NK Cells

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Lecture 11

• NK Cells
• Transplantation Immunology

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Cell Mediated Immunity

• CD4 T Cells
• CD8 T Cells
• NK Cells

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Natural Killer Cells (NK Cells)

• Lymphocytes
• No thymic development.
• Mouse
• granulated, large, nonphagocytic
• Effective in host defense against
• virus infected cells
• tumor cells

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Features of NK Cell-Mediated Cytotoxicity

• No priming, memory, specificity
• No MHC Restriction
• Response amplified by certain cytokines
• IFN?
• IFN?
• IL-12
• IL-15

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Induction of NK Cells During a Viral Infection
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NK Cell-Mediated Cytotoxicity

• Antibody-Dependent Cell-Mediated Cytotoxicity
• Direct NK Cell-Mediated Cytotoxicity
• Lack of cell surface MHC Class I
• Recognize cell-surface protein
• Influenza hemagglutinin

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Antibody-Dependent Cell-Mediated Cytotoxicity
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Direct NK Cell-Mediated Cytotoxicity
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Opposing Signal Model of Cytotoxicity By NK Cells
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Direct Killing of a Virus-Infected Cell by
Recognizing Viral Proteins on Target Cell
Surface in the Presence of Normal levels of MHC
Class I Expression
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Transplantation Immunology
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Transfusion vs. Transplantation

• Transfusion
• transfer of blood
• Ab-mediated reactions
• Transplantation
• transfer of any other tissue/organ
• T cell mediated reactions

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Graft survival?
Donor
Recipient (Host)
Autograft
Yes
Syngraft
Yes
No
Allograft
Xenograft
No
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B
A
T Cells
Memory
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Histocompatibility Antigens

• Transplantation Antigens
• Several loci, Several alleles at each locus
• Major (MHC) and Minor
• MHC Haplotype
• Total set of MHC alleles on each chromosome
• Heterozygous indiv. have 2 Haplotypes

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Role of T Cells in Acute Graft Rejection

• Adoptive Transfer Experiments
• Lack of Rejection in T-cell Deficient Individuals
  
• Histological Demonstration of CD4 and CD8 T
  cells Infiltration

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• The molecules that are recognized as foreign on
  allografts are called ALLOANTIGENS.
• The Lymphocytes that react with alloantigens are
  called ALLOREACTIVE

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Allogeneic Recognition
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Direct and Indirect Recognition of Alloantigens
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Direct Recognition

• CD4 T Cells recognize foreign MHC II molecules
• CD8 T Cells recognize foreign MHC I molecules

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Mixed Lymphocyte Reaction (MLR)

• In Vitro Model of Direct T Cell Recognition of
  Allogeneic MHC Mixed Lymphocyte Reaction
• Predictive Test of Cell-Mediated Graft Rejection

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Mixed Lymphocyte Reaction (MLR)
Donor
Recipient
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Effector Mechanisms in Allograft Rejection

• CD8 T cells lyse endothelial and parenchymal
  cells
• CD4 T cells can recruit and activate
  macrophages-graft injury by a DTH response
• Antibodies activate complement and injure graft
  vasculature

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Acute Rejection
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Chronic Rejection
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Role of Antibodies and Cell-Mediated Immunity in
Different Allograft Rejection
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Preventing Graft Rejection

• MHC Typing
• Blood
• PCR
• Immunosuppressive Therapy

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Treatment for Graft Rejection