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Diseases > T Cells > Flashcards

T Cells Flashcards

1
Q

T/F: An effector T cell is able to respond to specific antigen WITHOUT the need for costimulation?

A

True; effector T cells can respond to specific antigens without costimulation via B7(CD80)-CD28 interaction

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2
Q

What cytokines cause Th1 cells to proliferate? What cytokines do Th1 cells secrete?

A

IL-12, IFN-gamma, others that activate DC’s, macrophages, and NK’s

Secrete IL-2, IFN-gamma, and TNF-alpha

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3
Q

What transcription factor leads to Th1 cell development?

A

T-bet

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4
Q

What is the function of IFN-gamma?

A

Activates macrophages against intracellular microbes (classical activation), activates B cells to stimulate class switching and complement binding, and stimulates MHC II and B7 (CD80) expression

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5
Q

What is the function of Th1 cells?

A

Migrate to area of infection, sample antigen presented by macrophages, and fully activate macrophages to become better killers

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6
Q

What cytokine causes Th2 cells to proliferate? What cytokines do Th2 cells secrete?

A

IL-4

Secrete IL-4, IL-5, IL-13

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7
Q

What transcription factor leads to Th2 cell development?

A

GATA-3

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8
Q

What is the function of Th2 cells?

A

Stimulate IgE, mast cell, and eosinophil reactions against helminths; isotope class switching in B cells to IgE; support alternative macrophage development; some IgA class switching can also occur

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9
Q

What cytokine stimulates classically activated macrophages and what cytokines do they secrete? What is their function?

A

IFN-gamma

IL-1, IL-12, IL-23, and chemokines

Phagocytosis and inflammation

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10
Q

What cytokines stimulate alternatively activated macrophages and what cytokines do they secrete? What is their function?

A

IL-13 and IL-4

IL-10 and TGF-beta

Anti-inflammatory effects, wound repair, fibrosis

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11
Q

What cytokines cause Th17 cells to proliferate?

What cytokines do they secrete?

A

IL-1 and IL-6

Secrete IL-17 and IL-22

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12
Q

What transcription factor leads to the development of Th17 cells?

A

ROR-gamma-t

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13
Q

What is the function of Th17 cells?

A

Induction of inflammation and leukocyte recruitment in response to bacteria and fungi; they serve an important barrier function

First described in animal models of diseases such as multiple sclerosis, IBD, and RA

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14
Q

What receptor/ligand pair causes weak adhesion of naive T cells to HEV in lymph nodes?

A

L-selectin/L-selectin ligand

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15
Q

What receptor/ligand pair causes cells to stably arrest on HEV?

A

LFA-1/ICAM-1

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16
Q

What receptor/ligand pair causes the activation of integrins and chemotaxis through the HEV and to the lymph node?

A

CCR7/CCL19 or CCL21

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17
Q

What receptor/ligand pair causes weak adhesion of effector and memory T cells to cytokine-activated endothelium at peripheral sites of infection?

A

E and P selectin ligands/E and P selectins

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18
Q

What receptor/ligand pair causes effector and memory T cells to stably arrest on the endothelium?

A

LFA-1/ICAM-1 and VLA-4/VCAM-1

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19
Q

What receptor/ligand pair causes the activation of integrins and chemotaxis through the endothelium?

A

CXCR3/CXCL10

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20
Q

How do tissues retain effector cells that will actually respond to the infection and not effector cells that won’t respond?

A

New selectins and integrins are expressed when the effector cell is in the right place; if the effector cell is in the wrong place, it re-enters circulation

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21
Q

What effect do Th1 effector cells have on CD8+ T cells?

A

Enhance proliferation, differentiation, and cloning of activated CD8+ T cells by providing IL-2

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22
Q

What 2 mechanisms do CD8+ T cells use to kill infected host cells?

A

1) Cytotoxins delivered directly onto the surface of the infected cell; includes granzymes and perforin, which leads to apoptosis
2) FasL on CTL and Fas (CD95) binding on host cell, which induces apoptosis

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23
Q

What is the function of granzymes and perforin?

