Cytokines (class 1) Flashcards
What are Cytokines?
“Small soluble proteins that regulate the immune system’s innate and adaptive responses to infection
- communication molecules “
How are Cytokines induced?
Induced in response to specific stimuli
Stimuli - bacterial lipopolysaccharides, flagellin, other products; signaling through Tcell/Bcell receptors
How are Cytokines produced?
Occurs through the ligation of cell adhesion molecules or through the recogniction of foreign antigens/molecular patterns by host lymphocytes
Cytokine function and effects
- the communication molecules of the immune system
- Individual cytokines often act in concert with others -> cytokine concert/network -> regulation of leukocyte activity
Effects-in vivo- growth regulation and gene expression but many different cell types (includes leukocytes)
Autocrine stimulation of Cytokines
Affects are seen on the same cell that secreted it
Paracrine stimulation of Cytokines
Affects cells in close proximity
Endocrine stimulation of cytokines
AKA systemic; moved by the endocrine system
The major cytokine families
Tumor necrosis factor (TNF) Interferons (IFN) Chemokines Transforming Growth Factors (TGF) Colony-Stimulating Factors (CSF)
IL-3, erythropoietin (EPO) and granulocyte (G-CSF),
macrophage (M-CSF), and granulocyte-macrophage (GM-CSF) are all types of what?
What is their function?
Colony stimulating factors
- in response to inflammatory cytokines, the different CSF act on bone marrow cells and promote specific colony formation for the various cell lineages
What is the difference between cytokine related IL and unrelated IL
Unrelated-satisfy 3 criteria (genes were cloned, inducible in Leukocytes, biological activites in inflammatory processes must be cataloged
Cytokine pleiotropism
The cytokine has different affects on different cell types
[one cytokine -> multiple functions]
Cytokine redundancy
Overlapping effects of cytokines, because many share receptors –> altering of activity of the same genes
[multiple cytokines –> same function]
Cytokine synergy
Cytokines that work together –> amplified/different effects than individual cytokines
- multiple cytokines working together
Cytokine antagonism
A cytokine counteracts the effects of other cytokines
- one cytokine opposes the function of another
What are the cytokines of the innate immune system?
Type 1 interferons (alpha/beta) Tumor necrosis factor alpha interleukin 1 beta Interleukin 10 Transforming growth factor beta [Chemokines, IL-8, Fractalkine, RANTES, SDF-1alpha] (INF1a/B, TNFa,IL1B,IL10,TGFB)
What interferons interfere with viral replication
“*was once named for function of viral replication interferance then found other interferons that have other functions
- Now know its just type 1 interferons (alpha/beta) “
What is the function of Type 1 IFN?
Produce virally infected cells and by dendritic cells and induce production of proteins and pathways that can directly interfere with viral replication and cell division
- Activates NK cells and enhances expression of MHC class 1 proteins
- Also active against certain malignancies and other inflammatory processes
How are cytokines involved with the innate immune response?
Responsible for many physical symptoms
inflammation, fever, swelling, pain, cellular infiltrates into damaged tissues
What is the main function of the innate immune response and how do cytokines help?
To recruit effector cells to this area
TNF alpha, IL-1, chemokines and INF alpha and beta
TNF - alpha importance and function
Most prominent member of the TNF superfamily, which consists of at least 19 different biological functions
- secreted by activated monocytes and macrophages can T cells through its ability to induce expression of the MHC class 2 molecules, vascular adhesion molecules, costimulatory molecules (CD80/86, B7.1/B7.2) and chemokines exhists in both membrane -bound soluble forms and causes vasodilation and increased vasopermiability
- triggered by lipopolysaccharide, found in gram-negative bacteria
Describe the IL-1 family
Consists of the IL-1a, IL-1B and IL-IRA (receptor antagonist)
- Acts as an endogenous pyrogen and induces fever in the acute phase response through its actions on the hypothalamus
- induces the production of vascular cell-adhesion
How does IL- 1 alpha/beta differ from other IL - 1 family
IL-1a/b - proinflammatory cytokines produced by monocytes and Macs
IL-1B - responsible for most of the systemic activity attributed to IL-1, including fever, activation of phagocytes and production of acute phase proteins
How are cytokines involved in chronic inflammation?
TNF a and IL-1 - in rheumatoid synovial fluids and synovial membranes of patient w/ rheumatoid arthritis
TNF a - central mediator of pathological processes in RA and other inflammatory illnesses (ex Crohn’s disease)
Sepsis - see high levels of proinflammatory cytokines in the blood
Increased inflammatory cytokines seen in chronic HIV disease, atherosclerosis, psoriasis, binge drinking
What are chemokines?
Direct immune cells to places of interest
- Family of cytokines that enhance motility and promote migration of many types of WBCs toward the source of the chemokine