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Exam 4 Immuno
Terms in this set (78)
Development (maturation) of T cells, where does it take place?
What gene segments are rearranged for the alpha and beta chains?
Alpha: V and J
Beta: V, D and J
Are the RAG genes used in the rearrangement?
What makes up a pre-TCR?
Surrogate alpha chain (PreTa), B-chain, CD3 proteins (gamma, 2x epsilon, delta) and zeta chaind
IL-7: what does it do and when they exert their influence on developing T-cells
- essential for binding IL-7 secreted by thymic stromal cells - helps tell the T-cell what to do next in its maturation.
DiGeorge's syndrome: What is the cause? What chromosome is involved and what organ is involved?
A deletion in chromosome 22 in which the thymus fails to develop and T cells are absent
"Double negative" thymocytes; Why are they called this and where would you find them in the body?
do not have CD4 or CD8, in thymic stromal cell
Are RAG-1 and 2 working in somatic recombination of T-cells genes also? What about the 12/23 rule (1/2 turn rule)?
Which takes place first positive or negative selection?
Where does positive selection take place and where does negative selection take place?
positive selection takes place in the cortex of the thymus
negative selection takes place in the thymus medulla
Lifespan of a T cell, short or long compared to a B-cell.
T-cells are long lived than B-cells
If you are heterozygous for the MHC (HLA) genes, how many presenting MHC (HLA) molecules do you have?
Thymocytes gene rearrangement; β, γ and δ chain genes (when)
after the progenitor has been committed as a double-negative but at the same time as beta chain rearrangement
Deletion of the δ chain genes how does this happen and when does this happen?
delta chain is between V & J and is removed during the rearrangement of the alpha-chain
Which type of T cell receptor predominates αβ or γδ?
Rearrangement of a β-chain, how many possible attempts do they have to make a functional rearrangement?
Two attempts can be made to acieve a productive rearrangement of the B-chain locus
When are CD 4 and 8 co-expressed, before or after beta chain rearrangement? When is a thymoctye considered a single positive cell (before or after positive selection)?
2) Successful rearrangement of a beta chain gene induces expression of CD4 and CD8
What is positive selection? Where is it done, what cells mediate it, what is being checked and what happens to the T-cell?
- takes place in the cortex of the thymus
- mediated by cortical epithelial cells bearing complexes of class I and class II self-MHC and self-peptides.
- interactions between the TCR of thymocytes with self-MHC and self-peptide are tested.
Pre-TCR (look closely at the figures and signals that it provides).
What happens to the T-cells that fail positive selection?
does not receive a signal dies by apoptosis and is removed by macrophages
Positive selection and α chain rearrangement and number of possible receptors on the surface.
Once a T cell is positively selected, rearrangement of the alpha-chain stops.
What occurs in the thymus
Process of negative selection; TCRs; self-MHC and self-peptides; mediated by several cell types; dendritic cells and macrophages
γδ T cells do not undergo positive in thymus; why don't they need to?
they do not interact with MHC
Percentage of thymocytes survive the processes of maturation.
Does the thymus play a role in activation of naïve T cells? If not, where do the T cells meet their antigen? And which cells present antigen for activation?
- activation takes place in the secondary lymphoid tissues in the T-cell zone
- dendritic cells
Where do Dendritic cells settle in the secondary lymphoid tissue?
Where does central tolerance for T-cells take place?
Where does peripheral tolerance for T-cells take place?
secondary lymphoid tissues
A regulatory T-cell is a CD-4 or CD-8 T-cell?
What transcription factor is unique to T-reg cells?
Fate of a naïve T cell that does not encounter antigen in a secondary lymphoid organ
in the absence of activation mature T cells recirculate between the blood, the secondary lymphoid tissues, the lymph and the GALT.
What cells are Lymphocytes?
T, B and NK cells
What cells are Leukocytes?
all wbc, monocytes, eosinophils, neutrophils, lymphocytes and basiophils
AIRE. What does it stand for, what does it do and what organ in the body would you expect to find it in?
