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IHO Week 4 > B and T cell Maturation > Flashcards

B and T cell Maturation Flashcards

1
Q

Where in the body do B cells mature? WHen do they leave?

A

Bone marrow - they leave when they’re in the immature transitional stage

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2
Q

What acts as the initial BCR? What are the components?

A

membrane-bound IgM and signaling chains Ig-alpha and Ig-beta (CD79a and CD79b)

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3
Q

What will happen to the immature B cells in the periphery if they don’t experience antigen?

A

they’ll undergo apoptosis in a few weeks

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4
Q

What is the earliest stage of antigen-independent B cell development?

A

the progenitor B cell = pro-B cell

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5
Q

The pro-B cells are divided into three groups how?

A

early pro-B: express Tdt alone
intermediate pro-B: express both TdT and B220
Late pro-B: express B220, but downregulated Tdt

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6
Q

As the cell progresses through the pro-B cell stage, what else does it begin to express?

A

CD43, CD19, RAG-1 and RAG-2

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7
Q

As the late pro-B cell passes into the pre-B cell stage, what do they downregulate?

A

TdT, RAG1, RAG2 and CD43

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8
Q

What do pro-B cells express to allow them to bind to stem cell factor expressed on bone marrow stromal cells? What does this induce?

A

c-Kit

This induces the pro-B cell to proliferate and differentiate into pre-B cells

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9
Q

What are the two groups of pre-B cells?

A

large mitotically active

small non-dividing

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10
Q

What do both the large and small pre-B cells express in their cytoplasm? on their surfaces?

A

IgM heavy chains in the cytoplasm and a receptor complex on their surface (no light chain yet)

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11
Q

What do the large pre-B cells do as they pass into the small group?

A

They upregulate RAG1 and RAG2 so they can rearrange their Ig light chain genes

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12
Q

pre-B cells have a receptor for which cytokine that stimualtes them to divide and differentiate?

A

IL-7

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13
Q

What do Immature B cells express that pre-B cells didn’t?

A

Finally express surface IgM (with successfully rearranged heavy and light chains)

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14
Q

When the immature B cells further develop into mature B cells, what else do they express on their surface?

A

surface IgD

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15
Q

What phase do the mature B cells go thorugh when they first exit the bone marrow and migrate to the periphery?

A

thr transition phase

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16
Q

What cytokine signals through the BR3 receptor for the survival of pre-immune B-cell stages from the transition stage onwards?

A

B-lymphocyte stimulator (Blys)

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17
Q

What are some of the transcription facotrs involved in B cell generation?

A
  1. E2A and EBF (turned on by STAT5 ignalling)
  2. Pax5
  3. Sox4 and LEF1
  4. IRF4 and IRF8
  5. Bcl6
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18
Q

What happens in immunodeficiency XLA?

A

It’s a mutation in Bruton’s tyrosine kinase, which is a key enzyme involved in signal transduction downstream of the pre-BCR and BCR

Without that signalling, these patients have very vew circulating B cells and negligible serum Ig

(this agammaglobulinemia!)

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19
Q

What happens to the B cells in CVID?

A

You have reduced serum Ig, reduced memory B cells and less class switch recombinaiation or B cell activation

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20
Q

What happens to the B cells when there’s a mutation in CD40 ligand on T cells?

A

You don’t get the costimulatory signal from the Th to the B cells, so you have issues with class switching

21
Q

WHat happens first for the B cells - negative or positive selection? WHere

A

negative happens first - in the bone marrow (mostly)

22
Q

What are the three populations of B cells in the periphery? Which is most numerous?

A

Follicular B2 C cells - most common (and what we usually think of for the immune response)
B-1 B cells
Marginal zone B cells

23
Q

What are the two types of T-independent antigens that can activate B cells without Th help?

A

TI-1 - bacterial cell wall components like LPS

TI-2 - large polysaccharide molecules with repeating antigenic determinants (like bacterial flagellin)

24
Q

What class of B cells are activated by the TI antigens?

A

the B-1 B cells

25
Q

What does the B-1 B cell use to bind to the type 1 TI antigen? How does this affect what expansion occurs?

