T cell activation and differenciation

Process of naive T cell to activated

• APC - T helper cell CD4+ and T cytotoxic CD8+

• Cytokines released - IL-2R and IL-2

• Replicate

• Turn into effector cells or memory cells

• T helper effector cells = macrophages and B cells

• T cytotoxic effector cells = kill infected target cells, macrophage activation

• In lymphoid organs

memory cells

stay in the tissues and reemerge in the tissue when encounter infection again

T cell trafficking

• mature naive T cell leaves the thymus and enter the blood

• lymphocyte homing

  • naive T cells to the peripheral nodes

  • activated and memory T cells leave the nodes and go to the tissue

• up and down regulate certain CD molecules based on where it is moving

Time course and gene expression in T helper cells

• Early

  • cell cycle continues to get more copies

• Intermediate

  • communication molecules

  • production of cytokines

  • effector cells

• End

  • will go out and wander the body

Co stimulatory pairs

• 1st signal MHC II binds with TCR co receptor makes sure that they should bind

• 2nd signal co stimulatory pairs double check if they are actually supposed to bind

  • B7 - CD28 or CTLA-4

  • CTLA-4 non stimulatory signal turns off signal

2 signal hypothesis

• T cells require ag presentation as a first signal

• other molecular interactions can provide a second signal

• once activated T cell differentiation to effector forms

3 types of memory cells

• stem cell - see ag and right away become memory cell

• central

• effector - long lived been through an immune response, makes sure infection is already gone

  • normally when we use effector cells in an immune response they die after

memory cell ideas

• memory cells last for years but need to rep more to make sure you have some for when they get old

• once cells are specialized its hard for them to go back into cell cycle

Communication between molecules

• T helper and T cytotoxic with APC

• ICAM-1 - adhesion molecules that hold the two in place for them to communicate

• if it secretes cytokines it does not need a lot of that to respond

autocrine

• secrete and respond to same cell

• produce more cytokines to mount another response to a close cell and pull it in another direction

paracrine

• between nearby cells

• cytokines gain information about the enviro which influences what the T cell becomes

gene activation

activation of genes that regulate proliferation and effector function

activation and inhibition of T cells

• co stimulation

• CTLA-4 blocks co stimulation and then activation

• Ipilimumab block CTLA-4 which allows for co stimulation and activation

anergic T cells

• no co stimulatory interaction

• non apc will turn itself off when it doesn’t see co stimulation

• CTLA-4 strong inhibitory signal

Myeloid cells

• dendritic cells, macrophages

• once activated more readily aviable to T cells

lymphoid cells

• B cells

• even at rest produces MHC II

• ab will bind to ag

• phagocytize

• drop pH so that they separate

• ab back to the surface ag through lysosome becomes present in MHC II when it goes to the lymph nodes where T cells are

superantigen

• triggers a big immune response

• requires a specific MHC and v beta

• Immune responses can become too big

• Ex:

  • skin infection

  • food poisoning

  • toxic shock syndrome - staph can produce a superantigen under circumstances and activate a huge immune response

Type 1 response

• MHC and TCR

• co stimulation

• cytokines released IL-12

• produce TFN-gamma

• intracellular pathogens

  • viruses

  • bacteria

Type 2 response

• MHC and TCR

• co stimulation

• cytokines released IL-4

• produce IL- 4 IL-5 IL- 13

• extracellular pathogens

  • parasites

3rd signal

• what cytokines are around when the T cell is activated

• what kind of T cell it becomes

B cells in response to T cell cytokines

• also listen to all the cytokines produced by T cells

• activate B cell

• goes through proliferation - differentiation - class switching

T reg cells

• IL-2, TGF - beta

• FOX P3

• IL-10, TGF - beta

• regulation and suppression of immune and inflammation responses

Th17 cells

• IL-1,6,23, TGF-beta

• ROR-gammat

• IL-17A, IL-17, 22

• inflammation

Th2

• IL-4

• GATA3

• IL-4,5,13

• Allergic or parasitic infection

TFH

• IL-6,21

• Bcl-6

• IL-4,21

• B cell help

Th1

• IL-12,18, IFN-gamma

• T-Bet

• IFN-gamma, TNF

• Cell mediated immunity, macrophages activate, inflammation

TNF-beta key

• IL-6 decides if it will become Treg or Th17

  • low = Treg

  • high = Th17

Transcription factors

• T-Bet and GATA3 are inhibitory to each other

• pick one then they become less sensitive to the other signals that do different things

B cell help

T cells dont need to move far to help B cells in the follicle to get them to activate

T cell help

To help T cells they need to be able to move to the infected cell and kill it

Importance of Th subsets

If you use a T2 response for a virus the cell is more likely to die because it is not getting the correct response to clear it

Types of memory cells

• central memory cells

• effector memory cells

• arise very early in the immune response

• central memory cells come from previous effector memory cells

• effector cells come from fully differentiated effector cells

central effector memory cells

• longer lived easier to replicate

• secondary lymphoid tissues

• reactivated by the 2nd time it sees ag

• different subset based on its cytokines

effector memory cells

• 1st line defense

• shift back to effect or function when it encounter ag again

Functional immunity

• baby is foreign need to not engage a immune response to it

• T reg and inhibitory cytokines line the placental barrier

• retrotransposon insertion makes turning on FOXP3 easier which allows the body to not reject the baby