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HDID 1 > 9. Lymphocyte Development > Flashcards

9. Lymphocyte Development Flashcards

1
Q

lymphopoiesis is _____ antigen dependent

A

self

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2
Q

where does lymphopoiesis occur?

A

primary lymphoid organs

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3
Q

what are the three main branches/outcomes of lymphopoiesis?

A
  1. differentiation
  2. acquisition of antigen recognition (diversity, clonality, development checkpoints)
  3. proliferation
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4
Q

antibodies serve different functions at different stages of humoral response….explain how this pertains to membrane bound vs secreted Abs.

A

membrane bound antibodies on B cells recognize antigens to initiate response

secreted Abs neutralize and eliminate microbes and their toxins in the effector phase of humoral immunity

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5
Q

In cell-mediated immunity, the effector function of microbe elimination is mediated by what?

A

T lymphocytes themselves and by other leukocytes responding to the T cells (the antigen receptors of T cells are involved only in antigen recognition and T cell activation and these proteins are not secreted and do not mediate effector functions)

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6
Q

In antibodies, each light chain is attached to one heavy chain, and the two heavy chains are attached to each other - all by what type of bonds?

A

disulfide

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7
Q

how many V and C regions does each light chain have? each heavy chain?

A

light chain: 1 V and 1 C domains

heavy chain: 1 V and 3-4 C domains

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8
Q

which CDR contributes most to antigen binding?

A

CDR3

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9
Q

the two types of light chains, kappa and lambda, differ in which region? The 5 types of heavy chains (mu, delta, gamma, epsilon, alpha) differ in which region?

A

C region for both

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10
Q

the antigen receptors of naive B lymphocytes, which are mature B cells that have not yet encountered antigen, are what isotype?

A

membrane bound IgM and IgD

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11
Q

after stimulation by what do the antigen-specific B cell clones expand and ddifferentiate into progeny that secrete antibodies (some of the progeny of IgM and IgD progeny of the same B cells may produce antibodies of other heavy-chain classes via isotype switching)

A

antigen and helper T lymphocytes

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12
Q

although heavy chain C regions may switch during humoral immune responses, each clone of B cells maintains its specificity how?

A

V regions do not change

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13
Q

the strength with which one antigen-binding surface of an Ab binds to one epitope of an antigen is called what?

A

the affinity of the interaction (affinity increases with repeated stimulation - ie secondary immune response in affinity maturation)

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14
Q

the total strength of binding between antigen and antibody is much greater than the affinity of single antigen-antibody bond and is called what?

A

avidity of interaction

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15
Q

antibodies produced against one antigen may bind other, structurally similar antigens….this binding to similar epitopes is called what?

A

cross reaction

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16
Q

what proteins make up the BCR complex?

A

membrane bound Ig molecules, Igalpha, IgBeta (when BCR binds antigen, Iga and IgBeta transmit signals to the interior of the B cell that initiate the process of B cell activation)

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17
Q

what are myeloma cells and what makes them unique?

A

tumors of plasma cells and can be propagated indefinitely in tissue culture (but can’t grow in the presence of toxic drug)

18
Q

Fused cells containing both myeloma and normal B cell nuclei do what?

A

grow in the presence of drug because normal B cells provide missing enzyme…so can grow just these specific cells that don’t die, called hybridomas (can select a specific clonal line to produce monoclonal antibodies)

19
Q

what complex of proteins is associated with TCR to transmit some of the signals that are initiated when the TCR recognizes the antigen?

A

CD3 and zeta proteins (along with TCR make up the TCR complex)

20
Q

the development of lymphocytes from bone marrow stem cells involves commitment of hematopoietic progenitors to the B and T cell lineage, the ______ of these progenitors, the ________ and expression of antigen receptor genes, and _______events to identify and expand cells that express potentially useful antigen receptors

A

proliferation, rearrangement, selection

21
Q

______ interactions define T-lineage in the thymus.

A

Notch receptor-ligand interactions

22
Q

selective induction of ________ define B-lineage in bone marrow.

A

TFs EBF and Pax5

23
Q

antigen receptors are encoded by several gene segments that are separate from one another in the germline and that do what during lymphocyte maturation?

A

recombine

24
Q

what receptors are on the surface of proB and preB cells?

A

CD19+ (but IgM-)

25
Q

chromosome translocations and activating point mutations of ____ are found frequently in T-ALL.

