B-VII Cyto- & chemokines Flashcards
IL-7
Drive the survival memory T-cells. Also released by stromal cells in bone marrow to cause proliferation in pre-B-cells to pro-B-cells
Inflammatory cytokines
TNF-α, IL-1, IL-6
IL-12
APC can be stimulated to produce this by IFN-γ, binding of CD40 to CD40L, or microbes binding to TLRs. Causes differentiation of naive CD4+ cells to Th1 cells. Also activates NK cells, and ILC1.
Innate lymphoid cells
Tissue resident cells that turn signal cytokines into effector cytokines. They develop in the bone marrow from the lymphoid progenitor, but they dont have antigen receptors.
ILCs Type 1
NK cells in this category. Reacts to intracellular microbes, viruses, tumors. Responds to IL-12, IL-15, IL-18 which activates the NK cell to release granzymes+perforin and also IFN-γ. ILC1s release TNF-α also
ILCs type 2
Responds to large parasites, allergies, etc. Responds to IL-33 among others. Releases IL-4,5, 13, cause mucus production
ILCs type 3
Responds to extracellular bacteria, fungi. Responds to IL-23. Releases IL-17, IL-22, which causes release of AMPs, phagocytosis, and inflammation.
Which cytokine is important for proliferation?
IL-2
Which cytokines are inhibitory?
TGF-β, IL-10
How does IL-10 suppress the immune response?
Inhibits production of IL-12, which in turn will lower the amount IFN-γ.
What do chemokines do?
Cause immune cells with the right receptors to migrate to the places with highest chemokine concentration.
What are some places where chemokines are important?
In the traffic of naive cells to the lymph nodes, effector t-cells to infection sites, and to get the B and T cells to interact at the follicle edge
CC7
CC7 is high in T-cell area
CC5
CC5 is high in follicle area
What is the general definition of cytokines?
Molecular signals that bind to receptors, modify gene expression, and cause new biological effects.
Where do cytokines typically act? What happens if they are found in the blood?
Cytokines typically act near the site of production. If found in the blood, it usually indicates a severe infection.
Briefly describe the common signaling pathway triggered by cytokine receptors.
Ligand binding causes receptor dimerization, leading to activation of JAK, which phosphorylates tyrosine residues on the receptor. STAT proteins bind to these phosphorylated residues, are then phosphorylated by JAK, form dimers, and travel to the nucleus to bind DNA and change gene expression.
Name two key inflammatory cytokines and the cells that produce them during inflammation.
TNF-alpha and IL-1, both produced by macrophages during inflammation.
What is a key role of IL-7?
Survival of naïve and memory T-cells.
What are some functions of TNF-alpha?
It is an inflammatory cytokine produced by macrophages. It is also involved in leukocyte recruitment by causing endothelial cells to upregulate chemokine receptors.
What are some functions of IL-1?
It induces fever during inflammation and is produced by macrophages. It also causes endothelial cells to upregulate chemokine receptors.
What are some functions of IL-6?
It acts in the liver and stimulates the production of CRP, which can opsonize bacteria and activate phagocytosis.
What is the main function of Type I interferons (alpha, beta)?
Antiviral activity, induced rapidly after infection.
What is a key role of IL-12 in the early immune response?
Responds early to activate the adaptive immune system. It is stimulated by IFN-γ, CD40L, and microbes (via TLRs).
What is the role of IFN-γ in the context of Th1 responses?
It drives the differentiation of naïve CD4+ cells into Th1 cells and is involved in macrophage activation, isotype switching to IgG2a(mouse), and increased MHC expression in APCs.
What is the role of IL-4
It drives the differentiation of naïve CD4+ cells into Th2 cells and inhibits differentiation into Th1 cells. It also promotes isotype switching to IgE and IgG1/IgG4.
What is a key role of IL-17?
It is mostly found in the intestinal tract and can be involved in autoimmune responses. Causes production of chemokines , which in turn causes inflammation and neutrophil response. Produced by Th17 subset
What are chemokines and what are some of the cell types that produce them?
Chemokines are a class of signaling molecules involved in cell migration. They are produced by leukocytes, endothelial cells, epithelial cells, and fibroblasts.
What is the primary function of chemokines?
To direct cell migration (chemotaxis) by creating a chemical gradient that guides cells towards higher concentrations of the chemokine. They also affect the surface of endothelial cells to facilitate leukocyte binding and transmigration.
True or false. Cytokines are exclusively produced by immune cells.
False; endothelial cells are another group of cells that might produce cytokines
True or false. Interleukins (ILs) are cytokines that act between leukocytes.
True
True or false. Cytokines typically act over long distances in the body, similar to hormones.
False; in fact, a high concentration of cytokines in the blood indicate severe infections
True or false. When a cytokine binds to its receptor, it always leads to the immediate secretion of another type of cytokine.
False; cytokine might cause other biological effects, such as isotype switching.
True or false. JAK and STAT proteins are key components of a common signaling pathway utilized by many cytokine receptors.
True
True or false. IL-7 is primarily involved in activating macrophages during inflammation.
False. IL-7 is primarily involved in survival of memory and naive T-cells.
True or false. IL-12 primarily functions to inhibit the adaptive immune system.
False; IL-12 triggers the adaptive immune system, favoring Th1 responses.
True or false. IL-10 promotes the production of IFN-gamma.
False; IL-10 inhibits the production of IL-12, which in turn inhibits the production of IFN-gamma.
True or false. TGF-β, secreted by Treg cells, enhances the proliferation of effector T-cells.
False; It inhibits the proliferation
True or false. IFN-γ is a key cytokine in Th2 responses, promoting isotype switching to IgE.
False; IFN-gamma is associated with Th1 responses. IL-4 promotes IgE
True or false. Chemokines bind to receptors that belong to the GPCR family.
True
True or false. Chemotaxis is the movement of cells directed by a chemical gradient
True
Which cytokines are produced by macrophages?
IL-1, IL-6, TNF-alpha, IL-12
IL-2
Proliferation signal, which is released by activated T-cells and bind to other activated T-cells, causing clonal expansion
IL-1
Inflammatory cytokine. Activates production of IL-6 and activates lymphocytes
IL-6
Inflammatory cytokine. Activates lymphocytes, and triggers Th17. Stimulates production of CRP. Mainly acts in liver
TNF-α
Inflammatory cytokine, leads to increased vascular permeability so that IgG and complement protein can more easily enter tissue. Released by macrophages, ILC1
IFN-γ
Cause Th1 differentiation of helper T-cells. Released by Th1 cells, ILC1, NK cells. A signal to macrophages to kill the thing they have phagocytised. Cause isotype switching in B-cells
IL-33
Stimulate ILC2 and Th2
IL-4
Stimulate Th2. Released by Th2 and ILC2, causes class switching to IgE and IgG1 (mouse).
IL-5
Released by Th2 and ILC2. Recruits Eosinophils
IL-23
Triggers ILC3 and Th17
IL-17
Released by ILC3 and Th17. Results in production of chemokines.
IL-22
Released by ILC3 and Th17. Triggers endothelial cells to produce AMPs
TGF-β
Inhibitory cytokine.
