Cytokine Messenger Systems

Question 1

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

Answer 1

IL-7

Question 2

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 ___________.

Answer 2

Lymphoid

Survival

Question 3

Where is IL-7 secreted from?

Answer 3

Bone marrow

Thymic stromal cells

Question 4

What is the primary purpose of type I interferons?

Answer 4

Type I interferons = IFN-alpha and IFN-beta

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

Question 5

Where are type I interferons produced?

Answer 5

IFN-alpha: produced by leukocytes

IFN-beta: produced by fibroblasts

Question 6

What is the major function of M1 macrophages?

Answer 6

M1 = classical macrophages

Induced by innate immunity

Play a role in inflammation

Question 7

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

Answer 7

M2 = alternative macrophages

Induced by IL-4 and IL-13

Tissue repair and control of inflammation

Question 8

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

Answer 8

IL-10 and TGF-beta

Contraction of immune responses and anti-inflammatory properties

Question 9

What secretes TGF-beta and what does it do?

Answer 9

TGF-beta is secreted by many types of cells

Allows for repair without regulatory immune cells in the vicinity

Question 10

What secretes IL-10?

Answer 10

Macrophages
Dendritic cells
Treg cels

Question 11

What secretes IL-2?

Answer 11

CD4+ and CD8+ T cells

Question 12

What are the principle actions of IL-2?

Answer 12

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

Question 13

What secretes IL-4?

Answer 13

CD4+ T cells

Mast cells

Question 14

What is the principle action of IL-4?

Answer 14

B cell switching to IgE

Question 15

What cells secrete IL-5?

Answer 15

CD4+ T cells

Mast cells

Question 16

What is the principle action of IL-5?

Answer 16

Activation of eosinophils

Question 17

What secretes IFN-y?

Answer 17

CD4+ and CD8+ T cells

Natural Killer cells

Question 18

What is the principle action of IFN-y?

Answer 18

Activation of macrophages

Question 19

What is the cellular source of TGF-beta?

Answer 19

CD4+ regulatory T cells

Many other cell types

Question 20

What is the principle action of TGF-beta?

Answer 20

Inhibition of T cell activation; differentiation of regulatory T cells

Question 21

What transcription factor is associated with Th1 cells?

Answer 21

T-bet

Question 22

What transcription factor is associated with Th2 cells?

Answer 22

GATA-3

Question 23

What transcription factor is associated with Th17 cells?

Answer 23

RORyT

Question 24

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

Answer 24

IFN-y and IL-12 –> T-bet expression

Question 25

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

Answer 25

IL-4 --> GATA-3 expression

Question 26

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

Answer 26

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

Question 27

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

Answer 27

IFN-y Target cell: macrophages

Question 28

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

Answer 28

IL-4 IL-5 IL-13 Target cell: eosinophils

Question 29

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

Answer 29

IL-17 IL-22 Target cell: Neutrophils

Question 30

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

Answer 30

Th1

Question 31

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

Answer 31

Th17

Question 32

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

Answer 32

Th2

Question 33

What is the overall role of Th1 in disease?

Answer 33

Autoimmunity; chronic inflammation

Question 34

What is the overall role of Th2 cells in disease?

Answer 34

Allergy

Question 35

What is the overall role of Th17 in disease?

Answer 35

Autoimmunity

Question 36

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

Answer 36

Autocrine | CD25

Question 37

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

Answer 37

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

Question 38

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

Answer 38

Activates B cells to stimulate complement binding Stimulates class II HLA and CD80

Question 39

What effect do Th1 cytokines have on Th2 responses?

Answer 39

Th1 cytokines are inhibitory of Th2 responses

Question 40

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

Answer 40

Antigen recognition

Question 41

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

Answer 41

Delayed-type hypersenstivitiy (DTH)

Question 42

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

Answer 42

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

Question 43

What effect do Th2 cytokines have on Th1 responses?

Answer 43

Th2 cytokines are inhibitory of Th1 responses

Question 44

Th cells promot Ab _______ _________ by providing cytokine help

Answer 44

Class switching

Question 45

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

Answer 45

IgM

Question 46

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

Answer 46

IgE

Question 47

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

Answer 47

IgA

Question 48

What is the principle effector function of IgM?

Answer 48

Complement activation

Question 49

What are the principle effector functions of IgG1 and IgG3?

Answer 49

Opsonization and phagocytosis Complement activation Neonatal immunity (placental transfer)

Question 50

What are the principle effector functions of IgE and IgG4?

Answer 50

Immunity against helminths Mast cell degranulation (immediate hypersensitivity)

Question 51

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

Answer 51

TGF-beta APRIL BAFF

Question 52

What is the principle effector function of IgA?

Answer 52

Mucosal immunity (transport of IgA through epithelia)

Question 53

True or false: Th17 cells are anti-inflammatory

Answer 53

FALSE, they are highly pro-inflammatory

Question 54

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

Answer 54

Th17

Question 55

What are the 2 primary functions of Th17 cells?

Answer 55

Inflammation Barrier function Neutrophil activation Anti-microbial peptide production

Question 56

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?

Answer 56

Lepromatous leprosy

Question 57

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.

Answer 57

Intracellular | Macrophages

Question 58

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

Answer 58

Macrophages | Extremities

Question 59

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?

Answer 59

Tuberculoid leprosy

Question 60

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?

Answer 60

Lepromatous leprosy (high bacterial count) [note that this may be due to defective Th1 response, or just a dominant Th2 response]

Question 61

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?

Answer 61

Recovery

Question 62

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?

Answer 62

Disseminated infection

Question 63

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.

Answer 63

Low Granulomas; nerve Normal Normal

Question 64

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

Answer 64

High; disseminated Hypergammaglobulinemia T

Question 65

Why would someone with lepromatous leprosy be prone to asthma?

Answer 65

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

Question 66

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

Answer 66

IFN-y or IL-12 Goal is hyperactivation of macrophages in order to kill M. leprae pathogen

Question 67

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

Answer 67

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

Question 68

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?

Answer 68

X-linked SCID, IL-2Rgamma chain defect

Question 69

What is typical treatment for SCID?

Answer 69

IVIG, bone marrow transplant

Question 70

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

Answer 70

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

Question 71

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

Answer 71

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

Question 72

What immune function is ALWAYS impaired in SCID?

Answer 72

T cell function

Question 73

Patients with SCID present with recurrent persistent infection by ________ organisms

Answer 73

Opportunistic

Question 74

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

Answer 74

Based on if B cell function is directly impaired by molecular defect [B cell positive or B cell negative]

Question 75

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?

Answer 75

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