T Helper Lymphocytes

What is the first step in T helper cell activation?

TCR binds to MHC 2/antigen and CD4 binds to MHC 2

What is the second step in T helper cell activation?

Adhesion molecules bind (not really a signal)

       - LFA 1 on the T cell binds to ICAM-1 or ICAm-2 on APC

       - CD2 on T cell binds to LFA-3 on APC

What is the third step in T helper cell activation?

Co-stimulation CD28 on T cell binds to CD80 or CD86 on APC

What is the fourth step in T helper cell activation?

Cytokines

     - T cell produces IL-2 which binds to receptor on that T cell (autocrine)

           - IL-2 signals the T cell to proliferate à Clonal selection

     - Polarizing cytokines will be secreted by the APC and/or other immune cells in the secondary lymphoid tissues

         - T cells differentiate into effector cells and memory cells

What is the function of effector T helper cells?

Secrete cytokines that orchestrate the activity of other cells

What T helper cells in general are involved in cell mediated responses?

Th 1 and Th 17

What T helper cells in general are involved in humoral responses?

Th 2 and T FH

What T helper cells won’t we really learn about and why?

Th 9 or Th 22 since they are the newest

What does each subset of effector T helper cells have?

Each subset has distinct cytokines that induce expression of a master gene regulator

What is the function of the master gene regulator?

The master gene regulator regulates gene expression for cytokines

What are the cytokines that are regulated by the master gene regulator?

These cytokines are effector cytokines that are produced when the T_H cells are fully differentiated

What polarizing cytokines cause the differentiation into Th1 effector cells?

IL-12, IFN-gamma, and IL-18

The TH1 polarizing cytokines regulates what master gene regulator? What does the master gene regulator cause?

T-Bet which causes the release of the effector cytokines IFN - gamma, TNF-alpha, and TNF-beta

What is the function of Th1 effector cells?

Activate macrophages, Tc (cytotoxic) cells, inflammation

How do TH1 helper T cells activate macrophages?

Effector T cells express CD40L – When it binds to CD40, the effector T cell secretes effector cytokines

-It also requires TCR engagement

        - TCR binds to MHC 2/antigen

        - CD4 binds to MHC 2

True for all the effector cytokines

What polarizing cytokines cause the differentiation into Th2 effector cells?

IL-4

The TH2 polarizing cytokines regulates the master gene regulator? What does the master gene regulator cause?

GATA3 causes the release of effector cytokines IL-4, IL-5, and IL-13

What is the function of Th2 effector cells?

These cells help direct response to parasites

What are the Th2 effector functions?

IL-4 secretion results in B cell class switching to IgE

IL-5 and IL-13 secretion induces activation of granulocytes

What polarizing cytokines cause the differentiation into Th17 effector cells?

IL-6, IL-23, TGF-beta

The TH17 polarizing cytokines regulates the master gene regulator? What does the master gene regulator cause?

ROR gamma T causes the release of effector cytokines IL-17, IL-22

What is the function of Th17 effector cells?

These cells promote inflammation

What are the Th17 effector functions?

•Stimulate neutrophils to clear extracellular pathogens

•IL-17 promotes IL-8 secretion (IL-8 recruits neutrophils)

What polarizing cytokines cause the differentiation into T follicular helper effector cells?

IL-6, IL-21

The T follicular helper polarizing cytokines regulates the master gene regulator? What does the master gene regulator cause?

Bcl-6 causes the release of effector cytokines IL-4, IL-21

What is the function of T follicular helper effector cells?

These cells are necessary for activation and differentiation of B cells

What polarizing cytokines cause the differentiation into induced Tregs effector cells?

IL-2, TGF-beta

The induced Tregs polarizing cytokines regulates the master gene regulator? What does the master gene regulator cause?

FOXP3 causes the release of effector cytokines IL-10, TGF-beta

What is the function of induced Tregs effector cells?

These cells suppress immune responses