immunology test 2 Flashcards

1
Q

where does B cell development primarily occur?

A

bone marrow

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2
Q

What are the stages of a developing B cell?

A
  • Early Pro-B, Pro-B, Pre-B, Immature B
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3
Q

Which B cell phase undergoes Heavy Chain gene rearrangement?

A
  • Pro-B
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4
Q

What is the first checkpoint a developing Pro-B cell must pass in order to become a Pre-B cell? *

A

Expression of the Pre-BCR with functional heavy chain and surrogate light chain

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5
Q

What proteins form the surrogate light chain?

A
  • VpreB and Lambda5
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6
Q

What developing B cell stage undergoes light chain gene rearrangement?

A
  • Pre-B
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7
Q

What is the second checkpoint a Pre-B cell must pass in order to become an Immature B cell?

A

Express a BCR with functional light chains

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8
Q

What transcription factor in developing B cells allows the chromatin to open so that the Rag complex can land on the RSS promotor region and recombine genes?

A

Pax5

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9
Q

How do Bone Marrow Stromal Cells assist in B cell development?

A
  • SCF binds Kit on the Early Pro-B cell
  • IL-7 binds IL-7R on Late Pro-B cell and the Pre-B cell
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10
Q

How do Bone Marrow Stomal Cells assist in B cell Tolerance Induction?

A
  • Negative Selection
  • Bind auto-reactive B cell clones which can then undergo a second attempt at light chain gene rearrangement
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11
Q

How do Follicular Dendritic Cells assist in B cell maturation?

A
  • Attract the Immature B cell into the LN primary follicle
  • Deliver final maturation signals
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12
Q

How do precursor T cells enter the thymus?

A
  • High Endothelial Venule
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13
Q

What are the stages of T cell development? Where in the thymus would you expect each stage? *

A

CD3– (subcapsular region) | CD3++ (cortex) | CD4+/CD8+ (corticomedullary junction)

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14
Q

What is the first check point in T cell development?

A

Rearrangement of beta chain genes, expression of the pre-TCR with surrogate alpha chain by a CD3– cell

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15
Q

What transcription factor in developing T cells allows for gene rearrangement similar to B cells? *

A

Notch1 (also a signaling molecule)

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16
Q

What T cell stage expresses the full TCR? What checkpoint had to be met? *

A

CD3++, requires successful alpha chain rearrangement

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17
Q

What IL plays a role in both B and T cell development?

A
  • IL-7
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18
Q

What happens first, Positive or Negative selection?

A
  • Positive selection in the cortex first, then negative selection in the medulla
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19
Q

Negative selection protects against autoreactive T cell clones, and Positive selection determines CD4+ vs CD8+ T/F

A

T

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20
Q

During positive selection, developing CD8+ T cells bind ___ and developing CD4+ T cells bind ___

A
  • MHC I, MHC II
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21
Q

What do these letters stand for? VDJC

A
  • Variable, Diversity, Joining, Constant
  • Gene regions
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22
Q

Which regions are involved in heavy and beta chain gene rearrangements?

A

VDJC

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23
Q

Which regions are involved in light and alpha chain gene rearrangements? *

A

VJC (no D)

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24
Q

What is the process of heavy/beta chain somatic recombination?

A
  • D + J = DJ
  • V + DJ = VDJ
  • VDJ + C = VDJC
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25
Q

What is the process of light/alpha chain somatic recombination?

A
  • V + J = VJ
  • VJ + C = VJC
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26
Q

B cell activation involves which Th subtype?

A
  • T follicular helper cells
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27
Q

B cell activation involves crosslinking of BCRs which are clustered together in order to better recognize Ag in which form?

A
  • Native
28
Q

What two proteins associated with the BCR facilitate signal transduction? *

A

Ig-alpha, Ig-beta

29
Q

When cross-linked, receptor tyrosine kinases Blk, Fyn, and Lyn phosphorylate ITAMS on Ig-alpha/ beta allowing for Syk to bind promote B cell activation. True/False?

A

True

30
Q

B cell costimulation involves CD28 binding B7. True/False

A
  • False, B cell costimulation involves CD40 binding with CD40L expressed on Tfh cells.
31
Q

What cytokines induce Bcl6 expression (Tx factor) in a T cell promoting the differentiation into a T follicular helper cell?

A
  • IL-6, IL-21
32
Q

What cytokines to Tfh cells secrete?

A
  • IL-6, IL-10, IL-21
33
Q

Which APC is most likely to present Ag to a Naive T cell in the LN parafollicular cortex? *

A

DC (not Macrophages or B cells)

34
Q

A DC expresses costimuatory ligands inducibly or constitutively?

A
  • constitutively
35
Q

When interacting with DCs in the LN parafollicular cortex, which adhesion molecules undergo a conformational change from low -> high affinity when bound, prolonging cell-cell contact and immune synapse formation?

