Objectives and Vocabulary for Week # 11 Flashcards

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1
Q

Where does activation of naive T lymphocytes occur?

A

Typically in the secondary lymphoid organs, when they come in contact with APCs, specifically DCs.

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2
Q

What is the role of effector CD4+ and CD8+ effector cells?

A

CD4+ cells activate macrophages, B Cells, and other cells; CD8+ cells kill infected cells and activate macrophages.

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3
Q

What are the first and second signal in T lymphocyte activation?

A

1) Antigen recognition by the T cell receptor (specifically dendritic cells) 2) Co-stimulation

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4
Q

What happens to T cells that have signal 1, but not signal 2?

A

1) Die by apoptosis or 2) enter into a state of prolonged unresponsiveness.

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5
Q

CD28

A

T cell surface marker that binds to B7-1/2 (CD80 and CD86), which is present on the surface of APCs.

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6
Q

B7 molecules

A

(CD80 = B7-1 and CD86 = B7-2); expressed on the surface of APCs (DCs, Macrophages, and B lymphocytes); upregulated by TLR recognition of pathogen and the secretion of IFNg (Example of innate aiding adaptive); B7-2 is expressed constitutively at all levels and is then upregulated quickly after APC activation.

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7
Q

Bcl-2 and Bcl-Xl

A

anti-apoptotic proteins, promote survival; enhanced proliferation; increased metabolic activity; production of IL-2; and the differentiation of the naive T cells into effector and memory cells.

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8
Q

ICOS

A

(inducible co-stimulator, CD278); ligand is ICOS-L (CD275), which is expressed on dendritic cells, B cells, and other cell populations; responsible for the development and activation of follicular helper T cells, which is needed to create high affinity B cells.

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9
Q

CTLA-4

A

Cytotoxic T Lymphocyte antigen 4; inhibitory receptor; recognize B7 molecules just like CD28, but instead of activating T cell, it inactivates T cells by competitively inhibits CD28, remove B7 molecules from the surface of APCs, or deliver inhibitory signals that block activating signals from the TCR and CD28

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10
Q

PD-1

A

Programmed death 1; inhibitory receptor; PD-ligand interactions inhibit the activation of effector cells, especially in peripheral tissues.

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11
Q

CD40L

A

Present on the surface of T cells. Interacts with CD40 on the surface of APCs. Activates APCs to make them more potent by enhancing their expression of B7 molecules and secretion of IL-12 that promotes T cell differentiation.

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12
Q

Licensing

A

Activated T cells enable APCs to become more powerful stimulators; CD40L and CD40 interaction Activates APCs to make them more potent by enhancing their expression of B7 molecules and secretion of IL-12 that promotes T cell differentiation.

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13
Q

Describe the changes in outer surface of the T cell as it is activated. What are their purposes?

A

1) CD69 expression increased, causing decreased amounts of S1PR1 (sphingosine 1-phosphate receptor aids in migration out of lymph node) which keeps the lymphocyte in the cell. 2) CD25 (IL-2RA) Increased expression allows for T cell to respond to IL-2 3) CD40L enables CD4+ T cells to interact with macrophages and B cells. Enables APCs to become better APCs 4) CTLA-4, increased expression to regulate T cell response. 5) reduced expression of CCR7 and L- selectin (both are responsible for migration into the lymph nodes) 6) Increased expression of LFA-1 and VLA-4 receptors for E and P selectin respectively, responsible for migration to peripheral sites of infection 7) Increased expression of CD44 a receptor for the extracellular matrix molecule Hyaluronan, helps retain effector T cells in the tissues at sites of infection and tissue damage.

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14
Q

IL-2 and its role in T lymphocyte activation

A

1) Role: growth, survival, and differentiation factor for T lymphocytes 2) Produced by: mainly T cells (autocrine/paracrine function) 3) IL-2R receptors: present briefly on naive and effector T cells, while regulatory T cells always express high affinity IL-2 receptors;

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15
Q

How does IL-2 stimulate the survival, proliferation, and differentiation of antigen-activated T cells?

