Principles of Immunology T Cell-Mediated Immunity 3/28/06

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Principles of ImmunologyT Cell-Mediated
Immunity3/28/06

• Each of us needs to be the change we wish to see
  in the world
• Ghandi

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Word/Terms List

• ADCC
• Effector cells
• GVH reaction
• Perforin

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T Cell-mediated Immunity

• Principal function-Response to intracellular
  pathogens and cells expressing foreign antigens
• Recirculation-Naïve T cells circulate between
  the blood stream and the lymphatic system
• Antigen presentation-Naïve T cell cells only
  respond to APCs

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Priming of T Cells

• Three types of effector T cells
• CD8 (TC)
• CD4 (TH1)
• CD4 (TH2)
• Each type
• Responds to different types of Ags
• Activated by different Ag presentation
• Has different effector function

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T Cell Effector Types

• CD8
• Viruses and intracellular bacteria
• MHC I
• Cytotoxic effector cells
• CD4 TH1
• Bacteria and parasites in APCs
• MHC II
• Effectors activate macrophages, CTLs and induce B
  cells to produce opsonins
• CD4 TH2
• Extracellular bacteria and toxin producers
• MHC II
• Activate B cells to produce multiple antibody
  classes

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T Cell Adhesion

• T cells pass through endothelial cells
  (extravasation)
• Endothelial cells and T cells both have cell
  adhesion molecules (CAMs)
• Various CAMs

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Cell Adhesion Molecules

• Selectins
• Mucins
• Integrins
• Immunoglobulin superfamily

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APCs

• Dendritic cells
• Macrophages
• B cells

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Dendritic Cells

• Antigen presentation is sole function
• Antigenic uptake is followed by migration to
  lymph nodes
• Expression of MHC I, MHC II and B7
• Loses phagocytic property
• Secretes chemokines

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Macrophages

• Involved in both innate and adaptive immunity
• May destroy pathogens or present Ag to T cells
• Expression of MHC I, MHC II and B7
• Scavenges dead cells

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B Cells

• Binds soluble antigens
• Constitutively expresses MHC II
• Induced to express B7

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NK Cells

• 5 of lymphocytes
• Nonspecific cytotoxicity
• No TCR/CD3
• Not MHC restricted
• No memory

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CTL Cytotoxicity

• Conjugate formation
• Membrane attack
• Dissociation
• Target cell death

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Conjugate Formation

• Cell adhesion
• Recognition of MHC IAg on target cell

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Membrane Attack

• Granules in CTLs
• Perforin
• Granzymes
• Exocytosis of granule contents
• Perforin action similar to C9
• Granzymes act as nucleases
• Fas ligand to Fas triggers target cell death

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Dissociation and Target Cell Death

• CTL interacts for about five minutes
• Dissociates and can conjugate with other target
  cells
• Target dies after several hours

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Antibody-Dependent Cell-Mediated Cytotoxicity

• NK cells, macrophages, neutrophils
• Bind to Fc region of Ab
• Multiple cytotoxic mechanisms

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Graft vs. Host Reaction

• Immunocompromised recipient
• Lymphocytes of donor attack allogeneic antigens
  of recipient
• Splenomegaly