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HDM Final > Cytokine Messenger Systems > Flashcards

Cytokine Messenger Systems Flashcards

1
Q

What is the most important cytokine in induction of the lymphoid cell lineage?

A

IL-7

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2
Q

IL-7 causes differentiation of pluripotent stem cells into _________ progenitors, as well as proliferation of all cells in this lineage.

It is important for T cell ___________.

A

Lymphoid

Survival

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3
Q

Where is IL-7 secreted from?

A

Bone marrow

Thymic stromal cells

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4
Q

What is the primary purpose of type I interferons?

A

Type I interferons = IFN-alpha and IFN-beta

Directly inhibit viral replication by degrading mRNA, thus nonspecifically inhibiting protein synthesis

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5
Q

Where are type I interferons produced?

A

IFN-alpha: produced by leukocytes

IFN-beta: produced by fibroblasts

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6
Q

What is the major function of M1 macrophages?

A

M1 = classical macrophages

Induced by innate immunity

Play a role in inflammation

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7
Q

What induces M2 macrophages, and what is their major function?

A

M2 = alternative macrophages

Induced by IL-4 and IL-13

Tissue repair and control of inflammation

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8
Q

What are the 2 regulatory cytokines and what are their primary functions?

A

IL-10 and TGF-beta

Contraction of immune responses and anti-inflammatory properties

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9
Q

What secretes TGF-beta and what does it do?

A

TGF-beta is secreted by many types of cells

Allows for repair without regulatory immune cells in the vicinity

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10
Q

What secretes IL-10?

A

Macrophages
Dendritic cells
Treg cels

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11
Q

What secretes IL-2?

A

CD4+ and CD8+ T cells

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12
Q

What are the principle actions of IL-2?

A

Survival, proliferation, and differentiation of effector and regulatory T cells

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13
Q

What secretes IL-4?

A

CD4+ T cells

Mast cells

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14
Q

What is the principle action of IL-4?

A

B cell switching to IgE

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15
Q

What cells secrete IL-5?

A

CD4+ T cells

Mast cells

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16
Q

What is the principle action of IL-5?

A

Activation of eosinophils

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17
Q

What secretes IFN-y?

A

CD4+ and CD8+ T cells

Natural Killer cells

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18
Q

What is the principle action of IFN-y?

A

Activation of macrophages

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19
Q

What is the cellular source of TGF-beta?

A

CD4+ regulatory T cells

Many other cell types

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20
Q

What is the principle action of TGF-beta?

A

Inhibition of T cell activation; differentiation of regulatory T cells

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21
Q

What transcription factor is associated with Th1 cells?

A

T-bet

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22
Q

What transcription factor is associated with Th2 cells?

A

GATA-3

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23
Q

What transcription factor is associated with Th17 cells?

A

RORyT

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24
Q

What cytokines are required to differentiate a naive CD4+ T cell into a Th1?

A

IFN-y and IL-12 –> T-bet expression

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25
Q

What cytokines are required to differentiate a naive CD4+ T cell into a Th2?

A

IL-4 –> GATA-3 expression

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26
Q

What cytokines are required to differentiate a naive CD4+ T cell into a Th17?

A

TGF-beta, IL-6, IL-23 –> RORyT expression

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27
Q

What are the defining cytokines and target cells associated with Th1 cells?

A

IFN-y

Target cell: macrophages

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28
Q

What are the defining cytokines and target cell of Th2 cells?

A

IL-4
IL-5
IL-13

Target cell: eosinophils

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29
Q

What are the defining cytokines and target cell of Th17 cells?

A

IL-17
IL-22

Target cell: Neutrophils

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30
Q

Which specific T helper cell plays a role in host defense against intracellular pathogens?

A

Th1

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31
Q

Which specific T helper cell plays a role in host defense against extracellular pathogens?

A

Th17

32
Q

Which specific T helper cell plays a role in host defense against parasites?

A

Th2

33
Q

What is the overall role of Th1 in disease?

A

Autoimmunity; chronic inflammation

34
Q

What is the overall role of Th2 cells in disease?

A

Allergy

35
Q

What is the overall role of Th17 in disease?

A

Autoimmunity

36
Q

IL-2 is an ___________ signal that binds _______, which is constitutively expressed as a low affinity receptor

A

Autocrine

CD25

37
Q

What is the result of IL-2 ligation at the CD25 receptor?

A

Ligation induces expression of the alpha chain of the receptor, which increases its affinity

Binding of IL-2 to the now high affinity CD25 receptor promotes T cell proliferation and differentiation

38
Q

Other than activation of macrophages, what role does IFN-y play in the immune response?

A

Activates B cells to stimulate complement binding

Stimulates class II HLA and CD80

39
Q

What effect do Th1 cytokines have on Th2 responses?

A

Th1 cytokines are inhibitory of Th2 responses

40
Q

Th1 cells activate macrophages via IFN-y. What is this dependent on?

A

Antigen recognition

41
Q

Macrophage activation by Th1 cells is the basis for what type of reaction?

A

Delayed-type hypersenstivitiy (DTH)

42
Q

What is the macrophage’s response to activation by IFN-y?

A

Production of ROS, NO, and lysosomal enzymes

Secretion of inflammatory cytokines (TNF, IL-1, IL-12, chemokines)

Increased expression of B7 costimulators and MHC molecules

43
Q

What effect do Th2 cytokines have on Th1 responses?

A

Th2 cytokines are inhibitory of Th1 responses

44
Q

Th cells promot Ab _______ _________ by providing cytokine help

A

Class switching

45
Q

If a naive B cells is exposed to a nonspecific polyactivator (mitogen) like LPS, what will its isotype be?

