dont know (11)

Question 1

L15- Modes of cytokine action

Answer 1

autocrine manner: E.g. IL-2 being produced by maturing T cells following APC interaction stimulating their proliferation and maturation.
paracrine action towards mirons up to 1mm apart: E.g. IL-4 being released by Th2
cells to induce B cell class
switching
endocrine action, great distance, in the circulation to another cell: E.g. IL-6 and TNFα
modulate
hypothalamic
production of ACTH
-elevates temperature
and regulates lipid
metabolism

a
Cytokines are PLEIOTROPIC – one cytokine can have different (completely unrelated) effects on different target
cells. e.g: IL-4 in th2
Cytokines can be REDUNDANT– different cytokines can have the same effects on their target cells.
Cytokines can be SYNERGISTIC – different cytokines augment the response of each on its own. e.g: IFN-Y by th1 and TNF-alpha by macrophage increasing mhc 1 expression on many cell types.
Cytokines can be ANTAGONISTIC – different cytokines have opposite effects on the target cell. e.g: IL-4 and IFN-Y by th1/th2: il-4 drives class switching to IgE while ifn-y blocks this.

Question 2

L15- How does a cytokine activate its
target cell?

Answer 2

A cytokine will have no effect on a cell
unless it expresses a receptor for that
cytokine.
* Regulating the expression level of the
receptor is a means of controlling the
effect of the cytokine.
Cytokine receptors are almost as diverse as cytokines themselves
e.g: IL-1 BINDS TO IG-TYPE RECEPTORS
TNF-ALPHA TO TNFR-TYPE
IL-2 CYTOKINE RECEPTOR TYPE 1
IFN, IL-10 TO CYTOKINE RECEPTOR TYPE
Cytokine receptors frequents share subunits
Cytokine receptors are often modular, with distinct ligand-binding subunits and shared signaling subunits. This allows different cytokines to induce similar cellular responses by using common signaling pathways. In the case of IL-4 and IL-13, they share the IL-4 alpha chain, meaning they can trigger similar responses in cells.

Question 3

L15- Cytokines and Disease + Cytokine storm

Answer 3

X-linked severe combined
immunodeficiency (X-SCID).
* x-linked recessive trait - mutated IL-2Rγ
chain.
* IL-2Rγ shared between receptors for IL-
2, IL-4, IL-7, IL-9, IL-15 and IL-21.
* Isolation in a “bubble” was an early
prophylactic treatment.
* BM transplant – standard treatment.

Immune response is normally controlled by feedback mechanisms.
If these fail, too many cells are recruited and a systemic immune response results, releasing >150 mediators.
high fever, swelling and redness, extreme fatigue and
nausea
Causes unknown, results from infectious and non-
infectious diseases including (GVHD), acute respiratory
distress syndrome (ARDS), sepsis, Ebola, avian influenza,
Covid 19.

Question 4

L15- Rheumatoid arthritis?

Answer 4

systemic autoimmune disease
Chronic inflammation of joints
Pain, loss of function, invalidity
Multifactorial: gender, age, genetics,
environment
T cells, B cells, DC, macrophages,
neutrophils and fibroblasts
Cytokines: TNF-α, IL-1β, IL-6 and IL-17
Blocking TNF-a can dramatically reduce inflammation and
even reverse some of the cartilage damage (anti-TNF therapy)

Question 5

L15- cytokines for anti-viral, anti-bacterial and anti-tumour effects?

Answer 5

Interferon α (leukocyte) and interferon β (fibroblast)
* Prevents viral replication
* Increases MHC class I expression

Interferon-γ (T cells, NK cells)
* Induces macrophage activation
* Promotes Th1 differentiation
* Upregulates APC capacity (MHC I and II expression)

Question 6

L15- pro-inflammatory cytokines?

Answer 6

Tumour necrosis factor-α (mφ, T cells, NK cells)
* Increases leukocyte adhesion
* Activates macrophages

Interleukin-1 (mφ, DC)
* Increases adhesion factors
* Increases vascular permeability/dilation
* Induces DC maturation

Interleukin-6 (many cells)
* Increases adhesion factors
* Increases vascular dilation
* Induces DC maturation