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M1 > B Cell Development/Activation/Fx > Flashcards

B Cell Development/Activation/Fx Flashcards

1
Q

Types of epitopes

A
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2
Q

Mitogen

A

Chemical that induces cells to undergo mitosis - certain mitogens can trigger lymphocyte DNA replication and division in an antigen-independent manner

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3
Q

Hapten

A

Small, organic molecule that is foreign but too small to induce and adaptive immune response unless it is bound to a larger (typically protein) antigen

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4
Q

What portion of the Ab determines its class?

A

There are five different heavy chain constant regions, which dtermine the five different Ab classes

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5
Q

Complementarity determining regions (CDRs)

Abs

A

aka Hypervariable regions

Each heave and light chaincontains 3 sub-regions that strongly impact Ab/Ag binding affinities (but not ID of Ag)

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6
Q

Ig domains

A

Repetitive looped domains created by intra-chain disulfide bonds

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7
Q

IgD

A

Marker for naive, mature B cells - necessary for naive B cell activation

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8
Q

IgA

A

Monmer in serum and dimer in secretions

Dimer - two IgA molecules joined by a J chain

Mucosal immunity

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9
Q

B cell development before antigen contact

A
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10
Q

RAG deficiency

A

Cause of SCID - characterized by lack of T/B cell function

Inability to successfully recombine the TCR/BCR genes causing developing lymphocytes to undergo apoptosis

Pt’s present w/ failure to thrive, absent thymic shadow on CXR, and repeated severe bacterial/viral/ any other infections early in life

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11
Q

Bone marrow stromal cells in B cell development

A

Provide cell adhesion molecules (CAMs) and cytokines (i.e. IL-7) to nurture B cell development

Stromal cells also present Ag during negative selection

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12
Q

What simultaneously produces IgM and IgD in a mature, naive B cell

A
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13
Q

Which BCR gene is rearranged first?

A

The heavy cahin gene

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14
Q

What initiates immunoglobulin light chain gene rearrangement?

A

A functional μ (IgM) heavy chain protein

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15
Q

What type of selection do immature B cell clones undergo in the bone marrow?

A

Negative selection - if they react w/ self-Ags = apoptosis

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16
Q

When do immature B cells exit the bone marrow

A

After surviving negative selection - enter circulation and then secondary lymphoid tissue primary lymphoid follicles

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17
Q

What causes B cells to develop into mature B cells?

A

Interacting with DCs in a primary lymphoid follicle - DCs secrete cytokines that drive B cells to maturity

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18
Q

Alternative splicing of the H chain mRNA in mature, naive B cells

A

Does not change Ag-binding affinity or Ag specificity - it just allows the cell to express IgD and IgM versions of the BCR at the same time

19
Q

X-linked Bruton’s Agammagolbulinemia

A

Primary immunodeficiency that results from defects in the B cell-specific, Bruton’s tyrosine kinase (BTk) that is express early in B cell development

B cells fail to mature beyond the pre-B stage

Infants are usually well for first six months of life - subsequently develop recurrent infections - particularly w/ encapsulated bacterial and mucosal pathogens**

Circulating B cells and all Ig classes are absent

T cell development is unaffected

20
Q

Summarize B cell development

A
  1. Stem cell in bone marrow
  2. Successful rearrangement of μ heavy chain gene
  3. Successful rearrangement of κ or λ light chain gene & production of surface IgM BCR
  4. Negative selection in bone marrow
  5. Continuing development in primary lymphoid follicle
  6. Alternative splicing to make IgM and IgD
  7. Mature B cell
21
Q

Where does B cell activation occur?

