CHAPTER III – COMPLEMENT Flashcards
COMPLEMENT Meaning -
to Help or to make Complete
COMPLEMENT year
1890s
Coined the term:
Paul Ehrlich
Elucidate the control of the complement; Novel price
Jules Bordet
A primary part of the
Innate immune response
Substance under the
humoral-mediated immunity
Group of
30 different proteins
Designation
• Numerals (C1-C9)
• Letter symbols (factor D)
Cleavage Products – enzyme activation
a and b
named with a capital C followed by a
number
- results from the cleavage of a larger precursor by a protease
small letter
Ex. C3a/ C3b
• Larger fragment- designated as
• Smaller fragment- designated as
b
a
Exception:
C2 fragments
Larger-
smaller fragment-
C2a
C2b
Functions of Complement
- Lysis of cells, bacteria and viruses
- Opsonization
- Triggers specific cell functions, inflammation and secretion of immunoregulatory molecules
- Immune clearance: removal of immune complexes and deposition in the spleen and liver
Proteins and glycoproteins synthesized mainly by
liver hepatocytes
Most circulate in the serum functionally inactive forms as
proenzymes or zymogens
PRODUCES A
CASCADE PHENOMENON
WHERE THE PRODUCT OF ONE REACTION IS THE (?) OF THE NEXT
ENZYMATIC CATALYST
Heat Labile: destroyed when heated at
56°C for 30 mins
Anaphylatoxin
C3a, C4a, C5a
Increase Capillary Permeability
Role of C2b fragment
Chemotaxis
C5a
Virus neutralization
C4
Opsonization
C3b
They bind to receptors on mast cells and basophils
Anaphylatoxin
Induce degranulation and release of influx mediators including histamine
Anaphylatoxin
Can lead to edema if complement is not controlled
Increase Capillary Permeability
Attract cells and play important role in recruitment of wbc cells to an influx site
Chemotaxis
Enhances neutralization of viruses by homologous antibodies
Virus neutralization
C3b on particles such as bacteria or an Ab-Ab complex promotes the attachment and ultimate ingestion of the particles.
Opsonization
Initiated by: Antigen-antibody complex
CLASSICAL
First to be studied
CLASSICAL
Initiated by:
1. Aggregates of IgA
2. Yeast cell or zymogen
3. CVF
4. LPS
ALTERNATE/ ALTERNATIVE/ PROPERDIN LECTIN
Initiated by: With mannose and other similar sugars in the cell wall
LECTIN
Ab-dependent
CLASSICAL
ALTERNATE/ ALTERNATIVE/ PROPERDIN LECTIN
LECTIN
Ab-independent
Biological Functions
Initiation of Pathways
Phases of Complement Activation
Recognition event which will initiate complement cascade
INITIATION PHASE
Classical and alternate pathway differ at this phase
INITIATION PHASE
Activation of early components culminate in activation of C3 which is the critical component
AMPLIFICATION / ACTIVATION PHASE
Classical and alternate pathway differ at this phase
AMPLIFICATION / ACTIVATION PHASE
Culminates in target cell lysis
MEMBRANE ATTACK PHASE
Classical and alternate pathway is the same at this phase
MEMBRANE ATTACK PHASE
Begins with the formation of soluble antigen-antibody complexes or with binding of antibody to antigen on a suitable target such as a bacterial cell
CLASSICAL PATHWAY
IgM or IgG
CLASSICAL PATHWAY
Ag-Ab-IgM: conformational change in Fc : exposing a binding site for C1
CLASSICAL PATHWAY
Antibody is not required
ALTERNATIVE PATHWAY
Innate immunity
ALTERNATIVE PATHWAY
4 serum proteins: C3, factor B, factor D and properdin + C5 + C6789
ALTERNATIVE PATHWAY
Initiated by cell-surface constituents that are foreign to the host (gram + and gram - bacterial cell walls)
ALTERNATIVE PATHWAY
: proteins that recognize and bind to specific carbohydrate targets
Lectins
After initiation proceeds thru action of CA and C2 to produce C5 convertase
LECTIN PATHWAY
Activated by binding of mannose-binding lectin to mannose residues on glycoproteins or carbohydrates on the surface of microorganisms such as
Salmonella, Listeria, Neisseria, Cryptococcus and Candida
3 pathways : active C5 convertase to cleave C5 — C5a and C5b (initiates the final steps to form MAC)
Membrane Attack Complex
Forms a large channel through the membrane of the target cell enabling ions and small molecules to diffuse freely across the membrane
Membrane Attack Complex
105
C1 inhibitor (C1INH)
240
C1 inhibitor (C1INH)
Dissociates C1r and C1s from C1q
C1 inhibitor (C1INH)
88
Factor I
35
Factor I
Cleaves C3b and C4b
Factor I
150
Factor H