T cells Flashcards
Where do T cells come from?
Arise from bone marrow, but mature in the thymus
general location of T cells
circulate in the blood in length
what are T-cell receptors
They are antibody like receptors on the surface of T cells, which specialize in recognizing protein agents presented by MHC
number of T cells in the body
300 billon
killer T cells / cytotoxic T lymphocytes (CTLs)
- activated by MHC I being presented on cells (done by MOST cells)
- connects to the target cell
- convinces/triggers target (infected APC) to commit suicide
helper T cells
- activated by MHC II on APC
- secretes cytokines: IL-2, IFN-γ
Regulatory T cells
- keep the immune system from overreacting
- much is unknown about them
what is needed for T cells to function?
They must be activated
types of APCs that activate helper T cells
- activated dendritic cells
- activated macrophage
- activated B cells
requirements for activation
- TCR protein (α, β) for antigen
- Co-receptor proteins (CD4 or CD8) for MHC recognition
- Co-stimulatory molecules (B7 proteins)
- CD3 or four proteins (γ,δ, ε and ζ) for signaling
T-cell recognition occurs when
Occurs when the TCR recognizes its cognate antigen
T cell Receptors (TCR)
molecules on surface of T cell
- TCR only recognize peptides presented by MHC I or II
- Not diverse
- All TCRs on mature T cells are IDENTICAL
- Types: traditional (95%) = αβ Or non-traditional (5%) = γδ
T cell selection/maturation process
- If T cells sees “self” being presented by other cells, then the T cell commits suicide b/c it must be able to distinquish what is “self-made”
- If T cell recognizes “self” antigen, but does NOT get co-stimulation, it is rendered inactivated (anergized) and will eventually die. This processes is called “peripheral tolerance”
- If T cell sees non-self AND gets co-stimulated, it will be ACTIVATED
Non-traditional T cells
- They express γδ T cell receptors
- Abundant in intestine, uterus and tongue
- Less diversity than αβ receptor, thus more effective at recognizing protein fragments from invaders
- Less is known about this type
Recognition requires
- TCR (α, β)
- Co-receptor (CD4 or CD8)
Co-receptor
Either CD8 or CD4 on the T cell which recognizes MHC (I or II respectively)
- When T cells are in the thymus, they express both CD8 and CD4
- As T cell matures, one type of co-receptor is down regulated
CD4
Cluster of Differentiation 4
- Usually expressed by Helper T cells
- Attaches the TCR to MCH II
- Signals the T cell to HELP
CD8
Cluster of Differentiation 8
- Usually expressed by Killer T cells
- Attaches the TCR to MCH I
- Signals the T cell to KILL (the infected APC)
Types of Antigen Presenting Cells
- B cell
- Dendritic cell
- Macrophage
Co-stimulation
when other receptor(s) recognize other molecules
- Many molecules can co-stimulate T cells, but B7 is the major one used
- B7 (from APC) connects with CD28 receptor on T-cell
- Combination of co-stimulation depends on the Pathogen and the Area of the Body
Co-stimulation requires
- B7 on APC
- CD28 on T cell
B7
the major co-stimulatory molecule expressed on surface of APC
• Binds to CD28
CD28
Cluster of Differentiation 28
- is a Co-stimulator receptor on T cell
- triggered when it binds with B7
- Upon being triggered, it amplifies the signal and lowers the number of TCR crosslinks needed for T cell activation
Signaling requires
- CD3 (γ,δ, ε and ζ)
- CD28 on T cell
Signal resistance
may occur if connection btwn the receptor and nucleus of naïve T cell is weak.
