex (IgM or IgG)complex (IgM or IgG)

- - Fc portionFc portion of the antibody form of the antibody form a binding sitea binding site for for C1qC1q

- The - The numerical sequencenumerical sequence of the of the complement factorscomplement factors in in the classic pathway is:the classic pathway is:

C1q,r,s , C4, C2, C3, C5, C6, C7, C8, C9C1q,r,s , C4, C2, C3, C5, C6, C7, C8, C9

A) Classical PathwayA) Classical Pathway

The reaction sequence divided into three stages:The reaction sequence divided into three stages:1) Recognition stage: 1) Recognition stage:

- C- C1q1q act as the recognition element act as the recognition element

- It binds to Fc portion of IgM or IgG - It binds to Fc portion of IgM or IgG

- The activated C- The activated C11 molecule can cleave many C molecule can cleave many C44 molec. molec.

2) Activation stage: 2) Activation stage:

The complement components CThe complement components C44, C, C22, C, C33, C, C55, C, C66, C, C77, ,

CC88, C, C9 9 participate in that orderparticipate in that order

3) Membrane attack stage:3) Membrane attack stage:

Complement components CComplement components C5, 5, CC6, 6, CC7, 7, CC8, 8, CC9 9 participate participate where cell membrane damage and cell lysis occurwhere cell membrane damage and cell lysis occur

B) Alternative pathwayB) Alternative pathwayThis pathway is initiated by:This pathway is initiated by:

* Bacterial * Bacterial endotoxinendotoxin, polysaccharide , polysaccharide capsulecapsule, ,

aggregates of aggregates of IgEIgE and and properdinproperdin

* It * It startsstarts at at CC33 then C then C55, C, C66, C, C77, C, C88, C, C99

* The complement compon. * The complement compon. C1, C4, C2C1, C4, C2 are are by-passedby-passed

* * AntibodiesAntibodies are are not requirednot required to to initiateinitiate activationactivation of of

this pathwaythis pathway

* This * This pathwaypathway provides a means of provides a means of non-specific non-specific

resistanceresistance

Complement ActivationComplement ActivationClassical PathwayClassical Pathway CC11

CC4 4 CC22

CC3 3 Alternative pathwayAlternative pathway CC55

CC66

CC77

CC88

CC99

Membrane damageMembrane damage

Classic And Alterenative pathwaysClassic And Alterenative pathways

Classic Pathway Alternative pathwayClassic Pathway Alternative pathway

* Specific acquired immunity * Non-specific innate immunity* Specific acquired immunity * Non-specific innate immunity

* Initiated by antibody * Bacterial endotoxin, capsule* Initiated by antibody * Bacterial endotoxin, capsule

* Interaction of all components * C1, C4, C2 are by-passed* Interaction of all components * C1, C4, C2 are by-passed

* Properdin system not involved * Properdin system is involved* Properdin system not involved * Properdin system is involved

Biological Effects of ComplementBiological Effects of Complement

Beneficial effects:Beneficial effects:

1) Cytolysis:1) Cytolysis:

- activated complement proteins polymerize on cell - activated complement proteins polymerize on cell

surfaces of bacteria or erythrocyte to form pores surfaces of bacteria or erythrocyte to form pores

in its membrane (killing by osmotic lysis)in its membrane (killing by osmotic lysis)


2) Opsonization:2) Opsonization:

- binding of complement proteins opsonin (C3b)- binding of complement proteins opsonin (C3b)

to surfaces of foreign organisms or particlesto surfaces of foreign organisms or particles

- Phagocytic cells express specific receptors for - Phagocytic cells express specific receptors for

opsonins, so promote phagocytosisopsonins, so promote phagocytosis


3) Inflammatory response :3) Inflammatory response :

Small fragments released during complement Small fragments released during complement

activation have several inflammatory actions:activation have several inflammatory actions:

a) a) C5aC5a is is chemotacticchemotactic and and attract neutrophilesattract neutrophiles and and

macrophagesmacrophages

b) b) C5aC5a activateactivate phagocytes and neutrophils phagocytes and neutrophils

C) C) C3,C4 and C5C3,C4 and C5 are are anaphylatoxinsanaphylatoxins

Cause degranulation of mast cells and release of Cause degranulation of mast cells and release of

histamine and other inflammatory mediators histamine and other inflammatory mediators


4) Immune complex clearance:4) Immune complex clearance: - C3b facilitate binding of immune complex to several - C3b facilitate binding of immune complex to several

surfaces (erythrocytes) and enhance removal by liver surfaces (erythrocytes) and enhance removal by liver

and spleenand spleen

- binds erythrocytes to blood vessels , make them as - binds erythrocytes to blood vessels , make them as

easy prey for phagocytosis easy prey for phagocytosis

- C3 deficiency associated with Immunocomplex - C3 deficiency associated with Immunocomplex

disease and susceptibility to recurrent infectionsdisease and susceptibility to recurrent infections


5-Enhancement of antibody production:5-Enhancement of antibody production:

- - Binding of C3bBinding of C3b to its receptors on to its receptors on activated B cellsactivated B cells

(CR2) greatly enhances antibody production(CR2) greatly enhances antibody production

- Patient who are deficient in C3b produce- Patient who are deficient in C3b produce

much less antibodymuch less antibody than normal individuals and than normal individuals and

moremore susceptiblesusceptible to pyogenic infection to pyogenic infection


Harmful effects:Harmful effects:

- - If complement activate systematically on a large If complement activate systematically on a large

scale (Cm –ve bacilli)scale (Cm –ve bacilli)

-- If activated by an autoimmune response to host cells If activated by an autoimmune response to host cells

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Complement.ppt