Cytokines Flashcards
What are cytokines?
Hormone-like, soluble mediators secreted during an immune response
In __________ immunity, microbial and viral products stimulate macrophages and neutrophils to produce cytokines.
Innate
In ____________ immunity, cytokines are secreted by T-cells; they function to regulate T-cell growth and differentiation, as well as regulating the effector functions of T- and B-cells.
Adaptive
True or false: cytokines play a role in haematopoiesis.
True
__________ are highly potent, effective at low concentrations, and only briefly secreted.
Cytokines
What is pleiotropism?
One cytokine having several targets.
What is redundancy?
Many cytokines having the same function
Actions may be local or systemic, with ____________ and endocrine function.
Autocrine
Name three types of cytokine receptors.
General cytokine receptors
Chemokine receptors
TNF receptors
Cytokine receptors are generally not expressed on ___________ cells.
Resting
Once bound, _________ ____________ __________ (JAK) enzymes are activated, transducing the signal to the nucleus.
Protein tyrosine kinase
JAK enzymes activate _____________ _________ called signal transducers and activators (STAT).
Transcription factors
Tumour necrosis factor α (TNF-α) is sourced from ____________ __________, T-cells, mast cells, and NK cells.
Activated macrophages
TNF-α is produced by macrophages upon ligation of ______ by toll-like receptors.
LPS
________ augments TNF-α production.
IFN-γ
TNF-α is synthesised initially as a transmembrane protein, which is then cleaved by a membrane-associated __________________, releasing a 17kD polypeptide.
Metalloproteinase
What does TNF-α stimulate macrophages to secrete?
IL-1
TNF-α Stimulates ______________ actions of neutrophils.
Microbicidal
TNF-α induces vascular endothelial cells to express adhesion molecules, called ____________.
Selectins
List three functions of TNF-α in immunity.
Induces chemotaxis
Induces fever, as an endogenous pyrogen, by prompting the release of prostaglandins from the hypothalamus
Stimulates hepatocytes to increase synthesis of serum proteins, such as serum amyloid A and fibrinogen (acute phase response), causing intravascular thrombosis
Describe four potential adverse effects of TNF-α.
Prolonged production causes tissue wasting, or cachexia, by suppressing appetite
Prolonged production can cause hypotension
High serum levels cause severe metabolic disturbances
High serum levels can also cause septic shock, induced in response to LPS
Cell sources of ___________ include endothelial cells, epithelial cells, fibroblasts, and antigen-stimulated T-cells.
Chemokines
Chemokines are induced by ____________ through TLR, TNF, and IL-1.
Microbes
Chemokines stimulate _____________ movement and migration.
Leucocyte
True or false: some chemokines are produced in response to infection, while others are constitutively produced.
True
What type of receptors do chemokines engage with?
G-protein-coupled receptors, with seven transmembrane domains
Name two chemokine receptors for HIV.
CCR5
CXCR4
List three mechanisms of immunity induced by chemokines.
Increase the affinity of leukocytes for the endothelium
Enhance movement of leukocytes along their chemotactic gradients, by acting on actin filaments
Chemokines are specific to the cell type (e.g., CCL2 attracts monocytes; CCL11 attracts eosinophils)
Chemokines recruit cells to ___________ ____________ organs.
Peripheral lymphoid
True or false: chemokines promote angiogenesis and wound healing.
True
Chemokines promote migration of ___________ and memory T-cells.
Effector
What is interleukin-12?
Principal cytokine in response to intracellular microbes
IL-12 stimulates ________ production by T-cells and NK cells.
IFN-γ
IL-12 drives differentiation of T-cells into the Th1 (IFN-γ secreting) _____________.
Phenotype
IL-12 is produced by dendritic cells and ___________ _______________.
Activated macrophages
What do Type 1 interferons do?
Interfere with viral replication
Name two Type 1 interferons.
IFN-α and IFN-b
Type 1 interferons are secreted by ___________ ____________, dendritic cells and fibroblasts (IFN-b), and virally infected cells.
Mononuclear phagocytes
Production of Type 1 interferons is induced by viral nucleic acids, which bind to ligands and induce activation of __________ ____________ ____________.
Interferon regulatory factor
Receptors TLR3, TLR7, and TLR9 recognise __________ dsRNA .
Viral
State functions of Type 1 interferons.
Promote immunity to intracellular microbes by
Cause cells to synthesise enzymes which interfere with viral replication, e.g., 2’,5’ oligoadenylate synthetase
Induces an anti-viral state in neighbouring healthy cells
Increases expression of MHC class I
Increases CTL activity
Promotes naïve T cell differentiation to Th1 by upregulating IL-12 receptors
IFN-α is used in the treatment of ____________ ____.
Hepatitis C
What is IL-10?
An inhibitor of activated macrophages and dendritic cells, which controls innate immunity
True or false: is a non-covalently linked dimer.
True
Cell sources of ________ include macrophages and T-cells, and non- lymphoid cells (keratinocytes).
IL-10
State four biologic activities of IL-10.
Major anti-inflammatory cytokine
Inhibits IL-12 production and in turn IFN-γ production
Inhibits expression of co-stimulators and class II MHC molecules on macrophages and dendritic cells
Epstein-Barr virus has an IL-10-like gene, important for viral evasion of immunity
In ____________ immunity, cytokines stimulate proliferation, differentiation, and activation of effector T- and B-cells.
Adaptive
IL-2 is produced by activated _____ ___________ ___-________.
CD4+ helper T-cells