Module 5 Immulogy

B and T cell similarities [Slide 3]

Both are produced in bone marrow

B-cell vs T-cell maturation [Slide 3]

B cells mature in bone marrow

BCR vs TCR diversity [Slide 3]

BCR diversity uses somatic recombination and hypermutation; TCR diversity uses somatic recombination only.

Thymus [Slide 4]

Primary lymphoid tissue where T cells mature.

Thymocytes [Slide 4]

Immature T cells that develop within the thymus.

Thymic stroma [Slide 4]

Network of thymic epithelial cells surrounding developing thymocytes.

Thymus cortex [Slide 4]

Outer dense region packed with thymocytes.

Thymus medulla [Slide 4]

Contains mature thymocytes

Thymic involution [Slide 6]

Thymocytes are gradually replaced by fat beginning around age 1.

Immunosenescence [Slide 6]

Gradual reduction of immunocompetence with age.

T-cell precursor [Slide 7]

Leaves bone marrow

Thymic stromal cells [Slide 7]

Stimulate T-cell precursors to divide and differentiate.

Committed thymocytes [Slide 8]

Express T-cell markers such as CD2 but do not yet have a TCR.

Double-negative (DN) thymocytes [Slide 8]

Developing thymocytes that do not yet have a TCR.

Notch1 [Slide 9]

Receptor on DN thymocytes that binds Notch1 ligand on thymic epithelial cells.

Notch signaling [Slide 9]

Notch1 binding its ligand triggers intracellular signaling and gene expression for T-cell development.

DN thymocyte recombination [Slide 10]

DN thymocytes begin somatic recombination of αβ and γδ TCR components.

γδ T-cell pathway [Slide 10]

If productive γ and δ rearrangements occur first

αβ T-cell pathway [Slide 10]

If a productive β rearrangement occurs first

Pre-TCR [Slide 12]

Tests whether a functional β chain can bind a surrogate α chain called pTα.

Functional pre-TCR [Slide 12]

β chain + pTα + CD3 + ζ chain form the functional pre-TCR.

Pre-TCR signaling [Slide 13]

Triggers proliferation and expression of CD4 followed by CD8.

Double-positive (DP) thymocyte [Slide 13]

Developing thymocyte that expresses both CD4 and CD8.

DP thymocyte recombination [Slide 13]

Continues recombination of αB TCR

αβ TCR formation [Slide 13]

Productive α + β rearrangement produces an αβ TCR.

γδ T cells [Slide 13]

Productive γ + δ rearrangement produces γδ T cells that leave the thymus through blood.

Favored T-cell lineage [Slide 13]

The αβ T-cell lineage is favored.

Thymic selection [Slide 15]

αβ DP thymocytes undergo positive and negative selection.

Positive selection [Slide 16]

Identifies αβ DP thymocytes that can recognize self-MHC.

Positive selection cells [Slide 16]

Cortical thymic epithelial cells present self-antigen on MHC I and II.

Successful positive selection [Slide 16]

Moderate or high binding to self-MHC produces survival signals.

Failed positive selection [Slide 16]

Weak or no self-MHC binding leads to apoptosis.

Positive selection survival [Slide 16]

Less than 2% of thymocytes survive.

MHC I selection [Slide 17]

Recognition of MHC I produces an αβ CD8+ T cell.

MHC II selection [Slide 17]

Recognition of MHC II produces an αβ CD4+ T cell.

Single-positive T cell [Slide 17]

Mature thymocyte expressing either CD4 or CD8.

Negative selection [Slide 18]

Eliminates SP thymocytes that bind too strongly to self-antigen or self-MHC.

Negative selection location [Slide 18]

Occurs in the medulla with dendritic cells and macrophages.

Central tolerance [Slide 18]

Negative selection removes potentially self-reactive T cells.

Mature naïve T cells [Slide 19]

Leave the thymus and recirculate between blood and lymphatics.

Peripheral tolerance [Slide 19]

T cells responding to self-antigen can become anergic.

Mature T-cell lifespan [Slide 19]

Mature T cells can recirculate for many years.

Helper T cells (TH) [Slide 20]

Recognize pathogenic antigen on MHC II and produce effector and memory TH cells.

Effector helper T cells [Slide 20]

Activate cytotoxic T cells or B cells to help destroy pathogens.

Cytotoxic T cells (TC) [Slide 20]

Recognize abnormal self-antigen on MHC I and target abnormal self-cells.

Regulatory T cells (Treg) [Slide 20]

Suppress immune activities such as B cells

Cell-mediated immunity [Slide 21]

Immune response that activates T cells to proliferate and become effector cells.

Naïve T-cell antigen encounter [Slide 22]

Most naïve T cells encounter antigen in secondary lymphoid tissues.

Myeloid dendritic cells [Slide 22]

Capture antigens and bring them to secondary lymphoid tissues for presentation to naïve T cells.

Peripheral tissue infection [Slide 22]

Activates T cells in draining lymph nodes.