Innate Immunity and the Complement System Flashcards
PAMPs and DAMPs
Help the immune system recognize what is non self
Pathogen-associated molecular proteins unique to microbes)
Damage-associated molecular proteins (unique to injured self)
Pattern Recognition Receptors
Recognizes ~1000 distinct PAMPs and DAMPs
Multiple types and locations to maximize recognition of pathogens
2 things that PRRs recognize that can be found in self
ssRNA
CpG DNA
2 major groups that opsonize pathogens
Antibodies
Complement system
What type of pathogen is opsonization with antibody and complement required?
Encapsulated bacteria
2 main mechanisms to avoid self reactivity
- Context (if its found in a suspicious location, treat it like a problem)
- Clean up (if bits of self find their way into suspicious locations, clean up quickly before they get mistaken for a problem)
Release of immune mediators causes what 3 things
Increased vascular permeability
Influx of important proteins (complement, antibodies, clotting factors)
Influx of cells (innate and adaptive)
4 results of PRR activation
Cytokines
Chemokines
Cell adhesion molecules
Microbe-specific responses
2 key effectors of the complement system and what bits are they made of
C3 convertase (C4b2a) C5 convertase (C4b3a3b)
C3 convertase in alternative pathway
C3bBb
C5 convertase in alternative pathways
C3bBb3b
Function of
- C3 convertase
- C5 convertase
- Cleaves C3 into C3a and C3b
2. Cleaves C3 and C5
4 functions of complement
Opsonization (C3b)
Call for help (C3a and C5a)
Augment the immune response
Punch holes in cell (C5-9)
Membrane attack complex
C5b binds C6 and C7
C5b67 complex binds to membrane via C7
C8 binds to complex and inserts into the membrane
C9 molecules bind and polymerize
10-16 C9 molecules form a pore in membrane
Lectin pathway
When ficolin/MBL + MASPs bind carbohydrates they activate C4 and C2
These then form C3 and C5 convertases
Classical pathway
C1q interacts with pathogen surface or with antibodies bound to surface
Activates C4 and C2
These then form C3 and C5 convertases
Alternative pathways
C3 undergoes spontaneous cleavage
C3b binds factor B (cleaved by factor D) to make C3bBb (C3 convertase)
C3 convertase stabilized by Factor P
Add C3b again to make C5 convertase
If patients have recurrent cases of N meningitidis what should you do?
Check total complement levels (when they are not sick)
Consumption
Patients with autoimmune diseases are going to have chronically low levels of C3 and C4 because they are always being used
