Complement system - PART 1 - INTRO
Complement system - PART 1 - INTRO
The complement system - series of serum proteins that belong the innate immunity - first discovered as a heat labile product in the serum - helps in the humoral response - these serum proteins are synthesized in the liver + inflammatory cells - problems in production of these serum proteins ( especially in cases of Anorexia nervosa) lead to recurrent infections and reduced ability to fight infections Functions: - the overall and main function of the complement system is the ability to produce opsonins - a opsonin is a molecule that enhances phagocytosis - complement system fxn= also produces anaphylotoxins ---> these are molecules that have a high chemotactiv effect and tell WBC where to go during a infeciton - maintence of homestasis (removes immune complexes)
Overview the complement system is split into 3 different ways 1. 2. 3.
Classical pathway Mannose Binding Lectin pathway Alternative pathway
all 3 pathways converge at common point (see later)
The Classical Pathway -
has a role in innate and adaptive immunity (humoral response to be specific) can be activated in 2 ways; 1. direct binding of complex to the pathogen
-
2. binding to 1 IgM molecule OR TWO closely spaced igG molecules (hence this is how it helps in the adaptive immunity. (the c1 complex binds to these immunoglobulins) (highlight) , the order of the components in CLASSICAL pathway all have a C, (C1, C4, C2, C3).
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-
Activation of these break into 2 components , “a” and “b” a= small , b=big exception: C2 (otherway around)
THE C1 complex:(important in initiation of the pathway) -
has 6 arms C1Q:C1R2:C1S2
activation: - C1q binds to the pathogen directly OR binds to fc portion of Antibody (see above) -
C1q activation causes; C1s to be activated----> becomes esterase
-
C1s then cleaves 2nd component in pathway-------> C4 which forms .-------> C4a and C4b C4a= (FLOATS OFF INTO THE SERUM)
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C4b- ATTACHES TO PATHOGEN DIRECTLY
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C1s cleaves 3rd component ---> C2 into -----> C2a and C2b (a= BIG and b= small)
-
2b= FLOATS OFF INTO SERUM ***
-
2a=STICKS TO PATHOGEN NEXT TO 4B AND THIS FORMS ; C4b2a COMPLEX
C4bC2a= FORMS THE C3 CONVERTASE -C3 CONVERATSE= cleavees C3 into C3a and C3b (c3b= sticks to pathogen directly)
The Mannose binding Lectin Pathway
Components: - THE MBL complex (similar to the C1 complex) has two main components; - MASP -1 - MASP - 2 MASP= Mannose binding lectin Associated Serine Protease **
Activation -
similar to classical pathway in that it binds directly to the pathogen does not use antibodies to become activated binds to specific arrangement of mannose on bacteria ---> allows mannose binding lectin to bind*
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MBL binds to surface MASP 2 Activated MASP 2 causes cleavage of C4 +C2
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C4-----> C4a + C4b (b= Sticks to pathogen) (a= floats off into serum)
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C2-----> c2a + c2b (b=small bit and floats off into serum) (a= big bit and sticks to pathogen)
-
C4bC2a= again form the C3 convertase
-
C3 convertase= C3a + c3a ( C3a= goes to serum) (C3b= binds to pathogen)
Alternative Pathway Components: -
Serum Factor B Factor D C3 ( sort of ) Properdin (stabilizer protein)
Activation: -
activation through hydrolysis of C3 c3b - binds to pathogen surface OR can also bind to host surfaces (not specefic= this binding is only in the case of alternative pathway) Serum factor B= combines with C3b on cell surface Factor D= cleaves Serum Factor B----> Ba + Bb (Ba= floats into serum) (Bb= binds to cell surface ATTACHED TO C3b)
C3bBb= is a complex that is highly unstable---> to stabilize= Properdin (a protein that stabilizes the C3bBb complex c3bBb= FORMS THE C3 CONVERTASE COMPLEX ----> Cleaves C3- C3a +C3b C3a= floats off into serum= ANAPHYLATOXIN C3b- Opsonin
C5 Convertase
-
All pathways converge at the common point of C3 convertase each pathway has a different means of getting to the c5 Convertase
C5 Converatse: Classical pathway -
bacterial surface is coated with C3b C3b can do two things** 1. act as an opsonin
-
2. Combine with the C3 convertase complex (C4bC2a) to give the C5 convertase complex
C5 complex: For Classical PATHWAY - C4aC2b + 3b= C5 CONVERTASE -
C5 convertase ----> C5a + C5b
-
C5a (Anaphylatoxin)
-
C5b ( help to form the terminal pathway components )
***similar process for the MBL pathway***
C5 convertase : Alternative Pathway -
c3b can do two things 1 act as opsonin 2. combine with the C3 convertase complex to form the C5 convertase complex
C3bBb + 3b = C3bBbC3b = C5 convertase** -
c5a= anaphylatoxin C5b= helps in terminal complement activation
The complement system - series of serum proteins that belong the innate immunity - first discovered as a heat labile product in the serum - helps in the humoral response - these serum proteins are synthesized in the liver + inflammatory cells - problems in production of these serum proteins ( especially in cases of Anorexia nervosa) lead to recurrent infections and reduced ability to fight infections Functions: - the overall and main function of the complement system is the ability to produce opsonins - a opsonin is a molecule that enhances phagocytosis - complement system fxn= also produces anaphylotoxins ---> these are molecules that have a high chemotactiv effect and tell WBC where to go during a infeciton - maintence of homestasis (removes immune complexes)
Overview the complement system is split into 3 different ways 1. 2. 3.
