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T cells and T cell receptors
November 7 Lecture
45
Immunology
Graduate
11/07/2011

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Term
how are CR2 and Fc gamma the same? how are they different?
Definition
same: they are both found on b cells

different: have different functions
Term
what cleaves C3b?
Definition
factor I
Term
When C3b gets cleaved by factor I what are the generated breakdown products?
Definition
-c3d
-c3dg
-I (inactivated c3dg)).

These can utilize the breakdown product for their own regulation
Term
Cr2 receptor
Definition
-it is a receptor on b cells that binds to the active c3b products.
-Antigen is bound to membrane immunoglobin c3b or some breakdown product of it is bound to the antigen. This particular receptor can recognize the c3d and the membrane immunoglobin can bind to the antigen .
Term
In a b cell when the Cr2 and the membrane immunoglobin receptors are occupied, what does that mean?
Definition
this is a positive signal for b cell activation.
Term
list/explain the 3 different Cr receptors
Definition
• Cr1 on macrophages and neutrophils for phagocytosis.
• Cr1 on erythrocytes for circulating immune complexes
• Cr2, a membrane receptor on b cells that is involved in their positive activation.
Term
What Fc receptor is involved in phagocytosis?
Definition
Fc gamma R1

found on macrophages and neutrophils

pathogen has IgG bound on the surface of the bacteria; the phagocytic cell has Fc gamma1 receptors and these allow it to have phagocytosis of the bacteria
Term
Fc epsilon receptors
Definition
this receptor is on mast cells and basophils; it binds to newly synthesized IgE and desensitize those cells that cross link membrane IgEs on the mast cell’s surface
-- When the IgE binds to this receptor and the antigen gets cross-linked, it causes the mast cell to degranulate and release all of its baso-activated mediators such as (histamines, pain mediators such as thromboxaines and prostaglandins)
Term
- When the IgE binds to FC epsilon receptor and the antigen gets cross-linked, it causes the mast cell to degranulate and release all of its baso-activated mediators such as....
Definition
histamines, pain mediators such as thromboxaines and prostaglandins

-They areonly released when IgE is bound to Fc epsilon receptor, gets cross-linked and then sensitizes the cells to degranulate
Term
ADCC (antibody dependent cellular cytotoxicity)
Definition
-mediated by natural killer cells. Target cells bind to NK and this kills the target cells.
-The NK has the Fc gamma R3a receptor so if the target cell has some antibody bound to it (IgG), NK can use Fc gamma R3a receptor to attach to target through the antibody and deliver what’s called antibody dependent cellular cytotoxicity (or antibody dependent cell mediated cytotoxicity).

-This whole process is mediated by Fc gamma R3a
Term
what receptor is on NK cells and is used to attached to target cells to kill them?
Definition
Fc gamma R3a receptor
Term
Name all the different types of Fc gamma receptors
Definition
1) Fc gamma R1
2) Fc epsilon R1
3) Fc gamma R3a
4) Fc gamma R2b
Term
FcgammaR2b
Definition
rather than being a membrane receptor that activates b cells like FcgammaR3a, this receptor is a feedback inhibition mechanisms that actually shuts the b cells off.
Term
If FcgammaR2b receptor binds to the Fc of the soluble IgG what happens?
Definition
rather than sending a positive signal to the cell, it sends a negative signal to cell and it does not undergo further b cell activation
Term
Does Fc gamma R2b activate or inhibit b cell ?
Definition
It is an inhibitor
Term
CD4+ can be further fractionated/differentiated into different subtypes
Definition
1) Th-1 cells
2) Th-2 cells
3) Th-17 cells
4) t regulatory cells
Term
Th1 cells
Definition
a. Synthesizes its signature cytokine is Interferon gamma (IFN-gamma) that has many different properties - first described as substance that inhibits viruses (interferes with viruses)
Term
what is the signature cytokine for Th-1
Definition
Interferon gamma (IFN-gamma)
Term
What is the signature cytokine for Th-2 cells?
Definition
Interleukin 4 (IL-4)
Term
Th2 cells
Definition
Synthesizes its signature cytokine called Interleukin 4 (IL-4)
Term
Th17 cells
Definition
this is a CD4 subtype that is involved in inflammation
Term
T regulatory cells
Definition
this is a subtype of CD4+ cells that:
a.-regulate immune response by dampening it
b.Complex cells; Can be broken down into multiple subtypes: some are inducible some are constituent.
Term
Do both CD8+ and CD4+ cells have a TcR (t cell receptor for antigen)?
Definition
Yes!
Term
TcR (t cell receptor for antigen)
Definition
this receptor:
-sees antigen in unique context, only when antigen is presented by MHC
-Has a very short cytoplasmic tail, so when receptor binds to MHC complex this is not the basis of activation of the t cell
-Activation by cd3 and zeta zeta homodimer
Term
What 2 things activate TcR?
Definition
1)cd3
2) zeta zeta homodimer.
Term
what happens if either cd3 or zeta zeta homodimer are defective?
Definition
then the t cell receptor does not make it to the t cell surface
Term
How does the TcR work in a CD8+ cell?
Definition
it is very similar to what happens in CD4+ cells....