• Activation via co-stimulation (B7 + CD28) creates better connection thereby reducing resistance
CD3
the name given to the group of proteins that send signal to cell’s nucleus
Immediate changes of T cells upon activation
more cholesterol lipid rafts form, which contain numerous signaling molecules
- Naïve T cells have few rafts
- Experienced T cells have MANY rafts. They maintain the rafts and thus do NOT need co-stimulation for re-activation
Re-activation of T cells
- Dendritic cells first active T cells in lymph nodes
- Once T cell gets to battle site, they need to be re-stimulated (update info) by marcophages
- Re-activation is easy b/c the lipid raft has formed
Helper T cell Activation
Helper T cells constantly scan dendritic cells in lymph nodes. If it finds its cognate antigen:
• Adhesion molecules bind the Helper T with dendritic cell “immunological synapse”
- CD4 co-receptor on Helper T cell attaches to MCH II on dendritic cell
- CD40L attaches to CD40 on dendritic cell, which lengths life of dendritic cell
- Dendritic cell can the make more co-receptors (CD28) and co-stimulates (B7)
- Dendritic cell then goes on to activate other Helper T cells
- Activated Helper T cells proliferate (newly made Helper T are the same, thus they are specific for the cognate antigen)
- Activated Helper T cells make more IL-2 (positive feedback for division)
Functions of Helper T cells
- remains in blood and lymph, providing help for B cells and CTLs
- leave the blood and into the battle site to provide help for soldiers on the front line. Their help comes in the form of cytokines
cytokines
- many different kinds of cytokines
- secreted by helper T cells in specific combinations depending on stimuli/circumstance from battle site, which is surveyed by dendritic cells
- dendritic cells recognize patterns (PRR = TLR) on certain types of pathogens
- which cytokine is released, depends on inputs from dendritic cells
- once a T helper starts making a certain type of cytokine, it is committed
what are the major subsets of T cells that release cytokines?
Th1, Th2, and Th17
• Th => “T helper”
process for determining cytokines being released
- at the battle site dendritic cells recognize patterns (PRR = toll-like receptors) specific to certain types of pathogens
- Dendritic cell bring this information back to the lymph node, in order to activate Helper T cell
- Dendritic cell will display different co-stimulatory molecules on their surface depending on what type of invader it has encountered.
- Helper T cell scans the lymph node, finds the dendritic cell, engages in “immunological synapse”
- the input signal from DC to Helper T will determine what cytokine is released
Th1 cells
- reacts to: viral or bacterial attack
- response: classical cytokines (TNF, IFN-γ, IL-2)
- goals: promoting inflammation, activate infected macrophage and natural killer cells, provide help to B cell for antibody production
Th2 cells
the initial source of IL-4 which causes Th0 to bias in becoming Th2 is unknown
- reacts to: parasitic attack or food contaminated with pathogenic bacteria
- response: occurs when intestines are under attack (IL-4, IL-5, IL-13)
- goals: provide help to B cells for antibody production (especially IgE and IgA), proliferates T cells, stimulates mucus in intestine
Th17
Dendritic cells make transforming growth factor β (TGFβ) which causes Th0 to bias toward becoming Th17
- reacts to: fungal attack in some extracellular bacteria
- response” enhance neutrophil response, produces IL-17 (recruits neutrophils) and IL-21 (grows more Th17)
Th0
unbiased T helper cell
• retaining him and retaining ability to produce a wide variety of cytokines
- migrates to battle site and cytokine environment causes them to bias
- once a Helper T cell starts making a certain type of cytokine, it is committed
Killer T cell (CTL) activation
- In order for naïve CTL to be activated, it only need and activated Dendritic cell to present a cognate antigen on MCH I
- must get co-stimulatory signals from Dendritic cells
size of immune response
- is governed by the Helper T cell, through cytokines
- cytokines determine the number of Killer T cells being made.
- when dendritic cell and Helper T cell bind, they likely emit cytokines attracting CTL
- when all three cell types get together, immune response is much greater
How Killer T cells kill
- it delivers a package with perforin = pokes holes in the target cell’s membrane
- also delivers granzyme B = initiates a cascade that cause cell to commit suicide
- CTL connects its Fas Ligand to Fas receptor on target cell, which signals cell to commit suicide
Fas signaling
- Fas receptor is a death receptor on the surface of cells
- When Fas Ligand (from Killer T cells) binds to the receptor it triggers apoptosis
