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IM5004 Study Guide

IM5004 Study Guide - IM5004 Hot topics in Immunology Exam...

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IM5004 Hot topics in Immunology Exam Study Guide Chemokines in Cell trafficking 1 1. DC a. Capture antigen withing tissues b. Once antigen is captured, the DC losses its adhesiveness, travels through the blood stream c. Migrates into the afferent lymph vessel d. CCR7 is the receptor that binds naïve t cells to the HEV in the lymph node 2. CCR7 a. Expressed by Naïve T and B cells b. Also expressed my mature DC (after they leave the inflammatory site c. Chemokine ligands for CCR7 and CCL19 and CCL21 c.i. Found on the surface of the HEV and in the T-cell zones of the lymph node d. Function – to coordinate the primary immune response by establishing functional microenvironments in secondary lymphoid organs 3. CCR7 deficient mice a. Lymph node and PP are smaller, spleen is enlarged b. T cell population expanded in blood, spleen red pulp c. LN has a severe deficiency of naïve T cells and DC cells d. Migration of naïve b and t cells to the LN severly compromised e. Overall disturbed microarchitecture due to impaired entry and retention lymphocytes and DCs f. Altered morphology of DCs in the T cell areas of the LN g. Lack of fast primary B and T cell responses g.i. Contact sensitivity – ear swelling g.ii. Delayed type hypersensitivity – ear swelling g.iii. Humoral response to DNP-KLH antigen h. Inadequeate migration of naïve B and T and antigen bearing DC to LN i. Impaired antigen presentation j. Impaired T and B cell interaction 4. Differentiation and selection of T lymphocytes in the thymus a. Resident thymic epithelial cells (TEC) form infrastructure – stable stromal compartment a.i. Differentiation signals a.ii. Guiding route b. Hemopoietic cells enter via large venules at corticomedullary junction b.i. Proliferation b.ii. Lineage commitment b.iii. Selection c. APCs – macrophage, DCs d. Positive selection
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d.i. Low-affintiy/avidity recognition of peptide-MHC complex on thymic epithelial cell (TEC) recuses cell from programmed cell death d.ii. Cell converts into a single positive (either CD4 or CD8) e. Negative selection e.i. High avidity recognition of self peptide MHC complexes on thymic antigen-presenting cell e.ii. Recognition causes apoptosis in the cell 5. CCR7 needed for cortex to medullary migration of positively selected thymocytes a. CCR7 expression associated with change to SP b. CCR7 ligands (CCL19 and CCL21 in thymus b.i. Produced by medullary TEC b.ii. Localized in medulla c. In mice deficient in CCR7 or CCR7L mature SP arrest in cortex – do not accumulate in medulla d. In CCR7 deficient mice d.i. Thymocytes developed as usual d.i.1. Same frequency, maturation OK – TCR responsiveness, surface phenotype d.ii. Mature thymocytes were exported from thymus d.iii. Block exit d.iii.1. Mature CD62Lhi accumulated in cortex d.iv. Mature thymocytes exported directly from the cortex 6. CCR7 mediated cortex to medulla needed for central tolerance a. In CCR7 deficient mice a.i. Thymocytes did not aquire tolerane to lacrimal and salivary glands a.ii. Caused autoimmune exocrinopathy a.iii.
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IM5004 Study Guide - IM5004 Hot topics in Immunology Exam...

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