T-Lymphocytes Function, Development, Subpopulations
Activation of T-lymphocytes <ul><li>T-lym p hocytes can be stimula t ed only by complexes of antigen-HLA antigen.  </li></...
Thymic education <ul><li>Positive selection:  survival of cells reacting with low af f inity with HLA antigens expressed o...
Downloaded from: StudentConsult (on 18 July 2006 08:13 AM) © 2005 Elsevier  Interaction TCR-polypeptide-HLA molecule
Development of lymphocytes in the thymus
The Fate of T-lymphocytes in the Thymus
 
Downloaded from: StudentConsult (on 18 July 2006 11:18 AM) © 2005 Elsevier  V, D and J genes involved in T- and B- cell re...
Downloaded from: StudentConsult (on 18 July 2006 11:29 AM) © 2005 Elsevier  Activation and differentiation of  B -lymphocy...
Downloaded from: StudentConsult (on 20 July 2006 09:34 AM) © 2005 Elsevier  Activation and differentiation of T-lymphocytes
Subpopulations of T-lymphocytes <ul><li>Cytotoxic T-lymphocytes (CD8+): kill target cells. Activated by complex HLA-I –ant...
Central role of T-lymphocytes in specific immune response From:  http://pathmicro.med.sc.edu/ APC T h cell B cell Tc cell ...
Subpopulations of T- lymphocytes (all are CD3+) <ul><li>CD4+ </li></ul><ul><ul><li>„ Helper“ lymphocytes: T h 1, T h 2, T ...
Subpopulations of Th-lymphocytes <ul><li>T h 1 lymphocytes </li></ul><ul><ul><li>Produce IFN-  , IL-2, IL-3,  </li></ul><...
Fun ctions of T-lymphocytes
Development of Th1 and Th2 cells
T h 1 lym phocytes <ul><li>Producers of IFN-  , IL-2, IL-3. </li></ul><ul><li>Dif f erentiat e  after stimulation by IL-1...
Function of Th1 cells
T h 2 lymphocytes <ul><ul><li>Produce IL-3, IL-4, IL-5, IL-6, IL-10, IL-13 </li></ul></ul><ul><ul><li>Stimulation of antib...
Th2-lymphocytes are essential for stimulation of B-lymphocytes
Cytotoxic T-lymfocytes <ul><li>CD8+ </li></ul><ul><li>Foreign antigen s  are recogni z ed in complex with HLA-I class anti...
CD8 lym phocytes induce apoptosis of target cells
Types of regulatory T-lymphocytes Periphery From: Nature Immunology IL-10
T reg  lymphocytes <ul><li>Thymic development </li></ul><ul><li>Express CD4+CD25+ </li></ul><ul><li>Involved in tolerace o...
TR-1 Lymphocytes <ul><li>Antigen-induced regulatory CD4+ cells. </li></ul><ul><li>Develop from antigen stimulated T-lymhoc...
“ Supresor“ CD8+ lymphocytes (Ts) <ul><li>Existence of this subpopul at ion is not generally accepted  !!! </li></ul>
T- and B-cells antigen-speciphic receptors
 -T-lymphocytes <ul><li>Comprise approximately 5% of peripheral lymphocytes.  </li></ul><ul><li>CD3+, CD4-CD8- </li></ul...
Intraepitelial  T-lymphocytes <ul><li>TCR of    or   type </li></ul><ul><li>Low antigenic specificity </li></ul><ul><...
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Immunology v t-ly

