L3 - defence against infection Flashcards
infections can be ……
intracellular or extracelular
Intra require require cell-mediated immunity (T cells, NK cells)
- eliminate infected cells or activate macrophages to kill pathogens hiding within vesicles
extra - humoral response, antibodies,complement and phagacytosis
mechanism of ‘drinking in antigens’ by dendritic cells
pinocytosis
long projections maximise SA
estimated volume of mucosal surfaces in body that need protection
200m2
name the 3 types of complement pathway and where they work
alternative pathway - on pathogen surface
mannose-lectin binding pathway - lectin on pathogen surface
classical pathway - antigen:antibody complex
why is the complement pathway named this and what is it
Helps the system fight infection “complimenting” work oif immune system
made up of zymogens (inactive enzymes) that cause a cascade each cleaving and activating the next
where are the complement proteins/zymogens produced
liver
by hepatocytes then released into blood stream
describe the ALTERNATIVE complemnet pathway - detail
- C3 is spontaneously cleaved in serum by tick over activation = C3a and C3b
- C3b binds covalently via thioester bond to bacterial membrane
- Factor B binds to C3b but hydrolysed by factor D = C3bBb + Ba
- C3bBb is a C3 convertase = more C3a and C3b
- when 2 of these convertases dimerise forms a C5 convertase = (C3b)2Bb = produces C5a + C5b
what do all pathways lead to
a C3 convertase
= complement activation
functions of complement activation
- recruitment of inflamatory cells
- opsonisation of pathogens
- direct killing by MATC
factors involved in alternative complement pathway
C3
B
D
factors involved in mannose-lectin pathway
MBL
MASP-1
MASP-2
C4
C2
factors involved in classical pathway
C1q
C1r
C1s
C4
C2
which factors do classical and MB pathway have in common but NOT alternative
C4
C2
what is Mannose-binding lectin and what conc is it usauly found at
MBL is a protein found at low concentrations in blood normally
- when macrophages ingest bacteria they produce interleukin-6 = IL-6
- triggers hepatocytes in liver to prouce acute-phase proteins = MBL
- MBL binds to terminal mannose sugars on bacterial surfaces
what does MBL bind to in complement pathway and how does it do this
terminal mannose sugars on bacterial surface
MBL monomers form trimers with mannose recognition domains
describe the MBL complement pathway -detail
- MBL binds to mannose residues on bacterial surface
- MASP proteases (MBL-acsociated-proteases) cleave C4 and C2 in the protein
- C4b binds to bacterial surface and acsociates with C2a = C4bC2a
- C4bC2a is a C3 convertase
- the C3b produced by cleave of C3 ascociates with the C3 convertase produces a C5 convertase
C4bC2a + C3b = C4bC2aC3b
what don ficcolins do relative to the MBL complement pathway
bind ton acetelyated sugars onbacterial surface instead of mannose
via fibronectin domains BUT also activated MASPs to cleave C2 and C4
= exactly the same except from what it binds to
what does the C3 concertase at the end of the activatiting the complement pathways do - 3 different parts
- C3a and C5a:
peptide mediators of inflammation - phagocyte recruitment - C3b:
binds to complement receptors on phagocytes
opsonisation of bound pathogens
- MAC - Membrane-Attack-Complex
other complemts come togther to from lysis cauysing complex
facrtors nincolved in forming the membrane attack complex
C5b
C6
C7
C8
C9
formation of membrane attack complex
- C5b binds to C6 + C7 = C5b67
- complex binds to membrane of pathogen or cell via C7
- C8 binds to complex and inserts itself INTO the cell membrane
- C9 binds to complex and polymerises = fortming a pore in membrane
- Death of cell due to osmosis
defects in the complemnet pathway can cause what - C3 defect
C3 defects cause pyogenic indeftions
- staph and stept infections
- pus forming
= highlights C3 importance in opsonisation of bacteria
