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BLD + Pharm > BLD434 Section 3 > Flashcards

BLD434 Section 3 Flashcards

Immunology

1
Q

Pre-BCR

A

Receptor on the pre-BCR cell that allows for signaling to cause burst of proliferation of pre-B cell
- Consists of rearranged mu heavy chain, surrogate light chain (VpreB and lambda-5), and Ig-a and Ig-B

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2
Q

Surrogate light chain

A

(On pre-B cells) Consists of VpreB and lambda-5
- Allows small amounts of IgM to make it to the surface of pre-B cell

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3
Q

RAG-1/RAG-2

A

RAG complex; Recognizes RSS and cuts dsDNA for somatic recombination
- Transiently expressed only in pro-B cells for heavy chain recombination and pre-B cells for light chain recombination
- Gets turned off after recombination is achieved

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4
Q

CAM

A

Cell Adhesion Molecule
Proteins on the cell surface involved in cell-cell adhesion and communication. Keeps the developing B cell in contact with the stromal cell.

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5
Q

PAX-5

A

Main B cell transcription factor that locks the pre-B cell into B lymphocyte development. Once PAX-5 is turned on,

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6
Q

BTK

A

Bruton’s Tyrosine Kinase
- An enzyme essential for B cell signaling and development. If mutated, B cells will be stalled in the pre-B cell stage (XLA)

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7
Q

Polyspecific antibody

A

Abs capable of binding to multiple antigens due to their broad specificity, which can occur in certain situations such as during immune responses to diverse pathogens

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8
Q

Negative Selection

A

The process by which autoreactive (self-reactive) lymphocytes are eliminated during development to prevent autoimmunity.

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9
Q

Clonal deletion

A

The removal of autoreactive lymphocytes via apoptosis during negative selection.
Occurs if the lymphocyte’s receptor is crosslinked by self-antigen and cannot remove the self-reactivity by receptor editing.

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10
Q

Clonal anergy

A

A state of functional unresponsiveness to Ag activation in lymphocytes induced by exposure to soluble self-antigen, preventing activation of autoreactive cells.

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11
Q

Anergic

A

Self-reactive lymphocytes bind to self-Ag become inactivated and unresponsive to their specific antigens; developmental arrest.

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12
Q

Self-tolerance

A

The immune system’s ability to recognize ‘self’ and not react or attack it.

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13
Q

LT

A

Leukotoxin - Produced by B cells to provide maintenance (life) signals for FDC

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14
Q

BAFF

A

B cell-Activating Factor - Produced by FDC to provide life-saving and maturation signals to B cell

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15
Q

Primary lymphoid follicle

A

Where immature B cells congregate to interact with FDC to gain life-saving and maturation signal. Cell will die if it doesn’t get the signal in 3 days.

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16
Q

Secondary lymphoid follicle

A

A structure within lymphoid organs containing germinal centers where T cells and B cells migrate and (Ag-mediated) B cell activation, proliferation, and differentiation occur.

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17
Q

Germinal center

A

A cluster of developing B and T cells in the secondary lymphoid follicle. Here, B cells undergo proliferation, somatic hypermutation, and isotype switching in response to Ag.

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18
Q

Plasma cell

A

Terminally differentiated B cells that produce and secrete large amounts of antibodies to combat infections.

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19
Q

Centroblast

A

Large rapidly proliferating B cells in the germinal center (dark zone)

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20
Q

Centrocyte

A

Matured B cells (centroblasts) that have developed the highest affinity for Ag, located in the light zone of germinal centers
- Have undergone somatic hypermutation and isotype switching

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21
Q

Stages of B cell development

A

1) Stem cell
2) Pro-B cell
3) Pre-B cell
4) Immature B cell
5) Naive mature B cell

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22
Q

Stem cell stage

A

Stage 1
Undifferentiated precursor cell capable of self-renewal and giving rise to multiple cell lineages. Expresses CD34 protein.

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23
Q

Pro-B cell stage

A

Stage 2
Earliest B lineage cell. Heavy chain somatic recombination, then Mu heavy chain is expressed. Expression of surrogate light chain.

