1. Principles of Immunology T Cell-Mediated Immunity 3/28/06 “Each of us needs to be the change we wish to see in the world” Ghandi

2. Word/Terms List  ADCC  Effector cells  GVH reaction  Perforin

3. T Cell-mediated Immunity  Principal function-Response to intracellular pathogens and cells expressing foreign antigens  Recirculation-Naïve T cells circulate between the blood stream and the lymphatic system  Antigen presentation-Naïve T cell cells only respond to APCs

4. Priming of T Cells  Three types of effector T cells CD8 (T C ) CD4 (T H1 ) CD4 (T H2 )  Each type Responds to different types of Ags Activated by different Ag presentation Has different effector function

5. T Cell Effector Types  CD8 Viruses and intracellular bacteria MHC I Cytotoxic effector cells  CD4 T H1 Bacteria and parasites in APCs MHC II Effectors activate macrophages, CTLs and induce B cells to produce opsonins  CD4 T H2 Extracellular bacteria and toxin producers MHC II Activate B cells to produce multiple antibody classes

6. T Cell Adhesion  T cells pass through endothelial cells (extravasation)  Endothelial cells and T cells both have cell adhesion molecules (CAMs)  Various CAMs

7. Cell Adhesion Molecules  Selectins  Mucins  Integrins  Immunoglobulin superfamily

8. APCs  Dendritic cells  Macrophages  B cells

9. Dendritic Cells  Antigen presentation is sole function  Antigenic uptake is followed by migration to lymph nodes  Expression of MHC I, MHC II and B7  Loses phagocytic property  Secretes chemokines

10. Macrophages  Involved in both innate and adaptive immunity  May destroy pathogens or present Ag to T cells  Expression of MHC I, MHC II and B7  Scavenges dead cells

11. B Cells  Binds soluble antigens  Constitutively expresses MHC II  Induced to express B7

12. NK Cells  ~5% of lymphocytes  Nonspecific cytotoxicity  No TCR/CD3  Not MHC restricted  No memory

16. CTL Cytotoxicity  Conjugate formation  Membrane attack  Dissociation  Target cell death

17. Conjugate Formation  Cell adhesion  Recognition of MHC I:Ag on target cell

18. Membrane Attack  Granules in CTLs Perforin Granzymes  Exocytosis of granule contents Perforin action similar to C9 Granzymes act as nucleases  Fas ligand to Fas triggers target cell death

19. Dissociation and Target Cell Death  CTL interacts for about five minutes  Dissociates and can conjugate with other target cells  Target dies after several hours

21. Antibody-Dependent Cell-Mediated Cytotoxicity  NK cells, macrophages, neutrophils  Bind to Fc region of Ab  Multiple cytotoxic mechanisms

23. Graft vs. Host Reaction  Immunocompromised recipient  Lymphocytes of donor attack allogeneic antigens of recipient  Splenomegaly