A

In secondary lymphoid tissues (typically the follicle)

22
Q

T-cell dependent B cell activation signals

A
  1. BCR crosslinking by specific Ag plus BCR co-receptor complex (CD19, 21, and 81) activation - stimulates endocytosis of the BCR-bound antigen, B cell Ag presentation, and B cell migration to the T cell zone in secondary lymhpoid tissue
  2. CD4+ Th2 cells provide help through cytokines and direct physical interactions to drive B cell proliferation and differentiation

After antigen-mediated activation of a mature B cell - alternative splicing to produce IgD is turned off

23
Q

Plasmablasts

A

Secrete low affinity IgM - do not undergo affinity maturation

24
Q

Opsonization

A

Coating surface of extracellular path w/ IgG/C3b

Require Fcγ receptors on phagocyte surface (IgG)

or CR1 receptors (C3b)

25
Q

Ab-Dependent Cell-Mediated Cytotoxicity (ADCC)

A

NK cells and neutrophils bind to and kill target coated w/ IgG

NK cell use FcγR/CD16 receptors for this (binds to the Fc fragment)

26
Q

FcεRI

A

FcεRI - expressed by mast cells, basophils, and IL-5 activated eosinophils - coated w/ IgE

Parasite Ag crosslinking of FcεRI-bound IgE results in cellular degranulation and release of inflammatory mediators (i.e. histamine) and enzymes

Either kill or evoke tissue response that expels parasite

27
Q

Neutralization

A

IgG/A/M bind and inhibit pathogen infection or pathogen/toxin/venom damage to tissues

28
Q

Tissue distribution of IgM

A

Pentameric IgM does not enter tissues efficiently - mostly found in circulation

29
Q

Tissue distribution of IgA

A

Actively transported into colustrum and onto mucosal surfaces (trans-cytosis)

30
Q

Brambell receptor (FcRB)

A

Trans-cytoses IgG across vascular endothelium into either extracellular tissue space or across the placenta into fetal circulation

31
Q

Poly-Ig receptor (PIgR)

A

Trans-cytoses IgA dimers from the basolateral surface of mammary alveolar epithelial or mucosal epithelial cells to the apical surface of those cells (using an endocytic vesicale)

32
Q

Natural Passive Immunity

A

IgG and IgA from mother to child

IgG - crosses placenta (protects for ~ 6mo.)

IgA - secreted into breast milk and colostrum (confers protection in the oropharynx and the gut)

33
Q

Compared to IgG, is IgM lower/higher binding affinity for a given Ag?

A

IgM has a lower relative affinity than the other class types of Ig

34
Q

Effector functions of IgM

A

Neutralization and classical complement activation

35
Q

Effector functions of IgG

A
  1. Neutralization
  2. Classical complement activation
  3. ADCC (NK and neutrophil FcγR/CD16 dependent)
  4. Opsonization (neutrophil and macrophage FcγR dependent)
36
Q

What comformation of IgA is found in circulation and what is its effector function?

A

Monomeric IgA is found in circulation and promotes neutralization and opsonization

37
Q

A. Plasmablasts that secrete IgM
B. Activated B cell clones that have undergone class switching to IgA
C. Plasma cells that secrete IgG
D. Memory B cells that have Ige BCRs

A

Plasmablasts that secrete IgM

38
Q

Which processes has an IgG-secreting plasma cell MOST LIKELY undergone in the germinal center? (choose the SINGLE BEST answer)

A

Somatic recombination to switch from producing IgM to IgG and alternate mRNA splicing to switch from making the BCR to making secreted antibody

39
Q

Production of WHICH CYTOKINE induces B cell clones in a germinal center to class switch to produce IgA?

A

IL-5

40
Q
A

Nucleotides are added or subtracted at the DJ and VJ junctions in the BCR heavy and light chain genes but not in the TCR 𝛂 and 𝝱 chain genes

41
Q

Alternate splicing

A
  1. Used to simulataneously exrpess surface IgM and IgD in immature B cell
  2. Also allows to make a secreted form of the BCR and membrane receptor BCR
42
Q

Which immunoglobulin would have the least sequence variability between B cell clones

A

IgM

Lower variability because it is less somatically mutated compared to other antibody classes such as IgG or IgA. Additionally, IgM antibodies are often produced before the process of affinity maturation, which increases the variability of antibodies.

43
Q

What type of Ag can TCR bind?

A

Linear epitope Ags

44
Q
A

IL-4

Could have also listed IL-13

Both tell B cells to class switch to IgE

IL-4 also pushes the T cell response toward the Th2 response

M1 (53 decks)

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