PCB 3233Study GuideChapters 7 and 8Chapter 71. T cells develop in the thymus.2. The beta chain rearranges V, D and J, and the alpha chain rearranges V and J.3. RAG genes are used in rearrangement.4. A successful beta chain with a surrogate alpha chain (pre T alpha) makes up the pre TCR5. IL-7 is secreted by the thymic stromal cells; it tells the immature thymocytes what to do next during maturation. Notch-1 is present during all stages of maturation; signals are sent through this receptor.6. DiGeorge’s syndrome is a deletion in chromosome 22 which results in no thymus or an incomplete thymus which means no T cells. This syndrome resembles SCID.7. Double negative T cells don’t have CD4 or CD8 expressed. These cells would be found in the thymus.8. RAG-1 and RAG-2 are still present in T cells and the 12-23 rule still applies.9. Positive selection takes place before negative selection. Positive selection takes place in the cortex and is mediated by cortical epithelial cells. Negative selection usually takes place in the medulla and is mediated by bone marrow derived dendritic cells and macrophages. 10. Mature T cells will circulate in the blood for many years.11. If you are heterozygous for the HLA genes, you would have 12 different MHC molecules.12. During T cell gene rearrangement, beta, gamma and delta chains are all rearranged simultaneously. If the beta chain rearranges first, then the alpha, gamma and delta genes will be arranged simultaneously. 13. When the alpha chain is successfully rearranged, the delta chain gene will be deleted. 14. Alpha beta T cells predominate over gamma delta T cells.15. The beta chain has 4 attempts at rearrangement since there are 2 D, 2 J and 2 C gene regions.16. Successful rearrangement of the beta chain induces CD4 and CD8 expression.A thymocytes is considered a single positive cell when it only expressed CD4 or CD8, not both. This is done during positive selection. If a T cell interacts with MHC I, it will become a CD8 cell. If it interacts with MHC II it will becomea CD4 cell.17. Positive selection is the process to select the T cells that recognize HLA molecules. It takes place in the cortex of the thymus. It is mediated by corticalepithelial cells. Only 2% of T cells will bind to HLA. If a T cell recognized HLA, it will express one co-receptor, not both.18. The pre TCR triggers the thymocyte to proliferate and halt b-chain gene rearrangement, which ensures only one type of T-cell receptor b-chain isexpressed by the T cell. The pre T alpha (surrogate alpha chain) only has 1 domain.19. A thymocyte that does not pass positive selection will undergo apoptosis and be cleaned up by macrophages.20. Rearrangement of the a-chain locus continues throughout the 3-4 days of positive selection – hence a T cell can change the specificity of the TCR it expresses. Once a T cell is positively selected, rearrangement of the a-chain stops. Some double + T cells can express 2 alpha chains, one from mom and one from dad, which means there will be 2 different TCRs going through positive selection. It is rare to see both receptors recognize HLA molecules.21. Negative selection deletes T cells that bind to strongly to self MHC molecules. This process is mediated by bone marrow derived dendritic cells and macrophages. This occurs mostly in the medulla of the thymus.22. Gamma delta T cells don’t go through positive and negative selection becausethey don’t have to have antigen presented to them on MHC molecules.23. Only 2% of thymocytes survive positive and negative selection.24. The T cell zones of lymphoid organs are sites where naïve T cells are activated by antigen – which provokes the final phase of T-cell development and differentiation. Dendritic cells, macrophages, and B cells present antigen.25. The dendritic cells settle in the T cell zones of the secondary lymphoid tissue.26. Central tolerance for T cells takes place in the thymus.27. Peripheral tolerance takes place in circulation.28. Regulatory T cells are CD4 T cells and express CD25 and FoxP3. FoxP3 is unique to T regulatory cells. 29. Langerhans cells in the skin are phagocytic and take up pathogen and then migrate to secondary lymphoid tissue. This is what makes them so good at activating T cells.30. CCL 21 and CCL 19 are chemokines that call T cells to the lymph node from the HEVs.31. A naïve T cell that doesn’t encounter antigen in the lymph node will continue to circulate throughout the periphery for many years.32. Lymphocytes = T cells, B cells, and NK cells. Leukocytes= all white blood cells33. AIRE is a transcription factor present in the thymus which allows expression of organ specific antigen such as insulin.Chapter 834. 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 .35. L selectin on the T cell binds to GlyCAM-1 or CD34 (vascular addressins) on the blood vessel to initiate rolling adhesion. LFA-1 on the T cell then binds to ICAM-1 on the venule which is tight binding. 36. The four different types of adhesion molecules are selectins, which bind to vascular addressins, and integrins (LFA-1) which bind to the immunoglobulin superfamily members.37. If a naïve T cells enters the lymph through the blood, it enters by crossing thehigh endothelial veins.38. S1P is a cytokine that drags a T cell which hasn’t met its antigen out of the lymph node.39. TH1 and cytotoxic T cells will migrate out of the lymph node towards the site of infection, while TH2 cells stay in the lymph node.40. CTLA-4 is a high affinity B7 receptor that is present on activated T cells that serves as an antagonist to CD28. This slows down proliferation of the activated T cell. 41. CCL18 is secreted by dendritic cells to attract naïve T cells.42. If a naïve T cell interacts with a non-professional APC, that T cell will be rendered anergic. 43. Professional APCs have a co-stimulatory molecule expressed on their surface called B7.44. B7 expression is a direct consequence of infection, induced by interaction of a potential APC with microbial products via cell-surface receptors that contribute to innate immune response. So this means T cells can only be activated during an infection. 45. Langerhans’s cells are immature phagocytic dendritic cells present in the skin which contain large granules called Birbeck granules .46. Immature dendritic cells use DEC-205 which assists