Molecules + What They Do (Ben) Flashcards
1
Q
IL-4
A
- stimulates Th0 –> Th2 differentiation
- is also released by Th2 cell
- stimulates B cell isotype switch to IgE
- antagonistic to IFN-y production (+ other Th1 cytokines)
- (upregulates MHC-II)
- (promotes macrophage –> M2 cell differentiation)
2
Q
IL-13
A
- induces IgE secretion from B cells
- (induces MMPs which are anti-inflamm. in airways)
3
Q
FcƐRI
A
- high affinity IgE receptor (binds heavy chain Fc)
- important on mast cells/basophils/eosinophils
- essential in type I hypersensitivity
4
Q
Mast Cell Lipid Mediators
A
- PGD2, E2, F2α - incr. SM contraction / permeability
- LTC4, D4, E4 - incr. SM contraction / permeability
- LTB4 - neutrophil chemoattractant
5
Q
IL-5
A
- activates eosinophils in late phase type I HS reaction
- secreted by Th2 + mast cells
- (stimulates B cell growth / incr. Ig secretions)
6
Q
Mast Cell Enzymatic Granule Contents
A
- carboxypeptidase
- chymase
- tryptase
- (there are others, these were from lecture)
7
Q
Rheumatoid Factor
A
an IgM against your own IgG’s Fc regions
(complex settles in joints –> arthritis)
(other isotypes exist; IgM is most common)
8
Q
AIRE
A
- transcription factor in thymic medullary epithelial cells
- controls “promiscuous” gene expression of various antigens for process of negative selection
9
Q
CD3
A
- T cell marker in all T cell types (starting w/ pro-thymocyte)
- functions as TCR co-receptor
- its ITAMs are essential for TCR signaling
10
Q
CD4
A
- T helper cell surface glycoprotein
- functions as TCR co-receptor in APC interactions
- recruits Tyr kinase Lck to P-ate CD3 ITAMs for signaling
- (sounds like too much but I had a midterm MCQ about this)
11
Q
CD25
A
- Treg cell marker
- (is one subunit of a high affinity IL-12 receptor)
- (also found in T memory cells and others)
12
Q
CD8
A
- cytotoxic T cell surface marker
- acts at TCR co-receptor, binding MHC-I
- recruits Tyr kinase Lck to P-ate CD3 ITAMs
- (same as CD4 function, but in cytotoxic cells, had MCQ on this)
13
Q
CD56
A
- NK and NKT cell surface marker
- (plays role in cell adhesion)
14
Q
CD19
A
- B cell surface marker
- present in early B cell dev. stages, lost in plasma cells
- is a BCR co-receptor
- is intracellularly P-ated upon antigen binding, leading to recruitment of further kinases
15
Q
CD5
A
- B1 cell surface marker
- (lectures mentioned it as being on B1 … wiki says there is more on T cells… may not be important anyways)
16
Q
Classical C3 convertase
A
- AKA C4b2a
- cleaves C3 to C3a and C3b
- (results from C1q binding C1r -> C1r cleaving C1s -> C1s cleaving both C4 + C2 and their respective b and a fragments combining)
17
Q
MASP
A
- MBL-associated Serine Proteases
- involved in MBL pathway of complement activation
- cleave C2/C4 to form C3 convertase “C4b2a”
18
Q
alternative C3 convertase
A
- AKA C3bBb
- (formed from spontanous C3 cleavage -> C3b binds microbe + factor B -> factor D cleaves B and Ba fragment diffuses away leaving C3bBb)
19
Q
MHC III
A
- region of chromosome 6
- contains genes for C3b convertases (C2, C4, factor B) and TNFalpha
20
Q
C5 convertase
A
- formed when either C3 convertase binds more C3b
- can be C4b2a3b or C3bBb3b form
- cleaves C5 -> C5a + C5b
21
Q
MAC
A
- membrane attack complex
- formed when C5b binds C6/7/8 and 10-19 molecules of C9 to form a pore
22
Q
C1 inhibitor
(deficiency = what disease?)