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Immunology v t-ly

  1. 1. T-Lymphocytes Function, Development, Subpopulations
  2. 2. Activation of T-lymphocytes <ul><li>T-lym p hocytes can be stimula t ed only by complexes of antigen-HLA antigen. </li></ul><ul><li>The HLA antigen must be the same as HLA antigens of the person from whom the ly m phocytes originate= phenomenon of HLA restriction . </li></ul>
  3. 3. Thymic education <ul><li>Positive selection: survival of cells reacting with low af f inity with HLA antigens expressed on antigen-presenting cells in the thymus. Only those cells that recognize HLA antigen of the concrete person survive. The non-reacting cells die by neglect. </li></ul><ul><li>Negative selection – those thymocytes that react with high af f inity with complexes of HLA-autoantigens in thymus die by apoptosis. </li></ul><ul><li>It is supposed that more than 90-95% of thymocytes die during these processes. </li></ul>
  4. 4. Downloaded from: StudentConsult (on 18 July 2006 08:13 AM) © 2005 Elsevier Interaction TCR-polypeptide-HLA molecule
  5. 5. Development of lymphocytes in the thymus
  6. 6. The Fate of T-lymphocytes in the Thymus
  7. 8. Downloaded from: StudentConsult (on 18 July 2006 11:18 AM) © 2005 Elsevier V, D and J genes involved in T- and B- cell receptor formation
  8. 9. Downloaded from: StudentConsult (on 18 July 2006 11:29 AM) © 2005 Elsevier Activation and differentiation of B -lymphocytes
  9. 10. Downloaded from: StudentConsult (on 20 July 2006 09:34 AM) © 2005 Elsevier Activation and differentiation of T-lymphocytes
  10. 11. Subpopulations of T-lymphocytes <ul><li>Cytotoxic T-lymphocytes (CD8+): kill target cells. Activated by complex HLA-I –antigenic peptide. </li></ul><ul><li>Helper T-lymphocytes (CD4+): enable activation of macrophages (Th1) or B-cells (Th2) cells. They are activated by complex es HLA-II- antigenic peptide. </li></ul><ul><li>Regulatory T-cells (CD4+): important in maintenance of immune tolerance. </li></ul>
  11. 12. Central role of T-lymphocytes in specific immune response From: http://pathmicro.med.sc.edu/ APC T h cell B cell Tc cell NK Ag Ag Ag NK cell Cytokines Granulocyte Macrophage Cytokines Antigen-presenting cell
  12. 13. Subpopulations of T- lymphocytes (all are CD3+) <ul><li>CD4+ </li></ul><ul><ul><li>„ Helper“ lymphocytes: T h 1, T h 2, T h 17 </li></ul></ul><ul><ul><li>Regulatory T-lymphocytes : T reg , T h 3, TR-1 </li></ul></ul><ul><li>CD8+ </li></ul><ul><ul><li>Cytotoxic </li></ul></ul>
  13. 14. Subpopulations of Th-lymphocytes <ul><li>T h 1 lymphocytes </li></ul><ul><ul><li>Produce IFN-  , IL-2, IL-3, </li></ul></ul><ul><ul><li>Stimulation of macrophages, pro inflammatory effect </li></ul></ul><ul><ul><li>P robably p athogenic in multiple sclerosis, rheumatoid arthritis… </li></ul></ul><ul><li>T h 2 lymphocytes </li></ul><ul><ul><li>Produce IL-3, IL-4, IL-5, IL-6, IL-10, IL-13 </li></ul></ul><ul><ul><li>Stimulation of antibody production, including IgE </li></ul></ul><ul><ul><li>Included in pathogenesis of allergic diseases </li></ul></ul><ul><li>T h 17 l ymphocytes </li></ul><ul><ul><li>Produce IL-17 </li></ul></ul><ul><ul><li>I mportant in chronic inflammation  </li></ul></ul>
  14. 15. Fun ctions of T-lymphocytes
  15. 16. Development of Th1 and Th2 cells
  16. 17. T h 1 lym phocytes <ul><li>Producers of IFN-  , IL-2, IL-3. </li></ul><ul><li>Dif f erentiat e after stimulation by IL-12, IL-18, IFN-  </li></ul><ul><li>Pro-inflamma to ry ef f ect, stimulate function of macrophages. </li></ul><ul><li>Involved in pathogen esis of Crohn´s disease, multiple sclerosis… </li></ul><ul><li>Down-regulation of Th2 cells by production of IFN-  </li></ul>
  17. 18. Function of Th1 cells
  18. 19. T h 2 lymphocytes <ul><ul><li>Produce IL-3, IL-4, IL-5, IL-6, IL-10, IL-13 </li></ul></ul><ul><ul><li>Stimulation of antibody production, including IgE </li></ul></ul><ul><ul><li>Included in pathogenesis of allergic diseases </li></ul></ul><ul><ul><li>By producti o n of IL-10 suppress function of Th1 cells. </li></ul></ul><ul><ul><li>Th2 predominance in pregnancy. </li></ul></ul>
  19. 20. Th2-lymphocytes are essential for stimulation of B-lymphocytes
  20. 21. Cytotoxic T-lymfocytes <ul><li>CD8+ </li></ul><ul><li>Foreign antigen s are recogni z ed in complex with HLA-I class antigens. </li></ul><ul><li>Mechanism of cytotoxicity: perforin (induction of membrane po res ), vario u s mechanism inducing apopsosis of the target cell (granzymes, FasL, lymfotoxin). </li></ul><ul><li>Produce various cytokines (Tc1 and Tc2 cells) </li></ul>
  21. 22. CD8 lym phocytes induce apoptosis of target cells
  22. 23. Types of regulatory T-lymphocytes Periphery From: Nature Immunology IL-10
  23. 24. T reg lymphocytes <ul><li>Thymic development </li></ul><ul><li>Express CD4+CD25+ </li></ul><ul><li>Involved in tolerace of autoantigens </li></ul><ul><li>Comprise approximately 5-10% of peripheral CD4+ lymphocytes </li></ul><ul><li>Can be incuced also in periphery by foreign antigens. </li></ul>
  24. 25. TR-1 Lymphocytes <ul><li>Antigen-induced regulatory CD4+ cells. </li></ul><ul><li>Develop from antigen stimulated T-lymhocytes in the environment of IL-10. </li></ul><ul><li>Tolerance of foreign antigens. </li></ul><ul><li>Very similar are „ Th3 cells “ . </li></ul>
  25. 26. “ Supresor“ CD8+ lymphocytes (Ts) <ul><li>Existence of this subpopul at ion is not generally accepted !!! </li></ul>
  26. 27. T- and B-cells antigen-speciphic receptors
  27. 28.  -T-lymphocytes <ul><li>Comprise approximately 5% of peripheral lymphocytes. </li></ul><ul><li>CD3+, CD4-CD8- </li></ul><ul><li>Low antigenic speci ficity. </li></ul><ul><li>Thymus in not necessary for their development. </li></ul><ul><li>Other than HLA antigens may be involved in antigen presentation. </li></ul><ul><li>Increased in mycobacterial infections, Erlichiosis, listeriosis. </li></ul>
  28. 29. Intraepitelial T-lymphocytes <ul><li>TCR of  or  type </li></ul><ul><li>Low antigenic specificity </li></ul><ul><li>Extrathymic differentiation </li></ul><ul><li>The first line of the speciphic immune response </li></ul><ul><li>Usually CD8+ </li></ul>

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