Block 1 Lecture 7 -- B Cells and Antibodies Flashcards

1
Q

What Abs bind exist as dimers?

A

IgA

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2
Q

What Abs exist as pentamers?

A

IgM

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3
Q

What Abs exist as monomers?

A
IgD
IgG
monomeric IgA
IgE
IgM
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4
Q

What makes a B-cell response thymus dependent?

A

if Ag is protein

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5
Q

What are the effects of a helper-T cell response on a B cell?

A

1) isotype switching
2) affinity maturation
3) memory B cell response

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6
Q

What makes a B-cell response thymus-independent?

A

polymeric Ag (polysaccharides, glycolipids, nucleic acids)

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7
Q

What Abs are produced in response to PEG in 10-25% of patients?

A

IgM (T-independent)

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8
Q

What are the effects of a thymus-independent B cell response?

A

little isotype switching (maybe IgG)
no affinity maturation
no memory response

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9
Q

Describe the immunological synapse proteins between a T-B cell interaction.

A

B cell: pMHCII to TCR

    • CD40 to CD40L
    • CD80/86 to CD28
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10
Q

What are the effects of the T-B interaction?

A

1) T’s produce Tfh cells

2) IL2,4,5 = proliferation of B and short-lived plasma cells

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11
Q

Where does affinity maturation, memory response, and isotype switching take place?

A

in the germinal center of the lymph node (B cell follicle)

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12
Q

What cytokine from Th helps produce IgG?

A

IFN-y (from Th1)

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13
Q

What cytokine from Th helps produce IgE?

A

IL-4 (from Th2)

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14
Q

What cytokine helps produce IgA?

A

mucosal tissue and TGF-beta

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15
Q

What is the half-life of IgG?

A

23 days

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16
Q

What Ab has the shortest half-life?

A

IgE (2 days)

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17
Q

Function of IgA?

A

mucosal immunity

18
Q

Function of IgD?

A

naive B cell Ag receptor

19
Q

Function of IgE?

A

helminth immunity, allergy

20
Q

Function of IgG?

A

opsonization
complement
ADCC
neonatal immunity

21
Q

Function of IgM

A

naive B cell Ag receptor, complement activation

22
Q

What are examples of overactive B cell disorders?

A

leukemia, lymphoma, autoimmunity

23
Q

How are overactive B cell disorders treated?

A

1) Rituximab
2) Immunosuppressants
3) Cell therapy

24
Q

How does rituximab work?

A

targets CD20 on B cells to stimulate ADCC

25
Q

What is ADCC?

A

Ab-dependent cell-mediated toxicity (performed by macrophage, monocyte, or NK)

26
Q

What are CAR-T cells?

A

treatment for ALL, etc.

modified T cells include Ab that kills all B-cells

27
Q

What are examples of underactive B cell disorders?

A

XLA (X-linked agammaglobulinemia)
XHM (X-linked immunodeficiency with hyper IgM)
CVID (common variable immunodeficiency)

28
Q

What are therapies for underactive B cells?

A

IV Ig

29
Q

What is IV Ig?

A

pooled Abs from healthy donors

readminister q3-4 weeks (igG has 23 day t1/2)

30
Q

How are B cells activated (pathways)?

A

1) Ag

2) Complement

31
Q

How is a B cell activated by Ag?

A
BCR dimerization
-- Src-TK phosphorylate stuff
-- PLC = Ca + DAG, PKC
-- Ras pathways
generation of TFs
32
Q

How is a B cell activated by complement?

A

Microbe-C3d

    • recognized by IgM and CR2 receptors
    • kinase pathways
33
Q

Describe B cell development.

A

Stem – Pro – Pre – Immature – Mature

34
Q

Characteristics of pro-B cells

A

proliferation, beginning of mutations

35
Q

Characteristics of pre-B cells

A

1-chain Ag receptor

36
Q

Characteristics of immature B cells

A

2-chain Ag (undergoes positive or negative selection)

37
Q

What is a Complimentarity Determining Region

A

area of hypermutation in DNA of the Ag-binding regions of an Ab

38
Q

How many disulfide bonds in an Ab?

A

4

39
Q

What changes occur in the antigen-binding region of an antibody?

A

1) somatic hypermutation

2) VDJ recombination

40
Q

What changes occur in the Fc portion of an antibody?

A

isotype switching (heavy chain selection)

41
Q

What is the fx of FcRn

A

neonatal immunity and longer t1/2

42
Q

What is the mechanism of FcRn?

A

recycles IgG after endocytosis