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Immunology Exam 2 > Lecture 2 > Flashcards

Lecture 2 Flashcards

1
Q

What is [differentiation or commitment] of T-helper cells?

A

The phenotype of T-helper cells is determmined by the cytokines it releases.

They do not secrete random cytokines.

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2
Q

What type of response will Th1 cells initiate?

A

Cell-mediated immune response

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3
Q

What type of response will Th2 cells initiate?

A

Antibody mediated immune response

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4
Q

What type of response will Th17 cells initiate?

A

Inflammation and anti-bacterial response

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5
Q

What type of response will Tfh (follicular helper T cell) cells initiate?

A

Stay in LN and help B cells.

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6
Q

Cell-mediated immunity–> where T-cells are the effector cells. T cells are essential for eliminating microbes that survive and replicate inside cells and for eradicating infections by some extracellular microbes, often by recruiting other cells to clear the infectious pathogens. What are the 2 main types of cell-mediated immune reactions that eliminate different types of microbes?

A

CD4+ helper T cells secrete cytokines that recruit and activate other leukocytes to phagocytose (ingest) and destroy microbes.

CD8+ cytotoxic T lymphocytes (CTLs) kill any infected cell containing microbial proteins in the cytosol, eliminating cellular reservoirs of infection

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7
Q

How do naive CD4+ T-cells differentiate into Th2?

Stimulated cytokines?

TF?

Signature cytokines?

A

Differentiation is stimulated by IL-4.

Activates transcription factors: GATA-3 & Stat6, which together cause differentiation to the Th2 subset.

Signature cytokines: IL4, IL5, IL13

These cells produce more IL-4 and amplify Th2 response.

Role: respond to extracellular pathogens, allergy and asthma

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8
Q

How do naive CD4+ T cells differentiate into Th1?

A

Responds to intracellular bacteria and viruses.

Dendritic cells and macrophages release IL12

NK cells release IFN-y

Activate transcription factors: IFN-y, TNF, STAT4, T-bet

Function: promotes tumor immunity, intracellular pathogens, drives autoimmunity

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9
Q

How do naive CD4+ T cells differentiate into Th17?

A

Inducing cytokines: TGF-B and IL6

Transcription factors: IL-17A, IL-17F, IL-22, IL-21, CCL20, STAT3, RORyt

Function: controversial tumor immunity, breaks immune tolerance, extracellular bacteria, autoimmunity

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10
Q

How do naive CD4+ T cells differentiate into Treg?

A

Inducing cytokine: IL2 and TGF-B

Cytokines: TGF-B, IL10, IL35, STAT6, FOXP3

Functions: suppress tumor immunity, promotes immume tolerance, maintain lymphocyte homeostasis

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11
Q

Differentiation into Th cells.

APC process antigens and present it to the naive Th cells.

Secretion of _____–> differentiation into Th1 cell.

Secretion of _____–> differentiation into Th2 cell.

Secretion of ______–> differentiation into Th17 cell

A

Secretion of IL-12 -> differentiation into Th1 cell.

Secretion of IL-4 –> differentiation into Th2 cell.

Secretion of TGF-B and IL-6 –> differentiation into Th17 cell

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12
Q

What are the CD4+-positive helper cells?

A

Th1

Th2

Th17

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13
Q

Th1

Immune reaction:

Host defense:

Role in disease:

A

Immune reaction: activates macrophages and makes IgG

Host defense: Intracellular pathogens

Role in disease: autoimmune diseases, tissue damage assx with chronic infection

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14
Q

Th2

Immune reaction:

Host defense:

Role in disease:

A

Immune reaction: Activates mast cell and eosinophils, makes IgE, “alternative macrophage activation

Host defense: Helminthic parasites

Role in disease: allergic reactions

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15
Q

Th17

Immune reaction:

Host defense:

Role in disease:

A

Immune reaction: neutrophilic and monocytic activation

Host defense: extracellular bacteria and fungi

Role in disease: autoimmune inflammatory diseases

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16
Q

What is the first identified T-cell cytokine?

