2) Antigen Recep. & Gen. of Div., B Cell Dev., B Cell Activation, Antigen Presentation, NFkB pathways Flashcards

1
Q

Antigen receptors: TCR contains two transmembrane chains (X) and associates with the (Y) complex

A
X = Alpha-Beta or Gamma-Delta
Y = CD3
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2
Q

Antigen receptors: BCR is a membrane bound form of (X) and associates with the (Y) heterodimer

A
X = Ig
Y = IgAlpha and IgBeta
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3
Q

What does ITAM stand for?

A

Immunoreceptor Tyrosine based Activation Motifs

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4
Q

The BCR and TCR do not directly signal via cytoplasmic signaling molecules. The BCR and TCR complexes include accessory proteins that have cytoplasmic tails containing (X), which are able to initiate cytoplasmic signaling cascades

A

X = ITAMs

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5
Q

TCR Accessory Proteins:
CD3 complex: (X). Each has an (Y) in its tail. The 2 (Z) chains have no significant extracellular domains and form a homodimer. The (A) chains form two heterodimers

A
X =  δ, (2) ε, (2) ζ, and γ
Y = ITAM
Z = ζ
A = δ, γ and (2) ε
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6
Q

What are the 2 BCR Accessory Proteins?

A

Igα and Igβ

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7
Q

What is the ITAM Consensus sequence?

A

YxxL/Ix(6-8)YxxL/I

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8
Q

ITAM signaling. Major signaling pathway is initiated by (X) phosphorylation by (Y)

A
X = Tyr
Y = Src family kinases
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9
Q

B cell Development: Takes place in the ______

A

Bone Marrow

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10
Q

B Cell Development Pathway: 7 cell types in order

A
HSC
Early Pro B cell
Late Pro B cell
Large Pre-B
Small Pre-B
Immature B cell
Naïve Mature B cell (Follicular B cell)
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11
Q

B cell development: Hematopoietic Stem Cell (HSC). What is it?

A

Multipotent with no surface Ig

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12
Q

B cell development: Hematopoietic Stem Cell (HSC). What is the next step?

A

Common lymphoid progenitor

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13
Q

B cell development: Hematopoietic Stem Cell (HSC). If (X) is present (drives proliferation, but is not absolutely required for B cell development in humans- replaced by other factors) (Y) are expressed, turn on (Z) and cell becomes committed to the B cell lineage

A
X = IL-7
Y = EBF and E2A
Z =  PAX-5
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14
Q

B cell development: Hematopoietic Stem Cell (HSC). E2A and EBF induce PAX5 and also what 6 molecules?

A

RAG1/2. TdT, λ5, VpreB, Igα and Igβ

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15
Q

B Cell Development: Early Pro B cell. What is it?

A

A cell derived from a common lymphoid progenitor committed to the B cell lineage

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16
Q

B Cell Development: Early Pro B cell. What is its definable hallmark?

A

D(H) to J(H) rearrangement

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17
Q

B Cell Development: Late Pro B cell. Just a pro-B cell which is attempting (X) rearrangement. If it goes out of frame it dies. If (X) rearrangement is successful it is no longer a pro-B cell

A

X = V(H)-DJ(H)

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18
Q

B Cell Development: Large Pre-B cell. (X) productively rearranged, (Y) expressed at surface with (Z) heavy chain and (A) light chains (B) and in association with (C). This halts IgHC rearrangement (due to allelic exclusion) and leads to (D)

A
X = VDJ(H)
Y = pre-BCR
Z = μ
A = surrogate
B = VpreB and λ5
C = Igα and Igβ
D = proliferation
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19
Q

B Cell Development: Small Pre-B cell. VDJ(H) rearranged, (X) rearranging. Kappa is ALWAYS rearranged (Y)

A
X = V(k)->J(k)
Y = first
20
Q

B Cell Development: Immature B cell. VDJ(H) and VJ(L) rearranged. (X) expressed at the surface

A

X = IgM

21
Q

B Cell Development: Immature B cell. Selection for self-tolerance is next. What happens if BCR recognizes self-peptides too strongly?
If the cell sees self antigen strongly, receptor editing occurs at (X). The cell then re-expresses (Y) genes and undergoes further κ
rearrangement. If it fails on κ it then tries (Z) (there are four possible alleles, 2κ and 2 (Z), for test of whether the (X) is in-frame and no longer self-reactve: If all the possible rearrangements are self-reactive, the cell dies. (A) is a back up mechanism of central tolerance.
(B) signaling keeps B cells alive

A
X = IgLC
Y = RAG
Z = λ
A = Clonal deletion
B = Tonic
22
Q

B Cell Development: Naïve Mature B cell (Follicular B cell). (X)+ and circulating in the periphery, looking for antigen. Kept alive
by (Y)

A
X = IgM+ IgD+
Y = tonic signaling and BAFF
23
Q

What are the 5 functions of the Pre-BCR?

A
  1. Survival
  2. proliferation
  3. shutting off H-chain rearrangement (allelic
    exclusion)
  4. shutting off of surrogate light chain transcription
  5. opening kappa locus
24
Q

An X-linked gene downstream of pre-BCR is (X), a tyrosine kinase. Absence of (X) results in failure of pro-B to pre-B transition, and failure to make B cells, therefore no antibodies. (Y) is the disease

A

X = Btk
Y = X-linked
agammaglobulinemia

25
Q

B cell activation: Stimulation by T cell DEPENDENT antigens
i. The BCR signal is transduced via (X) ITAMs
ii. (Y) (lyn, fyn, blk) phosphorylate the ITAMs
iii. (Z) bind to the phosphorylated ITAMs and subsequently get
phosphorylated themselves
iv. A number of cascades are initiated, they can include (A) giving signaling for
development, proliferation, etc.
v. After initial stimulation by T cell dependent antigen (with (B) interaction)

A
X = Igα and Igβ
Y = Src family kinases
Z = Syk family kinases (syk)
A = NFκB, NFAT and AP-1
B = CD40L-CD40
26
Q

Is isotype switching (B cell activation), what is the fundamental or original Ab type?

