Term
| B cells, NK cells, and precursor T cells arise from where? |
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Definition
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Term
| Where do precursor/progenitor T-cells undergo differentiation/maturation ? |
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Definition
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Term
| What cytokine in thymus causes precursor T-cells to differentiate/mature ? |
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Definition
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Term
| What is somatic recombination in T-cell development ? |
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Definition
| Acquisition of a unique TCR leading to an array of T cells each expressing a different TCR |
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Term
| TCRs (T-cell receptors) are composed of what? |
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Definition
Two transmembrane polypeptide chains classified either as alpha / beta or gamma / delta
Most T-cells in body are alpha / beta |
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Term
| Each TCR is expressed on cell surface with what else ? |
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Definition
| Five invariant polypeptides collectively called CD3 |
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Term
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Definition
| Links the antigen binding receptor of T cell with signalling pathways |
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Term
| Each chain of T-cell receptor consists of what regions ? |
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Definition
| A variable and constant region |
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Term
| Each T-cell clone expresses TCRs with unique what ? |
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Definition
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Term
| TCR variable regions are composed of what ? |
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Definition
| V (variable), D (diversity), and J (joining) segments |
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Term
| TCRalpha and TCRbeta variable regions are composed of what? |
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Definition
TCRalpha is composed of V and J (VJ) segments
TCRbeta is composed of V,D,and J (VDJ) segments |
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Term
| Just like B cells, diversity of T cell repertoire is due to : |
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Definition
1)Multiple copies of germline V,D,J gene segments
2)Random selection and combination of V,D, J gene segments
3)Junctional diversity generated by addition or deletion of bases
4)Random assortment of TCRalpha and TCRbeta chains |
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Term
| During T-cell differentiation in thymic cortex, what molecules are expressed on cell surface ? |
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Definition
CD2
pre-TCR-CD3 complex
CD4
CD8
TCR-CD3 complex |
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Term
| The "pan marker" in T-cell differentiation is what ? |
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Definition
| CD2, it continues to be expressed throughout life of cell |
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Term
| Expression of what identifies developing thymocytes that have potential to express viable TCRs ? |
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Definition
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Term
| Expression of CD3 during thymocyte differentiation causes what ? |
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Definition
1) Proliferation of that developing thymocyte
2) Expression of CD4 and CD8 DP (double positive thymocyte)
3) Delivery of signals that direct somatic recombination of the TCR alpha chain |
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Term
| Pathway of TCR differentiation ? |
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Definition
| CD2->PreTCR-CD3->Pre-TCR-CD3-> **DP->TCR-CD3, DP->TCR-CD3 *SP |
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Term
| Somatic recombination in terms of TCR (T cell receptor) variability means what ? |
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Definition
| Process by which unique variable regions are created in the thymus |
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Term
| Somatic recombination of TCR variability is initiated by what? |
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Definition
| Recombinases, nucleoprotein products of the RAG-1 and RAG-2 genes (recombination-activating genes) |
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Term
| What is the TCR complex ? |
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Definition
| TCR and CD3 expressed on surface of T-cell |
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Term
| Construction of unique VJ and VDJ segments is the result of ? |
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Definition
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Term
| In any individual, somatic recombination can produce a repertoir of how many diff. TCRs ? |
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Definition
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Term
| As many as how many TCRs can be on any given cell ? |
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Definition
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Term
| "Hole in repertoire" means what ? |
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Definition
| There has not been a recombination event, and so no TCR with a specificity for a particular epitope-MHC |
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Term
| Allelic exclusion with TCRs means what ? |
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Definition
| If somatic recombination (VJ or VDJ recombination) is successful on one allele, then recombination will not occur on other allele |
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Term
| If somatic recombination is unsuccessful on both alleles, then what happens ? |
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Definition
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Term
| T cells that express a TCR that is of no value to the host (does not recognize self-MHC) do what ? |
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Definition
| Die passively in the thymus |
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Term
| Tolerance induction and screening / selection can only occur after thymocyte expresses ? |
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Definition
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Term
| Screening/selection of TCRs occur on ? |
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Definition
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Term
| Double positive (CD4+ / CD8+) thymocytes are selected to live or die depending on ? |
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Definition
| their interactive avidity of their TCR with self-antigen / MHC on thymic epithelial cells |
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Term
| Interactive avidity of TCR with self-antigen/MHC depends on ? |
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Definition
1)Intrinsic affinity of TCR for self-antigen/MHC complex
2)Density of TCRs
3)Density of self antigen / MHC complexes on thymic epithelium
