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Immunological synapse

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Shawn Felix

The immunological synapse is the contact point between a T cell and antigen presenting cell where signaling and protein segregation occurs. It is composed of concentric rings called the central, peripheral, and distal supramolecular activation complexes. Signaling occurs through redistribution and segregation of receptors and proteins at the cell surface through both passive binding and active lateral movement and vesicle transport. Immunological synapses play a role in processes like HIV persistence through virological synapse formation between infected and uninfected T cells.

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IMMUNOLOGICAL SYNAPSE Presented by Candice Churaman Charles Okonkwo Shawn Felix
An immunological synapse also known as a supramolecular adhesion complex (SMAC) is the cell to cell contact between the T cell, its co-receptors and the antigen presenting cell.
The site of contact is composed of concentric rings with each containing segregated cluster of proteins : Central supramolecular activation complex (cSMAC) - comprises of the T cell receptor, its co-receptor (CD 4 or CD 8), CD 28, CD 2 and PKC 慮
Peripheral supramolecular activation complex (pSMAC) - comprises of LFA1, ICAM-1 and talin Distal supramolecular activation complex (dSMAC) - enriched in CD 43, CD44 and CD 45
Enhancing signalling Terminating signalling and/or effector function Balancing signalling Directing secretion
The mechanism of immune synapse are: passive and active. Passive is defined as: binding and steric factors. (emerski and Shaw, 2006) The diagram on the left shows the mechanisms of redistribution and segregation of molecules at the cell surface. Fig.1: The mechanisms involved in synapse formation. (emerski and Shaw, 2006)
Active Mechanism: This is the lateral movement on the surface and polarised exocytosis of vesicular stores. (van der Merwe et al., 2000) There are various amounts of cell surface molecules which is transported from the intracellular vesicular compartments to the immune synapse. Examples of these are: FasL & CTLA-4. (van der Merwe et al., 2000) Fig.2: The transportation of cell surface molecules into the intracellular vesicular compartments. (van der Merwe et al., 2000)
IMMUNOLOGICAL SYNAPSE- Pathology : HIV as a case study Model of virological and immunological synapse formation in the contribution to HIV persistence Virological synapse (left panel) is mediated through interactions of gp41/gp1209(shown in red) on an HIV-infected CD4+T cell with CD4+ (brown) on the cell surface of an uninfected target CD4+ T cell. Interactions are stabilized by ICAM-1(green) and LFA-1(blue) and takes place even in the presence of ART. IS formation(right panel) initiated through interaction of MHC class II(green) on an APC and the TCR(red) of an Infected T cell may induce latency via inhibitory signals within the IS to reduce T-cell activation.
Trends in Immunological synapse Then Shows the contact region between T-cells and APCs that forms upon TCR stimulation with peptide MHC In addition to na誰ve and effector T cells, also found in other immune system cells. Example: CTLs, NK cells, NKTcells and B cells A concentric bulls eye structure consisting of 3 sub regions: cSMAC, pSMAC and DPC. Now TCR microclusters(MCs) containing additional signalling molecules defined as the minimal active signalling unit of IS Existence of kinapses, short lived asymmetric synapses, in motile T cells. Segregation of the cSMAC into two distinct sub regions a central, CD3high region(signal termination) and an outer CD3low annular ring enriched in CD28 and PKC慮,a site of sustained signalling.
Conclusion IS involves reorganization of not only cell surface receptors, but also actin and microtubule cytoskeletons leading to signalling and secretion Further work elucidating a clear pathway that regulates centrosome movement within immune cells is still required. References : J.C. Stinchcombe, G.M. Griffiths. The role of the secretory immunological synapse in killing by CD8+ CTL. Semin. Immunol., 15 (2003), pp. 301305 Colin L., Van Lint C. Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies. Retrovirology. 2009; 6:111. PubMed.
Angus, K. and Griffiths, G. (2013). Cell polarisation and the immunological synapse. Current Opinion in Cell Biology, 25(1), pp.85-91. emerski, S. and Shaw, A. (2006). Immune synapses in T-cell activation. Current Opinion in Immunology, 18(3), pp.298-304. Davis, D. and Dustin, M. (2004). What is the importance of the immunological synapse?. Trends in Immunology, 25(6), pp.323-327. Rodr鱈guez-Fern叩ndez, J., Riol-Blanco, L. and Delgado-Mart鱈n, C. (2010). What is an immunological synapse?. Microbes and Infection, 12(6), pp.438-445.
Van der Merwe, P. (2002). Formation and function of the immunological synapse. Current Opinion in Immunology, 14(3), pp.293-298. Van der Merwe, P., Davis, S., Shaw, A. and Dustin, M. (2000). Cytoskeletal polarization and redistribution of cell-surface molecules during T cell antigen recognition. Seminars in Immunology, 12(1), pp.5-21.
Immunological synapse