A

Aids in the production of anti-apoptotic protein Bcl-2; increases the production of effector cytokines IFNg IL-4

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16
Q

What cytokine is required for the survival and function of regulatory T cells?

A

IL-2; IL-2 has also been shown to stimulate proliferation and differentiation of NK cells and B cells.

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17
Q

Roles of effector T cells (CD4+ and CD8+)

A

CD4+: Activated B lymphocytes, Macrophages, and Dendritic cells CD8+: cytotoxic and kill infected cells

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18
Q

Blimp-1

A

Transcription factor that promotes the differentiation of memory cells.

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19
Q

Memory cells

A

Integral part of the adaptive immunity, characterized by their ability to survive in environments with little to no available antigen and mounts enhanced responses to pathogens previously encountered.

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20
Q

What proteins are released that keep memory T cells alive, even without survival signals?

A

Bcl-Xl and Bcl-2 are anti-apoptotic proteins, which prevent the release of cytochrome c from the mitochondria, which prevents apoptosis due to the lack of survival signals.

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21
Q

What cytokine is most important for the maintenance of memory CD4+ and CD8+ T cells?

A

IL-7, which is also important in early lymphocyte development and survival of naive T cells

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22
Q

Which cytokines induce the expression of anti-apoptotic proteins?

A

IL-7 and IL-15

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23
Q

What receptors are up-regulated in response to T cell recognition of antigen, to keep the T cells at the site of infection? What are their ligands?

A

1) VLA-4/5 and CD44 2) Fibronectin/(VCAM-1) and hyaluronan are the ligands respectively.

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24
Q

DTH

A

Delayed-Type Hypersensitivity, tissue damage caused by an immune response, damaged caused by CD4+ recruitment of leukocytes, which is characteristic of inflammation.

25
Q

Th1 cell (Signature cytokine, Immune reactions; Host defense, and Role in diseases)

A

1) IFNg 2) Macrophage activation / IgG production 3) Intracellular microbes 4) autoimmune diseases; tissue damage associated with chronic infections

26
Q

Th2 cell (Signature cytokine, Immune reactions; Host defense, and Role in diseases)

A

1) IL-4, IL-5, IL-13 2) Mast cells, eosinophil activation; IgE production; “alternative” macrophage activation 3) Helminthic parasites 4) allergic diseases

27
Q

Th17 cell (Signature cytokine, Immune reactions; Host defense, and Role in diseases)

A

1) IL-17A, IL-17F, IL-22 2) Neutrophilic, monocytic inflammation 3) extracellular bacteria; fungi 4) autoimmune inflammatory diseases.

28
Q

What chemokine receptors are on the surface of Th2 cells? What do they do?

A

Chemokine receptors CCR3, CCR4, and CCR8, which recognize chemokines that are expressed at sites of helminthic infection or allergic reactions, primarily in mucosal tissues

29
Q

What chemokine receptors are on the surface of Th17 cells? What do they do?

A

Chemokine receptor CCR6, which binds to CCL20, which is produced by various tissue cells and macrophages in some bacterial and fungal infections.

30
Q

What cytokines drive the differentiation of naive T cells to Th1 cells? Where are they produced?

A

Th1 differentiation is driven mainly by IL-12 and IFNg and occurs when microbes activate DCs, macrophages, and NK cells

31
Q

What cytokine is secreted by NK cells that are important to cell mediated immunity?

A

IFNg, causes Th1 differentiation and causes DCs and macrophages to produce IL-12

32
Q

How do Th1 cells promote differentiation of only their class of effector cells?

A

Th1 produces IFNg, which leads to more Th1 differentiation, but also inhibits Th17 and Th2 differentiation.

33
Q

What transcription factors are activated for Th1 differentiation?

A

1) IFNg leads to STAT1 and T-bet differentiation leading to greater IFNg production 2) IL-12 leads to STAT4 production, which also leads to IFNg production.

34
Q

What is the principal function of Th1 cells?

A

Activate macrophages; activate immunoproteosome; promotes the expression of MHC; increased expression of co-stimulators

35
Q

What is the principle cytokine that activates macrophages?

A

IFNg

36
Q

What type of cells produce IFNg?

