Principles of Immunology T CellMediated Immunity 32806 Each

Principles of Immunology T Cell-Mediated Immunity 3/28/06 “Each of us needs to be the change we wish to see in the world” Ghandi

Word/Terms List o o ADCC Effector cells GVH reaction Perforin

T Cell-mediated Immunity o. Principal function-Response to intracellular pathogens and cells expressing foreign antigens o. Recirculation-Naïve T cells circulate between the blood stream and the lymphatic system o. Antigen presentation-Naïve T cells only respond to APCs

Priming of T Cells o Three types of effector T cells n n n o CD 8 (TC) CD 4 (TH 1) CD 4 (TH 2) Each type n n n Responds to different types of Ags Activated by different Ag presentation Has different effector function

T Cell Effector Types o CD 8 n n n o CD 4 TH 1 n n n o Viruses and intracellular bacteria MHC I Cytotoxic effector cells Bacteria and parasites in APCs MHC II Effectors activate macrophages, CTLs and induce B cells to produce opsonins CD 4 TH 2 n n n Extracellular bacteria and toxin producers MHC II Activate B cells to produce multiple antibody classes

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

Cell Adhesion Molecules o Selectins o Mucins o Integrins o Immunoglobulin superfamily

APCs o Dendritic cells o Macrophages o B cells

Dendritic Cells o o o Antigen presentation is sole function Antigenic uptake is followed by migration to lymph nodes Expression of MHC I, MHC II and B 7 Loses phagocytic property Secretes chemokines

Macrophages o o Involved in both innate and adaptive immunity May destroy pathogens or present Ag to T cells Expression of MHC I, MHC II and B 7 Scavenges dead cells

B Cells o Binds soluble antigens o Constitutively expresses MHC II o Induced to express B 7

NK Cells o o o ~5% of lymphocytes Nonspecific cytotoxicity No TCR/CD 3 Not MHC restricted No memory

CTL Cytotoxicity o o Conjugate formation Membrane attack Dissociation Target cell death

Conjugate Formation o o Cell adhesion Recognition of MHC I: Ag on target cell

Membrane Attack o Granules in CTLs n n o Exocytosis of granule contents n n o Perforin Granzymes Perforin action similar to C 9 Granzymes act as nucleases Fas ligand to Fas triggers target cell death

Dissociation and Target Cell Death o o o CTL interacts for about five minutes Dissociates and can conjugate with other target cells Target dies after several hours

Antibody-Dependent Cell-Mediated Cytotoxicity o o o NK cells, macrophages, neutrophils Bind to Fc region of Ab Multiple cytotoxic mechanisms

Graft vs. Host Reaction o o o Immunocompromised recipient Lymphocytes of donor attack allogeneic antigens of recipient Splenomegaly