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Host Defense Exam 1 > T Cell Immunity I & II > Flashcards

T Cell Immunity I & II Flashcards

1
Q

What are Naive T cells?

A

Mature, recirculating T cells that have not yet encountered their Ag

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2
Q

What do effector T cells act on?

A

Target cells, not the pathogen itself

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3
Q

What cell surface markers can differentiate between naive and T memory cells?

A

Naive: CD45RA

T Memory: CD45RO

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4
Q

What 3 signals are required for T cell activation?

A

TCR recognizes peptide in the context of MHC

Engaging of co-stimulatory molecules
CD28 with CD80/86
CD40L with CD40

Induction of cytokine production and secretion which will help direct the fate of the T cell

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5
Q

What do activated T cells express, and to what do they respond?

A

high affinity IL2Rgamma(CD25) and respond to IL2

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6
Q

What drives the Th1 fate, what is the master transcription regulator, what cytokines do they produce, and against what do they act?

A

IFNgamma, IL12

Tbet

IFNgamma, IL2, LTalpha

Intracellular pathogens

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7
Q

What drives the Th2 fate, what is the master transcription regulator, what cytokines do they produce, and against what do they act?

A

IL4

GATA3

IL4, IL5, IL10, IL13

Extracellular pathogens

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8
Q

What drives the Th17 fate, what is the master transcription regulator, what cytokines do they produce, and what is their role?

A

TGFbeta (IL1), IL6, IL21, IL23

RORgamma-t

IL17, IL21, IL22

gut immunity - pathogen clearance at mucosal barriers

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9
Q

What drives the Thf fate, what is the master transcription regulator, what cytokines do they produce, and what is their role?

A

IL6

BCL6

IL6, IL10, IL21

Induce B cells to form germinal centers, stimulates the differentiation of B cells into plasma cells and memory B cells

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10
Q

What drives the iTreg fate, what is the master transcription regulator, what cytokines do they produce, and what is their role?

A

TGFbeta, IL2

FOXP3

TGFbeta, IL10

immune tolerance

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11
Q

What are Toll Like Receptors (TLRs) and what do they bind??

A

receptors on macrophages and dendritic cells that when bound can initiate cytokine production

bind soluble bacterial products and viral DNA/RNA
Pathogen Associated Molecular Patterns (PAMPS)
Danger Associated Molecular Patterns (DAMPS)
Microbial Associated Molecular Patterns(MAMPS)

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12
Q

What steps take place when an immature DC becomes a mature DC?

A

no longer can phagocytose

upregulates MHCII

upregulates CD80, CD86, CD40

migrates to lymphoid tissue

upregulates IL12 and IL18

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13
Q

Discuss a T cell passing through a lymph node

A

Enters via HEV

T cells not activated by Ag presented by a DC will exit via the cortical sinuses

T cells activated by Ag presented by a DC Will proliferate and lose the ability to exit the lymph node

Once activated T cells proliferate to effector T cells they will exit the lymph node

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14
Q

What responses are Th1 cells involved in, and against what are they directed?

A

involved in cell mediated inflammation and delayed-type hypersensitivity reactions

immunity against intracellular pathogens

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15
Q

What is IFNgamma, what cells produce it, and what does it do?

A

potent proinflammatory cytokine

signature cytokine of the Th1 response, also produced by NK and activated CD8 cells

IFNgamma activates macrophages
potent suppressor of the Th2 and Th17 responses

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16
Q

What is IL2, what cells produce it, and what does it do?

A

T cell growth factor for most T cells

critical growth cytokine produced by activated Th1 and CD8 cells, can act in a paracrine or autocrine mode

Growth factor for T cells, particularly Treg

defect can cause serious immunodeficiency

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17
Q

What is LTalpha, what cells produce it, and what does it do?

A

member of the TNFalpha family

produced by Th1, CD8, NK, B, and macrophages

Lymphoid organ development, maintenance of lymphoid microenvironment

implicated in rheumatoid arthritis and MS

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18
Q

In response to Th1 activation, what is the downstream response?

