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KN-Immunology Block 1 > L6: Antigen Presenting Cells / T cell Activation > Flashcards

L6: Antigen Presenting Cells / T cell Activation Flashcards

1
Q

What is trafficking of naive T cells driven by?

A

adhesion molecules

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2
Q

What are the three professional antigen presenting cells?

A

dendritic cells, macrophages, B cells

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3
Q

Where does activation of naive T cells occur?

A

exclusively in secondary lymphoid tissues.

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4
Q

What is required to activate a naive T cell?

A

2 signals:
TCR recognition of a cognate peptide:MHC complex
Co-stimulation signal (B7 binding to CD28)

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5
Q

Why is B7 crucial to naive T cell activation?

A

it is necessary for the co-stimulation signal. It can only be found on professional antigen-presenting cells (APCs)

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6
Q

How do T cells enter secondary lymphoid tissues?

A

through high epithelial venules, found in the cortex of secondary lymphoid tissues. There they are presented to antigens.

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7
Q

What happens if a T cell does not encounter an antigen in secondary lymphoid tissues?

A

It will recirculate into lymph until it reaches another lymphoid tissue and finds its antigen.

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8
Q

What are selectins?

A

lectins that bind to carbs: include L and P-selectin

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9
Q

What are mucin-like vascular addressins?

A

CD34, GlyCAM-1, MAdCAM-1

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10
Q

What are integrins?

A

they bind to various cell adhesion molecules. LFA-1 (lymphocyte function-associated antigen)

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11
Q

What are immunoglobulin superfamily members?

A

They are targets for integrin binding. Intracellular adhesion molecules (ICAMs), CD2, LFA-3

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12
Q

What does L-selectin do?

A

It lies on the surface of naive T cells and binds to CD34 on high epithelial venules (HEV) to allow T cell migration into secondary lymphoid tissue.

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13
Q

What is diepedesis?

A

outward passage of blood cells through intact vessel walls or into secondary lymph tissue.

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14
Q

How does diapedesis into secondary lymphoid tissue occur?

A

cirulating T cells enter the HEV in lymph node. They then bind their L-selectin to GlyCAM-1 and CD34 on the epithelial wall to initiate rolling interaction.
LFA-1 is activated by chemokines bound to extracellular matrix. LFA-1 then binds tightly to ICAM-1.
The tightening results in diapedesis and lymphocyte leaves blood and enters lymph node.

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15
Q

Once a T-cell is activated the adhesion molecule profile on its surface changes, which alters where it can go in the body.

A

the truth

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16
Q

What adhesion molecules would you expect to find on CD8 effector T cells? Which ones would you not?

A

they express LFA-1 and VLA-4
LFA-1 lets them interact with host cells outside of lymph tissue.
VLA-4 allows binding to activated endothelium (VCAM-1), allowing them to move into areas of inflammation.

Does not have L-selectin anymore because they have no need to enter secondary lymphoid tissue and cannot enter it.

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17
Q

Where are dendritic cells primarily found in lymph tissue?

A

Interspersed within the T cell zones of secondary lymphoid tissue, so they can present antigens to naive T cells

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18
Q

Where are B cells primarily found in lymphoid tissue?

A

B cell zones, until they get activated.

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19
Q

Which has the greatest presence of MHC before being activated by pathogen: dendritic cell, macrophage, B cell?

A

B cells constitutively have high presentation of MHC at all times, whereas dendritic and macrophages have low presentation until activated by bacteria or virus

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20
Q

When do B cells express high levels of costimulator B7? Macrophages? Dendritic cells?

A

B cells and macrophages - once they have recognized PAMPs in pathogens.
Dendritic cells - once they move into secondary lymphoid tissue they constitutively express B7, so they are the most efficient activators of T cells.

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21
Q

Where are dendritic cells found in the body?

A

ubiquitous throughout entire body

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22
Q

Where are macrophages found in body?

A

lymph tissue, connective tissue and body cavities

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23
Q

Where in the body are B cells found?

A

lymph tissue and peripheral blood

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24
Q

What are Langerhans cells? Where are they found and what do they do?

A

They are immature dendritic cells found near skin. They are easily infected by bacteria or viruses. When infected they migrate to the closest lymphatic system. Once they enter lymphoid tissue, they reside in T cell zones to present their antigen. It becomes matured and present high quantities of B7 to costimulate T cells.

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25
Q

Which would handle intracellular infections: CD8 or CD4?

A

CD8, which binds to MHC class II, that handles extracellular infections, Ab-mediated response.

26
Q

What is DC-CK? When is it produced by dendritic cells? What is its purpose?

A

DC-CK is a chemokine that attracts naive T cells. It is secreted by dendritic cells after they become activated and enter secondary lymphoid tissue.

27
Q

What are the differences between active and inactive dendritic cells?

A

active - high MHC I and II, B7, and secretes DC-CK.

Inactive doesnt do these

28
Q

Explain the process of B cell antigen presentation.

A 
Antigen binds to B cell receptor. Antigen is internalized by endocytosis.  Antigen Fragmented in lysosome and are presented on cell surface with MHC class II.
B cell then moves into T cell zone and tries to bind to effector CD4 T cell. Helper T cell will then help in activation of B cell.
29
Q

What is the molecular process for T cell activation?

A

LFA-1 on naive T cells bind to ICAM-1 on dendritic cell.
TCR then samples antigen:MHC on dendritic cells.
If it binds to antigen complex, conformational change in LFA-1 occurs that increases affinity to prolong cell-cell contact.
Signal transduction event occurs via CD3 that allows cell to know it has found its antigen (1st signal of activation).
CD28 on naive T cell then needs to bind to B7 costimulator on APC (dendritic or other professional presenter cell). (2nd signal)

IL-2 then drives proliferation and differentiation of T cell.

