Term
| the two types of t cells and what they synthesize... |
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Definition
1) CD4+ leads to Th1 and produces IFN-gamma
2) CD8+ leads to Th2 and produces IL-4 which induces expression of IgE (with cytokines)
These two cell types have capacity to regulate each other
Th-1 regulates Th-2 and vice versa |
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Term
| What are the properties of IFN-gamma? |
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Definition
1) Increases microbicidal activity (for things such as macrophages)
2) Induces expression of opsonizing antibodies
3) Increase MHC expression
These all work in concert with each other in order to more effectively destroy the pathogens |
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Term
| IL-4 (a Th-2 cytokine) induces what? |
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Definition
It increases IgE expression
This increases parasite removal but a negative consequence would be that it is also associated with allergies |
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Term
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Definition
- Made by t cells
- Induces eosinophil production/activity
- (also aids in parasite removal)
o Release granules
- IgE is going to sensitize mast cells, basophils, and eosinophils. Eosinophils through IgE can bind to parasites and by the release of granules can be lytic toward the parasite. |
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Term
| What lineage does IL 12 direct cells to? |
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Definition
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Term
| If IL-12 is not produced bc that pathway of gene expression isn’t activated in the APC bc of the nature of the microbe ingested, then what will happen? |
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Definition
-then the cytokine that’s going to direct the cell to a polarized Th-2 phenotype is going to be IL-4
-the cell makes its own IL-4 and directs itself to the Th-2 pathway |
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Term
| How are CD8s and CD4s generated? |
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Definition
-From bone marrow there are t cell precursors
-mature in thymus
-When they enter thymus through cortical region, they are double negatives (CD4- and CD8-) (also neg for CD3)
-change gene expression in cortical region (go from double negative to double positive; now CD4+ and CD8+)
-begin t cell receptor gene rearrangement |
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Term
| what type of cell will undergo gene rearrangement? |
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Definition
| Double positive cells will begin gene rearrangement |
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Term
| What are the two types of t cells (based on their structural makeup)? |
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Definition
1) Gamma-delta t cells
2) Alpha-beta t cells |
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Term
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Definition
-majority of t cells in body
-made up of an alpha chain and a beta chain
-alpha domain has a variable domain (variable alpha) and the beta chain has a variable domain (variable beta)
-alpha chain has a constant domain and the beta chain has a constant domain
-In terms of the relationship of this molecule to immunoglobin, it looks like an Fab |
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Term
| how does rearrangement work with an alpha-beta t cell? |
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Definition
-beta genes have V, D, and J segments just like immunoglobulin heavy chain.
-alpha chain is just like light chain with V and J gene segments.
-Beta is expressed first and binds itself with surrogate called surrogate alpha chain to make pre-t cell receptor that does the same thing that the pre-b cell receptor does with surrogate light chain (signals cell to stop undergoing rearrangement of beta chain and to now rearrange the alpha chain.)
-VDJ recombinase mediates these steps and TDT plays major role in diversification in the steps
-Junctional diversity occurs and is mediated by TDT. |
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Term
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Definition
| cells that are on their way to becoming t cells and fight through the thymus |
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Term
| what type of receptor do thymocytes first produce? |
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Definition
| -If they make some TcR (TcR low means that CD3 is low) (low bc they are just starting to make small amounts of the receptor for rearrangement) |
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Term
| explain how a t cell goes from being double negative to a mature t cell? |
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Definition
-They go from being double negative (no capacity to interact with MHC) to double positive in which now they have the capacity of intermediate stage of development to interact with MHC class 1 or MHC class 2 (which they will do in the thymus) the thymus expresses both MHC class 1 (CD8) and MHC class 2 (CD4) on parenchymal tissues and on APC’s and it is a choice which t cells make
then they have the decision to become a single positive t cell |
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Term
| explain the 2 types of single positive t cells |
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Definition
1)If the double positive interacts with MHC class 2 in the thymus then the cell upregulates CD4 and downregulates CD8. At the same time, the t cell receptor has engaged MHC and now we don’t say that they are low for TcR, we just say they are TcR positive and if they are TcR positive then they are Cd3 positive.