A

IL-2

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17
Q

______ functions mainy as a inhibitor or dampner, but stimulates differentiation of Treg cells.

A

TGF-B

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18
Q

IL-2

Action:

A
  1. Proliferation of T cells
  2. Helps regulatory T-cells survive
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19
Q

IFN-y

Action

A

Activates macrophages

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20
Q

IL-4

Action:

A

B cell switching to IgE

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21
Q

IL-5

Action

A

Activates eosinophils

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22
Q

IL-17

Action

A

Stimulates acute inflammation

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23
Q

IL-22

A

helps to maintain function of the epithelial barrier

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24
Q

TGF-B

A

Inhibits the activation of T-cells

Helps regulatory T-cell differentiate.

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25
Q

What are the general properties of T-cell cytkines

A
  1. Made transiently in response to a antigen
  2. Autocrine or paracrine
  3. Pleiotropic: each cytokine will have many actions
  4. Reduntant: many cytokines have the same activity. Thus, if you block one you may not receive desired effect
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26
Q

Development of Th1 Cells

A

Intracellular pathogen or virus

A. DC/Macrophage will release IL-12 –> activates transcription factor STAT4 and T-bet in the naive T-cell.

A1. NK Cells will release IFN-y–> activates transcription factor STAT1

B. T-cell will release IFN-y, which acts as a autocrine signal to and binds to itself to amplify the response and inhibit Th2 and Th17 from developing.

C. CD4+ T-cells–> Th1 cells.

D. Th1 cells release IFN-y

27
Q

Th1 Functions

A
  1. Activate macrophages
  2. Complimentary binding
  3. Opsonize IgG
28
Q

One of the functions of Th1 is to activate macrophages. How does this happen?

A
  1. Activated Th1 cell binds to class II HLA on the macrophage via the [TCR and CD4 molecule].
  2. T lymphocytes start to express CD40L, which interacts with CD40 (B7) on the macrophages.
  3. T cells secrete (IFN-γ), which binds to IFN-γ receptors on the macrophages.

*CD40L is induced

*CD40 (B7) is constitutive

29
Q

What will macrophages that are activated by Th1 cells do?

A
  1. Make ROS, NO, lysosomal enzymes that will kill the pathogens in the phagolysosomes.
  2. Secrete TNF, IL-1 and chemokines which cause inflammation and IL-12, which will promote the Th1 response.
  3. Increases the expression of MHC molecules and B7 (CD40 costimulators, which will amplify the T-cell repsonse.
30
Q

Development of the Th2 cell

A

Extracellular fungi and bacteria

  1. Mast cells and eosinophils release IL-4 –> activate transcription factors GATA-3 and STAT6.
  2. T cells will release IL-4, which amplifies the T-cell response and inhibits Th1 and Th17 from forming.
31
Q

Th2 Cell Function

A

Function:

  1. Alternative macrophage activation (M2): IL13 and IL4 shut down the activation of inflammatory macrophages, stopping damaging reacting.

Instead, the cytokines will activate macrophages that will secrete growth factors that help to repair tissue.

32
Q

Classically activated macrophages (M1)

A

Th1 cells under M1.

Macrophages kill bacteria and fungi via ROS, NO, lysosomal enzymes.

33
Q

Alternatively activated macrophages (M2)

A

Th2 cells undergo

IL-13 and IL-4 act on the macrophage, causing it to release IL-10 and TGF-B.

Result: anti-inflammatory effects, wound repair and fibrosis

34
Q

Naive CD4+ T lymphocytes may differentiate into Th1 cells, which activate phagocytes to kill ingested microbes, and Th2 cells, which inhibit classical macrophage activation. How does balance between these two influence the outcome of infections, such as Leishmania major?

A

Eliminating it requires macrophages to be activated via Th1 cells.

If Th2 cells are dominant, then the mice get the infection.

35
Q

Naive CD4+ T lymphocytes may differentiate into Th1 cells, which activate phagocytes to kill ingested microbes, and Th2 cells, which inhibit classical macrophage activation. How does balance between these two influence the outcome of infections, such M. Leprae?

