Lecture 10 - Differentiation and Function of CD4+ T Cells Flashcards

0
Q

What are the co-receptors also expressed in T cells?

A

CD4 and CD8

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1
Q

What percentage of T cells in circulation have alpha/beta TCRs?

A

90-95%

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2
Q

How many TCRs have to recognize a specific antigen, in order for the signaling cascade to be initiated?

A

2

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3
Q

True/False: alpha/beta chains have long intracellular domains.

A

False; they have short intracellular domains

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4
Q

Signaling is mediated by other proteins comprising TCR complex, which proteins have cytoplasmic tails long enough to signal?

A

CD3 proteins (gamma, delta, epsilon, zeta)

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5
Q

What is CD3?

A

A marker for counting the amount of T cells (CD4+ and CD8 T cells)

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6
Q

What components are needed to activate a T cell?

A

TCR, CD4 or CD8, and CD3

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7
Q

Where does activation of T cells occur?

A

Lymph Nodes

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8
Q

About how many naive T cells do dendritic cells “interview” every hour?

A

~500 naive T cells per hour

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9
Q

What are immature dendritic cells called, and do they express high levels of B7?

A

Langerhan’s cells; No

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10
Q

Describe the development of Langerhan’s cells into mature dendritic cells.

A

Antigen uptake from Langerhan’s cells in the skin –> Langerhan’s cells leave skin –> then enter lymphatic system –> then enter lymph node, once they enter the lymph node they become dendritic cells expressing B7 –> B7 dendritic cells then stimulate naive T cells

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11
Q

What are B7 proteins (CD80/CD86) and what are they expressed on?

A

Co-stimulatory molecules; expressed on professional antigen presenting cells

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12
Q

What is the receptor for B7 molecules and what kind of cell is this receptor expressed on?

A

CD28 receptor; expressed on T cells

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13
Q

Co-stimulation does what to the signal?

A

amplifies and improves the signal

bonus info: w/ co-stimulation ~100-fold fewer clustered TCRs are needed for activation

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14
Q

T cells proliferate in order to increase their numbers, what drives the proliferation?

A

IL-2 (T cell growth factor)

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15
Q

Do naive T cells have IL-2 receptors on their surface?

A

No

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16
Q

True/False: Activated T cells produce high numbers of IL-2 and express IL-2R.

A

True

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17
Q

What is IL-2’s function?

A

It is the T cell growth factor; it enhances resistance of activated T cells to apoptosis

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18
Q

Are Th1, Th2, and Th17, all CD4+ helper T cells or CD8 cytotoxic T cells?

A

They are all CD4+ helper T cells

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19
Q

What is(are) the cytokines associated with the Th1 molecule?

A

IFN-gamma

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20
Q

What are the immune reactions and roles in disease for Th1 molecules?

A

Macrophages activate IgG production; They play a role in autoimmune diseases, and tissue damage associated with chronic infections

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21
Q

What is(are) the cytokines associated with Th2 molecule?

A

IL-4, IL-5, IL-13

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22
Q

What are the immune reactions and roles in disease for Th2 molecules?

A

Mast cell and eosin activation, IgE production, “alternative” macrophage activation; they play a role in allergic diseases

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23
Q

What is(are) the cytokines associated with Th17 molecules?

A

IL-17A, IL-17F, IL-22

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24
Q

What are the immune reactions and roles in disease for Th17 molecules?

A

Neutrophilic, monocytic inflammation; they play a role in autoimmune inflammatory diseases

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25
Q

What type of response is induced by each subset of the T helper cells?

A
Th1 = activate cell-mediated immune response
Th2 = activate Ab-mediated immune response
Th17 = involved in inflammation and anti-bacterial response
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26
Q

The pathway of differentiation of T helper cells is?

A

Naive CD4 T cells (uncommitted)

27
Q

What is the development of Th1 cells?

A

IL-12 and IFN-gamma activate transcription factors (T-bet, STAT1, and STAT4) which stimulate differentiation of naive CD4+ T cells –> this lead to the development of Th1 subset

28
Q

Which inhibits the development of Th2 and Th17 and amplifies the Th1 cell response?

A

IFN-gamma

29
Q

What is the development of Th2 cells?

A

IL-4 activates GATA3 and STAT6, which stimulate differentiation of naive CD4+ T cells –> this leads to the development of the Th2 subset

30
Q

What is the development of Th17 cells?

A

IL-1, IL-6, IL-23 activate the transcription factors RORyt and STAT3 –> these stimulate the differentiation into the Th17 subset

IL-23 most important cytokine

31
Q

Which cytokine(s) promote the Th17 response by suppressing Th1 and Th2 and which amplify the response?

A

TGF-beta; IL-21

32
Q

What is the principal action of IL-2?