A

Macrophages will produce pro-inflammatory cytokines IL1, IL6, IL8, and TNFalpha

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19
Q

Discuss the features and function of IL1

A

IL1 is a proinflammatory cytokine that facilitates host response to stress

produced by a variety of cells, especially epithelial cells

promotes neutrophil growth and emigration from the bone marrow

Acts with IL6 on the CNS to promote fever and depression

has neuroendocrine effects on the adrenal gland

stimulates APCs to increase Ag presentation

Antagonist is IL1Ra

induces Th17 along with TGFbeta, IL6, IL21, IL23

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20
Q

Discuss the features and function of IL6

A

IL6 is a proinflammatory cytokine with similar effects as IL1, including fever and induction of acute phase protein (CRP)

promotes responsiveness to IL2, and accelerates Ag activation

required for Th17 development and possibly Thf development

strong differentiation effect of B cells in presence of other B cytokines

activates osteoclasts

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21
Q

Discuss the features and function of IL8

A

IL8 is a cytokine with chemotactic activity

most potent stimulus for mobilization and recruitment of neutrophils to infected tissue

produced mainly by neutrophils and macrophages, and by endothelial cells during intense inflammation reactions

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22
Q

What is Hypersensitivity Reaction Type IV: Delayed-Type Hypersensitivity

A

mediated by Ag specific Th1 and CD8 T cells

clinical situation where macrophage is part of pathological situation

can be applied to the reaction to mosquito bites

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23
Q

Discuss IL3/GM-CSF

A

released by activated Th1 cells, stimulates monocyte differentiate from HSC in the bone marrow. These will be attracted to the inflammed tissue where the Th1 cells are present

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24
Q

Discuss the features and functions of TNF-alpha

A

TNFalpha is a potent macrophage activator, is released by Th1 cells

potent activator of endothelial homing and adhesion molecules

upregulates MHC and other cytokines

induces apoptosis (local tissue damage) and angiogenesis

systemic effects include flu like symptoms and death

anti-TNF Ab can be used clinically to control it

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25
Q

What infection or antigenic stimulus will cause dominant production of IL4 by the activated T cell?

A

Soluble Ag

bacteria

multi-cellular parasites

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26
Q

When will IL4 production occur?

A

TLR signaling does not result in IL12 production

There are TLRs that stimulate the T cell to produce IL4 instead of IL12

Naive T cells engage in Ag recognition presented by B cells

27
Q

How does B cell and Th2 cell interaction result in the activation of both cells?

A

B cells take up antigen and present it via MHCII. Expression of co-stimulatory signals (CD40 on B cell, CD40L on T cell) and cytokines results in the activation of both cells.

Activated T cells produce cytokines such as IL4, IL5, IL6 which act on B cells to sustain B cell activation

28
Q

What are exogenous sources of IL4?

A

Mast cells
Basophils
Eosinophils
TCRdeltagamma

29
Q

What is necessary for a Th2 response, and how does it occur?

A

High levels of GATA3

TCR:peptide/MHCII and CD40:CD40L and CD28:CD80/86 stimulates low levels of GATA3 activity and the activation of the high affinity IL2Ralpha receptor and IL2

IL2 stimulates more production of GATA3, which stimulates IL4 production, which ramps up GATA3 activity even more

30
Q

What is the Th2 effect on B cells?

A

B cell proliferation and the release of Ab: make pathogen more attractive to macs and polys, increasing the binding of toxins, enhance the targeting of mutant/viral infected cells for killing

31
Q

Describe the features and function of IL4

A

initiates and is required for the Th2 response - it is released by Th2 cells and is a growth factor for Th2 cells

IL4 induces B cell growth and differentiation into plasma cells

on T cells, IL4 inhibits the development of Th1, even in high concentrations of IFNgamma

inhibits Th1 mediated macrophage activation, and is thus an anti-inflammatory

32
Q

What does IL5 do?

A

Eosinophil maturation and the recruiting of more eosinophils

33
Q

What does IL10 do?

A

Major drivers of B cell differentiation and isotype switching

Inhibits Th1 differentiation and dendritic cell function, and thus inhibits the production of pro-inflammatory cytokines IL-1, IL-12, TNF-alpha

Th2 cells are the major releasers of IL10, iTregs and Thf also release IL10

34
Q

What do IL5 and IL13 do?

A

drive allergic type-inflammatory responses such as asthma

35
Q

discuss the features and functions of Th17 cells

A

implicated in organ specific autoimmune diseases

produce 6 different kinds of IL17

36
Q

What does IL17 do?

A

Recruitment and activation of neutrophils and monocytes

induce expression of pro-inflammatory cytokines IL6 and IL8

37
Q

What does IL21 do?

A

Enhance B cell function

Contributes to Ab mediated pathology, such as hyper IgE syndrome, where patients are at constant risk of recurrent fungal and staph infections

38
Q

What does IL22 do?