A

TLR4 - you get polyclonal activation

BCR - you get clonal activation

26
Q

What antibody is produced in response to type 1 TI antigens? Can you develop memory this way?

A

IgM - no memory

27
Q

How does the B1 B cell bind to type 2 TI antigens? So what kind of activation/expansion is possible?

A

through cross-linking of the BCR only.

so you only get clonal activation (not polyclonal)

28
Q

What Ig type is formed in response to type 2 TI antigen? Is there a potential for a full B cell response?

A

IgM mostly, but there IS a potential for full B cell response as CD4+ T cells can be innvolved and produce the right cytokines for class switching

29
Q

Where are B1 B cells generally found in the body?

A

peritoneum

30
Q

What are the two ways the BCR can be stimulated?

A
  1. By having antigen cross-linking multiple IgM or IgD on the surface of the cell
  2. By having antigen bind one Ig and complement binding to both the antigen and CD21 on the B cell - so the complement binding does the cross stimulation
31
Q

What cytokines does the Th2 cell make to push B cell proliferation and differentiation?

A

IL2, IL4, and IL5

32
Q

How does the memory B cell response differ from the naive B cell response?

A
  1. faster - only 1-3 days to start producing antibody and peak is reached in 3-5 days
  2. stronger - makes more antibodies and the antibody affinity is much higher
  3. IgG and IgA (not IgM)
  4. thymus dependent (no independent - remember its membory)
  5. long-lived
33
Q

In the germinal centers, T and B cells that have recognized antigen try to find each other. What happens to the B cell if it doesn’t get Th help after SHM? WHat happens if it does - specifically, how does it become long-lived?

A

Doesn’t meet it’s T cell - dies by Fas-independent apoptosis

Does meet - starts to make Bcl-2 so it’s protected from apoptosis and becomes long-lived

34
Q

What signalling molecule must be made by thymic stromal cells in order for T cells to develop?

A

Notch

35
Q

DUring T cell development, there are multiple stages denoted by “double negative” which means?

A

they have neither the CD4 or CD8 (They’re starting to make the TCR, but don’t have the costimulators yet)

36
Q

What stage comes after the double negative stages?

A

Double positive - they have both CD4 and 8

37
Q

What CD marker is required for the T cells to relocalize to the thymus for education?

A

CD44

38
Q

What does the T cell undergo first - negative or positive selection?

A

positive selection in the thymus

39
Q

Positive selectio nis also known as what?negative selection?

A 
positive = restriction
negative = self-tolerance
40
Q

How many TCRs must be bound to activate the T cell? What’s the maximum?

A

Only one is necessary; 10 is the max

41
Q

What cytokine is the activated T cell use as an autocrine to increase further proliferation?

A

IL-2 - help generate the clone

42
Q

What do superantigens do and how do they do it?

A

They can bind both the MHC and TCR outside of the antgen groove by binding directly to CD28
Thus, they can provide the co-stimulatory signal to the T cell without the need of B7 - triggering a non-specific interaction to stimulate many T cells of different antigen specificity

43
Q

What does superantigen binding lead to?

A

shock - via massive release of IFN gamma and TNF alpha

44
Q

What cytokines will trigger formation of Treg cells? What do they secrete?

A

Trigger: IL-2 and TGF beta
Secrete: IL-10 and TGF beta

45
Q

What cytokines will trigger formation of Th17 cells? What do they secrete?

A

trigger: IL-1, IL-6, IL-23, TGF beta
secrete: IL17A< IL17F, IL22

46
Q

What cytokines will trigger formation of Th2 cells? What will they secrete?

A

Trigger: IL-4
Secrete: IL4, IL-5, IL-13

47
Q

What cyotokines will trigger formation of Follicular T cells/ What will they secrete?

A

trigger: IL-6 and IL-21
secrete: IL4, IL-21

48
Q

What cytokines will trigger formation of Th1 cells/ What will they secrete?

A

trigger: il-12, IFN gamma, IL-18

secrete; IFN gamma, TNF

IHO Week 4 (15 decks)

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