MMI 188B M2

T cells and B cells originate in

Bone marrow

T cells mature in

thymus

T cells and B cells undergo

receptor gene rearrangement and negative selection to remove self-reactive clones

T cells differentiate into

αβ T cells (majority) and γδ T cells (minority)

Mature T cells move to

secondary lymphoid tissues (LN, spleen, GALT) to find antigen

Involution of the thymus

age related degeneration of thymic tissue beginning about 1 year after birth, fat gradually replaces thymocytes

Immunosenescence

gradual decline of immune function with age, associated with thymic activity and diminished production of new t cells

Name the areas where thymocytes develop

Cortex: many immature thymocytes (top)

Medulla: many mature thymocytes (bottom)

Explain why thymectomy is less effective on adults

surgical removal of thymus - adults have self-renewing long lived peripheral T cells so little impact on their immune competence

Macrophage role in thymocyte progression

Engulf thymocytes that die during development

Hassall’s Corpuscles

act as active signaling centers, produce TSLP; cytokine is essential for activating myeloid dendritic cells w/in thymus

→ which induce differentiation of developing T cells into regulatory T cells (CD4+CD25+FoxP3+)

VITAL ROLE in central tolerance

may also be involved in apoptotic thymocytes

thymic stroma

network of epithelial cells that form structural framework supporting thymocyte development

thymic anlage

rudimentary thymic structure formed during embryogenesis from ectodermal cortical and endodermal medullary epithelial cells

Complete DiGeorge syndrome

genetic disorder in which thymus fails to develop, resulting in complete lack of T cells and severe immunodeficiency

Thymocytes commit to T cell lineage before rearranging their T cell receptor genes

Double-negative thymocytes (DN thymocytes) - early thymic T cell precursors that lack both CD4 and CD8 surface markers

CD4 and CD8 are

Co-receptors

Notch 1 drives T cell development by

binds to ligand on thymic epithelium → interaction produces protease to cleave intracellular domain from plasma membrane → soluble intracellular domain is translocated to the nucleus where it turns on the expression of genes essential for t cell development → removing repressive TFs and recruiting co-activating TFs

double positive thymocytes (DP)

immature T cells in thymus that express both CD4 and CD8 coreceptors on their surface

αβ and γδ T cells develop from what type of T cell progenitor?

Double negative T cell progenitor (CD2 positive)

Process of αβ and γδ T cells development

T cell precursors enter thymus and express CD34 but none of the mature T cell markers → as soon as they produce complete receptor, γδ cells can leave thymus and travel to other tissues via blood → rearrangement of genes resumes and productive α chain gene rearrangement produces double positive CD4 and CD8 αβ T cells → minority of thymocytes that resume rearrangement give rise to γδ cells

pTα (pre T alpha chain)

surrogate alpha chain in developing thymocytes

pre TCR formed when beta chain pairs with pTα, creates heterodimer that dimerizes into superdimer

Lymphocyte specific protein tyrosine kinase (Lck)

cytoplasmic tyrosine kinase that transduces signals from pre TCR through phosphorylation cascades

Pre T cell

thymocyte that successfully assembled pre TCR and received survival signals and progresses to the pre T cell stage

Difference between pre-T cell receptors and T cell receptor

Pre T cell receptor: 2 heterodimers of a beta chain and a pTα chain

if the beta chain has capacity to form functional T cell receptor → forms superdimer

functional pre T cell receptor: superdimer interacts with CD3 complex and