2)Alternatively, that same cell can interact not with class 2 but with class 1 bc it has CD8. CD8 allows it to bind to a nonpolymorphic portion of class 1 molecule. TcR is positive, CD3 is positive. |
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Term
| What are the 2 stages of selection? |
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Definition
1) positive selection
2) negative selection |
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Term
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Definition
-Stage where t cells engage MHC, going to be positively selected for their capacity to engage MHC. (called MHC binding)
-important because t cell must get antigenic signal from the MHC. If it goes through many rearrangement processes and cant recognize MHC , then it wont be useful in the immune system.
-We need to educate our own developing t cells to our own MHC molecules; this occurs in thymus. (Double positives are interacting with MHC class 1 or class 2 and what you are left with is single positive where they interact with MHC). |
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Term
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Definition
while t cell receptor can engage MHC, it doesn’t do so too strongly.
-These cells leave the thymus and become autoreactive. you select for t cells with MHC binding through positive selection but reduced or low avidity binding to MHC (basic pathway for how t cell receptors can be made but not too strongly)
-this maintains cell regulation |
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Term
| Involution of thymus. If thymus is site where t cells are maturing, what happens later in life when your thymus has involuted and your adult thymus becomes rudimentary (it doesn’t disappear completely but it becomes tiny) what is going on? |
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Definition
This is a concern in immunoscenescence. Once the thymus involutes, you are no longer creating more t cells, and immune system starts to look a little different.
-However, As you get older, polyclonality is restricted to oligoclonality and you have many memory cells to protect you from infections that you have already seen ; as you get older, you get a skewing effect toward only particular viruses. |
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Term
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Definition
the idea that as you get older, polyclonality is restricted to oligoclonality and you have many memory cells to protect you from infections that you have already seen
-as you get older, you get a skewing effect toward only particular viruses. Partly due to thymus involution |
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Term
| Do T cells undergo somatic hypermutation? |
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Definition
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Term
| Do B cells undergo somatic hypermutation |
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Definition
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Term
| describe the differences between b cells and t cells in terms of seeing/binding to antigen |
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Definition
For B cell:
- B cells can bind directly to native antigen (can actually bind to bacteria through that specific epitope)
For T cell:
-See antigen in fundamentally different way; must see processed antigen in context of MHC; you don’t want to have random mutations introduced to t cell receptor because they you could potentially lose binding to MHC after going through positive selection. Alterniatively you could increase avidity of cell receptor to itself and then you undergo negative selection. |
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Term
| What type of selection do B cells undergo in the bone marrow? |
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Definition
| usually negative selection so they dont act too strongly with self |
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Term
| why are b cells allowed to undergo somatic hypermutation? |
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Definition
| bc theres no constraints on MHC binding for b cell, but ultimately b cells undergo phenomenon selection where in marrow if they react too strongly with native self-antigens, they will undergo negative selection |
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Term
| Is VDJ recombinase constitutively on during life of b cell? |
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Definition
| No. It is only on during the process of rearrangement |
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Term
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Definition
-B cells undergo VDJ for heavy chain and VJ for light chain. VDJ recombinase is only on during the process of rearrangement.
-Once b cells are generated and then have membrane immunoglobin they interact w/ environment in bone marrow and can go through negative selection if bound to something native on our tissues.
-HOWEVER, B cells may have to rearrange another light chain; they attempt to upregulate VDJ recombinase after its been shut down b/c VDJ and VJ got rearranged, so its shut down and has a membrane immunoglobin, but if it interacts with something in the marrow it can undergo a subsequent stage of light chain rearrangement. to try to avoid apoptosis |
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Term
| What are some examples of receptor editing for a b cell? |
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Definition
-If it starts to rearrange kappa on one chromosome and is happy with that it will be fixed
-if it undergoes negative selection and it doesn’t like the fact that its reacting with self it can rearrange the other kappa.
-If it rearranges that one and still has a problem with what its producing it can try to rearrange lambda. And if it doesn’t like that it has another option to rearrange the other chromosomal lambda
-If it is satisfied with a subsequent rearrangement it leaves the marrow as a functional b cell. |
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Term
| what happens if a cell is still not happy with its receptor editing process? |
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Definition
| If it goes through multiple attempts to rearrange a light chain and still doesn’t survive negative selection or maybe makes a sterile transcript the cell will undergo apoptosis in bone marrow |
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