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24
Q

Pre-B cell stage

A

Stage 3
Transient expression of pre-BCR. Rearranged Ig heavy chain, begins V-J rearrangement of light chain, expresses surrogate light chain (VpreB, 5) and Ig, and Ig proteins

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25
Q

Immature B cell

A

Stage 4
B cell expressing IgM (mu chain) on the surface. Has mature BCR.

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26
Q

Naive mature B cell stage

A

Stage 5 (final)
Fully mature B cell presenting IgM and IgD on the surface; ready to encounter Ag

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27
Q

Why do pre-B cells undergo a burst of proliferation after signaling through the pre-BCR?

A

Amplification of the population of pre-BCR with successful heavy chain rearrangements.
- Beneficial because they can skip mu heavy chain rearrangement and increases the chance of getting a viable B cell after light chain rearrangement

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28
Q

When are RAG-1 and RAG-2 expressed during B cell development?

A

During the early stages - during somatic recombination of Ig genes in pro-B (for heavy chains) and pre-B cells (for light chains)

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29
Q

What percent of developing B lymphocytes make it through heavy and light chain rearrangement of somatic recombination?

A

Heavy = 66%
Light = 85%

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30
Q

Why does Ig light chain rearrangement have a higher success rate than heavy chain?

A
  1. Smaller gene segment pool (only V and J), less cuts required for recombination
  2. Light chain has 4 chances for successful rearrangement, while the heavy chain only has 2
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31
Q

What CD markers are used to identify B-1 lymphocytes?

A

CD5 (B-1 only) and CD19/CD20 (all B cells)

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32
Q

B-1 cells

A
  • produced in fetus
  • self-renewal capabilities
  • HIGH spontaneous Ig production
  • IgM&raquo_space; IgG
  • Low/No somatic hypermutation
  • respond to carbohydrate Ag
  • doesn’t require help from T cells
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33
Q

B-2 cells

A
  • Produced continuously after birth
  • No self-renewal – replaced from bone marrow
  • LOW spontaneous Ig production
  • IgG > IgM
  • High somatic hypermutation
  • require activation for Ab secretion
  • Respond to carbohydrate and protein Ag
  • Requires help from T cells
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34
Q

Receptor editing

A

B cells that express self-reactivity can undergo successive light chain gene rearrangements to edit their light chains to avoid negative selection.

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35
Q

B lymphocyte half-life after it exits the bone marrow and enters circulation

A

100 days

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36
Q

Path of B lymphocyte from entry to exit of a lymph node (assuming it’s not stimulated by Ag in the LN)

A

B cell enters via afferent lymph vessel, then through the HEV valve into the T cell area (primary follicle), then primary follicle in B cell area, then leaves via efferent lymph vessel

37
Q

Follicular Dendritic Cells (FDC)

A

Located in the primary lymph follicle where they secrete BAFF to induce a survival/maturation signal to naive B lymphocyte.

38
Q

What interaction triggers isotype switching and somatic hypermutation?

A

T cell interaction where Helper T cells present Ag to a B cell to stimulate it to mature

39
Q

Plasma cell (function & 4 locations)

A

To produce and secrete large amounts of Ab
May reside in red pulp of spleen, bone marrow, lymph node medulla, GALT

40
Q

3 main options for what a B lymphocyte can do functionally after Ag activation

A
  1. Antigen-activated B lymphoblast (alternative splicing to secrete Ig. Isotype switching and somatic hypermutation)
  2. Plasma cell secreting IgM or IgG (fighting the current infection)
  3. Memory cell (preparing for future infection)
41
Q

Stages of thymocytes

A

Double-negative thymocyte (Pro-T cell)
- missing CD4 and CD8
Double-positive thymocyte (Pre-T cell)
- express both CD4 and CD8
Single-positive T cell (Mature T cell)
- express CD4 or CD8

42
Q

pTa

A

surrogate TCR alpha chain (part of the Pre-TCR)

42
Q

What triggers commitment of uncommitted lymphoid progenitor to the T lymphocyte lineage and where does this interaction occur?

A

Notch 1 receptor on LP binding to delta-1 ligand in the cortex of the thymus.