-cd3 and the zeta zeta homodimer assemble with the TcR. TcR binds to APC (MHC plus peptide) the cd3 and zeta zeta homodimer in the membrane of the t cell give rise to subsequent steps of lymphocyte activation. Lymphocyte activation is absolutely crucial for initial activation signaling
Term
CD4 and CD8
Definition
are co-receptors on T cell surface

T cell receptor and CD4 on a t helper cell
T cell receptor and CD8 on cytotoxic t cell
Term
CD28
Definition
-this is a receptor on the t cell surface
-Plays unique role in activation
-Recognizes a unique ligand on the APC surface to ensure that the APC and the t cell are cross communicating effectively
Term
There are adhesion molecules on t cells. Why are they important?
Definition
-To get t cells out of the blood vessels and into CT ; t cells must engage an APC in order to get activated ; they need to go to site where antigen was processed and presented so they can mediate their effector function.
-These provide the ability to interact with vascular endothelium to initiate steps
-Different types that mediate the attachment steps that ensure cells interact with enough stability that the immunologic synapse survives for long enough for cells to be activated
2 prevalent types are:
1) LFA1
2) VLA-4
Term
Name the 2 types of adhesion molecules presented on t cell surface?
Definition
1) LFA1
2) VLA-4
Term
immunologic synapse
Definition
This is the term used to describe communication between t cells and b cells (or t cells and other t cells). They need to be connected for a while (for a few days) to ensure that necessary signaling steps are carried through.
Term
What are the 2 types of structural configuration for the TcR? And which is more prevalent?
Definition
1) Alpha-beta
2) Delta-gamma

Alpha-beta is more prevalent
Term
what property of the t cell allows it to leave the thymus?
Definition
if it is an alphabeta t cell receptor positive t cells
Term
Delta gamma t cells
Definition
are fewer in number than alpha-beta t cells (have repair mechanisms rather than destructive) by serving in effector function
Term
Describe the structure and function of the alpha-beta t cell receptor
Definition
-Has overall properties of the Fab portion of an antibody; bc the t cell receptor is never secreted, it is always associated with t cell membrane; the t cell does the work as the effector cell. You don’t need an Fc. (this has an overall structure like an MHC class 2 molecule). There are 2 components (alpha and beta). In the same way an antibody has variable and constant domains, the TcR also has variable and constant domains (variable alpha and variable beta) and (constant alpha and constant beta) thus it has even more properties similar to Fab portion of an antibody molecule. TcR’s just like membrane immunoglobin undergo gene rearrangement steps to give rise to functional molecules for alpha and for beta. For beta- they have same organization as heavy chain (V D and J)
For alpha- just like light chain (has V and J gene segments) so there is a lot of homology between these 2 systems. However the main difference is that b cells are undergoing rearrangement in marrow and t cells are in thymus. Steps of selection will determine which receptors to keep and which to remove by killing off the cells that bare those receptors.
Term
MHC also has alpha and beta chains.
Should you call them variable domains?
Definition
NO! they do NOT undergo rearrangement to get expressed
-we inherit one set from mom and one set from dad & express them constitutively on all cells that express either class 1 or class 2. Class 1 is expressed in all nucleated cells. Class 2 is expressed on all macrophages, dendritic cells, and b cells. These are constitutive! Always on!
Term
where is MHC class 1 expressed?
Definition
in all nucleated cells
Term
where is MHC class 2 expressed?
Definition
Class 2 is expressed on all macrophages, dendritic cells, and b cells.
Term
are MHC class 1 and 2 constitutive?
Definition
YES they are always on!
Term
CD4
Definition
- a coreceptor

-binds to non-polymorphic position in the beta2 domain of class 2 molecule; interacts with beta2 domain ( binds to a conserved portion of the class2 molecule on APC molecule (as a co-receptor) to give rise to further activation of the t cell
Term
MHC molecules while we don’t call the variable domains, they have polymorphic domains based on the alleles we inherit from our parents. What are the two different types?
Definition
1) Alpha 1
2) Beta 1
Term
MHC does NOT have a variable domain but instead has ________
Definition
a polymorphic region
Term
CD8 t cell
Definition
-Virus goes into target cell,
-target cell processes viral peptides in proteasome
-enters ER by TAP
-binds to class 1 and then complex gets transported to the plasma membrane surface with viral peptides and MHC class 1 (with long alpha chain with 3 domains and beta2 microglobulin) and TcR.
(Size of peptide that binds to MHC class 1 is nine AA’s in length) -CD8 which marks cytotoxic t cell, binds to alpha 3 binding domain to serve as a co-receptor for the cytotoxic t cell.
Term
what MHC class type does CD8 cells bind to?

What MHC class type does CD4 cells bind to?
Definition
CD8- MHC1
CD4-MHC2

8x1 = 4x2
Relationship always equals 8
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