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B Lymphocyte Ag Recognition Flashcards

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1
Q

What type of antigens can BCR recognize?

A

Proteins, polysaccharides, lipids, and nucleic acids

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2
Q

Do BCR’s have more or less diversity than TCRs?

A

Less

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3
Q

Which region of the BCR confers isotope and effector function?

A

Constant region- can also switch immunoglobulin from membrane bound to soluble

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4
Q

What happens to the specificity of B cells upon antigen binding?

A

Highly increased (but baseline BCR specificity is still higher than TCR)

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5
Q

What is the on and off rates of BCRs?

A

Rapid on-rate and variable off-rate

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6
Q

What is the complementarity determining region of BCRs?

A

Hypervariable area recognizing and contacting antigens

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7
Q

What is the structure and general function of IgA?

A

Dimer. Mucosal immunity

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8
Q

What is the structure and general function of IgE?

A

Monomer. Mast cell activator

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9
Q

What is the structure and general function of IgG?

A

Monomer. Fc dependent phagocytosis, placental transfer, opsonizer, complement system.

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10
Q

What is the structure and general function of IgM

A

Pentamer. Naive B cell antigen receptor and complement activation. Primary response**

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11
Q

What happens to IgG expressing B cells after activation?

A

Isotype switching and IgG release

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12
Q

What happens to high-affinity Ig expressing B cells following activation and differentiation?

A

affinity maturation= B cell makes Ab for repeated exposure (memory b cells)

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13
Q

When do B cell precursors rearrange their immunoglobulin genes?

A

After contact with bone marrow stromal cells

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14
Q

What is baseline variability in B and T cells?

A

Multiple V region genes (RAG1/RAG2)

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15
Q

What is combinatorial variability in B and T cells?

A

VDJ joining (limited by number of VDJ combinations)

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16
Q

What is junctional variability?

A

Inaccurate gene segment splicing for unlimited diversity.

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17
Q

What are the three types of junctional variability?

A
  1. exonuclease removal of nucleotides from V,D,J regions.
  2. terminal deoxyribonucleotidyl transferase (tdt) adds in nucleotides between V&D and D&J regions to form N regions.
  3. DNA addition before DNA break repair to form P regions.
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18
Q

What is second combinatorial variability in B and T cells?

A

H&L chain random assortment

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19
Q

What is somatic hypermutation?

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A

High frequency point mutations in IgG heavy chain and light chain in germinal B centers.

20
Q

What types of cells undergo somatic hypermutation?

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A

B cells only!

21
Q

What is the outcome of somatic hypermutation?

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A

Increases affinity of antibody for antigen and increases selective survival of that B cell for affinity maturation

22
Q

Which enzymes take part in somatic hypermutation?

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A

Activation-induced cytidine deaminase and APE1 (not in humans)

23
Q

What is heavy and light chain substitution?

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A

Pre-BCR undergoes heavy and light chain mRNA splicing to form IgM and IgD intermediates for positive and negative selection

24
Q

What are lambda-5 and VpreB?

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A

surrogate light chain components for B cell receptor chain substitution during devo

25
What is the function of FLT3/FLT3R?
Binding of FLT3R on FLT3 on BM stromal cell induces IL-7R expression (IL-7 = lymphocyte growth)
26
What is the function of stem cell factor in early B-cell development?
SCF on bone marrow stromal cell binds receptor kinase c-KIT for pro B cell proliferation
27
What is the function of CXCL 12?
Stromal cell-derived factor, SDF-1 involved in CNS development
28
What are the general steps to the germinal cell reaction?
1. B cell activation by Ag & helper T cells (CD40L + cytokines) 2. Migration of B cell into germinal center 3. B cell somatic mutation with varying affinities for antigen 4. B cells with high affinity membrane Ig bind FDCs and present to T cells 5. Binding to FDCs/ T cell interaction further activates the B cell and those cells survive. 6. Cells that don't bind die 7. Germinal center proliferation of surviving B cells
29
What is unique about the B cell germinal center reaction?
B cells can display the antigens on their own MHC II receptors (but usu presented to by DCs)
30
What are the steps to B lymphocyte activation?
1. Complement activation= C3d binds microbe 2. Ag binds BCR and complement binds CD19/CR2 or Ig-alpha/beta 3. Be cell activation via CD19 or Ig-alpha/beta signals
31
Does the BCR have a signaling component?
NO uses CD19 or Ig-alpha/ beta
32
Which immunoglobulin is present most during the initial reaction and which upon repeated exposure?
``` IgM= initial exposure IgG= repeated ```
33
Which signaling molecule determines the IgM isotope?
No signal, IgM = default
34
Which signaling molecule determines the IgG isotope?
IFN-gamma
35
Which signaling molecule determines the IgE isotope?
IL-4
36
Which signaling molecules determine the IgA isotope?
cytokines produced in mucosal tissue (TGF-beta, BAFF)
37
What is Omenn syndrome?
RAGnull mutation= no B cells in skin. Txt= BMT
38
What is SCID?
Defects in DNA repair = low Ig and TCR diversity. Tx= BMT
39
What is ataxia telangiectasia?
ATM null mutation= low B cells. Txt= Ab, vaccines, IVIG
40
What is AID deficiency?
low Ab diversity due to lack of class switching and hypermutation = high IgM numbers. Txt= IVIG
41
Describe thymus dependent Ab responses
Usually for protein Ag= IgM and subclass switching for affinity maturation and second response generation
42
Describe thymus-independent Ab responses
Polysaccharides, glycoproteins, and nucleic acid antigens. IgM generated but no affinity maturation and limited secondary response.
43
What are the two B cell types found in the spleen and other lymphoid organs?
Follicular B cells (B2) and marginal zone B cells
44
What is the function of follicular B cells (B2)?
Isotype-switched plasma cells that generate high-affinity antibodies against proteins
45
What is the function of marginal zone B cells?
Recognize lipids, polysaccharides and generate mainly short-lived plasma cells and IgM
46
What type of B cells are found in mucosal tissue and what is their function?
B1 cells- recognize lipids and polysaccharides. Produce mainly IgM and are short-lived plasma cells
47
How is the BCR signal terminated?
Ab/Ag binds B cell IgG receptor and Fc receptor. Fc receptor contains ITIMS that inhibit the ITAMS

Immunology (6 decks)

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