A

Granzymes: activate caspases

Perforin: necessary for delivery of granzymes

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24
Q

What is the function of IFN-alpha and beta and what cells produce them?

A

Inhibit replication of viruses and increases expression of MHC I on other infected cells; produced by NKs and DCs

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25
Q

What is the mechanism of NK cell killing?

A

Kill tumor cells and virus-infected cells by granzymes and perforin; enhanced by IFN-alpha and beta, IL-12

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26
Q

What cells are involved in antibody-dependent cell-mediated cytotoxicity and what Ig’s are involved?

A

NK’s, macrophages, monocytes, neutrophils, eosinophils; involves IgG and IgE; killing by lytic enzymes, TNF, and perforin

27
Q

A small percentage of effector cells will become memory cells to respond to a 2nd attack by the same microbe. What is responsible for these cells becoming memory effector T cells?

A

They express increased levels of anti-apoptosis protein Bcl-2

28
Q

What transcription factor leads to the development of Treg cells?

A

FOXp3

29
Q

What is the function of Treg cells?

A

They are responsible for deactivating the immune response from effector T cells; constitutively express CTLA-4 and CD25

CTLA-4 binds B7 and shuts co-stimulatory ligand signaling (binds more avidly than CD28)

30
Q

What are some regulatory receptors and what cells can be induced to express them?

A

CTLA-4; inductively on activated T cells

PD-1; inducible on T, B, and myeloid cells

31
Q

T/F: Memory CD4+ and CD8+ T cells do NOT require reactivation to regain their effector function.

A

False

32
Q

What cytokines are required for the survival of memory T cells?

A

IL-7 and IL-15

33
Q

Explain T cell exhaustion to chronic diseases. Why does this occur?

A

During an acute infection, T cells respond to the antigen, the microbe is killed, and memory T cells are formed; during chronic infections, the microbe is never completely killed or cleared, but the T cells still stop responding to the antigens

Why? Almost as soon as T cells are activated to become effector T cells, they begin to receive responses to regulate their responses and prevent the immune system from going wild, which eventually leads to no cytokine secretion, reduced proliferation, and no killing of the target cells

34
Q

What is the function of the TCR?

A

Antigen recognition

binds to the peptide and MHC

35
Q

What is the function of CD3 and zeta?

A

ITAMS; signal transduction

36
Q

What is the function of CD4 and CD8? What do they bind to?

A

signal transduction; they bind to the MHCII and MHCI respectively.

CD4 binds to the B2m portion of the MHCII

CD8 binds to the a3 portion of the MHCI

37
Q

What is the function of CD28? Where is she located and what is her receptor?

A

CD28 is on the surface of the T cells and she binds to the B7(CD80) on the APCs

Signal transduction is the main function here (costimulation)

38
Q

What is the function of CTLA4?

A

On the T cell and is involved in negative regulation; binds to the B7(CD80) on the APC as well

39
Q

What is the function of PD-1? And what does she bind to?

A

PD-1 is on the T cell and is involved in negative regulation of the cell; binds to PD-L1/2

40
Q

What is the function of LFA-1? And what does she bind to?

A

LFA-1 is on the surface of T cells and binds to the ICAM-1 that is found on the APCs; involved in adhesion of the two cells

41
Q

Describe what a mature naive T cell expresses

A 
CD4 or CD8 
CD28+ (involved in costimulatory ish) 
MHC/HLA class 1 (all nucleated cells) 
CD3 and zeta 
LFA-1 and VLA-4 adhesion molecules 
CCR7
42
Q

What is the function of CCR7?

