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

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

• 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

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

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

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

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

Destruction of target cells

• The initial step is conjugate formation

• Results from T cell recognizing processed antigen-class I MHC complexes

• 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

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

• 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

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)

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

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

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

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

• 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

Protective role of DTH

Assignment

• Continue reading Chapter16

• Review question 3 (pg 411)