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HDM - Final > Cytokine Messengers - Bowden > Flashcards

Cytokine Messengers - Bowden Flashcards

1
Q

What is the role of IL-7? 6

A

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

Important for T cell survival

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2
Q

Where is IL-7 produced? 6

A

Secreted from bone marrow and thymic stromal cells

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3
Q

What produces TNF? 7

A

TNF - tumor necrosis factor

Macrophages

T cells

Mast Cells

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4
Q

What are the main and secondary roles of TNF? 7

A

Activation of endothelial cells (inflammation/coagulation)

Neutrophil activation

Induces fever in hypothalamus

Induces apoptosis in many cell types

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5
Q

What is the role of TGF-β? 7

A

Inhibits inflammatory T cells

Th17 differentiation

Treg differentiation

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6
Q

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

A

Source - macrophages

Induces proliferation of NK cells

Induces proliferation of T cells

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7
Q

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

A

IL-18 secreted by macrophages

Induces NK cells and T cells to synthesize IFN-γ

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8
Q

What are the type 1 interferons? 7

A

IFN-α

IFN-β

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9
Q

What are the main roles of Type 1 IFNs? 7

A

Induces an antiviral state meaning:

increased HLA Class I expression on all cells

NK cell activation

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10
Q

What is the main role of IFN-γ?

A

Activation of macrophages

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11
Q

What type 1 IFN is produced by leukocytes

A

IFN-α

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12
Q

What type 1 IFN is produced by Fibroblasts? 8

A

IFN-β

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13
Q

How do Type I IFNs inhibit viral replication? 8

A

Degrade viral mRNA

Shuts down human protein synthesis

Secreted from viral infected cells to neighboring cells

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14
Q

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

A

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)

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15
Q

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

A

Monocyte (in circulation)

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16
Q

What are the 2 major functions of macrophages? 10

A

M1 Classical Macrophage Function

M2 Alternative Macrophage Function

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17
Q

What induces the M1 Macrophage function? 10

A

M1 - classical function

A monocyte that receives:

  1. ) TLR ligand binding
  2. ) Induction via IFN-γ
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18
Q

What induces the M2 Macrophages? 10

A

M2 - alternative function

A Monocyte that receives:

  1. ) IL-13
  2. ) IL-4
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19
Q

What is the main summary role of M1 Macrophages? 10

A

Induced by innate immunity and involved in inflammation

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20
Q

What is the main summary role of M2 Macrophages? 10

A

Play a role in tissue repair and inflammation control

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21
Q

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

A

Contraction of the immune response (anti-inflammatory properties)

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22
Q

What secretes IL-10? 11

A

Macrophages

Dendritic Cells

Tregs

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23
Q

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

A

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

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24
Q

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

A

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

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25
Q

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

A

IL-2 –> allows for addition of α subunit to finish TCR (autocrine signal)

IFN-γ –> activates macrophages

26
Q

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

A

Coming from a Ag-presented CD4+ T Helper Cell:

IFN-γ

IL-12

Transcription Factor: T-bet

27
Q

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

A

Coming from a Ag-presented CD4+ T Helper Cell:

IL-4

Transcription Factor: GATA-3

28
Q

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

A

Coming from a Ag-presented CD4+ T Helper Cell:

TGF-β

IL-6

IL-23

IL-1

Transcription Factor: RORγT

29
Q

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

A

Th1 –> Macrophages, defense against IC pathogens

Th2 –> Eosinophils, defense against Parasites (helminths)

Th17 –> Neutrophils, defense against EC pathogens

30
Q

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

A

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

31
Q

What do M1 Macrophages produce and do? 10

A

ROS + NO + lysosomal enzymes –> phagocytosis and bacteria killing

IL-1,12, and 23 –> inflammation

32
Q

What do M2 Macrophages produce and do? 10

A

IL-10, TGF-β:

Wound repair
Antiinflammatory effects
Fibrosis

33
Q

What cytokines are produced by Mast Cells? 12

A

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

IL-5 –> activation of eosinophils

34
Q

What role do Macrophages and Th1 play in disease? 14

A

Autoimmunity and chronic inflammation

35
Q

What role do Eospinophils and Th2 play in disease? 14

A

Allergies

36
Q

What role do neutrophils and Th17 play in disease? 14

A

Autoimmunity

37
Q

What do Th2 cells secrete? 14

A

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

IL-5 –> Eosinophil activation

IL-13 –> peristalsis, M2 activation

38
Q

What do Th17 cells secrete? 14

A

IL-17,22

39
Q

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

A

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

40
Q

What binds IL-2? 15

A

IL-2R or CD25 of Tcell

41
Q

How are T cells induced to proliferate? 15

A

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

42
Q

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

A

M1 Macrophage activation

Act. B cells to stimulate complement binding

Stimulates Class II HLA and CD80

43
Q

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

A

Th1 cytokines are inhibitors of Th2 responses

Th2 cytokines are inhibitors of Th1 responses

44
Q

What is Th1 activation dependent on firstly? 17

A

Dependent on Ag recognition (by a macrophage)

45
Q

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

A

IgG4 production

IgE production

46
Q

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

A

IgA production

IgG production

47
Q

What cytokines do Th17 produce? 21

Look at diagram, make sure you have all the detail!

A

IL-17 –> inflammation, neutrophil response, antimicrobial peptides

IL-22 –> increased barrier function, antimicrobial peptides

48
Q

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

A

Proinflammatory T cell

Multiple sclerosis
IBD
Rheumatoid arthritis

49
Q

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

A

Dx - lepromatous leprosy (M. Leprae)

Tx - dapsone, clozapine, rifampin

50
Q

How does Leprosy cause infection? 28

A

M. Leprae colonized macrophages and host cells multiplying within them

Can only be killed by IC killing of activated macrophages

51
Q

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

A

Intracellular infection

52
Q

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

A

Th1 - NFAT-c

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

53
Q

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

A

Tuberculoid leprosy

Lepromatous leprosy

54
Q

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

A

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

55
Q

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

A

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

56
Q

What causes Leishmania Major? What causes Mycobacterium leprae? 29

A

Leishmania major - protozoal parasite

Mycobacterium Leprae - Bacterium

57
Q

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

A

Dx: X-linked SCID (IL-2Rγ chain defect)

Tx: IV-Ig, Bone Marrow Transplant

58
Q

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

A

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

59
Q

IL-2 look at 43!

A

Heterodimer that becomes a trimer when α subunit gets added

60
Q

What is the classification of SCID based on? 42

A

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

61
Q

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

A

Caused by opportunistic infections

Failure to thrive

Dehydration

Fever

No lymphadenopathy (increased secondary lymphatic tissues)

62
Q

Diagram slide 45

A

(Will be helpful)

HDM - Final (15 decks)

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