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Chapter 10- T-cell maturation, Activation, & Differentiation. Where we’re going- Define these words Positive and negative selection Some terms for the steps along the way to maturity Be in awe of how complex activation is (not really- hard to test!), and understand the bottom line.

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chapter 10 t cell maturation activation differentiation
Chapter 10- T-cell maturation, Activation, & Differentiation
  • Where we’re going-
  • Define these words
  • Positive and negative selection
  • Some terms for the steps along the way to maturity
  • Be in awe of how complex activation is (not really- hard to test!), and understand the bottom line
the job of making functional t cells
The job of making functional T cells
  • Precursor mature, but naïve T cell (Th or Tc), activate, differentiate.
  • Doesn’t react to self
  • Binds to MHC
  • Able to respond to an antigen that it’s never met! (is that weird, or what???)
so some thought experiments
So some thought experiments
  • If a is able to recognize both an A and B haplotype, but the thymus only shows it the B haplotype- what kind of T cells will you produce?
slide8

Key point- the lymphocytes are not recognizing the A haplotype, because they are maturing in a B haplotype environment.

slide9

Lots of TCR diversity-

Some can’t bind MHC, or bind too well.

Some respond to self Ag’s

Double Positive thymocyte

another thought expt
Another thought expt.
  • If a T cell needs to see MCH I k haplotype, but you only show it MHC I d haplotype- will it develop?
another thought experiment
Another thought experiment
  • If a T cell is preset to respond to an antigen, and it sees that antigen in the thymus- what happens?
slide14

H-Y is male specific antigen!

Again, you only produce 1 type of T cell- should have either CD4+ or CD8+, and it binds to H-Y Ag!

activation
Activation
  • Activation of Thelper cells: We know that Th are needed for both B cell activation and Tc activation.- We’re concentrating on Th cell activation here.
  • Common features: pp 229-231:
  • -receptor-ligand interaction;
  • Transduction through a G protein- active w/GTP bound
  • Production of 2nd messengers: cAMP or Ca++.
  • Protein kinases & phosphatases activate or inhibit proteins.
  • The bottom line is IL2 secretion and response to its own secretion by an IL2 receptor and proliferation
chokingly complex what to remember
Chokingly complex- what to remember
  • Importance of CD3 and its ITAMS
  • Phosphorylation activates proteins
  • Cascade
  • G proteins,
  • 2nd messengers
  • Gene activation
  • Ongoing proliferation- IL2 and its receptor.
signal 1 and 2 tcr activation isn t the whole story
“Signal 1 and 2”- TCR activation isn’t the whole story
  • TCR activation is necessary, but not sufficient, to produce activation. It is called “signal 1”.
  • The T cell also needs “signal 2”- CD28-B7 interaction.
  • Its absence produces clonal anergy
differentiation
Differentiation
  • A cell then becomes an effector cell, or a memory cell.
  • Effector Th cell secretes certain cytokines- 2 basic types (or maybe three, with suppressors!)- the cytokines released affect whether the response is primarily antibody or primarily cell-mediated.
  • Effector Tc cells can kill their targets
  • Memory cells proliferate more readily upon a second stimulation.
key points to chapter 10
Key Points to chapter 10
  • Define maturation, activation, differentiation
  • Positive and negative selection, double negative and double positive thymocyte
  • Key components to activation signaling:
    • Phosphorylation
    • GTP
    • Key 2nd messenger- Ca++
    • The major effects- activating transcription factors
    • Bottom line- IL2 and IL2R for proliferation
signal 1 and 2 differentiation
Signal 1 and 2 & differentiation
  • Know signal1 and 2, and anergy
  • Differentiated Tc cells can now kill target
  • Th effectors do their work mainly by cytokine production
  • Memory cells- long-lasting, require less stimulation to activate/differentiate.
  • Review of superantigens