1. Immunology Chapter 16, Lecture 1 Richard L. Myers, Ph.D. Department of Biology Southwest Missouri State Temple Hall 227 Telephone: 417-836-5307 Email: rlm967f@mail.smsu.edu Homepage: http://creative.smsu.edu/biology/ myersr/index.html TopClass: http://creative.smsu.edu

2. Cell-mediated Immunity Provides immunity primarily through effector immune cells –antibody plays a secondary role if any Specific cells include –CD4 + T-cell subsets –CD8 + T lymphocytes others include macrophages, neutrophils, eosinophils, and natural killer cells –Cell-mediated immunity is also dependent upon a variety of cytokines

3. Cell-mediated immunity is responsible for the clearance of –intracellular pathogens –virus-infected cells –tumor cells –foreign grafts Two major divisions of cell-mediated immunity –effector cells with direct cytotoxic activity –subpopulation of CD4 + cells that mediate DTH

4. Effector T cells There are 3 types of effector T cells –CD4 + T H 1 –CD4 + T H 2 –CD8 + CTLs Effector cells characterized by –less stringent activation requirements –increased expression of cell-adhesion molecules –production of membrane-bound and soluble effector molecules

5. Cytotoxicity A cytotoxic reaction results in lysis of target cells Two general categories –cytotoxicity involving antigen-specific CTLs –cytotoxicity involving nonspecific cells NK cells macrophages Target cells include allogeneic cells, malignant cells and virus-infected cells

6. CTL-mediated cytotoxicity CTLs are class I MHC restricted –so CTLs can recognize any altered body cell Killing can be divided into two phases –activation and differentiation of CTLs –recognition of antigen-class I MHC complexes The result is target cell destruction

7. Activation and Differentiation Antigen necessary for activation –leads to increase in IL-2 –interaction with the antigen-class I MHC complex causes expression of IL-2R Result is CTL

8. Destruction of target cells The initial step is conjugate formation Results from T cell recognizing processed antigen-class I MHC complexes

9. The next step is membrane attack After conjugate is formed, a energy-requiring, Ca 2+ step occurs Membrane damage to the target cell begins The CTL then dissociates –binds to another target Within minutes, the target cell lyses

10. CTL-mediated pore formation Following CTL-target interaction, Ca 2+ dependent step occurs –triggered by calcium intracellular buildup This induces exocytosis –granules fuse with CTL membrane Release monomeric perforin into space between the cells

11. The released perforin molecules undergo a Ca 2+ conformational change Then bind to the target cell membrane Next insert into it The monomers polymerize forming cylindrical pores Target cells are destroyed

12. ADCC Some cells have receptors for the Fc region When antibody is bound to a target cell, receptor-bearing cell can bind to the antibody through Fc –therefore to target cell and lysis occurs –called antibody-dependent cell-mediated cytotoxicity (ADCC)

13. Mixed lymphocyte reaction Measurement of T cell proliferation in response to allogenic cells When lymphocytes from two different inbred strains are mixed, each responds Measure proliferation by measuring uptake of tritium-labeled thymidine 3 H incorporated into new DNA

15. Cell mediated lympholysis CTLs generated to allogenic cells (same species) Label target cells intercellularly with 51 Cr (yellow) Incubate CTLs with target cell Measure 51 Cr release upon death of target cell

16. Graft-versus-Host reaction GVH measures cell-mediated cytotoxicity Results when compotent lymphocytes given to immunocompromised host –graft attacks the host –host is not able to respond Examples are bone marrow transplants into patients following radiation, those with immunodeficiency diseases or autoimmune anemias

17. Delayed-type hypersensitivity Some subpopulation of activated T H cells will produce a localized inflammatory reaction when contacting antigen –called DTH –characterized by influx of large numbers of nonspecific inflammatory cells primarily macrophage tuberculin reaction is excellent example –may or may not lead to extensive tissue damage

18. There is a sensitization phase where the antigen with class II MHC presented by an APC produces a T DTH cell The activated T cells are CD4 + These cells secrete a variety of cytokines –will recruit and activate macrophages and other nonspecific inflammatory cells –this is an effective response –pathogens are eliminated A prologned DTH response can become destructive because of intense inflammation

20. Protective role of DTH

21. Assignment Continue reading Chapter16 Review question 3 (pg 411)