A
- binds C1r/C1s/MASPs to block C2/C4 cleavage
- thus inhibits C3 convertase production
- deficiency = hereditary angioedema (incr. bradykinin + complement auto-activation)
23
Q
DAF
A
- Decay Accelerating Factor
- accelerates decay of C4b2a / C3bBb
- acts as complement inhibitor
- (lack on RBCs can -> paroxysmal nocturnal Hgb-uria)
24
Q
Complement Factor I
A
- cleaves/inactivates C3b/C4b
- substrate must first bind CR1, MCP or factor H as co-factor before Factor I can work
- (microbes don’t have these co-factors -> complement is not inhibited from acting on them)
25
Q
CD59
A
- AKA MAC-inhibitory protein
- inhibits C9 from polymerizing with C5b678 to form pore
- lack can -> paroxysmal noctural Hgb-uria
26
Q
negative acute phase proteins
A
transferrin, albumin, fibronectin
27
Q
IL-6
A
- acute phase cytokine
- secreted by Th2 cells and macrophages
- induces hepatic production of other acute phase proteins
- stimulates cortisol release (at all levels of HPA axis)
- stimulates B cell -> plasma cell -> Ig secretion
- (inhibits other APPs TNF-alpha and IL-1)
28
Q
TNF-alpha
A
- acute phase cytokine
- produced mostly by activated macrophages, also Th cells, NK cells, granulocytes
- stimulates hepatic acute phase protein production
- (neutrophil activation, vasculitis, cachexia, apoptosis induction)
- (many more effects, will add later if important ones come up)
29
Q
IL-1
A
- acute phase cytokine
- secreted by activated macrophages, neutrophils + epithelium
- vasculitis; fever induction (via hypothalamus)
- induces hepatic APP production
- (synergistic with TNF-alpha)
30
Q
Hepatically-produced Acute Phase Proteins
(9 items … sorry)
A
- Complement
- MBL
- CRP - opsonin/compl. activator, binds polysacchs.
- Serum Amyloid Protein
- Surfactants SP-A/SP-D - alveolar opsonization
- Fibrinogen - and other clotting proteins
- α2-macroglobulin - protease inhibitor
- α1-antitrypsin - protease inhibitor
- Ceruloplasmin - binds serum Cu ions
31
Q
TAP1 / TAP2
A
- TAP = Transporter assoc. with Antigen Processing
- both help transport proteasome cleaved cytosolic peptides into rER to be bound to nascent MHC-I molecules
- are ABC transporters (use ATP)
32
Q
CLIP
A
- Class-II-associated Invariant Chain Peptide
- part of “Invariant Chain” (li) which binds peptide grooves of developing MHC-II within lysosomes to prevent binding of self-peptides
- is released after HLA-DM binds MHC-II in presence of antigen peptide
33
Q
Invariant Chain (li)
A
- binds nascent MHC-II peptide groove in rER
- facilitates MHC-II export to acidic lysosome vesicle from rER
- is cleaved by cathepsin S to leave CLIP fragment still bound to MHC-II
34
Q
HLA-DM
A
- binds to nascent MHC-II within lysosomes
- removes CLIP and allow MHC-II to bind antigen peptides
35
Q
H-Y antigen
A
- a “minor histocompatibility antigen” in transplantation
- incompatibility results in slower/milder rxn than MHC incompat.
- Y-linked, male tissue-specific antigen -> transplants from same sex are best
36
Q
FasL
A
- binds FasR receptor on other cells, inducing apoptosis
- found on CD8+ Tc cell membranes
- TM protein of TNF family
- also called CD95 ligand!!! (FasR = CD95)
- (can be solubilized by cleavage off membrane by MMP-7)
- (exists in immune priveleged cells such as cornea to bind FasR on incoming T cells + kill them)
37
Q
CD28
A
- T cell co-stimulatory membrane molecule
- receives stimulation from B7 (CD80) on APCs during antigen presentation
- CTLA4 can bind B7 in its place, and downregulate the T cell
38
Q
Foxp3
A
- transcription factor expressed by Treg cells
- important in normal gestational immunosuppression
39
Q
CCL19 / CCL21
A
- constitutively expressed in lymph node
- attract naive T cells and mature dendritic cells (via their CCR7 receptors) where antigen presentation will activate T cell and change its chemokine affinity to IL-8 so it can return to injured/infected tissues
40
Q
CD34
A
- Hematopoietic progenitor marker (there’s an MCQ on this)
- sialomucin (or mucosialin) adhesion molecule on high endothelial venule (HEV) cells
- binds L-selectin on T cells in rolling phase to allow their extravasation
41
Q
LFA-1
A
- an integrin on T cells
- binds ICAM-1 on endothelium during adhesion phase of extravasation