A

Th1, NK, CD8+,

37
Q

IFNg’s role in Class switching

A

IFNg acts on B cells to promote switching to certain IgG sublasses, IgG1 and IgG3 possibly IgG2a or IgG2c inhibits IL-4 dependent isotypes, such as IgE

38
Q

What is the role of IFNg in Th cell differentiation?

A

IFNg promotes Th1 differentiation and inhibits the development of Th2 and Th17 cells.

39
Q

How does IFNg promote antigen presentation?

A

IFNg stimulate the expression of MHC proteins, TAP, the proteosome, HLA-DM, and B7 costimulators on APCs

40
Q

What role does IL-10 play in Th1 regulation?

A

IL-10 is produced by Th1 cells, and inhibit the ability of DCs and Macrophages to activate Th1 cells. Negative feedback loop

41
Q

Describe Th1 mediated Classical Macrophage activation

A

CD40L from the T cell interacts with CD40 on the surface of macrophages. IFNg produced by the T cell also interacts with the APC. The macrophage response is the production of ROS, NO, lysosomal enzymes, secretion of cytokines IL-1, IL-12 and TNF and chemokines; increased expression of B7 costimulators, and MHC molecules.

42
Q

Th2 Overview. Responsibility and Effector functions

A

mediator of phagocyte independent defense (mostly parasites); eosinophils and mast cells play the most important role; also key in the development in allergic disease (produce IgE)

43
Q

How does the development of Th2 cells occur?

A

Th2 differentiation occurs in response to IL-4 and occurs in response to helminths and allergens

44
Q

How does IL-4 stimulate Th2 differentiation?

A

Activates the transcription factor STAT6, which together with TCR signals, induces the expression of GATA 3; GATA-3 a transcription factor that acts as a master regulator of Th2 differentiation;

45
Q

GATA-3

A

Master regulator of Th2 differentiation; leads to increased IL-4, IL-5, and IL-13; blocks Th1 differentiation by down-regulating IL-12R

46
Q

T-Bet

A

Master regulator of Th1 differentiation; production of IFNg

47
Q

What are the functions of Th2 cells?

A

Stimulate IgE, mast cell, and eosinophil mediated reactions that serve to eliminate helminthic infections.

48
Q

Functions of IL-4

A

Th2 differentiation and function; produced mainly by Th2 and activated mast cells; stimulates B cells to class switch, and produce IgE/allergic responses; also important for class switching to IgG4 in humans, and IgG1 in mice; inhibits switching to IgG2a and IgG2c (both of those classes are induced by IFNg/Th1)

49
Q

IL-4 and IL-13

A

1) Together inhibit defense against intracellular microbes (both inhibit production of IFNg) 2) Stimulate the recruitment of leukocytes; 3) IL-4 increases peristalsis in the gastrointestinal tract, while IL-13 increases mucus secretion from airway and epithelial cells.

50
Q

Classical Activation

A

Activation of macrophages via the IFNg/Th1 route; cause Macrophages to carry out microbicidal functions; inhibited by IL-13 and IL-4

51
Q

Alternative activation

A

IL-4/IL-13; Th2 mediated activation of macrophages; response is tissue repair, anti-inflammatory effects, wound repair, and fibrosis; inhibited by IFNg.

52
Q

Th17 subset overview

A

primarily involved in recruiting leukocytes (IL-17 mediated neutrophil inflammation) , inducing inflammation, and combating extracellular bacteria and fungi.

53
Q

What three cytokines lead to Th17 differentiation?

A

IL-6, IL-1, IL-23

54
Q

How are Th17 cells inhibited?

A

Inhibited by IL-4 and IFNg (Th2 and Th1 respectively)

55
Q

What transcription factors are important for Th17 development?

A

Stat 3 (IL-6) and RORgt (TFG-b)

56
Q

What cytokines do Th17 cells produce?

A

IL-17 and IL-22

57
Q

What cytokines do Th2 cells produce?

A

IL-4, IL-5, IL-13

58
Q

What cytokines do Th1 cells produce?

A

IFNg

59
Q

What is the role of IL-17?

A

induces neutrophil rich inflammation, stimulates the production of antimicrobial substances.