T cells Flashcards

1
Q

Where do T cells come from?

A

Arise from bone marrow, but mature in the thymus

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2
Q

general location of T cells

A

circulate in the blood in length

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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

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4
Q

number of T cells in the body

A

300 billon

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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
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6
Q

helper T cells

A
  • activated by MHC II on APC
  • secretes cytokines: IL-2, IFN-γ
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7
Q

Regulatory T cells

A
  • keep the immune system from overreacting
  • much is unknown about them
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8
Q

what is needed for T cells to function?

A

They must be activated

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9
Q

types of APCs that activate helper T cells

A
  • activated dendritic cells
  • activated macrophage
  • activated B cells
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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
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11
Q

T-cell recognition occurs when

A

Occurs when the TCR recognizes its cognate antigen

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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
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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
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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
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15
Q

Recognition requires

A
  • TCR (α, β)
  • Co-receptor (CD4 or CD8)
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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
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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
Q

Signal resistance

A

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
Q

CD3

A

the name given to the group of proteins that send signal to cell’s nucleus

27
Q

Immediate changes of T cells upon activation

A

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
Q

Re-activation of T cells

A
  • 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
Q

Helper T cell Activation

A

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
Q

Functions of Helper T cells

A
  • 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
Q

cytokines

A
  • 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
Q

what are the major subsets of T cells that release cytokines?

A

Th1, Th2, and Th17

• Th => “T helper”

33
Q

process for determining cytokines being released

A
  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
Q

Th1 cells

A
  • 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
Q

Th2 cells

A

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
Q

Th17

A

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
Q

Th0

A

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
Q

Killer T cell (CTL) activation

A
  • 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
Q

size of immune response

A
  • 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
Q

How Killer T cells kill

A
  • 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
Q

Fas signaling

A
  • 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