1
Q
Where do T cells come from?
A
Arise from bone marrow, but mature in the thymus
2
Q
general location of T cells
A
circulate in the blood in length
3
Q
what are T-cell receptors
A
They are antibody like receptors on the surface of T cells, which specialize in recognizing protein agents presented by MHC
4
Q
number of T cells in the body
A
300 billon
5
Q
killer T cells / cytotoxic T lymphocytes (CTLs)
A
- 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
6
Q
helper T cells
A
- activated by MHC II on APC
- secretes cytokines: IL-2, IFN-γ
7
Q
Regulatory T cells
A
- keep the immune system from overreacting
- much is unknown about them
8
Q
what is needed for T cells to function?
A
They must be activated
9
Q
types of APCs that activate helper T cells
A
- activated dendritic cells
- activated macrophage
- activated B cells
10
Q
requirements for activation
A
- 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
11
Q
T-cell recognition occurs when
A
Occurs when the TCR recognizes its cognate antigen
12
Q
T cell Receptors (TCR)
A
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
13
Q
T cell selection/maturation process
A
- 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
14
Q
Non-traditional T cells
A
- 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
15
Q
Recognition requires
A
- TCR (α, β)
- Co-receptor (CD4 or CD8)
16
Q
Co-receptor
A
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
17
Q
CD4
A
Cluster of Differentiation 4
- Usually expressed by Helper T cells
- Attaches the TCR to MCH II
- Signals the T cell to HELP
18
Q
CD8
A
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)
19
Q
Types of Antigen Presenting Cells
A
- B cell
- Dendritic cell
- Macrophage
20
Q
Co-stimulation
A
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
21
Q
Co-stimulation requires
A
- B7 on APC
- CD28 on T cell
22
Q
B7
A
the major co-stimulatory molecule expressed on surface of APC
• Binds to CD28
23
Q
CD28
A
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
24
Q
Signaling requires
A
- CD3 (γ,δ, ε and ζ)
- CD28 on T cell
25
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
26
CD3
the name given to the group of proteins that send signal to cell’s nucleus
27
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
28
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
29
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)
30
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
31
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
32
what are the major subsets of T cells that release cytokines?
Th1, Th2, and Th17
• Th =\> “T helper”
33
process for determining cytokines being released
1. at the battle site dendritic cells recognize patterns (PRR = toll-like receptors) specific to certain types of pathogens
2. Dendritic cell bring this information back to the lymph node, in order to activate Helper T cell
3. Dendritic cell will display different co-stimulatory molecules on their surface depending on what type of invader it has encountered.
4. Helper T cell scans the lymph node, finds the dendritic cell, engages in “immunological synapse”
5. the input signal from DC to Helper T will determine what cytokine is released
34
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
35
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
36
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)
37
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
38
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
39
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
40
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
41
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
Immunology - exam 2
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