Cytokines Flashcards
What are cytokines
Cytokines are messenger proteins of the immune systems and their role is to mediate the effector functions of the immune system, as well as to confer protection against invading organism.
They regulate the intensity and durations of the response.
The difference with chemokine is that chemokine ARE cytokines that induce chemotaxis and which move against a gradient.
Cytokines - general properties
1) Soluble proteins which are released by cells, bind to receptors on other cells and induce biological effect.
2) They have a high ligand/receptor affinity and are very potent so you only need a few to induce a strong effect
3) They have different acting pathways:
- endocrine - where they are released in the bloodstream to affect distant cell
- paracrine - where they are released to affect n early cells
- autocrine - where they are released but then bind to the receptor of the cell that produced them
4) They can mediate activation, proliferation and differentiation of target cells.
Effects can be Pleiotropy (one cytokines multiples effects (IL-4 - can activate, leads to proliferation of different cells)),
Redundancy (more than one cytokine have the same effect (IL-2, 4 and 5 - they all leads to B cell proliferation))
synergy (two or more cytokines needed to induce an effect (need IL-4 and IL-5 to induced class with to IgE))
antagonism (one cytokines can inactive the effect of an other cytokine (INF gamma block the class switching of B cell induced by IL-4))
5) their biological function include
induction of proliferation or enhancing survival (as well as can trigger death he)
migration
change in differentiation state
6) can be classify as innate immune system cytokines such as IL-1, TNF-A, CXCL-4 or the adaptive immunity cytokines such as IL-2, IL-4 and IL-17.
The specificity in the cytokine system
Upon Ag activation of a T cell, there are changes in the expression pattern of chemokine receptors and the receptors for proliferation/differentiation inducing cytokines - so they become very specific.
The cytokines are concentrated between the secreting cells and the target cells
Their half life is very short in the extracellular milieu so the cytokines have to act in a limited time frame
What distinguish the 6 family
The structure of the ligand and receptors
the nature of the signalling pathway induced
IL-b
Its production is stimulated by viral, parasitic or bacterial product.
It can be secreted very early in the immune response by macrophages and dentritic cells
It can act locally on capillaries to help leukocyte attraction to the inflame tissues
It can act systematically to signal the liver to produce acute phase proteins, induce fever and help activate the adaptive immune responses.
alarmins
they are endogenous mediators of innate immunity. They are often stored IC and then rapidly released in repines to an infection or tissue injury by the innate immune cells.
they have both chemotactic and activating effects on APCS
IL-1alpha and IL33 are parts of the alarming family. They are stored and the upon cell death they are released and activate signalling pathway
Many alarmins bind to GPCR to induce chemotaxis and sometimes TLR to induce cytokine productions.
They are basically there to augments host defense by increasing innate and adaptive immune response
dual cytokines IL1alpha and IL33
dual fonctions cytokines shares structural similarities. They typically contain a large N terminal tail, possessing the chromatin or DNA binding domain, as well as NLS that enables their intracellular nuclear function.
Most of dual functions proteins are naturally synthesized as active precursor proteins with the receptors interacting domain localized at the C terminal.
upon injury, release happens directly after necrosis and to produce these highly active mature cytokines, the precursors proteins are processed and cleaved by several innate immune cell proteases such as calpain AND GRANZYME B.
cytokine related diseases
inflammatory cytokine levels may win creased in
sepsis
bacterial toxic shock (by super antigens)
rheumatoid arthritis and TYPE2 diabetes
influenza and covid (cytokine storms)
severe acute respiratory syndrome
treatment - soluble TNF alpa receptor and monoclonal antibody against TNF alpha in Rheumatoid arthritis
to prevent rejection of transplantations, monoclonal antibody against the alpha chain of IL2R
but problems include
maintaining effective level
they have a short half life
can cause unpredictable side effect
