BIO 343 Lecture Notes - Lecture 7: Repressor, Dendritic Cell, Macrophage
Immunology Chapter 7: Development of T Lymphocytes
Hayden Casassa
• Events that occur in the Thymus
o Generation of TCR Diversity
▪ Happens while T cells develop in the thymus
o Thymic selection process
▪ Only T cells that can bind self-MHC survive whole those that bind too strongly with self-
MHC complexes are killed
▪ This selection ensures self-toleae so T ells do’t eat to the od’s peptides
o Maturation into T cell subsets (CD4 and CD8)
▪ 98% of developing T cells do not mature and die via apoptosis
• The TCR region is totally random with millions of combinations which is why
ost of the die uz the ae’t speifi fo atigei peptides
• T cell precursors migrate from the bone marrow to the thymus to mature
o Once they mature, they leave the thymus to travel to secondary tissues to circulate
• Thymus is most active and important in young people and atrophies (shrinks) with age
o T cells replaced with fat as we age (involution)
o Involution does not affect T cell immunity because T cells that leave the thymus are long-lived
and self-renew
• Structure of the Thymus
o Covered by a thin connective tissue capsule and lobulated by septa
o Dense outer layer is called cortex and the lighter middle region is called medulla
• Cellular Organization of the Thymus
o Thymic Stroma is network of epithelial cells that surrounds the immature T cells called
thymocytes
o Epithelial cells suoud the thotes… T ells coming from marrow arrive via cortico
edulla jutio… The the oe to dese ote aea ad as the atue ete the
medulla
▪ Therefore, more mature T cells in medulla
• Most macrophages and dendritic cells are here too
• Maophage futio hee is to phagotize apoptoti thotes that do’t
mature properly
▪ Cortex has more thymocytes
o Major difference in thymus vs lymph nodes is there is no lymphocyte circulation/drainage
▪ Whole pupose is to take peuso fo oe ao ad spit out atue T ells
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• Commitment to the T cell lineage and the formation of a Double Negative thymocyte is driven by
interactions with thymic stromal cells
o Thymic stromal cells produce growth factors like IL-7 which drive T cell development within the
thymus
o CD34+ uncommitted progenitor is expressed by hematopoietuc stem cells and expresses T-cell
specific adhesion marker CD2 but is a double negative (DN) thymocyte for CD4 and CD8
▪ The CD2 marker means it is destined to be a t cell
o CD2+ DN cells can either be alpha/beta T cells or gamma/delta T cells which are much less
common
• Overview of alpha/beta T cell development in the thymus
o Do’t iitiall express TCR but we have a pre-TCR
▪ “iila thig is e hae a suogate alpha so if e a’t aage eta hai the ell dies
o Then we have double positive expressing both CD4 and CD8
o Alpha hai eaages ad if it a’t the e udego apoptosis
o This gives rise to population of double positive cells expressing both CD4 and CD8
▪ These cells have true rearranged TCR
o At this poit e see the…
▪ Does this bind to self? Can it bind to MHC?
• If it fails then it undergoes thymic selection
• If it passes do we want a CD4 helper cell or Cytotoxic CD8?
• TCR B chain rearrangement
o If a TCR B hai is ade, it’s tested i the ER fo ailit to assoiate ith pTa hih is suogate
alpha chain
o If B chain binds properly, then heterodimer forms CD3 complex and Z chains forms pre-T cell
receptor
▪ This is first checkpoint
o Whe alpha hai is ade, it is tested to see if it a id to the B hai ad ake a eal TCR
▪ This is the second checkpoint
• Pre-T cell receptor on DN pre-T cells
o Once first checkpoint reached, two molecules of heterodimer can form Superdimer
o This superdimer can then interact with CD3 and Zeta chain to initiate expression of both CD4
and CD8 and the rearrangement of a chain gene
• If you have a double positive T cell with CD4 and CD8, what tissue could it be isolated from?
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