Innate Immunity Flashcards
(31 cards)
Big picture of Complement
OIL:
Opsonization
Inflammation
Lysis
Complement pathways
- Alternative
- Lectin
- Classic
First complement pathway to be activated?
Alternative
Alternative pathway steps
- C3 cleaved –> C3a & C3b
- C3b can bind microbe (or be inactivated)
- C3b forms C3 convertase (C3bBb)
- C3 convertase continues to convert C3 –> C3a & C3b
- C3b either:
a - acts as opsonin
b - forms C5 convertase (C3bBb5b) - C5 convertase converts C5 –> C5a & C5b
- C5b + C6-9) form membrane attack complex (MAC), which causes lysis
Lectin pathway steps
- MBP cleaves:
a. C4 –> C4a & C4b
b. C2 –> C2a & C2b - C4b + C3b form C3 convertase (C4b2b)
same as 4-7 for alternative pathway
Classical pathway steps
Requires antibodies (IgM & IgG)
- Ab bind bacteria, C1 binds Ab at another site
- Conformational change in C1, cleaves C2 & C4
follows the rest of the lectin pathway
Classical pathway starting points/trigger
C1qrs, C2, and C4
Fc portion of Ab (IgM, G1, G2, G3) or CRP with C1q
Lectin pathway starting points
Plasma-derived mannose-binding lectin/ MBL, C2 & C4
Alternative pathway starting points
C3, factor B, D, and properdin
What is opsonization?
Coating of pathogen with molecule that enhances phagocytosis by fixation of opsonins (C3b) on pathogen surfaces
Anaphylatoxins and function
C3a, C4a, C5a, increase vascular permeability
Chemoattractants and function
C3a and C5a, attract neutrophils and monocytes
MAC components and function
Membrane attack complex: C5b-C9
Creates perforations in cell membranes –> lysis
What recognizes C3b?
Complement receptor 1 (CR1)
MAC-induced lysis limitations
Only effective against microbes with thin cell walls, Neisseria species
Complement regulation: C3 convertase
down-regulated by decay-accelerating factor (DAF); displaces Bb from C3b
DAF deficiency
Uncontrolled complement activation –> RBC lysis, paroxysmal nocturnal hemoglobinuria (PNH)
Complement regulation: C1
C1-inhibitor: protease inhibitor that down-regulates C1r/s activation
C1-inhibitor deficiency
excessive vasoactive peptides (bradykinins) –> hereditary angiodema
C1, C2, C4 deficiency
Increased risk of immune complex disease (SLE)
C3 deficiency
Increased risk of encapsulated bacteria infection (pyogenic infections)
C5b-C9 deficiency
Increased susceptability to Neisseria infections (gonorrhoeae or meningitidis)
Neisseria meningitidis
Gram (-) cocci
Produces polysacc capsule
Fever + petechial rash + hypotension
The physiological role of innate immunity
To protect the host during the time between microbial exposure and adaptive immunity responses