A

Notch-1

26
Q

chromosome translocations and point mutations that disable ______ are found frequently in B-ALL.

A

Pax5, EBF

27
Q

in T cell maturation, which TCR chain is rearranged first?

A

Beta (preT) (then alpha (immature T))….or gamma/delta before any of that on the proT

28
Q

which Ig is rearranged first on B cells?

A

IgH (D-J on proB and V-DJ on preB)…makes IgM first!….then IgL (kappa or lambda on immature B cells)

29
Q

what enzyme mediates VDJ recombination?

A

VDJ recombinase (RAG1/RAG2 only expressed in immature B and T lymphocytes

30
Q

where do gamma/delta T cells localize?

A

epidermise and epithelium as well as other tissues, but very few and relatively unknown functions

31
Q

what makes up the pre-BCR complex?

A

mu chain, surrogate light chains (no variable domain), Igalpha and IgBeta

32
Q

first checkpoint in B cell development?

A
  • Pre-BCR delivers signals promote the survival and prolif of B lineage cells that have made a productive rearrangement at the IgH locus
    ○ Selects and expands the pre-B cells that express a functional mu heavy chain (essential component of BCR and pre-BCR)
    ○ Pre-B cells that make out of frame (nonproductive) rearrangements at the H locus fail to make mu protein, cannot express a pre-BCR or receive pre-BCR signals, and die by apoptosis
33
Q

pre-BCR and allelic exlusion

A
  • Pre-BCR complex also signals to shut off recombination of IgH genes on the second chromosome, because of which each B cell can express an IgH from only one of the two inherited parental alleles
    ○ Called allelic exclusion and helps ensure that each cell can only express a receptor of a single specificity
34
Q

pre-BCR light chain recombination

A
  • Pre-BCR also triggers recombination at the Igkappa light chain locus (the lambda chain is produced only if the recombined K chain locus fails to express a functional protein or if the K chain generates a potentially harmful self-reactive receptor and has to be eliminated via receptor editing.
35
Q

second checkpoint of B cell maturation

A

The light chain/mu chain form the complete IgM and delivers signals that promote survival

- Preserves cells that express complete antigen receptors and thus is the SECOND CHECKPOINT during B cell maturation
- Signals from receptor also shut off production of the recombinase enzyme and furhter recombination at the unrecombinedlight chain loci
- So each B cell produces either one kappa or gamma light chain from one of the inherited parental alleles
- Presence of 2 sets of light chain genes simply increases the chance of completing successful gene recombination and receptor expression
36
Q

immature B cell is the ____ expressing lymphocyte

A

IgM

37
Q

what is the final maturation step in B cell maturation?

A
  • Final maturation step involves coexpression of IgD with IgM, which occurs because in any given B cell, the recombined VDJ heavy chain gene exon may be spliced to Cmu exons or Cdelta exons, giving rise to mu or delta mRNA
    • Ability of B cells to respond to antigens develops together with the coexpression of IgM and IgD, but we don’t know why we need both

IgM+/IgD+ B cell is the mature B cell - able to respond to antigen in peripheral lymphoid tissues

38
Q

B cell negative selection

A
  • If immature B cell binds a multivalent antigen in the bone marrow w/high affinity, it may reactivate the VDJ recombinase, undergo additional light-chain V-J recombination, generate a different light chain, and thus change the specificity of the antigen receptor = receptor editing
    • Antigens most often found in bone marrow are self antigens that are abundantly expressed throughout the body
    • Negative selection may also involve deletion of self-reactive B cell
    • Therefore, negative selection eliminates potentially dangerous cells that can recognize and react against ubiquitous self antigens
39
Q

AIRE

A

autoimmune regulator - RF responsible for expression of many (but not all) ectopic self antigens in the thymic medulla

40
Q

autoimmun epolyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED)

A

human AIRE mutation (so inefficient negative selection and wind up with self-reactive T cells)

  • endocrinopathy (addison’s disease, hypoparathyroidism, hypogonadism, Type I DM, pancreas failure)
  • mucocutaneous cadidiasis
  • alopecia, keratitis
41
Q

Foxp3 is required for the developent of which cells?

A

CD4+CD25+ regulatory T cells

mutation:

  • enteropathy
  • type I DM
  • Eczema
Mus = x-linked
Hs= immune dysfunction polyendorrinopathy enteropathy x-linked syndrome (IPEX)

HDID 1 (24 decks)

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