A

IgM

27
Q

Isotype switching: Only the (X) region changes. Requires signals via (Y)

A
X = Fc (constant) "tail"
Y = CD40
28
Q

Isotype switching: Cytokine environment determines outcome: IL4 gives (X), TGF-β gives (Y)

A
X = IgE
Y = IgA
29
Q

Isotype switching: Mechanism:
There are switch regions and (X) upstream of each constant region, and when a particular isotype is selected (based on cytokine environment, etc) there is
transcription from the (X) through the selected constant region and then (Y) leads to incorporation of the new constant region.

A
X = I exons
Y = splicing
30
Q

B cell activation Step 2: Proliferation in the (X) and (Y) with eventual development of a B cell memory population

  1. (Y) occurs in dark zones of (X) in the (Z, organs)
  2. The mutations begin (A) of the rearranged V region and end (B) of that region
  3. This generates a set of B cells with diverse affinities for the instigating antigen—those with the highest affinity are selected on (C, cell type) to survive and proliferate (the others die)
A
X = germinal center
Y = somatic hypermutation
Z = lymph nodes/spleen
A = 5’
B = 3’
C = follicular dendritic cells (FDCs)
31
Q

Somatic Hypermutation only changes the (X) regions, not the (Y) region

A
X = variable
Y = Fc
32
Q

B cell activation Step 3: From plasma cells: secreted antibody due to selection of alternate (X) site which eliminates the (Y)

A
X = poly-A
Y = transmembrane exons
33
Q

B cell activation: What does AID stand for?

A

activation induced cytidine deaminase (DNA deaminase)

34
Q

B cell activation: What is the role of AID?

A

Required for class-switching and somatic hypermutation

35
Q

B cell activation: Stimulation by T cell INDEPENDENT antigens: carbohydrates with repeating patterns—signaling is almost identical.
1. No isotype switching, somatic hypermutation or memory response (so always (X)!)
2. (Y) antigen binds BCR and crosslinks the BCR
3. Co-receptor complex (Z)
(A): Complement fragment (B) bound antigen binds to both the BCR and the nearby (A) (complement receptor), thus clustering it with the BCR

A
X = IgM
Y = Multivalent
Z = (CD19/CD21/ less so CD81, unclear role)
A = CR2/CD21
B = C3d
36
Q

Antigen Presentation: What are the human and mouse versions of Class I MHC?

A
human = HLA-A, B, C
mouse = H2-K, D, L
37
Q

What is a Class I MHC complex made of?

A

α chain (transmembrane) and β-2 microglobulin (β2m, non-transmembrane) chain

38
Q

Class I MHC is expressed on (X) cell types, presents (mostly) (Y) protein, and is recognized by (Z) cells

A
X = all nucleated
Y = cytosolic
Z = CD8+ T
39
Q

Antigen Presentation: What are the human and mouse versions of Class II MHC?

A
human = HLA-DR, DP and DQ
mouse = I-A, I-E
40
Q

What is a Class II MHC complex made of?

A

α chain and β chain (both transmembrane)

41
Q

Class II MHC presents mostly (X) antigens and is recognized by (Y) cells

A
X = exogenous
Y = CD4+ T
42
Q

Class I MHC Antigen Processing:
i. α and β2m synthesized in (X), associate with (Y)
ii. α and β2m associate with each other and (Z)
iii. In the cytosol, proteins to be degraded are (A)
iv. The proteasome is augmented with three new β subunits in the context of inflammation by IFN γ, (B). This new proteasome creates peptides MHC I presentation ending
with the appropriate type of C-termini (mainly (C)) that can be recognized by
(Z)
v. (Z) transports peptides from the cytosol to the (X)
vi. The peptides then associate with MHC I in the (X), increasing the stability of the MHC I complex, which is then transported to the cell surface

A
X = ER
Y = chaperones
Z = TAP
A = ubiquitinated
B = iβ1, iβ2 and iβ5
C = aromatic amino acids
43
Q

Class II MHC Antigen Processing.

i. (X) are synthesized in the ER and associate with each other and an (Y) which prevents proteins from binding to the MHC-II complex
ii. The complex moves out of the ER to the Golgi and is targeted by the (Y) tail into acidic (Z)
iii. Proteases in the (Z) digest away most of the (Y), leaving only the “(A)” fragment in the peptide cleft of the MHC II
iv. (A) is then dislodged by (B) and antigen peptides can bind to the MHC II complex
v. MHC II complexes are then transported to the cell surface

A
X = α and β chains
Y = invariant chain (Ii) trimer
Z = late endosomes/lysosomes
A = CLIP
B = HLA-DM
44
Q

NFkB Signaling:

1) (X) (Receptors) signal to/release…
2) (Y) which interacts with…
3) (Z) (α,β,γ subunit —γ subunit = NEMO)
4) (Z) then degrades (A) releasing NFkB to the nucleus, inducing transcription of inflammatory genes

A
X = CD40, IL6-R, TNF-R, TLR
Y = TRAF
Z = IκB kinase
A = IκB
45
Q

TRAFs are (X) ligases that (Y) a target which leads to (Z) of a kinase upstream of Ikk (and DOES NOT drive proteosome mediated destruction unlike other instances of ubiquitination)

A
X = E3 Ubiquitin
Y = polyubiquitinate
Z = activation