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Immunological synapse

  • 1. IMMUNOLOGICAL SYNAPSE Presented by Candice Churaman Charles Okonkwo Shawn Felix
  • 2. An immunological synapse also known as a supramolecular adhesion complex (SMAC) is the cell to cell contact between the T cell, its co-receptors and the antigen presenting cell.
  • 3. The site of contact is composed of concentric rings with each containing segregated cluster of proteins : Central supramolecular activation complex (cSMAC) - comprises of the T cell receptor, its co-receptor (CD 4 or CD 8), CD 28, CD 2 and PKC 慮
  • 4. Peripheral supramolecular activation complex (pSMAC) - comprises of LFA1, ICAM-1 and talin Distal supramolecular activation complex (dSMAC) - enriched in CD 43, CD44 and CD 45
  • 5. Enhancing signalling Terminating signalling and/or effector function Balancing signalling Directing secretion
  • 6. The mechanism of immune synapse are: passive and active. Passive is defined as: binding and steric factors. (emerski and Shaw, 2006) The diagram on the left shows the mechanisms of redistribution and segregation of molecules at the cell surface. Fig.1: The mechanisms involved in synapse formation. (emerski and Shaw, 2006)
  • 7. Active Mechanism: This is the lateral movement on the surface and polarised exocytosis of vesicular stores. (van der Merwe et al., 2000) There are various amounts of cell surface molecules which is transported from the intracellular vesicular compartments to the immune synapse. Examples of these are: FasL & CTLA-4. (van der Merwe et al., 2000) Fig.2: The transportation of cell surface molecules into the intracellular vesicular compartments. (van der Merwe et al., 2000)
  • 8. IMMUNOLOGICAL SYNAPSE- Pathology : HIV as a case study Model of virological and immunological synapse formation in the contribution to HIV persistence Virological synapse (left panel) is mediated through interactions of gp41/gp1209(shown in red) on an HIV-infected CD4+T cell with CD4+ (brown) on the cell surface of an uninfected target CD4+ T cell. Interactions are stabilized by ICAM-1(green) and LFA-1(blue) and takes place even in the presence of ART. IS formation(right panel) initiated through interaction of MHC class II(green) on an APC and the TCR(red) of an Infected T cell may induce latency via inhibitory signals within the IS to reduce T-cell activation.
  • 9. Trends in Immunological synapse Then Shows the contact region between T-cells and APCs that forms upon TCR stimulation with peptide MHC In addition to na誰ve and effector T cells, also found in other immune system cells. Example: CTLs, NK cells, NKTcells and B cells A concentric bulls eye structure consisting of 3 sub regions: cSMAC, pSMAC and DPC. Now TCR microclusters(MCs) containing additional signalling molecules defined as the minimal active signalling unit of IS Existence of kinapses, short lived asymmetric synapses, in motile T cells. Segregation of the cSMAC into two distinct sub regions a central, CD3high region(signal termination) and an outer CD3low annular ring enriched in CD28 and PKC慮,a site of sustained signalling.
  • 10. Conclusion IS involves reorganization of not only cell surface receptors, but also actin and microtubule cytoskeletons leading to signalling and secretion Further work elucidating a clear pathway that regulates centrosome movement within immune cells is still required. References : J.C. Stinchcombe, G.M. Griffiths. The role of the secretory immunological synapse in killing by CD8+ CTL. Semin. Immunol., 15 (2003), pp. 301305 Colin L., Van Lint C. Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies. Retrovirology. 2009; 6:111. PubMed.
  • 11. Angus, K. and Griffiths, G. (2013). Cell polarisation and the immunological synapse. Current Opinion in Cell Biology, 25(1), pp.85-91. emerski, S. and Shaw, A. (2006). Immune synapses in T-cell activation. Current Opinion in Immunology, 18(3), pp.298-304. Davis, D. and Dustin, M. (2004). What is the importance of the immunological synapse?. Trends in Immunology, 25(6), pp.323-327. Rodr鱈guez-Fern叩ndez, J., Riol-Blanco, L. and Delgado-Mart鱈n, C. (2010). What is an immunological synapse?. Microbes and Infection, 12(6), pp.438-445.
  • 12. Van der Merwe, P. (2002). Formation and function of the immunological synapse. Current Opinion in Immunology, 14(3), pp.293-298. Van der Merwe, P., Davis, S., Shaw, A. and Dustin, M. (2000). Cytoskeletal polarization and redistribution of cell-surface molecules during T cell antigen recognition. Seminars in Immunology, 12(1), pp.5-21.