Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

BSMS204 Theme I Immunology > 8. Cytokines and chemokines > Flashcards

8. Cytokines and chemokines Flashcards

1
Q

What are cytokines?

A

Soluble mediators that are produced by a tissue or a cell and acts at a distance (from micrometres to several cm)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How do cytokines act?

A

All cytokines act by ligating their receptor (often two subunits) and triggering a signaling cascade leading to activated transcription of specific genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What determines cell differentiation and haematopoiesis?

A

cytokines

GM-CSF - multipotential haematopoietic stem cell

SCF, G-CSF, IL-6 = mast cell

GM-CSF -> myeloblast

EPO-> erythrocyte

TPO, IL-11 -> megakaryocyte

T-lymphocyte - Il-2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are interferons?

A

Anti-viral mediators – Interferons, identified (1957) as products of virus-infected cells that interfere with viral replication
IFN-alpha (made by lymphocytes)
IFN-beta (made by fibroblasts)
IFN-gamma (made by lymphocytes & NK cells)

IFN-gamma is a very poor antiviral molecule.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Immune activators

A

Lymphocyte-activating cytokines (IL-1)
T cell growth factors (IL-2, -7, -9, -15; they share a co-receptor)
Macrophage-activating cytokines (IFN-gamma)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Cytotoxins

A

Cytotoxins: identified as products of activated lymphocytes or macrophages that can kill tumor cells
tumor necrosis factor; TNF, also known as TNF-alpha

TNF is, in fact, a very poor antitumor molecule.
Don’t be mislead by the name

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What happened with TNF as an anticancer agent?

A

In the 1980s TNF was cloned and produced with the hope it would be an anticancer agent. However, it turned out to be too toxic

Same story for IL-1, as a lymphocyte activator tested in AIDS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Do the effector molecules made by T cells differ?

A

The three main types of armed effector T cells produce distinct sets of effector molecules with different functions. Th1 (T-helper) and Th2 cells act mainly by activating other cells (see previous lectures on innate immunity)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

CD8 T cells produce

A

cytotoxic effector molecules e.g. perforin, granzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Th1 cells produce

A

macrophage activating effectormolecules e.g. IFN-gamma and TNF-alpha

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Th2 cells produce

A

B-cell activating effector molecules

e.g. IL-4, IL-5, IL-10, TGF-Beta

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Activated Th1 cell cytokines

A 
IFN-gamma and CD40 ligand
Fas ligand or LT-alpha
IL-2
IL-3 and GM-CSF
TNF-alpha and LT-beta
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Immune-stimulating cytokine deficiency cause immunosuppression

A

component of the IL-2, IL-4 and IL-7 receptorsX-linked SCID (severe combined immunodeficiency) is caused by the genetic inactivation (by mutation) of one receptor that is a common signalling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How did they find out that TNF is an inflammatory mediator?

A

Studying immunopathegenesis of cachexia during infection

activated macrophages produce an inflammatory mediator (cytokine) that, among other things, induced cachexia.
When they had its sequence, they found it was identical to TNF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Cardinal signs of inflammation

A 
heat
swelling
redness
pain
tissue damage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What causes the cardinal signs of inflammation?

A

biological action of inflammatory cytokines (IL-1, IL-6, TNF…) on the vascular endothelium, or through production of prostaglandins or chemokines.

17
Q

Inflammation

A

Macrophages encountering bacteria in the tissues are triggered to release cytokines that increase the permeability of blood vessels, allowing fluid and proteins to pass into the tissues.
They produce chemokines that direct the migration of neutrophils to the site of infection.
The stickiness of the endothelial cells of the blood vessels is also changed, so that cells adhere to the blood vessel wall and are able to crawl through it; first neutrophils and then monocytes are shown entering the tissue from a blood vessel.

The accumulation of fluid and cells at the site of infection causes the redness, swelling, heat, and pain, known collectively as inflammation. Neutrophils and macrophages are the principal inflammatory cells. Later in an immune response, activated lymphocytes may also contribute to inflammation.

