Immunology Chapter 16, Lecture 1

1. ImmunologyChapter 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+ TH1 • CD4+ TH2 • 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, Ca2+ 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, Ca2+ 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 Ca2+ 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 • 3H incorporated into new DNA

15. Cell mediated lympholysis • CTLs generated to allogenic cells (same species) • Label target cells intercellularly with 51Cr (yellow) • Incubate CTLs with target cell • Measure 51Cr 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 TH 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 TDTH 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)