A

If patient has Th1–> tuberculoid leprosy

If patient has defective Th1 or dominant Th2–> lepromatous leprosy ( high bacterial count)

36
Q

Development of the Th17 Cell

A

Extracellular Fungi and Bacteria

  1. [IL1, IL6 and TGB-F] is released –> activates the transcription factors [RORyt and STAT3]
  2. T-cell wil release IL-21, which amplifies the generation of Th17 in an autocrine manner.
  3. TGF-B will also promote Th17 response by suppressing Th1 and Th2 cells from forming.
  4. M1 macrophages then release IL-23 to help activate Th17.
  5. Th17 cells then release IL 22 and IL-17 to protect from extracellular pathogens and is involved in tissue inflammation and autoimmunity.
37
Q

Th17 Functions

A
  1. IL-17 will produce chemokines and cytokines and recruit neutrophils and monocytes to the site of inflammation.
  2. IL-22 will maintain the epithelial barrier. (homeostasis)
38
Q

We have _____ levels of IL-17 and IL-22.

A

Constituitive.

39
Q

T-cells make up ___ of all lymphocytes in the blood. B-cells make up ___.

A

T-cells make up 70% of all lymphocytes.

B cells make up 30%.

40
Q

T-lymphocytes

Marker:

Typical % in blood:

All t-cells are ____ derived.

A

Marker: CD3

Typical % in blood: 100% of T cells

All T-cells are thymus derived.

41
Q

Helper T cells

Marker:

Typical % in blood:

A

Marker: CD4

Typical % in blood: 66%

42
Q

Cytotoxic T Lymphocytes (CTLs)

Marker:

Typical % in blood:

A

Marker: CD8

Typical % in blood: 33%

43
Q

Where does the activation and differentiation of CD8+ T cells occur?

A

Lymph nodes.

44
Q

Describe the activation and differentiation of CD8+ TCells

A
  1. Naïve CD8+ T cells recognize antigens + CD28-CD80 costimulation, presented by DCs in the LN.
  2. Proliferate and differentiate into CTLs and memory cells
  3. CD8+ CTLs will go from circulation to the site of antigen.
  4. CD8+ T cells recognize antigen in the tissue, release granules called lysosomes (which have perforin and granzymes).
    a. Secrete IFN-y, which activates macrophages.
    b. Differentiation involved transcription factor T-bet.
45
Q

Cells that are infected with intracellular pathogens, like viruses are ingested by DCs. What happens to the viral antigen?

A

It undergoes cross-presentation: it is released from the phagosome in cytoplasm of DC and then presented on class I MHC.

The same cross-presenting APC also display pathogens on class II MHC for CD4+ helper cells.

46
Q

The generation of effector CD4+ T cells ______ generation of CD8+ T cells.

A

PRECEDES.

CD4+ T cells –> CD8+ T cells

47
Q

Priming of naïve CD8+ T cells depends on what?

A

CD4+ T-cell mediated DC licensing (cross-presentation) via CD40-CD40L.

This occurs because DC’s need education or licensing (cross-presenation), which takes time.

48
Q

Mechanism of APC Licensing

A
  1. CD4+ recognizes antigen on the dendritic cell.
    a. Binds via MHC II
    b. CD4+ activated
  2. Delivers 1st signal to DC
    a. CD40L/CD40
  3. Delivers 2nd signal to DC
    a. Cytokines (IFN-y)
  4. Activated CD4+ Th increases expression of CD40L
    a. Can bind more DC’s
    b. Potentiates response
  5. CD40/CD40L and IFN-y interacts.
    a. Causes upregulation of CD80/CD86 on DCs
  6. Stimulates cross presentation: DCs become more efficient at activating CD8 T cells.
49
Q

What 3 ways are CTL developed?

A
  1. CD8+ T cells can recognize antigen + co-stimulators on APCs–> CTL differentiation without T-helper cells
  2. CD4+ helper T cells produce cytokines, that cause CTL differentiation
  3. Cross presentation
50
Q

Johnny got an acute viral infection. What is the role of CTLs in his case?

A

In the case of viruses or intracellular bacteria:

Acute infections–> CD8+ T Cells –> CTLs finds target cells and form an immunologic synapse–> release perforins and granzymes and kill the target cell.