A

protective immunity of the gut (restricts commensal bacteria to their niches)

induce expression of antimicrobial peptide

39
Q

Discuss the features and function of Thf T cells

A

facilitate humoral response by assisting B lymphocytes with the production of pathogen neutralizing Ab

Found in the B cell zones of secondary lymphoid tissue

recruitment to B cell zone is mediated by chemokine receptor CXCR5

40
Q

Where are fully mature Thf cells found?

A

The germinal centers interacting with B cells

41
Q

What is necessary for the development of Thf cells?

A

IL6, IL21, and BCL6

42
Q

What are the two types of CD4 T regulatory cells?

A

nTreg: developed in the thymus from DP thymocytes

iTreg: developed in peripheral lymphoid tissue

43
Q

How does FOXP3 regulate iTreg activity?

A

Production of IL2 is mediated by TCR signaling, both of which activate FOXP3 expression

continuous FOXP3 expression is required for suppression (induction?) of iTregs

FOXP3 mutation: IPEX

44
Q

Discuss Treg function

A

maintenance of self-tolerance, and regulate immune response

Mechanism of suppression: cell-cell contact! via inhibitory receptors such as CTLA4 and PD1

Mechanism of suppression: IL10 - act on APCs to reduce MHCII and CD80/86 activity, suppressing their functions

reduces the release of pro-inflammatory cytokines by mast cells

important for IBD and colitis

45
Q

What is the function of CD8+ cytotoxic T cells?

A

essential in controlling bacterial and especially viral infections

46
Q

What are the three phases of the CTL response?

A

Effector phase
Contracting phase
memory phase

47
Q

When does the effector phase of the CTL response take place?

A

1-2 days after infection

48
Q

What is the contracting phase of the CTL response?

A

When the source of infection is eliminated, most CTL die by apoptosis; ~5-10% survive

49
Q

Wha tis the memory phase of the CTL response?

A

The CTL that survive become memory T cells, can last up to 75 years in humans

50
Q

Where does CD8+ T cell activation take place?

A

occurs in periphery of the lymph nodes near the marginal sinus, to which both dendritic cells and CD8+ CTL migrate to from deeper T cell zones of the paracortical region

(Marginal sinus is Ag rich early in infection)

51
Q

What kind of cells does CD8 CTL recognize and kill?

A

foreign, mutated, and virally infected cells

52
Q

How does CD8 recognize the cells it will kill?

A

foreign peptide in context of MHCI on dendritic cells, which also produce IL12

53
Q

What other cells are required for the optimal activation of CTL cells?

A

NK cells, Ag specific CD4+ Thelper cells (Th1), or memory cells

54
Q

How do NK cells help in the activation of CTL?

A

detection of virus by NK cells results in the release of IFN-gamma which act on dendritic cells to up regulate CD40

55
Q

How do CD4 Th1 cells help in the activation of CTL?

A

activate DC, continue to release IL2, IL21, IFNgamma, which helps sustain the CD8 T cell response

56
Q

what is the sequence of events of a CTL and a target cell?

A

First adhesion molecules, then recognition of peptdie:MHCI –> the immunological synapse

57
Q

What is the mechanism of CTL killing?

A

contact mediated cytolytic effect: FAS-FASL mediated apoptosis and cytotoxic granules or lysosomes

58
Q

How does FAS-FASL mediated apoptosis work?

A

CD8 CTL expresses FASL which binds FAS on target cells

the activation of caspase 8 results in mitochondrial damage, other caspase activation, and eventually DNA fragmentation

59
Q

How does cytotoxic granules/lysosome mediated cell killing work?

A

perforin: complex forms pores in target cells

Granzyme B results in apoptosis, both caspase dependent and independent

granulysin: targets pathogen-infected cells

60
Q

What are the general functions of TCRgammadelta T cells?

A

mediators of the innate immune response

61
Q

discuss the characteristics of TCRgammadelta T cells

A

Ag is not presented via MHC, but rather by CD1a, b, c

Ag is not peptide, but rather phospholipids (endogenous and bacterial sources) or phosphoantigens (phsophorylated intermediate of stressed cells and pathogenic bacteria/protozoa)

62
Q

What are the different types of TCRgammadelta?

A

delta1: mucosa tissue, associated with epithelial cell functions
delta2: circulating, majority formed in fetal liver

63
Q

discuss TCRgammadelta in human disease

A

HIV: increase in delta1 and decrease in delta2

TB: active TB has a decrease in TCRgammadelta

parasitic infections increase gamma1

Host Defense Exam 1 (13 decks)

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