A
  • LFA-1 on the naive T cell binds to ICAM-1 on the APC
    What is the main function of p-SMAC? What is the function of c-SMAC?
  • p-SMAC:adhesion | c-SMAC:antigen binding
36
Q

What two signals are needed for activation of naive T cells?

A
  • Antigen signal TCR+CD4 binding MHC II, Survival and Expansion signal CD28 binding B7(CD80)
37
Q

CD4+ and CD8+ T cells express CD4/CD8 TCR co-receptors, and when bound to MHC enhance ITAM phosphorylation via Lck allowing ZAP70 to bind- True/False?

A

True

38
Q

What are three Tx factors that activate the IL-2 promoter?

A
  • NFkB, NFAT, AP-1
39
Q

Which of the IL-2R 3 chains are expressed when bound by IL-2?

A
  • the alpha chain
40
Q

Where are three points of control over T cell activation and proliferation?

A
  • APC needs to bind T cell, APC needs to express B7, IL2-R alpha chain must be expressed * APCs involve activation, then IL-2 promotes proliferation
41
Q

Which main cell types are involved in a CMI response? What is this response effective against?

A

CD4+ CD8+ Th1 Macrophages NK. Intracellular pathogens, anti-tumor immunosurveillance

42
Q

CD8+ cells must become sensitized by interacting with MHC I with costimulation of CD28 binding B7 and IL-2 release from CD4+ cells. T/F?

A
  • True
43
Q

Once sensitized, CTLs are Ag specific for Ag presented on MHC I and can participate in direct cell killing but still require costimulation. T/F?

A
  • False, once activated, CTLs do not require co-stimulation to kill.
44
Q

Which Ig isotype is expressed by plasma cells after B cells are receive signals from IL-4? Which HS reaction does this occur in?

A
  • IgE. HS I
45
Q

Which HS reaction is associated with T cells?

A
  • HS IV
46
Q

What form of antigen do IgG Abs seek in a HS II reaction? HS III?

A
  • Surface bound antigen. Soluble floating antigen.
47
Q

A HS IV reaction involves activation of Th1 cells via antigen (hapten) presentation and the presence of which two cytokines which enhance inflammation and signal the expression of the transcription factor T-bet?

A
  • IFN-gamma, IL-12
48
Q

What cytokines are produced by Th1 cells that promote a robust CMI response?

A

IL-2 (CD8->CTL), IFN-gamma (Macrophage, NK), TNF (Inflammation process)

49
Q

What cytokines induce Th1 differentiation?

A
  • IL-12, IFN-gamma
50
Q

What induces Th2 differentiation?

A
  • IL-4, induces GATA3 Tx factor promoting differentiation
51
Q

Th2 cells are involved in type I HS reactions against helminths and haptens (allergens) by releasing what two cytokines activating what two cell types?

A
  • IL-4 (Mast cells), IL-5 (Eosinophils)
52
Q

What ILs are released by mast cells?

A
  • IL-3, 4, 5, 13
53
Q

What vasoactive mediators are released by mast cells in a HS I reaction?

A
  • Histamine, TNF, Prostaglandins, Leukotrienes
54
Q

The expression of what transcription factor allows thymic epithelium to educate developing T cells in the thymus? When this transcription factor is not present, what condition develops? *

A

Tx factor: AIRE | no AIRE: APCED

55
Q

What transcription factor promotes differentiation into a Treg cell? What condition develops in its absence?

A
  • FoxP3 | noFoxP3:IPEX
56
Q

What cytokine promotes the expression of FoxP3 in the periphery?

A
  • TGF-Beta
57
Q

Treg cells have what protein that binds to B7 prevents further expression of IL-2 and T cell proliferation?

A
  • CTLA-4
58
Q

What inhibitory cytokine does a Treg secrete?

A
  • IL-10
59
Q

What is immunosurveillance?

A
  • Process of identifying and removing altered-self cells.
60
Q

Which phase of immunosurveillance is associated with tumor immunoediting?

A
  • Equilibrium phase
61
Q

The humoral immune response alone is sufficient for tumor cell removal. True/False *

A

False, TH1 derived CMI is necessary for effective tumor cell removal. CTL (IL-12) and Macrophage (IFN-y) activation, cytotoxic TNF secretion, NK activation (IL-12)

62
Q

What kind of tumor antigen is derived from a unique protein mutation that’s acquired during oncogenesis?

A
  • Tumor specific antigen
63
Q

Tumor associated antigens can be derived from abnormal(fetal) or excessive protein production. True/False

A

True

64
Q

What are three ways tumor cells evade immune responses?

A
  • Downregulation of surface molecules, reducing immunogenicity (MHC, B7, Antigenic modulation) * Induction of peripheral tolerance (Anergy induction, TGF-Beta & IL-10, Treg recruitment) * Creation of physical barrier
65
Q

How does monoclonal Ab cancer therapy work?

A
  • TSA specific Ab be conjugated to cytotoxic drugs
  • Abs enhance NK killing via ADCC, can act as opsinins and aid in phagocytosis