L10 Flashcards

1
Q

What Ab dominates primary exposure response to antigen? Secondary exposure?

A

Primary - IgM

Secondary - IgG or whatever isotype was selected for that pathogen in making memory cells (parasitic worms = IgE)

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2
Q

What parts of somatic diversification of B cells happens at the bone marrow? Describe it.

A

VDJ Recombination

  • immature B cells ONLY
  • RAG 1/2
  • Antigen INDEPendent
    1. Heavy chain recomb (allelic exclusion if needed)
    2. Light chain (receptor editing if needed)
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3
Q

What parts of somatic diversification of B cells happens in secondary lymph organs?

A
  1. Somatic hypermutation
  2. Class switch recombination
    - Both AID dependent
    - MATURE B cells only
    - Antigen dependent
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4
Q

What is SHM?

A

= affinity maturation
Point mutations made to heavy or light chain VARIABLE regions
- Where CDRs are coded

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5
Q

What is CSR?

A

= isotype switching

Recombination of HEAVY C genes

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6
Q

What chemokine receptor gets upregulated in naive B cells for movement to secondary lymph organs?

A

CCR7

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7
Q

What chemokine receptor gets upregulate in B cells to move into circulation/out of lymph organs?

A

CXCR5

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8
Q

What is the difference between how DC in T cell zones vs FDCs are made?

A

DC in T cell zones - from hematopoietic precursors

FDC - derived @ lymph node

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9
Q

What is the TAPPA receptor on B cells? What happens when this is bound?

A

CD19 + CD81 + CR2 (CD21)
Complement receptor
Signals via PI3 kinase
Lowers threshold of activation for B cell

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10
Q

Which cell surface molecule is distinguishing for B cells?

A

CD19

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11
Q

Which complement does CR2 bind?

A

3d & i3b

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12
Q

What 3 things happen after a B cell binds its BCR in the periphery?

A

Acts as an APC - phagocytosis of receptor + antigen

  1. Mitosis –> clonal expansion
  2. ↑CCr7 to move to lymph nodes
  3. Low level IgM secretion
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13
Q

Why are antigen-specific B cells more likely to receive help from antigen-specifc T cells?

A

CONCENTRATION EFFECT

APC property of B cell to present on MHC2

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14
Q

How do you mount an immune response with memory against carbohydrates?

A

Couple with protein carrier

Alone would get B cell stimulation - but no memory

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15
Q

What is the difference between a primary vs secondary lymphoid follicle?

A

Secondary has germinal center!

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16
Q

How do Ab-antigen-complement complexes stimulate a response in the lymph node?

A

Enter via subcapsular sinus
Macrophages with CR3 bind iC3b molecules
Macrophages phagocytose the complex - present to naive B cells in follicle
Naive TAPPA complex binds
Passes complex to FDCs - present antigen on Fc gamma receptor or CD21
Antigen binds specific B cell

17
Q

What happens once a specific B cell has bound an antigen-complement complex presented by FDC?

A

↑CCR7 to move to T/B border
↑CXC5 production (chemokine) to pull the T cells to the border too
↑CD40 expression for co-stimulation

18
Q

What are the 2 paths that a B cell can take after meeting a T cell at the follicle border?

A
  1. T cell saw B cell with high affinity receptor - good to go! Become a plasma cell and secrete those Abs
  2. T cell saw B cell that needs a better BCR
    - ↑CCR7 –> back into germinal center
    - CSR & SHM
19
Q

What 2 signals are needed to determine the recombination fate of B cells needing more maturity?

A

CD40L & appropriate cytokine
Upregulates AID
Cytokines det which switch boxes open for recomb of VDJ gene

20
Q

What cytokine induces IgG B cells?

A

IFN gamma

21
Q

What is the primary role of IgGs?

A

Opsonization for phagocytosis

22
Q

What is the primary role of IgM?

A

Complement activation

23
Q

What cytokine induces IgE B cells?

A

IL4

24
Q

What cytokine induces IgA B cells?

A

TGF beta - those produced by mucosal tissues

25
Q

What is the germinal center reaction?

A

@ light region of germinal center
Switched B cells present new receptor to FDCs to see if they pass the self test
Yes –> plasma/memory cells
No - anergy/apoptosis

26
Q

What are centroblasts?

A

Dark region of germinal center
Where B cells are undergoing SHM and CSR
Cell division!!!

27
Q

What are centrocytes?

A

Where B cells in germinal center have stopped dividing

Undergoing the germinal center reaction

28
Q

What causes type 2 hyper IgM syndrome? Give symptoms.

A

AID deficiency due to inactivating mutation

Symptoms: repeated bacterial infections

29
Q

WHAT IS THE CLASSIC HISTO FINDING for type 2 hyper IgM syndrome?

A

Histo: ENLARGED GERMINAL CENTERS

  • Send B cells here for SHM & CSR but can’t do anything about it!
  • Only get primary IgM response from B cells - no class switching
30
Q

What causes type 1 hyper IgM syndrome? Give symptoms? What is the primary histo finding?

A

CD40/CD40L mutations
No T-B cell interaction –> never send anything to GC
NO GERMINAL CENTER FORMATION ON HISTO
High IgM but no other isotypes
Same symptoms as type 2 - repeated bacterial infections