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Immunology 2019 > Lecture 12 > Flashcards

Lecture 12 Flashcards

1
Q

Each subset of T helper cells tends to produce a specific set of cytokines which determine the _____. What specific cell type is activated in order to generate these various T helper cell subsets?

A

Phenotype

Th0 cells are activated in order to generate the various subsets of T helper cells

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2
Q

For the following T helper cell subsets, generally describe how they specifically contribute to the immune response.

Th1 cells:

Th2 cells:

Th17 cells:

Tfh cells:

Also, describe the CD4/CD8 affiliation of all of these subtypes.

A

Th1 cells: activate a cell-mediated immune response

Th2 cells: activate an Ab-mediated immune response

Th17 cells: are involved in inflammation and antibacterial response

Tfh cells (follicular helper T cells): remain in the LN and help B cells

All of these subtypes are CD4-positive cells

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3
Q

for the following subtype of T helper cell, state the Signature cytokine(s) it produces, Immune reactions it is involved in, the type of host defense it plays a major role in, and the Types of diseases it can cause.

Th1 Cells

A

Th1 Cells
Signature cytokine: IFNgamma

Immune reactions: Macrophage activation ; IgGproduction

Host defense: against Intracellular microbes

Types of diseases: Autoimmune diseases that cause collateral tissue damage (ex. Type 1 diabetes)

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4
Q

for the following subtype of T helper cell, state the Signature cytokine(s) it produces, Immune reactions it is involved in, the type of host defense it plays a major role in, and the Types of diseases it can cause.

Th2 Cells

A

Th2 Cells
Signature cytokine: IL-4, IL-5, and IL-13

Immune reactions: Mast cells/Eosinophil activation ; IgE production

Host defense: against Helminthic parasites

Types of diseases: Asthma

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5
Q

for the following subtype of T helper cell, state the Signature cytokine(s) it produces, Immune reactions it is involved in, the type of host defense it plays a major role in, and the Types of diseases it can cause.

Th17 Cells

A

Th17 Cells
Signature cytokine: IL-17A, IL-17B, and IL-22

Immune reactions: Neutrophilic/monocytic inflammation

Host defense: Extracellular bacteria/fungi

Types of diseases: Autoimmune inflammatory diseases (ex. Inflammatory bowel disease)

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6
Q

Describe what it means to say that cytokines are produced Transiently

A

This means that cytokines are provided ONLY when they are needed (responsive production of cytokines)

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7
Q

Describe why it is important that cytokines act in an autocrine or paracrine fashion. What if they don’t behave this way?

A

this keeps the cellular responses to cytokines localized (too much immune response to cytokines causes collateral damage)

If cytokines are inducing systemic effects, then there is a severe infection or autoimmunity reaction taking place

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8
Q

Define Pleiotropism as it pertains to cytokines produced by T cells and why it is good and bad

A

Pleiotropism: each cytokine has multiple biological actions

This good bc it provides diversity of actions, however it reduces the level of clinical utility (its not specific enough with it’s actions to be useful)

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9
Q

Define Redundancy as it pertains to cytokines produced by T cells. Explain why this makes cytokines a bad target for therapeutic inhibition as a form of treatment.

A

Redundancy: multiple cytokines may share the same or similar biological activities

Even if you block a single cytokine production method, there are many more ways that it will be produced (blocking is useless)

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10
Q

Which cytokine that is produced by T cells was the first one to be discovered? Which cytokine is most well known to act as a dampener of immune responses?

A

IL-2 was the first cytokine produced by T cells to be identified

TGF-Beta is the cytokine produced by T cells that functions mainly as a dampener/inhibitor of immune responses

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11
Q

For the following Cytokine produced by T cells, state it’s function and the cellular source(s) of it.

IL-2

A

IL-2
Function: T cell proliferation and regulatory T cell survival

Cellular Source: Activated T cell

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12
Q

For the following Cytokine produced by T cells, state it’s function and the cellular source(s) of it.

IFN-gamma (interferon-gamma)

A

IFN-gamma
Function: Activation of Macrophages

Cellular Source: CD4+ and CD8+ T cells ; NK cells

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13
Q

For the following Cytokine produced by T cells, state it’s function and the cellular source(s) of it.

IL-4

A

IL-4
Function: B cells switching to IgE

Cellular Source: CD4+ cells and Mast cells

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14
Q

For the following Cytokine produced by T cells, state it’s function and the cellular source(s) of it.

IL-5

A

IL-5
Function: Activation of Eosinophils

Cellular Source: CD4+ T cells, Mast cells, and Innate Lymphoid cells

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15
Q

For the following Cytokine produced by T cells, state it’s function and the cellular source(s) of it.

IL-17

A

IL-17
Function: Stimulation of Acute Inflammation

Cellular Source: CD4+ T cells and many other types

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16
Q

For the following Cytokine produced by T cells, state it’s function and the cellular source(s) of it.

IL-22

A

IL-22
Function: Maintenance of the Epithelial barrier function

Cellular Source: CD4+T cells, NK cells, and Innate lymphoid cells

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17
Q

For the following Cytokine produced by T cells, state it’s function and the cellular source(s) of it.

TGF-Beta

A

TGF-Beta
Function: Inhibition of T cell activation AND differentiation of Regulatory T cells

Cellular Source: CD4+ T cells and many other types

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18
Q

Compare IL-23 and IL-12 in terms of their subunits, receptors, and effects

A

IL-23 is a pro-inflammatory cytokine composed of p19 and p40 subunits

IL-12 shares the same p40 subunit as IL-23

HOWEVER, they both have different receptors and different effects on cells

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19
Q

For the following pathogen, state the DC cells cytokines that will be produced, the transcriptional factors that will be activated by them, and the specific subset of T cell that will develop due to the stimulation of those specific transcriptional factors.

Intracellular microbes (such as mycobacteria)

A

Intracellular microbes
DC cytokine(s):
IL-12
IFN-gamma (from NK cells NOT DCs)

Trans. Factors:
T-bet
STAT1
STAT4

Subset of T cell:
Th1 cell

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20
Q

For the following pathogen, state the DC cells cytokines that will be produced, the transcriptional factors that will be activated by them, and the specific subset of T cell that will develop due to the stimulation of those specific transcriptional factors.

Helminths

A

Helminths
cytokine(s):
IL-4 (from Mast cells and Eosinophils NOT DCs)

Trans. Factors:
GATA-3
STAT6

Subset of T cell:
Th2 cell

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21
Q

For the following pathogen, state the DC cells cytokines that will be produced, the transcriptional factors that will be activated by them, and the specific subset of T cell that will develop due to the stimulation of those specific transcriptional factors.

Extracellular microbes (such as fungi or bacteria)

A 
Extracellular microbes
DC cytokine(s):
IL-1
IL-6
IL-23
TGF-beta

Trans. Factors:
RORgammat
STAT3

Subset of T cell:
Th17 cell

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22
Q

Explain in detail the process by which Th1 cells are created from naive CD4+ T cells.

A

IL-12, produced by DCs(and resident tissue macrophages) activates transcription factors T-bet and STAT4

IFN-gamma, produced by NK cells, activates transcription factor STAT1

BOTH of these cytokines (from different cells obviously) must occur to stimulate the differentiation Th1 cells

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23
Q

Once a Th1 cell is developed, state it’s amplification and inhibitory functions

A

Th1 cells amplify the production of more Th1 cells by producing IFN-gamma (which acts in an autocrine manner)

Th1 cell production of IFN-gamma also inhibits the differentiation of Th2 and Th17 cells

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24
Q

Explain in detail the process by which Th2 cells are created from naive CD4+ T cells.

A

IL-4, produced by Mast cells and Eosinophils, activates transcription factors GATA-3 and STAT6

GATA-3 and STAT6 stimulate the differentiation of Th2 cells

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25
Q

Once a Th2 cell is developed, state it’s amplification and inhibitory functions

A

Th2 cells produce IL-4, which amplifies the differentiation of more Th2 cells

Th2 cell production of IL-4 also inhibits the differentiation of Th1 and Th17 cells

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26
Q

Explain the role of the cytokines that are involved in the production of Th17 cells

A

IL-1, IL-6, and TGF-beta activate the transcription factors RORgammat and STAT3 to stimulate the DIFFERENTIATION of Th17 cells

IL-23 is the cytokine that ACTIVATES Th17 cells (after they have been formed via differentiation)

27
Q

What transcription factors induce the production IL-21 and

then what does it do?

A

IL-21 is induced by RORgammat and STAT3 (Th17 transcription factors)

IL-21 then amplifies the generation of Th17 cells in an autocrine manner

28
Q

What Cytokine is produced by Th17 cells in order to protect from extracellular pathogens and is also involved in inflammation and autoimmunity.

A

IL-17

29
Q

Which cytokine, that is involved in the production of Th17 cells, may suppress the development of Th1 and Th2 cells.
(this amplifies the production of Th17 cells as well)

A

TGF-Beta

30
Q

Describe the process of “death by neglect” and state what percentage of T cells in the thymus that this process kills off.

A

Death by neglect is the process that eliminates T cells which would be nonfunctional due to an inability to bind to MHC

Death by neglect kills of 90% of all T cells in the thymus

(of the remaining 10%, only half of them will be chosen for positive selection and will be exported to the periphery)

31
Q

Compared to the high avidity to self antigens in T cells that undergo negative selection (apoptosis) and the low avidity of T cells that undergo positive selection, what level of avidity causes a cells to be selected to become a T reg cell? why?