18
Q

TNF-mediated diseases

A 
1-Septic shock
2-Multiple organ failure
3-Respiratory distress syndrome
4-Rheumatoid arthritis
5-Inflammatory bowel disease
6-Graft-versus-host rejection
7-Diabetes
8-Pulmonary fibrosis

(where TNF is a pathogenic mediator and where inhibition of TNF is protective in animal models)

19
Q

Which cytokines are involved in allergy?

A

While Th1 cytokines are important in inflammatory diseases, Th2 cytokines are important in allergic diseases

The Th1/Th2 differentiation
is often viewed as a balance

20
Q

TH1 cytokines from CD4

A

IFN-gamma, IL-12, IL23

21
Q

TH2 cytokines from CD4

A

IL4

22
Q

TH1 cytokines

A

IFN-gamma -> inflammation

23
Q

TH2 cytokines

A

IL4, IL5, 9 and 13
allergy
anti-inflammation

24
Q

TH17 cytokines

A

IL17 -> inflammation

25
Q

Treg cytokines

A

IL-10, inhibit activity of other T cells

anti-inflammation

26
Q

Chemokines

A

Chemotaxis
Discovered originally by neutrophils chasing bacteria

Then to explain infiltration of leukocytes

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

27
Q

Examples of some chemokines

A

MCP-1/CCL-2

IL-8

28
Q

CCL2 effect

A

causes macrophages to accumulate at site of infection - by chemotaxis

29
Q

Therapeutic use of interferons

A

IFN-gamma Macrophage activation

IFN-beta (MS) “immunomodulation”

30
Q

Host defence therapeutic uses

A

Host defense
IL-2 (melanoma, renal cell carcinoma)

IFN-alpha (hairy cell leukemia, Kaposi, viral hepatitis)

31
Q

Haematopoiesis cytokines used in therapy

A

GM-CSF (myeloreconstitution following bone marrow transplant, chemotherapy-induced neutropenia)
G-CSF (chemotherapy-induced neutropenia)
IL-11 (thrombocytopenia in oncology)
EPO (anaemia)

32
Q

Cytokines pathogenesis

A

Anti-TNF and sTNFR (R.A., Chron’s, ulcerative colitis, psoriasis)
IL-1Ra (rheumatoid arthritis, cryopyrin-associated periodic syndromes, CAPS)
Anti-IL-6, IL-6R (R.A.),
Anti-IL-17, -12, -23 (psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn)

Anti-IL-5 (Reslizumab, Mepolizumab; approved FDA 2016-2017) for asthma and eosinophilic granulomatosis
Anti-IL-4R (Dupilumab; approved FDA 2017 for atopic dermatitis (eczema)

33
Q

Types of cytokine inhibitors

A

Cytokine inhibitors include: antibodies anti-cytokine or their soluble receptors (to mop them up); antibodies to their receptor (to block their binding site)

34
Q

Antireceptor antibodies

A 
Anti-TNF (infliximab, adalimumab...)
Anti-IL-1R (rilonacept)
Anti-IL-6R (tocilizumab, sarilumab...)
Anti-IL-17R (brodalumab)
Anti-IL-12/IL-23
 (ustekinumab, briakinumab)
35
Q

Anti-cytokine antibodies

A

Anti-IL-1beta (canakinumab)
Anti-IL-6 (siltuximab)
Anti-IL-17 (ixekinumab, secukinumab)

36
Q

Soluble receptors

A

Soluble TNFR (etanercept)

37
Q

IL-1R antagonist

A

anakinra

38
Q

What is an example of an antibody that targets more than one thing?

A

Ustekinumab is an antibody directed against the p40 subunit of IL-12 and IL-23, so it inhibits both.

Approved for psoriasis and Crohn’s disease

39
Q

Side effects of anti-cytokine therapy

A

Side effects of anti-TNF, anti-IL-17, anti-IL-6 include increased susceptibility to TB and serious opportunistic infections, including listeria, pneumocystosis and others

BSMS204 Theme I Immunology (22 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions