Cytokine receptors Flashcards
What are the cytokines?
Cytokines regulate cellular communication, proliferation, differentiation and they regulate immune responses. They modulate cell functions and act by different classes of cytokine receptors. Chemokines are chemotactic compounds and act by G-protein coupled receptors. Cytokines and chemokines are two groups that are structurally different.
What are the cytokine receptors?
They are receptors of cytokines, proteins of low molecular weight and are secreted from immune cells. In general, the cytokines are not stored but they their expression is tightly and rapidly controlled
What is the role IL-1 family?
The interleukin-1 family are cytokines involved in immune and inflammatory responses. This family consists of 11 cytokines.
Characteristics of IL-1 family
Produced without a conventional signal peptide, (which means they do not follow the classical endoplasmic reticulum-Golgi secretory pathway), they are synthesized as inactive cytoplasmic precursors. Activation of these cytokines involves proteolytic cleavage which are then secreted through unconventional pathways.
What is IRAK (IL-1-receptor-associated kinase)? What is its role?
Upon IL-1 stimulation, IRAK associates with the IL-1 receptor, becoming activated. After activation, IRAK dissociates from the receptor and translocates from the cytoplasm to the nucleus. This translocation is essential for propagating the signal that ultimately leads to the expression of IL-1β and other inflammatory genes.
Structure of TGFβ-family cytokines
homodimers in a butterfly shape, the dimers are linked by disulfide bonds
Secretion of TGFβ-family cytokines
Secreted as precursors that are cleaved into active and latency associated peptide. Both cleaved fragments remain associated and inactive until separated by stimulus.
How is the production of cytokines triggered?
Stimulation of cells of the innate immune system. Stimulation of APCs (antigen presenting cells) by the adaptive immune system, as well as by the cytokine-dependent modulation of cytokine expression.
What is the role of scavenger receptors?
They are on immune cells and they trigger cytokine release by recognizing and binding various ligands (LDLs, PAMPs, DAMPs). These ligands can contribute to atherosclerosis, infections and tissue damage, respectively. The binding of these harmful ligands to SRs triggers immune responses aimed at neutralizing and removing the threats. This binding results to the transcription of pro-inflammatory cytokines like IL-1β, resulting in a pro-inflammatory response aimed at combating harmful stimuli.
How do the CD40 ligands contribute to immune response?
When T cells recognize antigens, they become activated. This activation causes T cells to express a CD40-ligand on their surface. The CD40 ligand then binds to CD40 receptors on macrophages. This binding triggers a signaling cascade inside the macrophages, leading to the production and release of pro-inflammatory cytokines, such as IL-6 and IL-1. These cytokines are crucial for immune responses as they enhance the activity of macrophages and help regulate inflammation.
What is the role of Toll-like receptors?
When the TLRs recognize PAMPs or DAMPs (by the innate immune system) they initiate signaling cascades that promote the release of pro-inflammatory cytokines IL-1, IL-6, TNF-α. These cytokines activate downstream signaling pathways as NF-κΒ and MAPK leading to the transcription of cytokine genes.
Why do we need the activation of NF-κΒ and MAPK pathways?
NF-κΒ and MAPK leading to the transcription of cytokine genes. The cytokine release helps recruit and activate immune cells, induce inflammation, and initiate the adaptive immune response, ultimately aiming to eliminate the threat and promote tissue repair.
What is the relation of Alzeheimers Disease with cytokines?
AGEs, S100 proteins, and amyloid-β bind to their receptor RAGE. This binding initiates inflammatory and cytokine cascades that harm neuronal function and survival leading to Alzeheimer’s disease.
Describe in detail the triggered signaling pathways that lead to Alzheimer’s disease.
AGEs, S100 proteins, and amyloid-β bind and activate the receptor RAGE. This binding initiates inflammatory and cytokine cascades that harm neuronal function and survival. When these ligands interact with RAGE on immune cells like macrophages and microglia, it activates downstream signaling pathways, including NF-κB and MAPK cascades. This leads to the transcription and subsequent release of pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α. The release of these cytokines initiates and amplifies inflammatory responses, which can contribute to the pathogenesis of various diseases, including diabetes, cardiovascular disorders, and neurodegenerative conditions. The RAGE-ligand interaction also induces the production of reactive oxygen species (ROS), further exacerbating inflammation and oxidative stress.
TGFβ cascade
TGFβ binds to its receptors then TGFβ-R2 phosphorylates TGFβ-R1 initiating a signaling cascade. The signaling pathway can be inhibited by SMADs (SMAD6/7), FKBP12.
