Development and Activation of T Lymphocytes (11)

Three outcomes of T cell maturation and selection initially

TCR gamma-delta, apoptosis, and TCR alpha-beta

What occurs after positive selection of TCR alpha-beta?

Differentiates into CD4+/CD8+ thymocyte and then further to CD4+, CD8+, or apoptosis

What is the result of negative selection of CD4+?

Mature CD4+ or apoptosis

What is the result of CD8+ after negative selection?

Mature CD8+ or apoptosis

CD4+/CD8+ thymocyte receptor binds self-peptide: self-MHC class I

CD8+ T cell

CD4+/CD8+ thymocyte receptor binds self-peptide: self-MHC class II

CD4+ T cell

What does the receptor bind in order for positive selection of CD4+/CD8+ thymocyte to CD8+ T cell?

Self-MHC class I

What does the receptor bind in order for positive selection of CD4+/CD8+ thymocyte to CD4+ T cell?

Self-MHC class II

CD8+ and CD4+ T cells are?

Single-positive thymocytes

What happens to CD4+ or CD8+ T cells that bind with high affinity to self MHC/peptide?

Deleted (clonal deletion)

CD4+ or CD8+ T cells that bind with high affinity to self MHC/peptide are deleted

Central tolerance

What are factors of central tolerance?

1. Expression of tissue-specific proteins in the thymus in small amounts

2. Deletion of self-reactive T cells during negative selection

Tissue-specific proteins in the thymus

Transcription factor AIRE

What does AIRE stand for?

autoimmune regulator

What mediates positive selection of immature thymocytes?

Cortical epithelial cells

What mediates negative selection of immature thymocytes?

Dendritic cells

What is peripheral tolerance?

Suppression of self-reactive T cells that escaped negative selection in thymus

What happens to some self-reactive CD4 T cells during negative selection?

Diverted to become suppressor cells

What are characteristics of regulatory T cells?

Have TCRs specific for self-antigens and have use of transcriptional factor FoxP3

What is the function of regulatory T cells?

Suppress activation and proliferation of self-reactive CD4 and CD8 T cells

Flow of naive lymphocytes

efferent lymph, blood, HEV (lymph node)

Flow of effector lymphocytes

efferent lymph; blood; intestine, skin, or lung; afferent lymph; and lymph node

What does HEV stand for?

high endothelial venules

The process of lymphocytes leaving the bloodstream and entering specific tissue sites

Lymphocyte homing

What guides lymphocyte homing?

1. Chemokines secreted by cells at homing site and corresponding chemokine receptors on lymphocyte surfaces

2. Homing receptors on lymphocytes surface and vascular addressins on endothelial cell surfaces

What do selectins bind to?

Mucins

Proteins that contain lectin domain

Selectins

Heavily glycosylated proteins

Mucins

What do integrins bind to?

Ig superfamily molecules

Heterodimer protein family

Integrins

Contain Ig-type domain

Immunoglobulin superfamily

What does L-selectin on naive T cells allow?

Allows them to extravasate through HEVs

What are the steps of extravasation of naive T cells?

Rolling adhesion, activation & arrest of rolling, and diapedesis

What allows for rolling adhesion of the T cell?

Binding of L-selectin to GlyCAM-1 and CD34 allows rolling interaction (Selectin)

What allows for activation of T cells during extravasation?

LFA-1 is activated by chemokines bound to extracellular matrix (Chemokine)

What allows for arrest of rolling of T cells during extravasation?

Activated LFA-1 binds tightly to ICAM-1

Lymphocytes leaves blood and enters lymph node

Diapedesis

What are the two signals required for T cell activation?

1. TCR - MHC/peptide

2. CO-stimulatory molecules CD28 - B7 (CD80, CD86)

What does IL-2 cause in T cells?

Proliferation

Steps of IL-2 induced T cell proliferation

1. Binding of IL-2 to the high-affinity receptor sends a signal to the T cell

2. The signal sent from the IL-2 receptor induces T cell proliferation

What is required for T cell activation?

Co-stimulatory signal (CD28 - B7, CD80, CD86) and antigen-specific signal (TCR - MHC/peptide)

What leads to anergy in the T cell?

Absence of co-stimulatory signal

What inhibits T cell activation?

CTLA-4

Characteristics of antigen-presenting cells

1. Express MHC I and MHC II

2. Express co-stimulatory molecules

3. Uptake of antigen

4. Antigen presentation via MHC I & II

5. Presence in secondary lymphoid tissues

Dendritic cell migration pathway:

Non-lymphoid tissues, afferent lymph vessel, lymph node

What happens with dendritic cells in non-lymphoid tissues?

Increased antigen uptake and decreased antigen presentation

What happens with dendritic cells in lymph nodes?

Decreased antigen uptake and increased antigen presentation

How are naive CD8 T cells activated?

dendritic cells infected with virus capable of activating them on their own

dendritic cells with some viruses need help from CD4 T cells