A

T-cell growth stimulation

33
Q

What is the principal action of IL-4?

A

B cell switching to IgE

34
Q

What is the principal action of IL-5?

A

activation of eosinophils

35
Q

What is the principal action of IFN-gamma?

A

activation of macrophages

36
Q

What is the principal action of TGF-beta?

A

Inhibition of T cell activation

37
Q

What is the principal action of IL-17?

A

Protection from extracellular pathogens, inflammation and auto-immunity

38
Q

What is the main function of classical macrophage activation and what T cell subset induces classical macrophage activation?

A

enhanced microbial killing; Th1 cell

39
Q

What is the main function of the alternative macrophage activation pathway and which subset of T helper cells induces alternative macrophage activation?

A

Complement binding and opsonizing IgG antibodies

40
Q

What are the functions of Th17 cells?

A
  1. secrete IL-17 and IL-22
  2. secretion of the cytokines causes inflammation, neutrophil response, anti-microbial peptides, and increased barrier function
  3. main function: recruiting leukocytes and inducing inflammation
41
Q

How are CD8+ T cells activated?

A

cross-presentation of antigens to CD8+ T cells

42
Q

What are the steps of CD8+ T cell activation?

A

activated in the lymph node by dendritic cells loaded with antigens (recognize class I MHC) –> activated CD8+ cells proliferate and leave lymph nodes

43
Q

What is cross-presentation?

A

specialized dendritic cells ingest infected cells, transfer the protein antigens into the cytosol and process the antigens to enter the class I MHC antigen presentation

44
Q

What is the role of helper T cells in the activation of CTLs?

A

They produce cytokines that stimulate CTL differentiation

45
Q

CD8+ T cells are activated in the lymph nodes, and recognize class I MHC-associated antigen, once activated they leave the lymph nodes. CTLs are activated to release what?

A

granule contents = perforin and granzyme

46
Q

Do the gamma/delta T cells recognize the MHC-associated peptide antigens?

A

No

47
Q

What do gamma/delta cells NOT express?

A

CD4/CD8 co-receptors

48
Q

What are the functions of gamma/delta cells?

A
  1. first line of defense
  2. regulatory cell
  3. bridge between adaptive and innate responses
49
Q

How are the gamma/delta cells a component of adaptive immunity?

A
  1. provide junctional diversity via the rearrangement of TCR genes
  2. develops a memory phenotype
50
Q

How are gamma/delta cells considered to be part of the innate immunity?

A

A restricted TCR may be used as a pattern recognition receptor.

51
Q

Are gamma/delta TCRs more or less diverse than alpha/beta TCRs?

A

Less diverse

52
Q

What type of antigens do gamma/delta TCRs recognize?

A

Unpresented antigens

53
Q

What other molecules do NKT cells share properties with?

A

Natural Killer cells and T cells

54
Q

What kinds of molecules do NKT cells recognize?

A

Self and foreign lipids and glycolipids

55
Q

How are lipids and glycolipids presented in regards to NKT cells?

A

They should be presented within non-polymorphic CD1d molecule (Ag presenting complex like MHC)

56
Q

IFN-gamma, IL-4 and GM-CSF are produced in large quantities in what cells?

A

NKT cells

57
Q

Deficiency or dysfunction of NKT cells leads to..?

A
  1. Autoimmunity
  2. Cancers
  3. Progression of asthma
58
Q

T cells which specific recognize antigens, receive signals through their antigen receptors, that increase the affinity integrins for their ligands. What are these two integrins?

A

VLA-4 and VLA-5

58
Q

Th1 cells but NOT Th2 cells express high levels of which chemokine receptors?

A

CXCR3 and CCR5

59
Q

Which T cell subset expresses high levels of E and P selectin?

A

Th1

60
Q

Th2 cells express which chemokine receptors

A

CCR3, CCR4, CCR8

61
Q

Th17 cells express which types of chemokine receptors?

A

CCR6 which binds to chemokine CCL20

62
Q

What is IFN-gamma’s effect on B cells?

A

promotes switching to certain IgG subclasses (IgG2a or IgG2c) and inhibits switching to IL-4-dependent isotypes (IgE)

63
Q

What is the negative feedback loop associated with Th1 cells?

A

Th1 cells produced IL-10 which functions mainly to inhibit dendritic cells and macrophages, which suppresses Th1 activation

64
Q

Th1 CD40 signals activate transcription factors NF-kB and AP-1, and IFN-gamma activates STAT1. These stimulate expression of enzymes of macrophages. What are these enzymes? What type of macrophage activation is this?

A

Phagocytic oxidase (creates ROS), inducible nitric oxide synthase (creates NO) and lysosomal enzymes