T Cell Development

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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

Word/Terms List

 ADCC

 Effector cells

 GVH reaction

 Perforin

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

Priming of T Cells

 Three types of effector T cells

 CD8 (T

C

)

 CD4 (T

H1

)

 CD4 (T

H2

)

 Each type

 Responds to different types of Ags

 Activated by different Ag presentation

 Has different effector function

T Cell Effector Types

 CD8

 Viruses and intracellular bacteria

 MHC I

 Cytotoxic effector cells

 CD4 T

H1

 Bacteria and parasites in APCs

 MHC II

 Effectors activate macrophages, CTLs and induce B cells to produce opsonins

 CD4 T

H2

 Extracellular bacteria and toxin producers

 MHC II

 Activate B cells to produce multiple antibody classes

T Cell Adhesion

 T cells pass through endothelial cells

(extravasation)

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

 Various CAMs

Cell Adhesion Molecules

 Selectins

 Mucins

 Integrins

 Immunoglobulin superfamily

 Dendritic cells

 Macrophages

 B cells

APCs

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

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

B Cells

 Binds soluble antigens

 Constitutively expresses MHC II

 Induced to express B7

NK Cells

 ~5% of lymphocytes

 Nonspecific cytotoxicity

 No TCR/CD3

 Not MHC restricted

 No memory

CTL Cytotoxicity

 Conjugate formation

 Membrane attack

 Dissociation

 Target cell death

Conjugate Formation

 Cell adhesion

 Recognition of MHC I:Ag on target cell

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

Dissociation and Target Cell Death

 CTL interacts for about five minutes

 Dissociates and can conjugate with other target cells

 Target dies after several hours

Antibody-Dependent Cell-Mediated

Cytotoxicity

 NK cells, macrophages, neutrophils

 Bind to Fc region of Ab

 Multiple cytotoxic mechanisms

Graft vs. Host Reaction

 Immunocompromised recipient

 Lymphocytes of donor attack allogeneic antigens of recipient

 Splenomegaly

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