51
Q

What is the purpose of immunologic synapses?

A

They make sure that bystander cells are not injured when CTLs react against infected cells.

52
Q

CTLs kill target cells by lyosome granules via granule exocytosis from the CTL and enter the target cell. What are the two major ways CTLs kill?

A
  1. Fas-FasL Mediated apoptosis
  2. Granzyme Mediated Apoptosis
53
Q

Fas-FasL Mediated Apoptosis Mechanism

A

CTLs activate FasL, which binds to Fas on target cells. This recruits procaspase-8, which is converted to caspase 8 via FADD adaptor.

a. Type 2 cells (ex. virus infected)

i. Caspase 8 cleaves Bid
ii. Bid causes the release of Cytochrome C.
iii. Cytochrome C + Apaf-1 + ATP –> activate caspase 9.
iv. Caspase 9 activates caspase 3.
v. Caspase 3–> degrades ICAD inhibitor, activating CAD (caspase-activated DNase)
vi. CAD–> degrades DNA–> kills cell
b. Type 1 cell (ex. Thymocytes)
i. Caspase-8 directly cleaves Caspase-3
ii. Caspase 3–> degrades ICAD inhibitor, activating CAD (caspase-activated DNase)
iii. CAD–> degrades DNA–> kills cell

54
Q

Granzymes A, B and C are all what?

A

Serine protoeases

55
Q

Granzyme mediated apoptosis mechanism

A

a. Perforin (which is homoglous to C9 compliment protein) forms a pore on the target cells
b. Perforin and granzymes are internalized by the target cell, thinking it is protecting itself.
c. Within the cell, Granzyme B activates caspase-3.
d. Target cell dies.

56
Q

When a intracellular pathogen invades, how to CD8+ T cells and CD4+ T cells react?

A

They WERK together :)

57
Q

How do CD8+ T cells and CD4+ T cells work together?

A

When Intracellular bacteria are phagocytozed by macrophages, some of the bacteria may escape into the cytoplasm.

  • CD4+ T cells make IFN-y and IL-2 to activate macrophage to kill those phagocytozed.
  • CD8+ T cells kill pathogens in the cytsol.
58
Q

How do CD8+ CTLs react when there infection?

A
  1. Viruses can infect cells and using its material to replicate. During this process, some of the viral proteins inside the cell are degraded into peptide fragments and presented on MHC Class 1 molecules to CD8+ T-cells
  2. APCs take up the virus
  3. Viral peptides are presented on MHC Class 1 molecules via the cross-presentation pathway.
  4. CD4+ T cells recognize MHC class II on APCs.
  5. Next to this interaction, CD4+ T cells can activate DCs by interaction of CD40 with CD40L on the DC
  6. Activated DCs increase the expression of CD80/CD86.
    a. They interact with CD28 on naïve CD8+ T-cells
  7. TCR and CD28 signaling will activate the CD8+ T cell.
  8. Activated CD8+ T cell will differentiate CD*+T cells that recognize MHC class I-peptides on virally infected cells. Binding of the TCR to the MHC class I peptide complex leads to the activation of CD8 T cells and the release of lysosomal granules and the production of cytokines TNF-alpha and IFN-y.
59
Q

Some bacteria can evade cell-mediated immunity. How does myobacteria do so?

A

inhibits phagolysosome fusion.

60
Q

Some bacteria can evade cell-mediated immunity. How does herpes simplex virus do so?

A

Inhibits antigen presentation by interfering with TAP transporter

61
Q

Some bacteria can evade cell-mediated immunity. How does CMV do so?

A

Inhibition antigen presentation by two methods

  1. class I MHC molecule is not removed from the EA
  2. proteasome activity is inhibited.
62
Q

Some bacteria can evade cell-mediated immunity. How does EBV do so?

A
  1. Inhibits antigen presentation by inhibiting proteosome activity.
  2. Production of IL-10, inhibition of macrophage and DC activation
63
Q

Some bacteria can evade cell-mediated immunity. How does pox virus do so?

A

Inhibition of effector cell activation: produces soluble cytokine receptors

Immunology Exam 2 (10 decks)

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