A

T reg cells are selected with avidity to self antigens JUST LOWER than the level of avidity found in T cells that will undergo negative selection.

This is bc T reg cells, when activated, are immune response dampeners so having a high avidity to self antigens makes sense.
This allows T reg cells to control autoimmune responses of T cells with high avidity to self antigens bc they ALSO have high avidity to self antigens.

32
Q

A CD4+ cell has a high TCR self-reactivity level. What transcription factor does it need to produce in order to become a T reg cell and avoid death via negative selection (due to it’s high level of self-reactivity)?

A

It must express FOXP3

33
Q

Which subset of CD4+ T cells functions to activate macrophages and stimulate B cells to switch to IgG expression (allowing them to conduct complement binding and opsonization).

A

Th1 cells

34
Q

The CD40L gene is located on which chromosome?

A

The X-chromosome

35
Q

Of the following options, describe which is expressed constitutively and which is expressed in an inducible manner.

CD40

CD40L

A

CD40 is expressed constitutively

CD40L is expressed in an inducible manner

36
Q

State the 3 functions that a Classically activated resident tissue macrophage will perform.

A
  1. secretion of cytokines (TNF, IL-1, IL-12, chemokines)
  2. Increased expression of MHC and costimulators (B7 molecules)
  3. Killing of phagocytosed bacteria (it will just hang on to stuff in endosomes prior to being classically activated)
37
Q

Besides the TCR signals and CD28/B7 signaling interactions, state the 2 signals that are required in order to cause classical activation of a resident tissue macrophage

A

Signal 1: IFN-gamma

Signal 2: CD40 to CD40L interaction

38
Q

For the following Cytokine(s), state what function they would induce on a Th2 and Tfh cell.

IL-4:

IL-4 and IL-13: (this one has 2 different functions that will occur)

IL-5:

A

IL-4: causes B cells to produce IgE antibodies

IL-4 and IL-13:

  1. Alternative macrophage activation (tissue repair)
  2. Intestinal mucus secretion and peristalsis

IL-5: Eosinophil activation

39
Q

Which CD4+ T cell subtype is responsible for Classical activation and alternative activation of macrophages. Include the Cytokines they produce to initiate their respective Macrophage activation.

A

Th1 cells conduct classical activation of Macrophages by secreting IFN-gamma

Th2 cells conduct alternative activation of Macrophages by secreting IL-13 and IL-4

(both of these processes block each other, which makes sense bc they are almost opposite in function)

40
Q

Compare the function of Classically activated and alternatively activated Macrophages.

A

Classically activated macrophages cause inflammation and microbicidal actions (phagocytosis and killing of pathogens)

Alternatively activated macrophages induce anti-inflammatory effects and wound repair (via fibrosis and granuloma formation)

41
Q

What does M1 and M2 activated macrophages stand for?

A

M1 = classically activated macrophages

M2 = alternatively activated macrophages

42
Q

When it comes to ratios of IL-17 and IL-22 (both of which Th17 cells produce), describe what it looks like in times of homeostasis and times of Inflammation. Include the functions that occur at these 2 different ratios of Th17 cytokines as well.

A

High IL-17 levels induces Inflammation (IL-22 is low at this time)
Functions: inflammation and neutrophil response

High IL-22 levels controls homeostasis (IL-17 is low at this time)
Functions: Increased barrier protection

(both ratios produce antimicrobial peptides)

43
Q

Why does IL-15 stimulate T cell proliferation? Compare this level of proliferation with the level of proliferation that occurs due to IL-2 exposure.

A

bc it’s receptor shares a common gamma-chain with IL-2

IL-2 induces a “potentiated response” while IL-5 induces a “suboptimal response”
IL-2 creates a stronger response

44
Q

Out of IL-15 and IL-2, which of these stimulates CTL differentiation with and which stimulates CTL differentiation without helper T cells?

A

IL-15 stimulates CTL differentiation WITHOUT helper T cells

IL-2 stimulation stimulates CTL differentiation WITH helper T cells

45
Q

Explain what CD4+ helper T cells do that causes a “potentiated response” that is larger than the suboptimal response achieved by CD8+ cells secreting IL-15.

A

CD4+ helper cells enhance the ability of DC’s to stimulate CTL differentiation by secreting IFN-gamma

this causes increased levels of IL-12 and therefore a greater response

46
Q

Nontraditional gamma/delta T cells are ____-like cells and are found in what areas of the body?

A

innate-like

They are found in epithelial surfaces of the body

47
Q

What do nontraditional Gamma/Delta cells recognize? what types of cells present these?

