Lecture 27- Adaptive Immunity, Cell Mediated Responses

Characteristics of Cell Mediated Responses

-respond to intracellular pathogens and abnormal body cells-

1) viruses

2) cancer cells

3) intracellular protozoa

4) intracellular bacteria

Development of T cells Occurs in Several Locations

produced in RBM and matures in thymus, circulation and surveillance in lymph and blood, migration to lymph nodes, GALT, and spleen

T cells have…?

TCRs which allow antigen recognition

Specificity of TCR

1) TCRs don’t recognize epitopes directly

2) TCRs only bind epitopes associated with an MHC protein

3) T cells act primarily against cells that harbor intracellular pathogens

4) Some T cells act against body cells that produce abnormal cell surface proteins

How Many Antigens can T cells in the Body Recognize?

T cell receptor diversity occurs through VDJ recombination like antibodies, human has about 2e11 naive T cells at any time, there are 10 of each naive T cell clone, 2e10 different T cell receptors in the body at any given time

3 Types of T cells

1) Helper T cells (Th), CD4+ T-cells

2) cytotoxic T cells (Tc), killer T cells, CD8+

3) regulatory T cells (Tr, Treg)

Helper T cells (Th) 2 Functions

1) secrete interleukin 2, 4, 5, and interferon gamma

2) recognize target and help regulate B cells and cytotoxic T cells

-TCR and CD4

Cytotoxic T Cells

1) secrete perforin, granzyme

2) directly kills target cells

-TCR, CD8, and CD95L

Regulatory T cells

1) secretes interleukin 10 (IL-10)

2) represses adaptive immune responses

TCR, CD25, and CD4

Th Cells activate…?

Tc cells to induce a cytotoxic response, TCR MHC-I and CD8 all bind together

1) antigen presentation

2) Th differentiation

3) clonal expansion

4) self stimulation

Mechanism of Tc Killing

1) perforin granzyme pathway

2) CD95 pathway

Perforin Granzyme Pathway

involves synthesis of special killing proteins

CD95 pathway

mediated through glycoproteins on body’s cells

Memory T cells

some activated T cells become memory T cells, persists for moths or years in lymphoid tissues, immediately functional upon subsequent contacts with epitope MHC complexes specific to its TCR

Memory Responses

more effective than the primary response, faster and stronger

Kinetics of T cell Response

1) naive T cells, antigen presence

2) T Cell activation, proliferation to effector T cells

3) effector T cell death to memory T cells

Regulation of T cells

response is controlled to prevent T cell response to autoantigens, T cells require additional signals from an antigen presenting cell, interaction of T cell and antigen presenting cell stimulates the T cell to respond to the antigen

Regulatory T Cells (Tregs)

moderate cytotoxic T cell activity

Regulatory T cells Responsible for…?

1) de activation of T cells

2) killing of activated T cells

3) reduction of antigen presentation

4) sensing dead T cells