30
Q

What form of IL-2 receptor is found on naive T cell?

A

moderate affinity form composed of beta and gamma chain.

31
Q

What happens to IL-2 after both activation signals are received on a naive T cell?

A

cell begins to produce higher quantities of IL-2 with the expressed alpha chain (now has gamma, beta and alpha chains and has very high affinity). Now when it binds to signals, it will drive proliferation.

32
Q

What are the back up mechanisms of T cell tolerance?

A

B7 co-stimulation required for T cell activation. This usually requires that an infection be ongoing.

33
Q

What happens if B7 binds to CD28 before TCR binds to a MHC antigen to give the 1st activation signal?

A

absolutely nothing. but this does happen frequently.

34
Q

When are MHC and B7 expressed in macrophages?

A

after they phagocytose something with recognizable PAMPs. It can now provide both signals of activation to naive T cells.

35
Q

Which requires a higher threshold of activation: CD4 or CD8 T cells?

A

CD8, it kills cells it recognizes so more control is better. Has built-in regulatory fail-safes.

36
Q

What are the additional controls for CD8 activation?

A

Only dendritic cells have strong enough B7 and antigen MHC class I signals to activate CD8 on its own. Other APCs require additional signal. CD4 T Helper 1 cell must bind and be activated, then that will induce high levels of B7 to allow activation of CD8 Effector T cell.

37
Q

What is an armed effector T cell?

A

a fully differentiated T cell that is ready to perform its effector function. It does not equire co-stimulation to perform function. Expresses a different array of adhesion molecules that directs them to appropriate tissues.

38
Q

What are the three primary types of effector T cells?

A

CD8, CD4 TH1, and CD4 TH2 T cells.

39
Q

What is the role of activated CD8 T cells?

A

to kill any cell presenting its cognate antigen on an MHC class I molecule.

40
Q

What is perforin? Granzymes? granulysin?

A

perforin - small proteins that aggregate and insert into membranes causing pore formation
granzymes and granulysin - enzymes that initiate the caspase cascade that results in programmed cell death

41
Q

What cytokines do CD8 T cells produce?

A

IFN-gamma - important for dealing with intracellular pathogens.
LT - a powerful inflammatory cytokine

42
Q

Can both TH1 and TH2 cells provide second activation signal to B cells?

A

Yes. but they promote different kind of class switching

43
Q

What do TH1 cells do?

A

they activate macrophages and B cells. Important in intracellular infection. IFN-gamma is released and CD40 ligand on the surface binds to CD40 on macrophage to activate it.

44
Q

WHat is IFN-gamma?

A

primary cytokine that activates macrophages

45
Q

What type of infections are IL-4, IL-5,10,13 and TGF-beta needed for?

A

they promote class switching to fight extracellular infection

46
Q

How do CD4 T cells differentiate into TH1 or TH2 cells?

A

after being activated and proliferating, the cytokine environment they are exposed to will determine differentiation.
If IL-12 and IFN-gamma –> TH1
If IL-4, IL-6 –> TH2

47
Q

Which T helper cells promote production of opsonizing antibodies such as IgG1?

A

TH1 cells.

Yes, TH2 cells promote B cell production of antibodies, but it is TH1 involved in opsonizing antibodies.

48
Q

What is the most potent inducer of TH1 differentiation?

A

IL-12. It also promotes production of INF-gamma which promotes TH1 differentiation.

49
Q

What do NK cells do during viral infections?

A

by innate immunity, they non-specifically kill virally infected cells and release large amounts of INF-gamma, which drives TH1 differentiation.

50
Q

What do NK T cells do?

A

They respond to pathogens and parasites and secrete IL-4, which promotes differentiation of CD4 TH0 cells into TH2.

51
Q

Ignoring cytokine environment, if low affinity and low concentration of antigen, what type of helper cell will develop? High affinity and high concetration?

A

TH2. If low antigen concentration and low affinity, it is probably extracellular.

During intracellular infections, there is a high concentration of antigens/high affinity so TH1.

52
Q

What are Treg cells (T regulatory cells)?

A

population of T cells is to suppress T cell activation. They differentiate into Tregs during thymic development. They have large receptor repertoire that is biased towards self-peptides. They express transcription factor Foxp3 which drives production TGF-beta and IL-10, which are cytokine that suppress immune responses

53
Q

What will a TH0 cell that secretes IL-10 differentiate into?

A

TH2. IL-10 downregulates TH1 differentiation and promotes TH2.

54
Q

What will a TH0 that is around IL-12 and IFN-gamma differentiate into?

A

TH1

55
Q

What will a TH0 cell that encounters a lot of IL-4 differentiate into? What cytokines will it produce? Will this help with intra or extracellular infections?

A

TH2.
It will produce IL-4 and IL-5.
It will help with extracellular infections.

56
Q

What is the transcription factor that drives expression of cytokines in TGF-beta and IL-10. What type of T cell is this? When would it have differntiated?

A

FoxP3.

Treg cells differentiate during thymic development.

57
Q

What are T helper 17 cells (TH17)?

A

They are pro-inflammatory cells that have an important role in anti-microbial immunity at epithelial/mucosal barriers.

58
Q

What drives TH0 to differentiate to TH17?

A

TGF-beta, IL-6, IL-21, and IL-23.

59
Q

What cytokines do TH17 cells produce and what is their role?

A

They produce IL-17, which is involved in neutrophil recruitment and activation.
AND
IL-22, which stimulates epithelial cells to produce anti-microbial agents.

60
Q

If IL-2 is absent, what will TH0 cells differentiate into?

A

nothing. It is absolutely required for T cell proliferation.

KN-Immunology Block 1 (12 decks)

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