Classical pathway Mannose Binding Lectin pathway Alternative pathway
all 3 pathways converge at common point (see later)
The Classical Pathway -
has a role in innate and adaptive immunity (humoral response to be specific) can be activated in 2 ways; 1. direct binding of complex to the pathogen
-
2. binding to 1 IgM molecule OR TWO closely spaced igG molecules (hence this is how it helps in the adaptive immunity. (the c1 complex binds to these immunoglobulins) (highlight) , the order of the components in CLASSICAL pathway all have a C, (C1, C4, C2, C3).
-
-
Activation of these break into 2 components , “a” and “b” a= small , b=big exception: C2 (otherway around)
THE C1 complex:(important in initiation of the pathway) -
has 6 arms C1Q:C1R2:C1S2
activation: - C1q binds to the pathogen directly OR binds to fc portion of Antibody (see above) -
C1q activation causes; C1s to be activated----> becomes esterase
-
C1s then cleaves 2nd component in pathway-------> C4 which forms .-------> C4a and C4b C4a= (FLOATS OFF INTO THE SERUM)
-
C4b- ATTACHES TO PATHOGEN DIRECTLY
-
C1s cleaves 3rd component ---> C2 into -----> C2a and C2b (a= BIG and b= small)
-
2b= FLOATS OFF INTO SERUM ***
-
2a=STICKS TO PATHOGEN NEXT TO 4B AND THIS FORMS ; C4b2a COMPLEX
C4bC2a= FORMS THE C3 CONVERTASE -C3 CONVERATSE= cleavees C3 into C3a and C3b (c3b= sticks to pathogen directly)
The Mannose binding Lectin Pathway
Components: - THE MBL complex (similar to the C1 complex) has two main components; - MASP -1 - MASP - 2 MASP= Mannose binding lectin Associated Serine Protease **
Activation -
similar to classical pathway in that it binds directly to the pathogen does not use antibodies to become activated binds to specific arrangement of mannose on bacteria ---> allows mannose binding lectin to bind*
-
MBL binds to surface MASP 2 Activated MASP 2 causes cleavage of C4 +C2
-
C4-----> C4a + C4b (b= Sticks to pathogen) (a= floats off into serum)
-
C2-----> c2a + c2b (b=small bit and floats off into serum) (a= big bit and sticks to pathogen)
-
C4bC2a= again form the C3 convertase
-
C3 convertase= C3a + c3a ( C3a= goes to serum) (C3b= binds to pathogen)
Alternative Pathway Components: -
Serum Factor B Factor D C3 ( sort of ) Properdin (stabilizer protein)
Activation: -
activation through hydrolysis of C3 c3b - binds to pathogen surface OR can also bind to host surfaces (not specefic= this binding is only in the case of alternative pathway) Serum factor B= combines with C3b on cell surface Factor D= cleaves Serum Factor B----> Ba + Bb (Ba= floats into serum) (Bb= binds to cell surface ATTACHED TO C3b)
C3bBb= is a complex that is highly unstable---> to stabilize= Properdin (a protein that stabilizes the C3bBb complex c3bBb= FORMS THE C3 CONVERTASE COMPLEX ----> Cleaves C3- C3a +C3b C3a= floats off into serum= ANAPHYLATOXIN C3b- Opsonin
C5 Convertase
-
All pathways converge at the common point of C3 convertase each pathway has a different means of getting to the c5 Convertase
C5 Converatse: Classical pathway -
bacterial surface is coated with C3b C3b can do two things** 1. act as an opsonin
-
2. Combine with the C3 convertase complex (C4bC2a) to give the C5 convertase complex
C5 complex: For Classical PATHWAY - C4aC2b + 3b= C5 CONVERTASE -
C5 convertase ----> C5a + C5b
-
C5a (Anaphylatoxin)
-
C5b ( help to form the terminal pathway components )
***similar process for the MBL pathway***
C5 convertase : Alternative Pathway -
c3b can do two things 1 act as opsonin 2. combine with the C3 convertase complex to form the C5 convertase complex
C3bBb + 3b = C3bBbC3b = C5 convertase** -
c5a= anaphylatoxin C5b= helps in terminal complement activation
