Week 3 Flashcards
(61 cards)
What is the step-by-step pathway of the classical complement pathway?
1) Antibody binds to antigen
2) C1q portion of C1 complex (C1q2r2s) binds to Fc portion of antibody
3) Activated C1s cleaves C4 and C2 –> C4a + C4b + C2a + C2b
4) C4b + C2a –> C2a4b (C3 convertase)
5) C3 convertase cleaves C3 –> C3a + C3b
6) Some C3b binds to C4b2a –> C4b2a3b (C5 convertase)
7) C5 convertase cleaves C5 –> C5a + C5b
8) C5b binds to C6-9 = MAC
What is the step-by-step pathway of the alternative complement pathway?
1) C3 spontaneously hydrolyzes –> C3a + C3b
2) C3b binds with Factor B C3bB
3) Factor D cleaves C3bB –> C3bBb + Ba
4) C3bBb (C3 convertase) hydrolyzes C3 –> C3a + C3b
5) C3b binds with C3bBb –> C3bBb3B (3B reprsents newly cleaved C3b)
6) C3bBb3B (C5 convertase) cleaves C5 –> C5a + C5b
7) C5b binds to C6-9 = MAC
What are the early pathway steps in the classical complement pathway?
C1 complex (C1qr2s2), C2, C4, C3
What are the late pathway steps in the classical and alternative complement pathway?
C5 - C9
What consequences are associated with the early complement pathway defects?
Invasive infections with encapsulated microbes
Lupus or glomerulonephritis are common issues
What consequences are associated with the late complement pathway defects?
Invasive infections with Neisseria species
What is the CH50 test?
Test to diagnose late complement pathway defect
AB-coated sheep blood is added to patient’s serum. Look at how many sheep RBCs are lysed
What are the functions of C1-INH? Is it soluble or membrane bound?
C1-INH binds to C1r and C1s of the C1 complex, which inhibits cleavage of C4 and C2
C1-INH inhibits the Kinin-Kallikrein System, which is involved in vasodilation, vascular permeability, and blood pressure.
What is the consequence of defective C1-INH?
Hereditary angioedema
-Characterized by attacks of rapid swelling in various tissues
Triggered by
- Trauma
- Surgery
- Emotional stress
- And dental procedures (can be life-threatening)
What is C3 Nephritic Factor (C3NeF)? Is it soluble or membrane bound?
Autoantibody that prolongs the half-life of C3bBb
What is the consequence of C3NeF?
Membranoproliferative Glomeruloneohritis Type II
-kidney disfunction due to deposits of immune complexes in the glomeruli
What is factor H? it soluble or membrane bound?
Competes with factor B by preventing the formation of C3Bb (alternative pathway)
soluble
What is factor I? Type of activity?
Has serine protease activity to cleave C3b –> inactive C3b (iC3b)
What is Membrane Cofactor Protein (MCP aka CD46)
Membrane bound protein located on self-cell membranes via GPI anchors
What is the consequence of defective Factor H?
Hemolytic Uremia Syndrome
What is the consequence of defective Factor H or Factor I or Membrane Cofactor Protein (MCP)?
Hemolytic Uremia Syndrome (HUS)
What is leukocyte adhesion deficiency?
Inability of leukocytes to migrate to site of infection/inflammation
What is chronic granulomatous disease?
Defect with NADPH oxidase complex preventing proper oxidative bursts
What is primary immunodeficiency?
congenital immunodeficiency that can affect effector and regulatory arms of immune system
often caused by mutations in specific genes
What is secondary immunodeficiency
non-genetic immunodeficiency that is secondary to something else (chemotherapy, malnutrition, burns, HIV, etc)
Type 1 necrotizing soft tissue infection microbe(s) and treatment
aerobes and anaerobes
foul odor, grey discharge, crepitus (crackling skin)
surgery
Beta-lactam + Beta-lacatmase inhibitor combo
Type 2 necrotizing soft tissue infection microbe(s) and treatment
streptococcus pyogenes
surgery
Beta-lactam + beta-lactamase inhibitor combo PLUS clindamycin for GAS toxin inhibition
Type 3 necrotizing soft tissue infection microbe(s)
marine vibrio species
fresh or brackish (salty) water exposure
What are the common etiologies of necrotizing soft tissue infections?
Type I, Type II, Type II, and MRSA
