Cytokine Messengers - Bowden

Question 1

What is the role of IL-7? 6

Answer 1

Pluripotent stem cells differentiation into lymphoid progenitors (T, B, and NK cells)

Important for T cell survival

Question 2

Where is IL-7 produced? 6

Answer 2

Secreted from bone marrow and thymic stromal cells

Question 3

What produces TNF? 7

Answer 3

TNF - tumor necrosis factor

Macrophages

T cells

Mast Cells

Question 4

What are the main and secondary roles of TNF? 7

Answer 4

Activation of endothelial cells (inflammation/coagulation)

Neutrophil activation

Induces fever in hypothalamus

Induces apoptosis in many cell types

Question 5

What is the role of TGF-β? 7

Answer 5

Inhibits inflammatory T cells

Th17 differentiation

Treg differentiation

Question 6

What is the principal source of IL-15? What is the role of IL-15? 7

Answer 6

Source - macrophages

Induces proliferation of NK cells

Induces proliferation of T cells

Question 7

What secretes IL-18? What is its role? 7

Answer 7

IL-18 secreted by macrophages

Induces NK cells and T cells to synthesize IFN-γ

Question 8

What are the type 1 interferons? 7

Answer 8

IFN-α

IFN-β

Question 9

What are the main roles of Type 1 IFNs? 7

Answer 9

Induces an antiviral state meaning:

increased HLA Class I expression on all cells

NK cell activation

Question 10

What is the main role of IFN-γ?

Answer 10

Activation of macrophages

Question 11

What type 1 IFN is produced by leukocytes

Answer 11

IFN-α

Question 12

What type 1 IFN is produced by Fibroblasts? 8

Answer 12

IFN-β

Question 13

How do Type I IFNs inhibit viral replication? 8

Answer 13

Degrade viral mRNA

Shuts down human protein synthesis

Secreted from viral infected cells to neighboring cells

Question 14

What is the role of Endogenous pyrogens on bone-marrow epithelium and DCs? 9

Answer 14

Pyrogens - IL-1/IL-6/TNF-α

Bone Marrow - Neutrophil mobilization for phagocytosis

Dendritic Cells - TNF-α stimulates DC migration to lymph nodes and maturation (start of adaptive response)

Question 15

Before it’s a macrophage it’s a _______? 10

Answer 15

Monocyte (in circulation)

Question 16

What are the 2 major functions of macrophages? 10

Answer 16

M1 Classical Macrophage Function

M2 Alternative Macrophage Function

Question 17

What induces the M1 Macrophage function? 10

Answer 17

M1 - classical function

A monocyte that receives:

1. ) TLR ligand binding
2. ) Induction via IFN-γ

Question 18

What induces the M2 Macrophages? 10

Answer 18

M2 - alternative function

A Monocyte that receives:

1. ) IL-13
2. ) IL-4

Question 19

What is the main summary role of M1 Macrophages? 10

Answer 19

Induced by innate immunity and involved in inflammation

Question 20

What is the main summary role of M2 Macrophages? 10

Answer 20

Play a role in tissue repair and inflammation control

Question 21

What is the combined role of TGF and IL-10? 11

Answer 21

Contraction of the immune response (anti-inflammatory properties)

Question 22

What secretes IL-10? 11

Answer 22

Macrophages

Dendritic Cells

Tregs

Question 23

What is unique about the repair process induced by TGF-β? 11

Answer 23

Induces repair without regulatory immune cells having to be in the vicinity

Question 24

What are all the cytokines produced by CD4+ T helper cells and what is the function of each? 12

Answer 24

IL-2 –> full development of TCR, α subunit

IL-4 –> B cell class switching IgM to IgE

IL-5 –> Act. Eosinophils

IFN-γ –> macrophage activation

TGF-β –> T cell act. Inhibition + induction of Treg cells

Question 25

What are all the cytokines produced by CD8+ Cytotoxic T cells and what is their function? 12

Answer 25

IL-2 --> allows for addition of α subunit to finish TCR (autocrine signal) IFN-γ --> activates macrophages

Question 26

At the site of infection what would induce Th1 development? 13

Answer 26

Coming from a Ag-presented CD4+ T Helper Cell: IFN-γ IL-12 Transcription Factor: T-bet

Question 27

At the site of infection what would induce TH2 development? 13

Answer 27

Coming from a Ag-presented CD4+ T Helper Cell: IL-4 Transcription Factor: GATA-3

Question 28

At the site of infection what would induce TH17 development? 13

Answer 28

Coming from a Ag-presented CD4+ T Helper Cell: TGF-β IL-6 IL-23 IL-1 Transcription Factor: RORγT

Question 29

What are the target cells of Th1, Th2, and Th17 and what do these targets cells defend the host against? 14

Answer 29

Th1 --> Macrophages, defense against IC pathogens Th2 --> Eosinophils, defense against Parasites (helminths) Th17 --> Neutrophils, defense against EC pathogens

Question 30

What part of the immune response do we consider IFN's to be? 8

Answer 30

Part of the innate system because they shut down human protein synthesis

Question 31

What do M1 Macrophages produce and do? 10

Answer 31

ROS + NO + lysosomal enzymes --> phagocytosis and bacteria killing IL-1,12, and 23 --> inflammation