- autoimmune regulator
- presents antigens not normally produced by the antigen to T cells during development
- medulla of the thymus
What are the reasons for the several day delay in a primary response.
once an antigen-specific T cell is trapped in the lymph node by an APC and activated it takes several days for the activated T cell to proliferate and differentiate into effector T cells .
LFA-1, ICAM-1, L-selectin, vascular addressin. Know the homing and cell to cell adhesion slides.
- L-Selectin (on T cells): interact with vascular addressins on surface of HEV venules (CD34 & GlyCAM-1)
- LFA-1 (on T cells): activated by chemokines it binds to extracellular matrix.
- ICAM1 (on epithelial): Binds to LFA-1
- Vascular addressin (on epithelial): binds to L-selectin
Know the 4 different types of leukocyte adhesion molecules
Selectins - bind carbohydrates. Initiate leukocyte endothelial interaction.
vascular addressins - binds to L- selectin. Initiate leukocyte-endothelial interaction
integrins - binds to cell adhesion molecules and extracllular matrix. Strong adhesion
immunoglobulin super familiy- Cell adhesion. targets for integrins
If a naïve T-cell comes into the lymph node from the blood, what does it enter through?
leave the lymph node in the efferent lymph and join the blood stream.
What is S1P? What does it do?
T-cells that haven't met the antigen and are drawn out of the lymph node and continue to recirculate until it meets it's antigen
Know which types of T cells migrate to site of infection after activation and which one stays in the secondary lymphoid tissues (lymph node).
TH2 stays, TH1 goes
What is CTLA-4? What does it bind to and what is the result of it binding?
- an activated t-cell that expresses another B7 receptor
-binds B7 twentyfold more strongly than does CD28 and functions as an antagonist.
- slows down activation and limits cell proliferation.
What cell will put up CTLA-4 on its surface?
What chemokine directs the naïve T-cells to the T-cell area to check the dendritic cells MHC molecules?
CCL21 and CCL19
What happens when a naïve T cell interacts with an antigen presented by a cell that is not a professional antigen presenting cell?
become anergic (no B7 to activate it)
What does a P-APC have that other cells don't have?
MHC class 2 and CD28 proteins that bind B7 molecules on the APC
Is B7 always produced by dendritic cells? If not, when do they make it?
- expression is a direct consequence of infection, induced by interaction of a potential APC
Langerhan's cells, what and where are they?
Immature dendritic cell with large granules
Mature Dendritic cells vs. Immature Dendritic cells. What do they do different and what kind of surface molecules do they have (DEC 205 vs. DC-SIGN)?
Immature DC: DEC205 facilitates phagocytosis and pinocytosis of antigens.
-ex: langerhans cells
Mature DC: Increase expression of B7 co-stimulators, MHC molecules and adhesions molecules like DC-SIGN
-ex: interdigitating reticular cells
T-cell priming/activation (definition)
presenting the T cell with an antigen
What is Macropinocytosis and which cell can did you learn can utilize it?
- mainly immature dendritic cells
- used to take up antigens by engulfing extracellular fluid (ECF)
What does IL-2 do and when is it made
- used for proliferation and differentiation of activated T cells
- it is made by activated and effector T cells
What is the point of T-cell priming? What does activation mean? (look at transcription factors that are initiated). What is changed in the cell and what are the major gene/genes produced from that change?
- become an activated or effector cell
- carry out other functions
- can be T-reg, TH1, TH2, or CD8
What are ITAM's? what can bind to them?
- Immunoreceptor tyrosine-based activation motifs
- found on tails of CD3s (from the TCR protein complex)
Associate with cytoplasmic protein tyrosine kinases
What are DAG and IP3, what do they do? What is ZAP 70 and when is it activated (which cell type and when)
-DAG is diacylglycerol and IP3 is inositol triphosphate, these activate the transcription factors NFkB, NFAT and AP-1 which change the pattern of gene expression and control cell division, proliferation and differentiation to effector T-cells.