A

chemokine receptor that is expression on T cells that recognizes the chemokine that are produced in the T cell zones

increases the expression of CXCR5, which binds to ish on the B cell (this is more detailed but like whatever)

43
Q

Describe the activation of a DC from the tissues to T cell activation

A
  1. The DC binds to an Ag and starts the process of activation
  2. Loss of adhesive markers and the up regulation of CCR7 (chemokine receptor)
  3. Increase expression of MHC/HLA (probably MHCII unless a viral infected cell was accidentally phagocytized), CD80 expression increases (costimulation)
  4. travel to the lymph nodes and mature as they go
  5. Present the Ag to the T cell in the cortex
44
Q

Describe the migration of T cells on their hunt to find their Ag match

A

Naive T cells enter the lymph node through the high endothelial venues that are present, and they go to the cortex (They T cell binds to the Lymph node coal L selection, and is halted by the LFA-1/ICAM-1 binding then CCR7 recognizes CCL19 and CCL21 and it is able to enter)

Here they encounter a bunch of potential suitors from the APC’s.

IF they find a match, then they proliferate and develop into effector cells

IF they do not, they leave the node through the lymphatic system and keep searching the other nodes for their Ag match

45
Q

Describe the differences in proliferation of the CD4 and CD8 cells

A

CD4 cells increase 100X to 1000X and CD8 cells increase 100,000X

46
Q

Describe how all of the players that are involved in the immunological synapse are able to work together. (including the first and second signals that are involved in co-stimulation)

A

The TCR binds to the peptide that is brought in by the MHC of the APC, and then the integrins that are present on the T cell are brought from a low affinity to a high affinity (first signal)

ex:

CD40L is expressed on the T cell and CD40 is expressed on the APC
B7(CD80) is expressed on the APC and CD28 is expressed on the T cell

The SECOND signal maintains the specificity of the response to the epitope ie everything above binds and holds everything together

47
Q

What are the components that are on a T cell that are involved in signal transduction?

A 
CD4(or8) 
CD3 and zeta 
CD28
CTLA4 (inhibitory) 
PD-1(inhibitory)
48
Q

Describe T cell activation in detail (NFAT pathway)

A
  1. The immunological synapse is formed
  2. Lck (src family) kinase comes in and phosphorylates the ITAMS that are present on the CD3 and zeta units
  3. This attracts ZAP70 (tyrosine kinase) to the site, where it binds to the ITAMS and is phosphorylated by Lck
  4. ZAP70 is activated and phosphorylates the PLC(gamma)1
  5. PLCgamma 1 cleaves PIP2 in to IP3 and DAG
  6. IP3 increases the cytosolic concentration of Calcium which activates calcineurin (phosphatase)
  7. Calcineurin removes phosphates from NFAT, activating it to go into the nucleus and up regulate proteins including IL-2 and IL-2R which is important in T cell proliferation
49
Q

Describe T cell activation in detail (NFkB or AP-1 pathways)

  1. DAG
  2. Ras/Rac
  3. PI3 kinase
A
  1. The immunological synapse is formed
  2. Lck (src family) kinase comes in and phosphorylates the ITAMS that are present on the CD3 and zeta units
  3. This attracts ZAP70 (tyrosine kinase) to the site, where it binds to the ITAMS and is phosphorylated by Lck
  4. ZAP70 is activated and phosphorylates the PLC(gamma)1
  5. PLCgamma 1 cleaves PIP2 in to IP3 and DAG
  6. DAG is able to go activate PKC which then phosphorylates NFkB of AP-1

Ras/Rac pathway

  1. The immunological synapse is formed
  2. Lck (src family) kinase comes in and phosphorylates the ITAMS that are present on the CD3 and zeta units
  3. This attracts ZAP70 (tyrosine kinase) to the site, where it binds to the ITAMS and is phosphorylated by Lck
  4. ZAP70 is activated and phosphorylates Itk which is able to phosphorylate the GDP/GTP exchanger
  5. GTP is added to Ras/Rac which then actives ERK and JNK that can activate NFkB or AP-1

PI3 kinase:

  1. The immunological synapse is formed
  2. Lck (src family) kinase comes in and phosphorylates the ITAMS that are present on the CD3 and zeta units
  3. This attracts ZAP70 (tyrosine kinase) to the site, where it binds to the ITAMS and is phosphorylated by Lck
  4. ZAP70 is activated and phosphorylates the PI3 kinase which activates PIP3.
  5. PIP3 then activates the Akt and mTOR enzymes that can activate NFkB or AP-1 and lead to increased protein synthesis
50
Q

Who is CDC25?

