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204- Immunology > Regulating the immune response > Flashcards

Regulating the immune response Flashcards

1
Q

What is the mechanism of action of cytokines?

A

They act by ligating their receptor (often two subunits) and triggering a signalling cascade –> activated transcription of specific genes

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2
Q

Using the diagram of haematopoiesis to help you, identify the KEY cytokine involved in differentiation of a multipotential hematopoietic stell cell into a common myeloid progenitor/ common lymphoud progenitor

A

GM-CSF

Others:
IL3, SCF

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3
Q

Using the diagram of haematopoiesis to help you, identify the KEY cytokines involved in differentiation of a common myeloid progenitor into:

  • Megakaryocyte
  • Erthrocyte
  • Mast cell
  • Myeloblast
A
  • TPO, IL11
  • EPO
  • SCF, G-CSF, IL6
  • GM-CSF
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4
Q

Using the diagram of haematopoiesis to help you, identify the KEY cytokine involved in differentiation of a small lymphocyte into a T lymphocyte

A

IL2

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5
Q

Using the diagram of haematopoiesis to help you, identify the KEY cytokines involved in differentiation of a myeloblast into:

  • basophil
  • neutrophil
  • eosinophil
  • monocyte
A
  • G-CSF, GM-CSF
  • G-CSF, GM-CSF
  • IL5, GM-CSF
  • GM-CSF
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6
Q

Which category of cytokines interfere with viral replication?

Give three examples and the cells which make them

A

INTERFERONS are anti-viral mediators

IFN-a made by lymphocytes
IFN-b made by fibroblasts
IFN-y made by lymphocytes and NK cells. Very poor antiviral molecule

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7
Q

States three immune activators and their role

A
  1. Lymphocyte activating cytokines (IL1)
  2. T cell growth factors (IL2)
  3. Macrophage activating cytokines (IFN-y)
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8
Q

What are cytotoxins?

Give an example

A

Identified as products of activated lymphocytes or macrophages than can kill tumor cells

TNF (aka TNF-a) which is actually a very poor antitumor molecule

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9
Q

There are two populations of CD4+ T cells. What are they and how do their functions differ?

A

Th1- MACROPHAGE ACTIVATING EFFECTOR MOLECULES
e.g. IFN-y , TNF-a

Th2- B CELL ACTIVATING EFFECTOR MOLECULES

e. g.IL4, IL5
- also cause release of IL10, TGT-B

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10
Q

What kind of cells are CD8+ T cells?

What effector molecules do they employ?

A

Cytotoxic (Killer) T cell

- perforin, granzymes, granulyisin, fas ligand

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11
Q

Briefly state effects of the following cytokines made by Th1

  1. IFN-y and CD40 ligand
  2. Fas ligand/LT-a
  3. IL2
A

IFN-y and CD40 ligand
- activates macrophage to destroy engulfed bacteria

Fas ligand/LT-a
- kills chronically infected cells releasing bacteria to be destroyed by fresh macrophages

IL2
- induces T cell proliferation, increasing numbers of effector cells

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12
Q

Briefly state effects of the following cytokines made by Th1

  1. IL3 + GM-CSF
  2. TNFa + LT-B
A
  1. Induces macrophage differentiation in bone marrow

2. Activated endothelium to induce macrophage binding and exit from blood vessel as site of infection

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13
Q

What causes X linked SCID

A
  • genetic inactivation (by mutation) of one receptor that . is a common signalling component of the IL2,IL4 and IL7 receptors
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14
Q

How was the role of cytokines in inflammation discovered?

How do they cause inflammation (consider the cardinal signs)

A

Studying the immunopathogenesis of cachexia in infection

Bacteria trigger macrophages to release cytokines and chemokines which cause vasodilation and increased vascular permeability (redness, heat, swelling). Inflammatory cells migrate into tissue releasing mediators that cause pain

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15
Q

State 3 TNF mediated disease

What is meant by this?

A
  • RHEUMATOID ARTHRITIS
  • INFLAMMATORY BOWEL DISEASE
  • septic shock
  • multiple organ failure
  • respiratory distress syndrome
  • graft v host rejection
  • diabetes
  • pulmonary fibrosis

TNF is a pathogenic mediator and inhibition of it in animal models is protective

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16
Q

Generally speaking what kind of disease are Th1 cytokines and Th2 cytokines important in respectively.

A

TH1- Inflammatory diseases

TH2- allergic disease

17
Q

Which cytokines are produced by the 4 subsets of CD4 T cells?

What are their functions

A

Th1: IFNy
- inflammation

Th2: IL4,-5,-9,-13
- allergy, anti-inflammation
Th17: IL17
- inflammation
Treg: IL10
- anti-inflammation (inhibit activity of other T cells)
18
Q

What is the function of chemokines?

A

Chemotaxis: migration towards a gradient

  • neutrophils chase bacteris
  • leukocytes invade infection

Important in the homing and migration of cells of the immune system
= role in development

19
Q

Give 2 examples of chemokines and the cell type they act on

A

MCP 1/CCL2- Monocytes

IL8- Neutrophil

20
Q

Consider the cytokines with a role in host defence

Which disease can they be used in therapeutically?

A

IL2- melanoma, renal cell carcinoma

IFNa- hair cell leukaemia, kaposi, viral hepatitis

21
Q

What is the therapeutic use of the following cytokines:

  1. EPO
  2. GM-CSF
  3. G-CSF
  4. IL11
A
  1. Anaemia
  2. Myeloreconstruction following bone marrow transplant, chemotherapy-induced neutropenia
  3. chemotherapy-induced neutropenia
  4. Thrombocytopenia in oncology
22
Q

What is the therapeutic use of the following anti-cytokines:

  1. Anti-TNF
  2. IL-1RA
  3. Anti IL6
A
  1. RA, Crohns, Ulcerative colitis, psoriasis
  2. RA, CAPS
  3. RA
23
Q

What is the therapeutic use of Anti-IL17, -12, -23

A

Psoriasis, psoriatic arthritis, akylosing spondylitis, Chrohn

24
Q

How do cytokine inhibitors work?

For each MOA, give an example

A

Anti-receptor
- Anti TNF, IL-1R, IL-6R, IL-17R, IL-12

Anti cytokine
- Anti IL-1b, IL6, IL17

Anti soluble receptor
-Soluble TNFR

25
Q

What is Ustekinbumab?

A
  • Antibody against p40 subunit of IL12 and IL23

- approved for psoriasis and crohns

26
Q

Why are cytokines describes as pleitropic

A
  • Act on many different targets
27
Q

Why do side effects arise in using anti cytokine in treatment

A
  • Due to their role in innate immunity
  • Side effects of anti-TNF, anti-IL17 and anti IL-6 include increased susceptibility to TB and serious opportunistic infections (listeria, pneumocystosis)

204- Immunology (16 decks)

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