- (LFA = leukocyte function-associated antigen)
42
Q
ICAM-1
A
- AKA CD56
- binds LFA-1 on T cells during adhesion phase of extravasation
- (ICAM = intercellular adhesion molecule)
43
Q
IL-2
A
- T cell proliferation
- “self renewal” of memory CD8+ cells after immunization
- (NK / B cell activation + proliferation)
44
Q
HLA-B53
(probably less important, very specific + was in a seminar)
A
- MHC-I variant which conveys protection against malaria
- presents 9 AA peptides with proline in position 2
45
Q
CD20
A
- B cell surface marker
46
Q
CTLA-4
A
- alternate inhibitory receptor on T cells for B7 aka CD80 (normally co-stimulatory, but is inhibitory when binds CTLA-4)
- (soluble CTLA-4 drugs bind B7 and block it from activating T cells via CD28)
- (AKA CD152)
47
Q
B7
A
- membrane molecule expressed by activated APCs
- is co-stimulatory if it binds CD28 or inhibitory if it binds CTLA-4 on T cells
- (has two forms (B7-1 + B7-2) with alternate names CD80 / CD86, respectively)
48
Q
Cytokines involved in class switch to IgA
A
- TGF-B
- IL-5
- IL-2
49
Q
Cytokines involved in class switch to IgM
A
- IL-5
- IL-4
- IL-2
50
Q
Cytokines involved in class switch to IgG
A
- IL-4
- IL-6
- IL-2
- IFN-y
51
Q
Cytokines involved in class switch to IgE
A
- IL-4
- IL-13
52
Q
CD40
A
- found on B cells -> stimulation via CD40L from Th cells stimulates T-dependent IgA class switch in mucosa
- also acts as co-stimulatory molecule on APCs for their activation -> increases its own expression + TNF-R expression + ROS/NO production
53
Q
what two cytokines are secreted by inflammasomes?
A
IL-1beta
IL-18
54
Q
IL-12
A
- stimulates Th0 –> Th1 differentiation
- stimulates IFNy and TNFalpha secretion from T and NK cells
- secreted by dendritic cells, macrophages, neutrophils
55
Q
PD-1 and PD-L1
A
- PD-1 is a programmed death receptor on activated T, B and myeloid cells
- PD-L1 is its ligand expressed by APCs -> binds to T cell PD-1 as negative co-stimulation
- PD-L1 can also bind to B7 (CD80) on APCs and decrease its co-stimulatory effects on CD28 on T cells (sorry)
- (PD-1 = CD279 and PD-L1 = CD274)
56
Q
CD1d
A
- non-polymorphic MHC-I-like molecule
- presents glycolipid molecules which are recognized by iNKT cells’ invariant TCRs
57
Q
IL-10
A
- anti-inflammatory cytokine produced by Treg and Breg cells
- suppresses CD4+ cells
- also produced by monocytes
58
Q
IL-7
(this one may be less important, but showed up in a figure on a slide)
A
maintains survival of resting naive T cells (CD4+/CD8+ cells not yet stimulated)
59
Q
Cytokines which also stimulate adrenal corticosteroid production.
Other than immune cells, where are they synthesized?
A
IL-1 and IL-6
made in neurons, glia, pituitary and adrenal glands
60
Q
H1R
A
- histamine R on endothelium
- HA binding increases permeability
- (is other places too, this was all she said in seminar)
61
Q
H2R
A
- histamine R on vascular SM + gastric parietal cells
- causes vasoconstriction + HCl release
62
Q
H4R
A
- histamine R on eosinophils
- can recruit eosinophils to site of allergen
63
Q
T-bet
A
- transcription factor promoting Th0 -> Th1 differentiation
64
Q
GATA3
A
- transcription factor promoting Th0 -> Th2 differentiation
65
Q
ROR-gamma-T
(RORyT)
A
- transcription factor promoting Th0 -> Th17 differentiation
66
Q
FGF-7 and IGF-1
A
- released by gamma-delta T cells to repair cells
67
Q
artemis endonuclease
A
- in VDJ recombination, adds palindromic sequences on the shorter strand of the gene cleaved by RAG recombinases (to match the bases on the longer strand)
68
Q
TDT
A
- terminal deoxynucleotidyl transferase
- adds 3-5 base pairs on end of VDJ segments after artemis endonuclease adds palindromic sequences
- may result in a frame shift, and this is the mechanism for “junctional diversity” of VDJ recombination
69
Q
AID and UNG
A
- AID = activation induced cytidine deaminase
- UNG = uracil-N-glycosylase
- both are somatic hypermutation enzymes
70
Q
IL-2Ry
A
- IL-2 receptor that is mutated in SCID (severe combined immunodeficiency disorder)
- issues with RAG recombinases in this disease lead to no lymphocyte function
71
Q
IL-21
A
- secreted by follicular Th cells to help B cells class switch and differentiate into plasma cells
