Cytokines Flashcards
Define cytokines.
They are small soluble proteins that regulate the nature, intensity and duration of the immune response by exerting a variety of effects on immune cells
What does Auto-, Para-, and Endocrine mean for cytokines?
- Autocrines works on its origin cell
- Paracrines are transfered to another cell
-Endocrines are transported to an organ
What is Pleiotropism, Synergy, Antagonism, and Redundancy in cytokines?
- Pleiotropism is when a cytokine can interact with different cells and give different effects
- Synergy is when two different cytokines interact with the same cell to give a stronger effect
- Antagonism, is when they inhibit each other
- Redundancy means functional overlap
JAKs are targets for treatment of
inflammatory conditions and STATs are signal transducers and activators of transcription. How does JAK/STAT signaling work?
Cytokine binds to receptors which activates JAK. It recruits STATs to the receptor and JAk dimerizes and phosphorilyzes it. STATs are then imported to the nucleus which results in gene change.
What are the major Innate pro-inflammatory cytokines
- TNF which is involved with vasodilation and leukocyte recruitment
- IL-6 signals the liver to produce acute phase proteins and induces fever
-IL-1 b, causes fever and hyperalgesia (extensive pain). They are also involved with leukocyte recruitment
Virus infected cells can have PRRs that detects infection in the cell which leads to the production of antiviral cytokines. What are these antiviral cytokines called and function?
Type 1 inteferons (IFN-a and IFN-b) are produced and are early mediators of antiviral defense since T-cells arrive later.
They bind to other cells and to itself to prevent viral replication via enzymes.
What are chemokines?
They are a subclass of cytokines which attracts of immune cells in a process called chemotaxis
What are the two main functions of chemokines?
1) Recruitment of cells to inflamed/infected tissue
2) Regulation of the homeostatic movement of cells around the body. (Homeostatic chemokines are produced by thymus and
lymphoid tissues. )
Tell me an example of how chemokines are used in B-cell activation
When B-cells and T-cells migrate towards they have recipocating chemoattracts.
Receptor – ligand(s)
CXCR5 (on T-cell) => CXCL13
CCL19 and CCL21 <= CCR7 (on B-cell)
Dependant on which cytokines are released by the dendritic cells, the T helper cell can enter different subsets. Which subset are there?
Th1, Th2, Th17, Treg
Th cell subsets secrete different cytokines, which? Also name what their effects are.
Th1 => IFN-y
It activates macrophages and enchances killing against intercellular pathogens
Th2 => IL-4, IL-5, IL-13
It activates defence against parasites.
IL-5 activates eosinophils
IL-4 and IL-13 induces intestinal mucus sectretion & peristalsis
Th17 => IL-17, IL-22
IL-17 activates neutrophils
IL-22 increases the barrier function of tissue cells
Both activates the production of antimicrobial peptides
Against extracellular pathogens
Treg => IL-10, TGF-b
dampening of immune activation (immunoregulation and tolerance)
What does the dysregulation of these cytokines lead to?
IFN-y => autoimmunity
IL-4, IL-5, IL-13 => allergy
IL-17, IL-22 => autoimmunity
There are two types of Tregs, n/t Tregs and pTregs. Describe the two ways Tregs can develop.
1) In the thymus the n/t Tregs develop. An APC presents a self antigen to the naive CD4+ T cell and releases cytokines (TGF-b, IL-10) into it. Which turns it into a Treg and the central transcription factor is switched to FOXP3.
2) In the lymph nodes the pTregs develop. An APC presents self-antigen or foreign antigen to the naive CD4+ T cell and releases cytokines (TGF-b, IL-10) into it. Which turns it into a Treg and the central transcription factor is switched to FOXP3.
What is FOXP3 responsible for?
It is responsible for many of the Treg mechanisms of immune regulation.
Name the 3 Treg mechanisms of immunoregulation.
1) Treg releases IL-10 and TGF-b which dampen/inhibits the activation of immune cells
2) Consumption of IL-2
Autocrine IL-2 stimulation causes cloning of activated T-cell. The Treg carries higher numbers of IL-2 receptors which causes the cytokines to bind to the Treg instead of the T cell. Since the T-cell lacks IL-2 => inactive state => apoptosis
3) Expression of co-inhibitory molecules
Treg inhibits the 2nd signal of the activation of T cells. CTLA-4 (from the Treg) binds with a higher affinity to CD80/86 (from APC) than CD28 (from the inactive T-cell). Therefore the APC will bind to the Treg than the T cell inactive T-cell => apoptosis