-ZAP 70 is a cytoplasmic protein tyrosine kinase which binds to the phosophorylated tyrosines on the zeta chain of the T-cell receptor complex. This is activated when T cells are activated by an antigen.
What cell/s is B7 on? What cell is CD28 on? What do they do when they come together?
- To activate a T cell
CTL's recognize peptide on MHC I. Which cells can present with MHC I?
- almost all cells can present with MHC1
- all nucleated cells.
Know the distribution of the 3 different P-APC's in the lymph node.
- dendritic T-cell area in the lymph node
- macrophages Distributed throughout the whole lymph node
- B-cells: located only in the follicle
Definitions of autocrine (same) and paracrine (local)
- Autocrine: hormones that affect the cell that produced it (self receptors)
- Paracrine: hormones that affect surrounding cells (local)
What molecules carry out the effector functions of T cells? (cytokines and cytotoxins)
Cytokines, cytotoxins, and chemokines
Know the pathways CD 8 T cells use to cause apoptosis.
-Know the cytotoxins names
- cytotoxins: perforin and granulysin create pores in the cell membrane, granzymes enter and cleave proteins.
- granzymes activate nucleases, RNases and proteases which leads to the breakdown of DNA, RNA and proteins.
What are VLA-4 and VCAM-1 responsible for? Homing to where?
- expressed on activated T cells, guides T cells to site of infection by binding to VCAM-1
- expressed on endothelium of blood vessels in inflamed tissue, binds to VLA-4 on T cells
Can effector T cells be stimulated in the absence of co-stimulatory signal?
Activation of Macrophages. What is needed? And which cells activate them?
- IFN-γ and CD40
- TH1 cells and CD8 T cells secrete IFN-γ
- CD40L on TH1 cells interact with CD40R on macrophages
Can Th1 cytokines affect Th2 differentiation and vise-versa?
What is the only cell that can activate a CD8 T-cell without help
What is another way to get a CD8 T-cell activated if a Dendritic cell needs help?
IL-2 which can be secreted by CD4 or CD8 T-Cells
What T cell bias is seen in Tuberculoid vs. Lepromtous leprosy? Can you tell which disease state it is by looking at the cytokine profile?
- Tuberculoid= TH1 bias, higher amounts of IFN-Gamma cytokines
- Lepromatous= TH2 bias, higher amounts of IL-4 cytokines.
What kind (molecules in our book) of signaling would you expect to see JAK's and STAT's in?
Cytokine Receptor Signaling
Can CD-8 T cells kill more than one cell? Or are they similar to Neutrophils where they can only kill one cell then they die themselves?
- Yes, they can kill more than one cell.
- They attach to the infected cell, release their granules unto the cell, detach and remake their granules. The move on to the next infected cell and do the same thing.
When you See CXCL or CCL, would you know right away what is being talked about?
Th1 cells activate _______________
Th2 cells activate ______________.
What are the unique transcription factors for each of the CD4 T cells?
Th1 - T-bet
Th17 - ROR(gamma)T
TH2 - GATA3
TFH - IL-21
Know the cytokines I mentioned in class that cause differentiation of each of the CD4 T cells.
Th1 - IL-12 and IFN gamma
Th17- IL-6 and IL-21
Tfh- IL-16, TGF-Beta, and IL 23
T Reg- TGF- Beta
Know the cytokines I mentioned in class that are secreted by each of the effector T cells.
Th1 - IL-12 and INF-gamma
IL-6 - Activates TF BcI6 which makes Tfh Effector
Th2- Il-4 and Il-5
Treg- TGF-B and IL-10
Where would a natural T regulatory cell differentiate in the body and where would an induced T regulatory cell differentiate in the body?
What 2 cells is CD40-CD40L interaction needed for activation?
THF and B-cells
Notch-1: what does it do and when they exert their influence on developing T-cells
at all stages of maturation in the thymus signals are sent through this receptor to drive the T-cell in their differentiation.
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