42
Q

Medulla of the thymus

A

inner part of the thymus lobule (lighter areas) – medullary epithelial cells, macrophages, dendritic cells, (and mature thymocytes).

42
Q

thymic involution

A

Thymic involution is the gradual decline in thymus (TECs) and function that occurs as early as age 1.

43
Q

Cortex of the thymus

A

the outer part of the thymus lobule (darker area) – cortical epithelial cells, thymocytes (developing T cells), macrophages.

44
Q

List the proteins that compose the pre-TCR

A

TCR-beta, pTa, CD3 complex, zeta chain, and CD and CD8

45
Q

Describe somatic recombination of the TCR gene loci during thymocyte development

A
  1. B, G, D TCR simultaneously rearrange, then it’s a race:
  2. If TCR G, D recomb. first, then it commits to GD T cell lineage.
  3. If TCR B recomb. first, then burst of prolif. so the daughter cells do a second round of somatic recomb. of the a, G, D genes.
    3a. Step 2 can happen
    3b. If TCRa undergoes somatic
    recomb., then T cell commits to aB T cell lineage and expresses aBTCR, CD4 and CD8
46
Q

Normal proportional of aB to GD T cells produced after birth

A

90% are alpha-beta T cells

47
Q

What cells undergo positive vs. negative selection?

A

Positive selection = aB T cells
Negative selection = B cells and aB T cells
***GD T cells DON’T undergo any selection

48
Q

Positive selection in aB T cells

A

(in thymus) Testing whether the TCR can bind to our own MHC and interact with MHC
- Determines if it will be CD4+ or CD8+
- Carried out by cortical epithelial cells

49
Q

Negative selection: B cells vs aB T cells

A

B – To make sure they aren’t self-reactive

aB T – To remove the self-reactive cells (Will kill any thymocyte that bind with moderate to high affinity to our own MHC I or II expressed on Thymic DC, which is what carries this selection out)

50
Q

Function of dendritic cells in the thymus

A
  • express naive and memory cells
  • present Ag to T cells
  • promote T-cell tolerance
51
Q

Macrophages

A
  • eat T cells that don’t pass the positive selection
    in the cortex
  • can only activate memory cells
  • present Ag to T cells at a lower level
52
Q

AIRE

A

Autoimmune Regulatory Protein
- Expressed primarily in medullary thymic epithelial cells
- Turns on low level of expression of every gene in the thymus so they can be presented in self MHC for negative selection

53
Q

Strength of TCR binding in selection

A

In positive selection - want affinity to be low
In negative selection - if there is high affinity for self-Ag (MHC), the cell will undergo apoptosis.

54
Q

Central Tolerance

A

Deletion of self-reactive T lymphocytes in the thymus by negative selection; induced by apoptosis.

55
Q

Peripheral Tolerance

A

Control of T lymphocyte activation in the periphery; induced by anergy or by control of Treg cells

56
Q

Treg

A

Regulatory T cells, of the CD4 subset.
Suppress the T activation of CD4+ cells in the periphery by self-Ag to make sure there’s no self-tissue attacking.
Allow for peripheral tolerance.

57
Q

Two-signal hypothesis

A
  1. TCR binding to MHC+peptide
  2. B7 binds to CD28 on naive CD4+ or CD8+
58
Q

CTLA-4

A

Cytotoxic T-Lymphocyte Associated-protein 4
Receptor on Treg that binds to B7 with 20-fold strength of CD28 (blocks CD28 from binding).
This inhibits the activation and proliferation of T cells, leads to apoptosis of effector cell

59
Q

2 ways foreign Ag can reach the secondary lymphoid tissues to activate an adaptive immune response

A
  1. Being carried by DC
  2. Through lymph fluid
60
Q

Selectins and Integrins

A

selectins provide low affinity adhesion (cell rolling on HEV)
integrins provide high-affinity adhesion between cells (firm attachment to HEV and diapedesis)

61
Q

3 functions of leukocyte adhesion molecules prior to naive T cell activation by APC

A
  1. Naive T cell rolls through secondary lymphoid tissue venules
  2. Tight binding and extravasation by diapedesis
  3. T cell and APC interaction in secondary lymphoid tissues (adhesion) in the LN
62
Q

Importance of IL-2 in T cell responses and how do immunosuppressive drugs (Cyclosporin A and Rapamycin) short-circuit this signal?

