immunology chapter 16, lecture 1 richard l. myers, ph.d. department of biology southwest missouri...
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ImmunologyChapter 16, Lecture 1
• Richard L. Myers, Ph.D.
• Department of Biology
• Southwest Missouri State
• Temple Hall 227
• Telephone: 417-836-5307
• Email: [email protected]
• Homepage: http://creative.smsu.edu/biology/myersr/index.html
• TopClass: http://creative.smsu.edu
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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
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• 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
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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
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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
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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
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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
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Destruction of target cells
• The initial step is conjugate formation
• Results from T cell recognizing processed antigen-class I MHC complexes
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• 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
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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
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• 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
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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)
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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
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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
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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
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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
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• 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
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Protective role of DTH
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Assignment
• Continue reading Chapter16
• Review question 3 (pg 411)