6.2 Alternative pathway for complement proteins Flashcards
Alternative pathway is formely known as?
Properdin pathway
What are the components of alternative pathway?
C3 and C9, Factor B, Factor D, and properdin
What bypasses in alternative pathway from classical pathway?
C1, C4, C2
NOTE: Steps for alternative pathway
- C3 is hydrolyzed by water to form C3b
- This then binds to Factor B then attaches to target cells
- Factor B is cleaved by Factor D (Ba, Bb) which then forms C3bBb which is C3 convertase
- More C3bBb is formed which is stabilized by properdin (C3bBbP)
- This then form C3bBb3b (C3bBbP3b) from an extra C3b which is C5 convertase
Non-specific recognition of CHO in bacterial cell wall
Mannose-binding lectin pathway
what is bypass in Mannose-binding lectin pathway?
C1
Homologous with C1q?
MBL
MASP 1, 2, 3 has a similar function to?
C1r and C1s
MASP meaning?
MBL associated serine proteases
When MBL binds to _________, MASP-2 autoactivates and cleaves C4 and C2
Mannose
NOTE: Uncontrolled activation and action of complement proteins can lead to tissue damage
NOTE: Cell-bound and plasma regulatory proteins to regulate complement proteins
Occurs at three levels of complement activation and action:
- Regulation of classical complement pathway action
- Regulation of C3 conversation on both classical and alternative pathway
- Regulation of membrane attack complex
What is the Regulator protein for regulation of activation
This disscociates C1r and C1s from C1q
C1 inhinbitor (C1 INH)
Regulator Protein in regulation of C3 convertase that cleaves C3b and C4b
Factor I
Regulator Protein in the regulation of C3 convertase that Dissociates C3bBb (Alternating)
Decay accelerating factor (DAF) and Factor H
Regulator Protein in the regulation of C3 convertase that Dissociates C4b2a (Classical)
DAF (CD 55) and C4 biniding protein (C4BP)
Regulator Protein in the regulation of C3 convertase that Binds C3b and C4b making them available for degradation by Factor
This delivers them to factor I
CR1 (CD35)
Regulator Protein in the regulation of C3 convertase that Most efficient cofactor of factor I-mediated C3b cleavage
MCP (CD 46)
Regulation of MAC that inhibits formation of MAC
Homologous Restriction Factor (HRF)
Membrance inhibitor of reactive lysis (MIRL)
S protein (Vitronectin)
Increases vascular permeability by binding to basophils and mast cells which trigger the release of histamine
C3a, C4a, C5a
Anaphylatoxins
One of the agents that causes vascular permeability
Histamine
Production of large amount of C3b molecules
Opsonins
Influence the migration of phagocytosis to the site of injury?
C5a
Chemotactic factors
Receptors for C3b / iC3b
What complement is expressed by phagocytes
Opsonins mediated recognition and clearance of circulating immune complexes
CR1, CR3, CR4
Receptor for inactivated C3b which is found on B lymphocytes
Target receptor of Epstein Bar virus
CR2
Found on basophil and mast cells, phagocytes, and epithelial cells
Degranulation that leads to the release of inflammatory mediators
Receptors for anaphylatoxin
C3aR and C5aR
SLE-like syndrome; increased susceptibiliy to bacterial infections
C1q, C1s
SLE-like syndrome; URT disease, chronic kidney disease
C1r
SLE; glomerulonephritis; pyogenic infection
C4
SLE; increased susceptibility to bacterial infection; recurrent infectious diseases
C2
SLE-like syndrome; recurrent bacterial infection
C3
Complement deficiencies that can cause Neisseria infection
C5-C9
Deficient regulator proteins that can cause Hereditary angiodema
C1 inhibitor
Deficient regulator proteins that can cause Paroxysmal nocturnal hemoglobinuria
DAF (CD55), MIRL (CD59)
Deficient regulator proteins that can cause Recurrent pyogenic infection
Factor H, and Factor I MBL
Deficient regulator proteins that can cause Pneumococcal disease, sepsis, Neisseria infection
MBL
Deficient regulator proteins that can cause Neisseria infection
Properdin
Deficient regulator proteins that can cause Pneumococcal disease
MASP-2
DAF and MIRL are anchored in phospholipid called?
Phosphatidylinositol
What anticoagulant used to destory C1 by chelating Calcium (Ca2+)?
EDTA
What anticoagulant inhibits the cleavage of C4 by activated C1
Heparin
Why inactivate complement proteins
Interferes reading
What sample is used in VDRL from syphilis
Pre heated serum
What temp and time inactivates C1, C2, C4
56 C for 30 mins
What temp and time inactivates Factor B
50 C for 20 mins
NOTE: Serum becomes anti complementary upon storage
What test is used for quantitative?
Radial immunodiffusion and Nephelometry
What test is used for qualitative
Hemolytic titration Assay
in Hemolytic titration Assay this used for classical pathway which determines the amount of patient serum required to lysed 50% of SENSITIZED cells (Cells coated with antibodies)
CH50
What is the principle for CH50
The higher the patient’s serum is decrease in complement functions
in Hemolytic titration Assay, this uses buffer such as, ethylene glycol tetra-acetic acid a, and MgCl (Calcium chelator)
AH50
Not all antigens are susceptoble to complement-mediated lysis T or F
T
Complement activity can be destroyed in-vitro?
T
IgM and IgG are the only antibodies that can activate the Alternative pathway
F, Classical pathway is dependent to immunoglobulin
Complement is bound to all antigen-antibody complexes provided that the antibody is of proper isotype
T
Complement is found in all mammalian sera, and sera of most lower animals
T
Complement of one species will usually will react with antibodies of other species
T
Complement can contribute to chemotaxis, anaphylaxis, opsonization, and other physiologic functions
T
