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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

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

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Page 1: 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

Principles of Immunology

T Cell-Mediated Immunity3/28/06

“Each of us needs to be the change we wish to see in the world”

Ghandi

Page 2: 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

ADCC Effector cells GVH reaction Perforin

Page 3: 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

T Cell-mediated Immunity

Principal function-Response to intracellular pathogens and cells expressing foreign antigensRecirculation-Naïve T cells circulate

between the blood stream and the lymphatic system

Antigen presentation-Naïve T cell cells only respond to APCs

Page 4: 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

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

Page 5: 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

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

Page 6: 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

T Cell Adhesion

T cells pass through endothelial cells (extravasation)

Endothelial cells and T cells both have cell adhesion molecules (CAMs)

Various CAMs

Page 7: 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

Cell Adhesion Molecules

Selectins

Mucins

Integrins

Immunoglobulin superfamily

Page 8: 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

APCs

Dendritic cells

Macrophages

B cells

Page 9: 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

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

Page 10: 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

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

Page 11: 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

B Cells

Binds soluble antigens

Constitutively expresses MHC II

Induced to express B7

Page 12: 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

NK Cells

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

Page 13: 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
Page 14: 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
Page 15: 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
Page 16: 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

CTL Cytotoxicity

Conjugate formation Membrane attack Dissociation Target cell death

Page 17: 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

Conjugate Formation

Cell adhesion Recognition of MHC I:Ag on target cell

Page 18: 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

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

Page 19: 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

Dissociation and Target Cell Death

CTL interacts for about five minutes Dissociates and can conjugate with

other target cells Target dies after several hours

Page 20: 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
Page 21: 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

Antibody-Dependent Cell-Mediated Cytotoxicity

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

Page 22: 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
Page 23: 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

Graft vs. Host Reaction

Immunocompromised recipient Lymphocytes of donor attack

allogeneic antigens of recipient Splenomegaly