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BMS 150 > Immunology 3 > Flashcards

Immunology 3 Flashcards

1
Q

Complement aids:

A
  • phagocytosis
  • destruction of microorganisms
  • inflammation
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2
Q

what are the 3 pathways of complement activation?

A
  • alternative pathway
  • mannose-binding-lectin (MBL) pathway
  • classical pathway
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3
Q

explain the alternative pathway of complement activation

A

complement component 3 (C3) acts as a pattern-recognition receptor - binds to the surface of a pathogen

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4
Q

explain the mannose-binding-lectin (MBL) pathway

A

triggered by binding of MBL (another pattern-recognition receptor) to mannose-containing CHO on bacteria/viruses

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5
Q

explain the classical pathway for complement activation

A

when antibodies bind to a pathogen, C1q binds to the Fc portion of those antibodies

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6
Q

all activation pathways lead to the production of what?

A

a stable C3 convertase

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7
Q

what does C3 convertase do?

A

C3 convertase cleaves C3 -> C3b and C3a

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8
Q

C3b forms a part of what?

A

C5 convertase

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9
Q

what forms the C5 convertase?

A

when C3b binds to the C3 convertase

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10
Q

what does C5 convertase do?

A

it cleaves C5 into C5a and C5b

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11
Q

what does C5b do?

A

becomes associated with the cell wall/membrane of the microbe and causes lysis as it activates other components of complement (C6-C9)

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12
Q

what do C5b + C6 + C7 + C8 + C9 do

A

form a large pore in the microbial membrane and cause lysis

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13
Q

what is C3bBb?

A

it converts C3 -> C3a + C3b
basically a C3 convertase but in the alternative pathway

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14
Q

explain the alternative pathway in more detailed

A

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

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15
Q

what is properdin

A

a circulating protein that helps stabilize the C3bBbC3b complexes on the bacterium to form the stable C3 and C5 convertases

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16
Q

C5 convertase of the alternative pathway is produced by?

A

C3bBbC3b + properdin

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17
Q

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…

A

cleave C2 and C4

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18
Q

cleaved C2 and C4 produces what?

A

C3 convertase (C4bC2a)

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19
Q

what is MAC and its sequence of events

A

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

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20
Q

what else can C3a and C5a do?

A

cause vasodilation, increased vascular permeability, smooth muscle contraction and histamine release from mast cells

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21
Q

why is the alternative pathway the first responder, and the lectin/classical path/ways more effective later?

A

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

22
Q

what is TLR1

A

can detect mycobacteria (like TB) and gram negative bacteria

23
Q

what is TLR2

A

can detect peptidoglycans

24
Q

what is TLR3

A

detect double-stranded RNA (only found in viruses)

25
Q

what is TLR4

A

detect lipopolysaccharide (LPS)

26
Q

C-type lectin receptors detect what?

A

detect carbohydrate components of many microbes
- found on the cell membrane, so they don’t detect pathogens in the cytosol

27
Q

what are NOD-like receptors

A
  • present in the cytosol
  • activation of NLR leads to activation of Nf-KB and AP-1
28
Q

RIG-like receptors

A
  • present in cytosol
  • detect viral RNA
    activate: NF-KB and interferons
29
Q

what are DAMPs

A

molecular “signals” that are present when a cell is damaged

30
Q

what is the specific Nod-like receptor that is capable of detecting a wide range of DAMPS and PAMPS called?

A

NLRP3

31
Q

when a DAMP activates NLRP3, it associates with caspase 1 and activates it by forming a large molecular complex known as an

A

inflammasome

32
Q

what are the 2 major effects of caspase 1?

A
  • activation of pro-IL-1-beta to IL-1-beta
  • insertion of a cell membrane pore - gasdermin - into the cell membrane
33
Q

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 ?

A

lyse and die
pyroptosis

34
Q

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?

A

IL-1 beta

35
Q

what is the 2 step process to generate and release IL-1

A

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

36
Q

what are “cellular sentinel”

A

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

37
Q

cellular sources of IL-1

A
  • macrophages/monocytes
  • dendritic cells
  • keratinocytes
  • epithelial cell
  • endothelial cell
38
Q

cellular sources of TNF-alpha

A
  • macrophages/monocytes
  • dendritic cells
  • mast cells
  • NK cells
  • epithelial cells
39
Q

cellular sources of IL-6

A
  • macrophages/monocytes
  • dendritic cells
  • NK cells
  • epithelial cells
  • endothelial cells
40
Q

elevated levels of inflammatory cytokines - IL-6 in particular - cause the liver to increase the secretion of useful proteins in the bloodstream known as ?

A

acute phase proteins

41
Q

what are some major acute phase proteins?

A
  • C-reactive protein (CRP)
  • ferritin
  • hepcidin
  • mannose-binding lectin (MBL)
  • serum amyloid protein A (SAA)
42
Q

what does ferritin do?

A

binds to serum iron with high affinity

43
Q

what does hepcidin do?

A

interferes with the transport of iron to the bloodstream

44
Q

what are serum amyloid protein A (SAA)

A

modulates the activation of the inflammasome and TLRs

45
Q

what are the 2 major groups of interferons

A

group 1 - IFN-a and IFN - b
group 2 - IFN-y

46
Q

what is the role of group 1 interferons?

A

to interefere with viral replication

47
Q

what is the role of group 2 interferons?

A

activates macrophages and pushes the adaptive immune system

48
Q

how do interferons interfere with viral replication inside cells?

A
  • inhibit of protein translation in the presence of viral RNA
  • degrading viral mRNA
  • inhibition of viral protein assembly
49
Q

T or F: NK cells have “activating” and “inhibitory” receptors

A

True

50
Q

what do NK activating receptors do?

A

detect molecules expressed on the membrane of cells that are infected by viruses or have developed into cells that may be malignant

51
Q

what do NK inhibitory receptors?

A

detect molecules that are typically expressed by “normal” cells

52
Q

T or F: NK cells surveying decreases greatly in the presence of Type 1 IFN

A

False

BMS 150 (15 decks)

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