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IHO Week 4 > B and T Cell Maturation - Diebs > Flashcards

B and T Cell Maturation - Diebs Flashcards

1
Q

Early pro B cell expresses?

A

TdT

c-Kit —>binds to stem cell factor expressed on BM stromal cells

induces pro B cell to proliferate and differentiate into pre B cells

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2
Q

Intermediate pro B cell expresses….

A

TdT and CD45R

c-Kit

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3
Q

Late pro-B cell expresses…

A

CD45R and have downregulated TdT

c-Kit

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4
Q

Late pro-B cell —-> pre B cell stage

What is downregulated?

A
  • TdT
  • RAG-1, RAG-2

CD43

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5
Q

As cell goes through pro-B stage, Ig heavy chain genes are rearranged.

What begins to be expressed?

A

CD43

CD19

RAG-1

RAG-2

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6
Q

When do Ig light chains rearrange?

A

As cells go from large mitotically active pre B cells —–> small non-dividing pre B cells

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7
Q

What is the importance of IL-7?

A

-promotes B cell lineage development

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8
Q

Blys (B lyphocyte stimulator) importance?

A

survival of pre-immune B cell stages from transition stage onward

-signals through its receptor BR3

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9
Q

IL-4, IL-3, L-BCGF importance?

A

-initiating the process of B cell differentiation after activation

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10
Q

Immunodeficiency XLA

A
  • Block at the pro B cell to large pre-B cell transition in bone marrow
  • Mutated enzyme: Bruton’s tyronsine kinase (Btk)
  • pts have very few circulating B-cells and negligible serum Ig
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11
Q

Common variable immunodeficiency (CVID)

A
  • impacts later stages of B cell development
  • reduced serum Ig, memory B cells, class switch recombin, and B-cell activation
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12
Q

Transitional Immature B cells T1 vs T2?

A
  • T1: membrane bound IgM
    • goes through negative selection
  • T2: membrane bound IgM and IgD
    • goes through negative selection during hypersomatic mutation
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13
Q

What is T-independent B cell activation?

What type of B cell is activated?

A
  • Small # of antigens can activate B cells without MHC II restricted T cell help
    • === T-independent antigens (TI)
  • Activates B1 B cells
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14
Q

General stuff about B1 B cells and T independent activation:

Where?

Memory produced?

Isotype produced?

A
  • Where: peritoneal and pleural cavities
  • Isotype produced: Lots of IgM
  • Memory produced: very little, never get switch to IgG
  • No somatic hypermutation
  • Don’t require help from T cells
  • Respond to carbohydrate antigens :)
  • These are innate functioning B cells (only have IgM and CD5)
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15
Q

TI 1 vs TI2 antigens

A
  • TI-1 antigens: bacterial cell wall components – LPS
  • TI-2 antigens: large polysaccaride molecules with repeating antigenic determinants (Ficoll, dextran, polymeric bacterial flagellin, poliomyelitis virus)
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16
Q

B cell response to TI 2 antigen?

A
  1. B1 B cells bind to TI 2 antigen through cross-linking of BCR
    • ​​Specific/clonal activation since it’s thru BCR
  2. TI 2 antigens can ONLY stimulate mature B cells
  3. Mostly IgM is produced
17
Q

B cell response to TI 1 antigens?

A
  1. B1 B cell binds to LPS through TLR4 or BCR
    • TLR4 = nonspecific = polyclonal activation. Any B cell with TLR4 will divide
      • Stimulate both immature and mature B cells
    • BCR = specific = clonal activation
  2. Only IgM is produced
18
Q

Polyclonal vs clonal expansion?

A

Polyclonal: nonspecific, epitope is recongized by a lot of antibodies and all those proliferate

Clonal: specific, derived from one B cell

19
Q

What cytokine is secreted by APC and help with activation of B cells?

20
Q

What cytokines stimulate division of B cells?

A

Th1 —-> IL-2

Th2 —> IL4

21
Q

What cytokines stimulate differentiation of B cells?

A

IFN-gamma (Th1)

IL-4, IL-5, IL-6, IL-10, IL-13 (Th2)

22
Q

T dependent B cell activation

What type of B cell is activated?

What is the outcome of this activation?

A

Activates Follicular (B-2) B cells

Major site: secondary lymphoid organs

Outcome: production of IgG and memory

Express: CD19/21, IgM, IgD, CD23

23
Q

T dependent B cell activation:

How is the B cell activated?

A
  • IgM binds an antigen and displays it on MHC II
    • -CD21 can regonize complement..
  • APC will secrete IL-1 to activate B cell
  • Then B cell will bind Th2 cell and it will help it divide and differientate with cytokines
24
Q

Double negative thymocytes express:

DN1:

DN2:

DN3:

DN4:

A

DN1: c-Kit++, CD44+

DN2: c-Kit++, CD44+, CD25+

DN3: c-Kit+, Cd25+, pre-TCR, CD3+

DN4: pre-TCR, CD3+

25
Q

Function of CD44?

A

required for relocalization to thymus

26
Q

Changes in TCR during development?

A

DN3, DN4, DP have the Pre-TCR that has a dummy alpha chain

Once you check that the beta chain is function you put the TCR alpha chain out

27
Q

Signals required for activation of Naive T cells?

A
  1. TCR signaling
  2. Costimulatory interaction
  3. Cytokine signaling (IL-2 and IL-12)

IHO Week 4 (15 decks)

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