A

The IL-2 receptor which is important in T cell proliferation

the IL-2R is typically at a low affinity until activation of the T cell

51
Q

Describe anergy and what causes it

A

A state that a T cell is in where it is unresponsive and tolerant.

It is caused by T cells recognizing an antigen without binding any of the costimulatory ish resulting in a lack of cytokines and stimulation

52
Q

What is the importance of IL-2

A

IL-2 is an autocrine signal that allows for T cell proliferation and differentiation

53
Q

How are T cells that have found their Ag in the lymph node “trapped” in the cell?

A

Transient expression of CD69, which binds to S1PR that impairs migration of the T cell (decreases S1PR1 expression), and it is not until 5 days later that the S1PR1 expression increases and the cell is able to travel into the periphery

54
Q

Describe Th1 cells in regards to

  1. Defining cytokines
  2. principal target cells
  3. major immune reactions
  4. host defense
  5. role in disease
A
  1. IFNgamma
  2. Macrophages
  3. Macrophage activation
  4. Intracellular pathogens
  5. Autoimmunity, chronic inflammation
55
Q

Describe Th2 cells in regards to

  1. Defining cytokines
  2. principal target cells
  3. major immune reactions
  4. host defense
  5. role in disease
A
  1. IL-4, IL-5, IL-13
  2. Eosinophils
  3. Eosinophil and mast cell activation
  4. Helminths
  5. Allergies
56
Q

Describe Th17 cells in regards to

  1. Defining cytokines
  2. principal target cells
  3. major immune reactions
  4. host defense
  5. role in disease
A
  1. IL-17, IL-22
  2. Neutrophils
  3. Neutrophil recruitment and activation
  4. Extracellular bacteria and fungi
  5. Autoimmunity, inflammation
57
Q

Describe Tfh cells in regards to

  1. Defining cytokines
  2. principal target cells
  3. major immune reactions
  4. host defense
  5. role in disease
A
  1. IL-21
  2. B cells
  3. Antibody production
  4. Extracellular pathogens
  5. Autoimmunity
58
Q

How do CD4 cells help with the production of CD8 cells? What is this process called?

A

CD4 cells produce IFNgamma and IL-2 that are able to help the APC and the CD8 cell out

(see picture on slides 26 and 27)

called cross stimulation

59
Q

Describe the migration of activated Th cells

A
  1. T cell is activated in the lymph node and starts to move to the edge of the follicle (edge of the T cell zone)
  2. As the T cell moves, it decreases the expression of CCR7 (because you dont need the receptor that recognizes the cytokines that are released in the T cell zone because you’re leaving) and increases the expression of CXCR5 (which binds to the chemokine that are produced in the B cell follicles)
  3. The B cell comes to the T cell (has to up regulate CCR7 and down regulate CXCR5 because the exchange happens in the T cell zone on the edge)
  4. costimulatory molecules are increased and the T cells start expressing CTLA-4
60
Q

Describe T reg cells

A 
CD4+ T cells 
influenced by IL2 and TGF-B 
express CTLA4 and CD25 
transcription factor is FOXP3 
secrete IL10 and TGFB
61
Q

Describe gamma delta T cells

A

less than 5%

found at the epithelial boundaries, usually in the gut

Ag restricted, as there is a limited number of peptides that it can bind but it is able to recognize non-protein Ags

Not MHC/HLA restricted

62
Q

True or false: the immune serum protects against intracellular microbes

A

FALSE: the immune system DOES NOT protect against intracellular microbes

63
Q

What is the major difference between effector T cells and resting naive T cells?

A

Effector T cells DO NOT require any CD80B7/CD28 costimulation!!!

Diseases (8 decks)

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