A

IL-2 is an autocrine growth factor secreted by Th1 cells.

63
Q

What 3 factors can influence the choice of a naive CD4 T cell to a functional subset choice and which is dominant?

A
  1. (Dominant) Tissue origin of activating DC (mucosal tissue, skin tissue, etc.)
  2. Cytokines induced by innate response to infection
  3. Types of infectious agents that will activate pattern recognition receptors
64
Q

Th1

A

T-bet (transcription factor) activates secretion of IL-2, IFN-Y, and LT

65
Q

Th2

A

GATA3 (transcription factor) activates the secretion of IL-4 and IL-5

66
Q

Th17

A

RORYT (transcription factor) activates the secretion of IL-17 and IL-22

67
Q

TFH

A

Bcel-6 (transcription factor) activates the secretion of IL-21

68
Q

Treg

A

FoxP3 (transcription factor) activates the secretion of TGF-B and IL-10

69
Q

What cytokine is needed in high concentration to activate a naive CD8+ T cell to a Tc? What aid the APC in this activation process?

A

IL-2 and MHC

70
Q

After activation in the secondary lymphoid tissue, where do TFH, Th1, Th2, and Tc reside?

A

TFH - germinal center
Th1, Th2, Tc - body tissues (infection site)

71
Q

Adhesion (homing) receptors on effector T vs naive T lymphocytes

A

Effector T cells
- Lose L-selectin expression
- Gain VLA-4 to home to inflamed BV endothelium

72
Q

CD40 ligand function (related to effector T cell function)

A

CD40L on a TFH binds to CD40 on the B cell responding to Ag, activating the B cell

73
Q

IL-2

A

Cytokine secreted by Tc and Th1
- Keeps T cells active

74
Q

IL-4

A

Cytokine secreted by Th2 and TFH
- Isotype switch factor for IgE production
- Autocrine growth factor for Th2 to keep them active

75
Q

IL-5

A

Cytokine secreted by Th2
- Eosinophil growth factor

76
Q

IL-10 & TGF-B

A

Cytokine secreted by Th2 and Treg
- Suppress activation of Th1, Th2, Th17
- Prevent autoimmune diseases and allergies to harmless environmental Ag

77
Q

IL-21

A

Cytokine secreted by Th17 and TFH
- Autocrine support of effector function
- Recruit TFH cells to germinal center

78
Q

IFN-Y

A

Cytokine secreted by Tc, Th1, TFH
- Activate macrophages & carry out cell-mediated immunity

79
Q

GM-CSF

A

Cytokine secreted by GM-CSF
- Stimulate WBC production (neutrophils, eosinophils, basophils)
- Increases myelopoiesis

80
Q

TNF-a

A

Inflammatory cytokine secreted by Th1
- Macrophage activation, viral infections, cellular cytotoxicity

81
Q

LT

A

Cytokine secreted by Tc and Th1
- Activate macrophages & carry out cell-mediated immunity

82
Q

Linked recognition

A

T-dependent antibody responses require the activation of B cells by helper T cells that respond to the same antigen.
Goal = make sure the T cell help provided during an immune response to a pathogen is directed at antigen-specific B cells responding to that same pathogen
- Cells involved: TFH, MHC II, Naive B cell, CD40L, and CD40
- If process fails, the B cell will not undergo isotype switching or somatic hypermutation

83
Q

B cell co-receptor complex

A

CD19 (transduce signal from CD21)
CD21 (bind to opsonized C3d, activates complex)
CD81 (adapter protein that holds the B cell co-receptor complex to the BCR)

84
Q

T-dependent B lymphocyte Ab response

A
  • majority of Ab from B cells are T-dependent
  • produces IgG (high affinity Ab)
  • Ag-specific memory response
85
Q

T-independent B lymphocyte Ab response

A

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