A

IgM

46
Q

If a naive B cells is exposed to a nonspecific polyactivator (mitogen) like LPS in addition to IL-4, what will its isotype be?

A

IgE

47
Q

If a naive B cells is exposed to a nonspecific polyactivator (mitogen) like LPS and TGF-beta, what will its isotype be?

A

IgA

48
Q

What is the principle effector function of IgM?

A

Complement activation

49
Q

What are the principle effector functions of IgG1 and IgG3?

A

Opsonization and phagocytosis

Complement activation

Neonatal immunity (placental transfer)

50
Q

What are the principle effector functions of IgE and IgG4?

A

Immunity against helminths

Mast cell degranulation (immediate hypersensitivity)

51
Q

What cytokines associated with mucosal tissues contribute to IgA class-switching?

A

TGF-beta
APRIL
BAFF

52
Q

What is the principle effector function of IgA?

A

Mucosal immunity (transport of IgA through epithelia)

53
Q

True or false: Th17 cells are anti-inflammatory

A

FALSE, they are highly pro-inflammatory

54
Q

_______ cells were first described in animal models of diseases like MS, IBS, and RA

A

Th17

55
Q

What are the 2 primary functions of Th17 cells?

A

Inflammation
Barrier function
Neutrophil activation
Anti-microbial peptide production

56
Q

A patient presenting with progressive neurological symptoms in the setting of skin rash as well as numerous acid-fast bacilli clumps and foam cells in the skin biopsy would indicate what diagnosis?

A

Lepromatous leprosy

57
Q

Leprosy is characterized by cutaneous lesions, neuropathic changes, and deformities.

It is a __________ bacteria (which are relatively rare) that colonizes _____________ and other host cells and multiplies within them.

A

Intracellular

Macrophages

58
Q

M. leprae can only be eliminated by intracellular killing by activated ______________

It grows best at 86 degrees F, hence predominant growth of lesions occurs on ____________

Clinical symptoms vary, depending on type of immune response to the mycobacterium

A

Macrophages

Extremities

59
Q

The balance between a Th1 and a Th2 response to M. leprae can influence the outcome of infection.

What is the outcome in those that exhibit a Th1 response?

A

Tuberculoid leprosy

60
Q

The balance between a Th1 and a Th2 response to M. leprae can influence the outcome of infection.

What is the outcome in those that exhibit a Th2 response?

A

Lepromatous leprosy (high bacterial count)

[note that this may be due to defective Th1 response, or just a dominant Th2 response]

61
Q

The balance between a Th1 and a Th2 response to Leishmania major (protozoal parasite) can influence the outcome of infection in mice.

What is the outcome in those that exhibit a Th1 response?

A

Recovery

62
Q

The balance between a Th1 and a Th2 response to Leishmania major (protozoal parasite) can influence the outcome of infection in mice.

What is the outcome in those that exhibit a Th2 response?

A

Disseminated infection

63
Q

Tuberculoid leprosy results from a dominant Th1 response, characterized by organisms present at low to undetectable levels

It has _____ infectivity

Produces ___________ and local inflammation as well as peripheral _______ damage.

_____ serum Ig levels

______ T-cell responsiveness and a specific response to M. leprae antigens.

A

Low

Granulomas; nerve

Normal

Normal

64
Q

Lepromatous leprosy results from a dominant Th2 immune response characterized by florid growth of organisms in macrophages.

It has _____ infectivity and results in __________ infection in bone, cartilage, and diffuse nerve damage.

In terms of Ig levels, patients exhibit ________________.

Low or absent _____ cell responsiveness, and No response to M. leprae antigens

A

High; disseminated

Hypergammaglobulinemia

T

65
Q

Why would someone with lepromatous leprosy be prone to asthma?

A

Their default to the Th2 response results in high levels of IL-4 production –> IgG and mast cell degranulation/activation

Also IL-5 –> eosinophils

Both IL-4 and IL-5 are big in atopic disease, increasing the risk of asthma

66
Q

Which cytokine might be beneficial to a patient with lepromatous leprosy?

A

IFN-y or IL-12

Goal is hyperactivation of macrophages in order to kill M. leprae pathogen

67
Q

What is the downside to infusing someone with IFN-y for Lepromatous leprosy?

A

Nonspecific systemic hyperactivation of macrophages will lead to constant state of fever, malaise, body aches, etc.

68
Q

If genetic testing reveals random inactivation of the mother’s X chromosome, as well as mutational analysis revealing a defect in the IL2RG gene with deletion of a single nucleotide, what is a possible diagnosis?

A

X-linked SCID, IL-2Rgamma chain defect

69
Q

What is typical treatment for SCID?

A

IVIG, bone marrow transplant

70
Q

How effective is a bone marrow transplant for someone with X-linked SCID + IL-2Ry chain defect?

A

For case presented in class: 3 months post BMT showed that T cells were positive to activation by recall Ags. Patient remained unable to produce IgG, so IVIG will continue throughout life

71
Q

Why do B cell defects manifest later than T cell defects in SCID?

A

Passive Ab transfer from mom via placenta and breastfeeding provide temporary protection

72
Q

What immune function is ALWAYS impaired in SCID?

A

T cell function

73
Q

Patients with SCID present with recurrent persistent infection by ________ organisms

A

Opportunistic

74
Q

Since T cell function is always impaired in SCID, what is classification of SCID based on?

A

Based on if B cell function is directly impaired by molecular defect

[B cell positive or B cell negative]

75
Q

Most patients with SCID present around 3 months of age with life-threatening, recurrent opportunistic infections.

What are some of the other abnormal clinical findings associated with SCID, noting that these are due to infection, not the immunodeficiency itself?

A

Failure to thrive
Dehydration
Fever
No lymphadenopathy (increased secondary lymphatic tissues)

HDM Final (12 decks)

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