Immunology 3 Flashcards
Complement aids:
- phagocytosis
- destruction of microorganisms
- inflammation
what are the 3 pathways of complement activation?
- alternative pathway
- mannose-binding-lectin (MBL) pathway
- classical pathway
explain the alternative pathway of complement activation
complement component 3 (C3) acts as a pattern-recognition receptor - binds to the surface of a pathogen
explain the mannose-binding-lectin (MBL) pathway
triggered by binding of MBL (another pattern-recognition receptor) to mannose-containing CHO on bacteria/viruses
explain the classical pathway for complement activation
when antibodies bind to a pathogen, C1q binds to the Fc portion of those antibodies
all activation pathways lead to the production of what?
a stable C3 convertase
what does C3 convertase do?
C3 convertase cleaves C3 -> C3b and C3a
C3b forms a part of what?
C5 convertase
what forms the C5 convertase?
when C3b binds to the C3 convertase
what does C5 convertase do?
it cleaves C5 into C5a and C5b
what does C5b do?
becomes associated with the cell wall/membrane of the microbe and causes lysis as it activates other components of complement (C6-C9)
what do C5b + C6 + C7 + C8 + C9 do
form a large pore in the microbial membrane and cause lysis
what is C3bBb?
it converts C3 -> C3a + C3b
basically a C3 convertase but in the alternative pathway
explain the alternative pathway in more detailed
C3 forms C3a and C3b spontaneously in the bloodstream, but is degraded quickly under normal conditions
- factor B, a circulating protein, is also spontanesously cleaved to a protein known as Bb
- Bb complexes with C3b to form C3bBb which then converts C3 -> C3a + C3b
what is properdin
a circulating protein that helps stabilize the C3bBbC3b complexes on the bacterium to form the stable C3 and C5 convertases
C5 convertase of the alternative pathway is produced by?
C3bBbC3b + properdin
for the lectin and classical pathways, when C1q detects a bound antibody or MBL detects mannose on a membrane, they bind complement activating proteins which…
cleave C2 and C4
cleaved C2 and C4 produces what?
C3 convertase (C4bC2a)
what is MAC and its sequence of events
MAC = membrane attack complex
C5b triggers assembly of complex of C5b, C6, C7, and C8
upon binding to C7, C8 will insert into membrane
induces polymerization of C9 forming pore in membrane
what else can C3a and C5a do?
cause vasodilation, increased vascular permeability, smooth muscle contraction and histamine release from mast cells
why is the alternative pathway the first responder, and the lectin/classical path/ways more effective later?
C3 is aways present in the bloodstream (constantly produced by the lvier)
if a microbe is present, C3b instantly binds to the cell wall/membrane - if properdin and Bb also bind, then the stable C3 convertase forms very quickly
what is TLR1
can detect mycobacteria (like TB) and gram negative bacteria
what is TLR2
can detect peptidoglycans
what is TLR3
detect double-stranded RNA (only found in viruses)
what is TLR4
detect lipopolysaccharide (LPS)
C-type lectin receptors detect what?
detect carbohydrate components of many microbes
- found on the cell membrane, so they don’t detect pathogens in the cytosol
what are NOD-like receptors
- present in the cytosol
- activation of NLR leads to activation of Nf-KB and AP-1
RIG-like receptors
- present in cytosol
- detect viral RNA
activate: NF-KB and interferons
what are DAMPs
molecular “signals” that are present when a cell is damaged
what is the specific Nod-like receptor that is capable of detecting a wide range of DAMPS and PAMPS called?
NLRP3
when a DAMP activates NLRP3, it associates with caspase 1 and activates it by forming a large molecular complex known as an
inflammasome
what are the 2 major effects of caspase 1?
- activation of pro-IL-1-beta to IL-1-beta
- insertion of a cell membrane pore - gasdermin - into the cell membrane
if there are enough gasdermin produced, then the cell will ? this can lead to activation of neighboring cells and this type of cell death is ?
lyse and die
pyroptosis
what is one of the most important pro-inflammatory cytokines and has a wide range of effects and is released in very large quantities by macrophages in response to significant infection or tissue damage?
IL-1 beta
what is the 2 step process to generate and release IL-1
step 1 (priming) - detection of PAMPs or DAMPs -> synthesis and storage of large quantities of pro-IL-1
step 2 (release) - continued or larger DAMP or PAMP stimuli -> NLRP3 activation -> caspase 1 activation -> conversion of pro-IL-1 to IL-1 -> IL-1 release
what are “cellular sentinel”
resident macrophages in tissues just circulating when individual does not have disease or infection
- often express most PAMP and DAMP receptors -> secrete large quantities of pro-inflammatory cytokines
cellular sources of IL-1
- macrophages/monocytes
- dendritic cells
- keratinocytes
- epithelial cell
- endothelial cell
cellular sources of TNF-alpha
- macrophages/monocytes
- dendritic cells
- mast cells
- NK cells
- epithelial cells
cellular sources of IL-6
- macrophages/monocytes
- dendritic cells
- NK cells
- epithelial cells
- endothelial cells
elevated levels of inflammatory cytokines - IL-6 in particular - cause the liver to increase the secretion of useful proteins in the bloodstream known as ?
acute phase proteins
what are some major acute phase proteins?
- C-reactive protein (CRP)
- ferritin
- hepcidin
- mannose-binding lectin (MBL)
- serum amyloid protein A (SAA)
what does ferritin do?
binds to serum iron with high affinity
what does hepcidin do?
interferes with the transport of iron to the bloodstream
what are serum amyloid protein A (SAA)
modulates the activation of the inflammasome and TLRs
what are the 2 major groups of interferons
group 1 - IFN-a and IFN - b
group 2 - IFN-y
what is the role of group 1 interferons?
to interefere with viral replication
what is the role of group 2 interferons?
activates macrophages and pushes the adaptive immune system
how do interferons interfere with viral replication inside cells?
- inhibit of protein translation in the presence of viral RNA
- degrading viral mRNA
- inhibition of viral protein assembly
T or F: NK cells have “activating” and “inhibitory” receptors
True
what do NK activating receptors do?
detect molecules expressed on the membrane of cells that are infected by viruses or have developed into cells that may be malignant
what do NK inhibitory receptors?
detect molecules that are typically expressed by “normal” cells
T or F: NK cells surveying decreases greatly in the presence of Type 1 IFN
False