A

They recognize “non-peptide antigens” that are upregulated by stressed cells

(these non-peptide antigens resemble PAMPs or DAMPs)

48
Q

Gamma/delta cells react very rapidly with cytokine production. Explain why they are able to react so quickly. Also, stat the 3 cytokine-induced functions that nontraditional cells induce in response to tissue stress

A

Nontraditional cells acquire a pre-activated phenotype that allows them to conduct rapid effector functions (there are no naive Nontraditional T cells)

  1. pathogen clearance
  2. inflammation
  3. tissue homeostasis
49
Q

What do all of the following have in common with one another?

Protective immunity against extra/intracellular pathogens
Tumor surveillance
Modulation of innate and adaptive immune responses
Tissue healing and epithelial cell maintenance
Regulation of physiological organ function

A

These are all “physiological roles” of Nontraditional gamma/delta T cells

50
Q

True or False:

Nontraditional T cells detect stress-induced molecules by using both TCR and non-TCR molecules that act separately, synergistically, or additively to activate effector functions. explain

A

True

The TCR is a requirement but the non-TCR molecules create different activation combinations that create varying effector functions.

51
Q

Nontraditional T cells are generated through _____ rearrangement of V, D and J gene segments. Describe the Role they play and the repertoire of nontraditional T cells

A

Somatic

they have a limited repertoire and they play a nonredundant role in various pathological processes

52
Q

True or False:

Nontraditional cells express both CD4 and CD8 molecules. explain.

A

False

Nontraditional cells express NO CD4 and CD8 molecules

53
Q

State the 3 functions of Gamma/delta nontraditional T cells

A
  1. Serve as the first line of defense
  2. Immunoregulation
  3. Bridging between innate and adaptive immunity responses
54
Q

What cell type is considered to be the first line of innate immune defense? Describe how this cell can also help with adaptive responses.

A

Natural Killer T cells (NKT) are the first line of innate immune defense

They secrete cytokines that stimulate alpha/beta T cell differentiation (aids in the adaptive immune response)

55
Q

True or False:

NKT cells secrete cytokines and can also perform phagocytosis and killing of pathogens. explain.

A

FALSE

NKT cells ONLY secrete cytokines. NK cells are capable of phagocytosis/pathogen killing (don’t confuse these)

56
Q

30-50% of _____ T cells are NKT cells. NKT cells also constitute what percentage of all peripheral blood T cells?

A

hepatic

0.2% of all peripheral blood cells

57
Q

True or False:

NKT cells express T cell markers (TCR, CD40L, CD3, CD4) and NK cell markers (CD56+). explain

A

True

NKT cells express the TCR that is generated after VDJ recombination BUT, like innate immune cells, they do not develop immunological memory.

58
Q

NKT cells represent a heterogenous group of ___/____ T cells. Describe it’s beta and alpha chains.

A

CD3+/CD56+

They express an invariant TCR alpha chain and a variable beta chain

59
Q

What do NKT cells recognize? (2 things)

A

self and foreign lipids and glycolipids

60
Q

Compare CD1d molecules and CD1c molecules (include the cells they are found on)

A

CD1d molecules are found APC’s and they present “lipids and glycolipids” to NKT cells for recognition

CD1c molecules are found on APC’s and they present “non-peptide antigens” to Nontraditional gamma/delta T cells (like PAMPs and DAMPs)

61
Q

True or False:

NKT cells secrete Cytokines and chemokines that always work to promote immune responses in one way or another. explain.

A

False

NKT cells secrete cytokines or chemokines that EITHER promote or suppress immune responses.

62
Q

State the 3 conditions that may occur due to dysfunction or deficiency of NKT cells.

A
  1. autoimmunity (type I diabetes or atherosclerosis)
  2. Cancers
  3. Asthma
63
Q

When an NKT cell recognizes a glycolipid presented on the CD1d protein of an APC, state the 2 functions the NKT cell will undergo and what affect that has on the APC.

A

NKT cells release cytokines and express CD40L

This results in activation of the APC

64
Q

Compare the Direct activation method and Indirect activation method of NKT cells.

A

Direct activation method: NKT recognizes lipid-Cd1d complex on the surface of a tumor cell and secretes inflammatory cytokines (IFNgamma) to directly mediate the killing of the tumor cell, which is carried out by NK cells.
(directly kills the tumors)
(M1 phenotype = immune cells are attacking)

Indirect activation method: NKT recognizes lipid-Cd1d complex on the surface of Tissue-associated Macrophages (TAMs, which are immunosuppressive) and secretes IL-12 to help NK cells overcome the immunosuppression effects of the TAM.
(kills the immunosuppressive cell AND tumors)
(M2 phenotype = immune cells are repairing/creating stroma)

Immunology 2019 (22 decks)

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