immunology test 2 Flashcards
where does B cell development primarily occur?
bone marrow
What are the stages of a developing B cell?
- Early Pro-B, Pro-B, Pre-B, Immature B
Which B cell phase undergoes Heavy Chain gene rearrangement?
- Pro-B
What is the first checkpoint a developing Pro-B cell must pass in order to become a Pre-B cell? *
Expression of the Pre-BCR with functional heavy chain and surrogate light chain
What proteins form the surrogate light chain?
- VpreB and Lambda5
What developing B cell stage undergoes light chain gene rearrangement?
- Pre-B
What is the second checkpoint a Pre-B cell must pass in order to become an Immature B cell?
Express a BCR with functional light chains
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?
Pax5
How do Bone Marrow Stromal Cells assist in B cell development?
- SCF binds Kit on the Early Pro-B cell
- IL-7 binds IL-7R on Late Pro-B cell and the Pre-B cell
How do Bone Marrow Stomal Cells assist in B cell Tolerance Induction?
- Negative Selection
- Bind auto-reactive B cell clones which can then undergo a second attempt at light chain gene rearrangement
How do Follicular Dendritic Cells assist in B cell maturation?
- Attract the Immature B cell into the LN primary follicle
- Deliver final maturation signals
How do precursor T cells enter the thymus?
- High Endothelial Venule
What are the stages of T cell development? Where in the thymus would you expect each stage? *
CD3– (subcapsular region) | CD3++ (cortex) | CD4+/CD8+ (corticomedullary junction)
What is the first check point in T cell development?
Rearrangement of beta chain genes, expression of the pre-TCR with surrogate alpha chain by a CD3– cell
What transcription factor in developing T cells allows for gene rearrangement similar to B cells? *
Notch1 (also a signaling molecule)
What T cell stage expresses the full TCR? What checkpoint had to be met? *
CD3++, requires successful alpha chain rearrangement
What IL plays a role in both B and T cell development?
- IL-7
What happens first, Positive or Negative selection?
- Positive selection in the cortex first, then negative selection in the medulla
Negative selection protects against autoreactive T cell clones, and Positive selection determines CD4+ vs CD8+ T/F
T
During positive selection, developing CD8+ T cells bind ___ and developing CD4+ T cells bind ___
- MHC I, MHC II
What do these letters stand for? VDJC
- Variable, Diversity, Joining, Constant
- Gene regions
Which regions are involved in heavy and beta chain gene rearrangements?
VDJC
Which regions are involved in light and alpha chain gene rearrangements? *
VJC (no D)
What is the process of heavy/beta chain somatic recombination?
- D + J = DJ
- V + DJ = VDJ
- VDJ + C = VDJC
What is the process of light/alpha chain somatic recombination?
- V + J = VJ
- VJ + C = VJC
B cell activation involves which Th subtype?
- T follicular helper cells
B cell activation involves crosslinking of BCRs which are clustered together in order to better recognize Ag in which form?
- Native
What two proteins associated with the BCR facilitate signal transduction? *
Ig-alpha, Ig-beta
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?
True
B cell costimulation involves CD28 binding B7. True/False
- False, B cell costimulation involves CD40 binding with CD40L expressed on Tfh cells.
What cytokines induce Bcl6 expression (Tx factor) in a T cell promoting the differentiation into a T follicular helper cell?
- IL-6, IL-21
What cytokines to Tfh cells secrete?
- IL-6, IL-10, IL-21
Which APC is most likely to present Ag to a Naive T cell in the LN parafollicular cortex? *
DC (not Macrophages or B cells)
A DC expresses costimuatory ligands inducibly or constitutively?
- constitutively
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?
- 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
What two signals are needed for activation of naive T cells?
- Antigen signal TCR+CD4 binding MHC II, Survival and Expansion signal CD28 binding B7(CD80)
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?
True
What are three Tx factors that activate the IL-2 promoter?
- NFkB, NFAT, AP-1
Which of the IL-2R 3 chains are expressed when bound by IL-2?
- the alpha chain
Where are three points of control over T cell activation and proliferation?
- 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
Which main cell types are involved in a CMI response? What is this response effective against?
CD4+ CD8+ Th1 Macrophages NK. Intracellular pathogens, anti-tumor immunosurveillance
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?
- True
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?
- False, once activated, CTLs do not require co-stimulation to kill.
Which Ig isotype is expressed by plasma cells after B cells are receive signals from IL-4? Which HS reaction does this occur in?
- IgE. HS I
Which HS reaction is associated with T cells?
- HS IV
What form of antigen do IgG Abs seek in a HS II reaction? HS III?
- Surface bound antigen. Soluble floating antigen.
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?
- IFN-gamma, IL-12
What cytokines are produced by Th1 cells that promote a robust CMI response?
IL-2 (CD8->CTL), IFN-gamma (Macrophage, NK), TNF (Inflammation process)
What cytokines induce Th1 differentiation?
- IL-12, IFN-gamma
What induces Th2 differentiation?
- IL-4, induces GATA3 Tx factor promoting differentiation
Th2 cells are involved in type I HS reactions against helminths and haptens (allergens) by releasing what two cytokines activating what two cell types?
- IL-4 (Mast cells), IL-5 (Eosinophils)
What ILs are released by mast cells?
- IL-3, 4, 5, 13
What vasoactive mediators are released by mast cells in a HS I reaction?
- Histamine, TNF, Prostaglandins, Leukotrienes
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? *
Tx factor: AIRE | no AIRE: APCED
What transcription factor promotes differentiation into a Treg cell? What condition develops in its absence?
- FoxP3 | noFoxP3:IPEX
What cytokine promotes the expression of FoxP3 in the periphery?
- TGF-Beta
Treg cells have what protein that binds to B7 prevents further expression of IL-2 and T cell proliferation?
- CTLA-4
What inhibitory cytokine does a Treg secrete?
- IL-10
What is immunosurveillance?
- Process of identifying and removing altered-self cells.
Which phase of immunosurveillance is associated with tumor immunoediting?
- Equilibrium phase
The humoral immune response alone is sufficient for tumor cell removal. True/False *
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)
What kind of tumor antigen is derived from a unique protein mutation that’s acquired during oncogenesis?
- Tumor specific antigen
Tumor associated antigens can be derived from abnormal(fetal) or excessive protein production. True/False
True
What are three ways tumor cells evade immune responses?
- 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
How does monoclonal Ab cancer therapy work?
- TSA specific Ab be conjugated to cytotoxic drugs
- Abs enhance NK killing via ADCC, can act as opsinins and aid in phagocytosis