Question 32

What do M2 Macrophages produce and do? 10

Answer 32

IL-10, TGF-β: Wound repair Antiinflammatory effects Fibrosis

Question 33

What cytokines are produced by Mast Cells? 12

Answer 33

IL-4 --> B cell class switching IgM to IgE IL-5 --> activation of eosinophils

Question 34

What role do Macrophages and Th1 play in disease? 14

Answer 34

Autoimmunity and chronic inflammation

Question 35

What role do Eospinophils and Th2 play in disease? 14

Answer 35

Allergies

Question 36

What role do neutrophils and Th17 play in disease? 14

Answer 36

Autoimmunity

Question 37

What do Th2 cells secrete? 14

Answer 37

IL-4 --> M2 macrophage activation, peristalsis, B cell Class switch IgM to IgE IL-5 --> Eosinophil activation IL-13 --> peristalsis, M2 activation

Question 38

What do Th17 cells secrete? 14

Answer 38

IL-17,22

Question 39

Who secretes IL-2 and what type of signal is it? 15

Answer 39

T cells secrete IL-2 and it's an autocrine signal

Question 40

What binds IL-2? 15

Answer 40

IL-2R or CD25 of Tcell

Question 41

How are T cells induced to proliferate? 15

Answer 41

IL-2 binds CD25 (IL-2R) in a low affinity state α subunit of CD25 receptor expressed CD25 now able to bind IL-2 in a high affinity state T cell proliferates

Question 42

What is the role of IFN-γ released by Th1? 16

Answer 42

M1 Macrophage activation Act. B cells to stimulate complement binding Stimulates Class II HLA and CD80

Question 43

What is the relationship between Th1 and Th2? 16, 18

Answer 43

Th1 cytokines are inhibitors of Th2 responses Th2 cytokines are inhibitors of Th1 responses

Question 44

What is Th1 activation dependent on firstly? 17

Answer 44

Dependent on Ag recognition (by a macrophage)

Question 45

In a naive B cell Ig Chain what happens if you induce with IL-4? 19

Answer 45

IgG4 production IgE production

Question 46

In a naive B cell Ig Chain what happens if you induce with TGF-β? 19

Answer 46

IgA production IgG production

Question 47

What cytokines do Th17 produce? 21 | Look at diagram, make sure you have all the detail!

Answer 47

IL-17 --> inflammation, neutrophil response, antimicrobial peptides IL-22 --> increased barrier function, antimicrobial peptides

Question 48

What is the main function of Th17? What disease are Th17 involved in? 21

Answer 48

Proinflammatory T cell Multiple sclerosis IBD Rheumatoid arthritis

Question 49

What's the Dx and treatment: Gradual loss of sensation on back of hand, hypo-pigmented lesions on elbows, wrists, and hands. Lesion expansion. No eyelashes or eye brows. Varying response to pinprick test. Elevated Neutrophils everything else normal IgG elevated everything else normal Biopsy: Multiple acid-fast bacilli in clumps, foam cells 22, 23, 24, 25, 26, 27

Answer 49

Dx - lepromatous leprosy (M. Leprae) Tx - dapsone, clozapine, rifampin

Question 50

How does Leprosy cause infection? 28

Answer 50

M. Leprae colonized macrophages and host cells multiplying within them Can only be killed by IC killing of activated macrophages

Question 51

What type of infection does M. Leprae result in? 28

Answer 51

Intracellular infection

Question 52

What transcription factor induces Th1? What transcription factor induces Th2? 29

Answer 52

Th1 - NFAT-c Th2 - GATA-3 | c-MAF | NIP-45

Question 53

What are two types of infection as a result of M. Leprae? 30

Answer 53

Tuberculoid leprosy Lepromatous leprosy

Question 54

What's the difference between Tuberculod leprosy and Lepromatous leprosy? 30

Answer 54

Lepromatus: Highly infective, disseminated. Neuropathological infection (schwann cells) major deformity. Low T cell response and hypergammaglobulinemia Tuberculoid: Organisms present at low levels with localized inflammation. Normal T cell response and serum Ig levels

Question 55

Which cytokine might be beneficial to a patient with lepromatous leprosy? 32

Answer 55

IL-12 and IFN-γ to push the shift towards Th1 (from the leaning Th2 state)

Question 56

What causes Leishmania Major? What causes Mycobacterium leprae? 29

Answer 56

Leishmania major - protozoal parasite Mycobacterium Leprae - Bacterium

Question 57

What is the dx and tx: Male with healthy sister 3 months: dry cough and runny nose, 4 months: ottis media (ear infection), oral polio and DPT vaccination given 5 months: dry cough, recurrent otitis media, re-immunized chest X-ray - bilateral pneumonia (treated with clarithromycin) 6 months: thrush (yeast), diaper rash, not gaining weight, tachypnea ``` WBCs - low Lymphocyte count - low Differential of periphery - 99% B cells Ig titers are all very low No recall of immunizations RBCs - normal + pseudomonas aeruginosa + respiratory syncytial virus (RSV) ``` 34, 35, 36, 37, 38, 39, 40

Answer 57

Dx: X-linked SCID (IL-2Rγ chain defect) Tx: IV-Ig, Bone Marrow Transplant

Question 58

What are the two main issues associated with SCID? What cells are present in Severe Combined Immunodeficiency (SCID)? 41

Answer 58

Severe B and T cell dysfunction - T cells always absent - B cells MAY be absent (B cell pos or neg) - NK cells MAY be absent Persistent opportunistic infections

Question 59

IL-2 look at 43!

Answer 59

Heterodimer that becomes a trimer when α subunit gets added

Question 60

What is the classification of SCID based on? 42

Answer 60

Whether or not the pt is B cell + or B cell -

Question 61

What are the clinical presentations of SCID and what are they caused by? 44

Answer 61

Caused by opportunistic infections Failure to thrive Dehydration Fever No lymphadenopathy (increased secondary lymphatic tissues)

Question 62

Diagram slide 45

Answer 62

(Will be helpful)