4)Density of antagonistic peptide complexes |
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Term
| What is negative selection of T-cells? |
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Definition
| Thymocytes are eliminated or inactivated if recognition exceeds a pre-determined threshold |
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Term
| Negative selection occurs in what 2 places? |
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Definition
| First in thymic cortex and second in thymic medulla |
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Term
| Insignificant interactive avidity with thymic epitelial cell results in? |
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Definition
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Term
| Positive selection and preferential expansion of T cells occurs when ? |
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Definition
| Avidity of recognition is intermediate (between these two extremes) |
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Term
| Following screeing/selection of thymocytes, there is transition of double positive thymocytes to ? |
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Definition
| Single positive thymocytes expressing either CD4 or CD8 |
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Term
| Is negative selection within the medulla more finely-tuned than in the cortex ? |
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Definition
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Term
| Expression of autoimmune regulator protein which is encoded by AIRE gene does what ? |
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Definition
| Plays a critical role in promiscuous/ectopic expression of tissue-restricted proteins in thymic epithelial cells (TECs), particularly medullary TECs |
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Term
| Presence of AIRE protein in medullary TECs allows insulin to be ? |
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Definition
| Allows insulin to be transcribed in the thymus and presented in context of MHC for recognition by thymocytes |
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Term
| AIRE gene mutation results in what ? |
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Definition
APECED Syndrome or APS1 (autoimmune polyglandular syndrome type 1)
APECED is defined as subnormal functioning of several endocrine glands concurrently |
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Term
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Definition
APECED is defined as subnormal functioning of several endocrine glands concurrently. It is an autoimmune syndrome.
APECED manifests as chronic mucocutaneous candidiasis, hypoparathyroidism, autoimmune adrenal insufficiency |
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Term
| Migration of naive lymphocytes from blood into lymph nodes occurs at specialized post capillary venules called |
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Definition
| HEV (high endothelial venules) |
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Term
| Extravasation of naive lymphocytes into tissues at HEV requires what things? |
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Definition
1)Interaction of L-selectin on lymphocytes with its ligand on endothelial cells to induce lymphocyte rolling
2)Activation of integrins (ex: LFA-1) present on lymphocytes increasing their adhesiveness to HEV
3)Lymphocyte secretion of matrix metalloproteinases that degrade collagen
4)Transendothelial migration of lymphocytes into the tissues |
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Term
| Sequence of events for central tolerance for effector T cells |
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Definition
| 11 steps starting with expression of CD2 |
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Term
| nTregs (Natural Tregs) are what? |
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Definition
| Regulatory cells, not effector cells |
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Term
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Definition
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Term
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Definition
| Arise as a separate lineage in the thymus and exit to periphery where they are important in controlling self-reactive T cells |
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Term
| Are nTregs deleted when their TCRs recognize high affinity MHC peptide complexes ? |
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Definition
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Term
| Reduced numbers of nTregs or reduced expression of FOXP3 leads to what ? |
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Definition
| Predisposition to autoimmune and inflammatory disorders like asthma and colitis |
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Term
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Definition
| Where immune system does not attack and destroy healthy "self" tissues |
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Term
| First step in "self tolerance" is what ? |
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Definition
| Central tolerance or elimination of self-reavtive T cells and B cells in thymus and bone marrow |
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Term
| What mediates peripheral tolerance (down regulation of immune response to self and foreign antigens) ? |
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Definition
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Term
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Definition
| Maintain peripheral tolerance to "self" antigens and negatively control immune responses to "allo/non self" antigens |
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Term
| Depletion of nTregs does what ? |
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Definition
| Enhances immune responses to pathogens, and in animals leads to tumor rejection |
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Term
| Mutations in FOXP3 causes what? |
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Definition
IPEX (immune dysregulattion, polyendocrinopathy, enteropahty, X-linked) syndrome.
IPEX presents as watery diarrhea, eczema, and Type 1 diabetes
Bone marrow tx and large amounts of immunosuppression are required |
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Term
| 2 mechanisms of nTreg suppression are ? |
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Definition
| Bystander suppression and infectious tolerance |
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Term
| Tregs modify activity of what cells ? |
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Definition
| Dendritic cells, monocytes, and macrophages |
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Term
| What happens in bystander suppression ? |
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Definition
| Activated Treg cell is able to suppress other effector cells expressing TCRs with different antigen specificities |
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Term
| What happens in infectious tolerance ? |
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Definition
| Occurs when other naive CD4+ T cells interact with different Class 2 MHC-epitope complexes on the same APC |
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