Exam 2

Question 1

What are the three signals needed for T-cell activation?

Answer 1

1) Recognition - TCR binds MHC and either CD4 or CD8 is co-engaged
2) Co-stimulaiton - The APC must express B7 which will bind to CD28 on the T-cell and will send transcription factor activating cascade to the nucleus activating IL-2 and IL-2 receptor production. These self made growth factors initiate proliferation.
3) Differentiation - Signal comes in form of cytokine. For CD4+ signal comes from DC for CD8+ comes from a Th1 cell.

Question 2

What are the broad stages of T-cell development

Answer 2

1) ETP –> Early T lineage precursor
2) Thymocyte –> developing t-cell
3) T-cell

Question 3

How are APCs activated?

Answer 3

Toll like receptors, tissue damage, and via cytokine signaling

Question 4

Where does positive selection occur and what is it?

Answer 4

Positive selection occurs in the cortex of the thymus (the outer region) and it is a process by which T-cells recognize self through MHC molecules and drop either CD8 or CD4 to become single positive rather than double positive.

Question 5

Where does negative selection occur and what is it?

Answer 5

Neg selection occurs in the medulla the inner lighter portion of the thymus and it is where T-cells which recognize self too strongly are killed in the gauntlet of death leading to a 2% survival rating.

Question 6

What occurs in the first three stages: ETP, —> pre-TCR

Answer 6

1) First the cortical epithelial cells produce a chemical called Notch-1
2) Notch-1 binds a notch-1 receptor on the ETP which activated and up-regulates CD3 manufacture and adds them to the cell surface.
3) The expression of CD3 initiates gene rearrangement
4) Then the beta chain gene rearrangement occurs which subsequently associates with the pTalpha (pre-T cell receptor alpha)

Question 7

What are the five stages of T-cell development?

Answer 7

1) ETP – early T-lineage precursor
2) Double negative with cd3
3) Double negative with CD3 and Pre-TCR
4) Double positive with CD3, mature TCR, CD4 and CD8
- Undergoes positive selection
5) Single positive. Undergoes positive selection.

Question 8

What does notch-1 do?

Answer 8

Notch one is a signalling molecule used in tissue differentiation and is the signal for the T-cell program and signals to progenitor cells to begin t-cell differentiation

Question 9

What are the four events that the pre-TCR signals?

Answer 9

1) beta chain allelic exclusion
2) proliferation
3) expression of both CD8 and CD4
4) alpha chain gene rearrangement

Question 10

What follows alpha chain gene rearrangement and double positiveness

Answer 10

The t-cells first undergo positive selection where they use their mhc molecules to interact and recognize self, when this is done they pull down and stop expressing either CD4 or CD8

Then they undergo negative selection where the cells which recognize self too strongly are killed.

Question 11

Where does positive selection occur?

Answer 11

The cortex and negative selection occurs in the medulla

Question 12

What are the five stages of B-cell development?

Answer 12

1) common lymphoid progenitor
2) pro-B-cell
3) pre-B-cell
4) Immature B-cell
5) Mature B-cell

Question 13

What is the function of CXCL-12?

Answer 13

This is constitutively produced by bone marrow stromal cells and it retains the b-cells in the bone marrow

Question 14

What is the function of cKit and its interaction with SCF (stem cell factor)

Answer 14

This interaction stimulates the expression of IL-7R the receptor for IL-7
Once IL-7R binds IL-7 another cascade leads to the expression of IG-alpha and IG-beta which are the first defining B-cell membrane receptors

Question 15

What are the steps between CLP (common lymphoid progenitor) the the Pre-B cell? And what is the pre B-Cell?

Answer 15

1) CXCL-12 is produced constiutivley by the stromal bone marrow cells which binds CXCR-4
2) Then the CLP attaches to the stromal cells via VLA (very late antigen) and VCAM-1 (vascular cellular adhesion molecule)
3) then C-kit binds SCF (stem cell factor) this transduces a signal prompting the production of IL-7R which then binds IL-7
4) The binding of IL-7 leads to a second signal where two things happen
-rag1 and rag 2 begin heavy chain gene rearrangement and the first true B-cell receptors go up IG-alpha and IG beta. In the pro-b-cell stage the heavy chain is only in mRNA form but the IG-a and b go up on the surface.
———————————————–
Pre-B-celll stage
1) is marked by the presence of the heavy chain the IG-alpha and IG-beta and the surrogate light chains

Question 16

What three events does the pre-BCR signal (pre-BCR is the IG alpha and beta and the heavy chain with surrogate light chain)?

Answer 16

1) the signal is initiated by binding with an unknown ligand.
2) This signal which is transduced by IGa and IGb signals the halting of heavy chain gene rearrangement via allelic exclusion
2) The pre-B-cell begins to proliferate
3) The progeny begin light chain gene rearrangement
4) the progeny are following light chain gene rearrangement considered immature B-cells

Question 17

What are the four fates of immature B-cells

Answer 17

1) Anergy — remember that mature B-cells have both IgD and IgM when the cells when they are initially testing self reactivity do so with with only IgM. When IgM binds self molecules weakly and therefore transduces a weaker signal the cell pulls down the IgM and only expresses IgD. These cells usually die of neglect.
2) Apoptosis- the cells react to strongly with self and then undergo programmed cell death.
3) Ignorance – reacts very weakly to self with no crosslinking and is allowed to live. But if these same antigens stick to one another and crosslink its possible for an immune response against self to be initiated
4) No rxn to self and they then then migrate to the periphery

Question 18

What is the difference between an immature and mature DC

Answer 18

Immature DC: express low levels of antigen presentation molecules, they instead express high levels of PRR (pattern recognition receptors) and they are highly phagocytic

Mature DC- changes into a cell that is now excellent at presenting antigen to naive T-cells

Question 19

What are the steps to DC movement to the lymph node.

Answer 19

1) An antigen binds a PRR such as a TLR
2) this send a signal to put up CCR-7
- -this binds CCL-21 which is a chemokine that allows the DC to chemotax
3) this causes the expression of B7 and the MHC it then migrates to the lymph node and then activate the T-cells

Question 20

What are the steps to T-cell activation

Answer 20

1) signal recognition
- TCR bings specific peptide in TCR:antigen:MHC complex
- CD4 or CD8 also engaged
2) Co-stimulation
- B7 from APC binds CD28 on t-cell
- this transduces a signal for IL-2 and IL-2R. The binding of IL-2 causes proliferation via activation of the cell cycle. This is called autocrine self feeding
3) the Tcell then differentiates into an effector subtype

Question 21

What are the CD4 T-cell subtypes

Answer 21

Th1, Th2, Th17, and Treg t cells

Question 22

What are the subtypes of CD8 T-cells?

Answer 22

CTL

Question 23

Functions of IgM

Answer 23

Has the lowest affinity for epitope is balanced by pentameric form.
Found mainly in blood, and is the number one activator of compliment.

Question 24

Functions of IgG

Answer 24

Main Ab in blood over time. It is the main ab found in tissue due to its small size. Has strong neutralization and opsonization and strong compliment activation. Thus it is termed the jack of all trades.

Question 25

Functions of IgE

Answer 25

Activates degranulation via attachment to Fc receptors. Poor opsonization, compliment activation, and neutralization. Primary role in parasitic infections hence degranulation acitvation.
Sensitization –> role in allergies

Question 26

Function of IgA

Answer 26

Found in mucosa. Very strong neutralization weak on everything else.
Transported via transcytosis from lamina propria through cells. Secretory component attaches and is responsible for anchoring to mucus otherwise it would just float away.