Cytokines Flashcards
Cytokines: Definition
Soluble proteins that regulate immune system’s innate and adaptive responses
- Communication molecules
- Can be induced in response to stimuli or through T and B receptors
Cytokine: Extra
Production and collaboration
Production: through ligation of cell adhesion molecules or through recognition of antigens/molecular patterns by host lymph
- Cytokines often act in concert with each other
- Network of cytokine expression = regulates leukocyte activity
Cytokine: Effects
In vivo: regulation of growth, differentiation, gene expression by many cell types
How Do Cytokines Exert Effects?
3 ways
Autocrine: affecting the same cell that secreted it
Paracrine: affecting target cell close by
Endocrine: systemically and far travel
Cytokines: Differentiation
Major families: tumor necrosis factor (TNF), interferons (IFN), chemokines, etc.
Colony stimulating factors (CSFs): IL3, EPO, etc.
What do Colony Stimulating Factors CSF do?
Act on bone marrow
- specific cell lineages to develop
Cytokines: Interleukins
3 criteria
IL-1 through IL-36
Three criteria
1. Have had genes cloned
2. Must be inducible in leukocytes
3. Biological activities in inflammatory processes must be catalogued
Cytokine: Properties
4 different ways they work
Pleiotropism: one cytokine multiple functions
Redundancy: multiple cytokines, same function
Synergy: amplified or different effects when working together
Antagonism: counteraction, activation vs. inhibitory cytokines
Cytokines of the Innate Immune System
6 of them
- Type I Interferons (IFN a, IFN b)
- Tumor Necrosis Factor (TNF)
- Interleukin 1beta (IL-1b)
- Interleukin 10 (IL-10)
- Transforming growth factor beta (TGF b)
- Chemokines (several)
Type I Interferons: Purpose
3 things
Interfere with viral replication and cell division
- Activates NK cells (because viruses can downrate MHC class I expression)
- Enhances MHC class I proteins
- Active against other inflammatory processes
Cytokines: Inflammation
Recruits effector cells to area: causes fever or swelling, inflammation
Cytokines: Tumor Necrosis Factors
Innate immunity
TNF-a: most prominent one
- Secreted by active monos and macros, activates T cells through induction of MHC class II expression and other things
- Causes vasodilation and increased vasopermeability
- Main trigger is lipopolysaccharide: G- bacteria
Cytokines: Interleukins
3 ILs, what do they do?
IL-1 family: IL-1a, IL-1b, IL-1RA (receptor antagonist)
- IL-1a and IL-1b: proinflammatory cytokines, made by macros and monos
- IL-1b: most systemic activity, fever, phagocyte activation, acute phase protein production
- IL-1: endogenous pyrogen, induce fever in acute phase response
- IL-1: makes vascular cell-adhesion molecules
- Recognition of lipopolysaccharides by TLR 4 on monos and macros, makes IL-1b
Cytokines: Chronic Inflammation
Many disease states have chronically increased inflammatory cytokines, they predict mortality
- Seen in rheumatoid arthritis, Chrohn’s disease, sepsis, HIV, binge drinking, etc.
- TNF-a and IL-1 common
Chemokines: Definition
Family of cytokines that enhance motility and promote migration toward the source of chemokine
Chemoattractant cytokines
- Can activate some cells
- Immune cells move toward they
- Some induced, some constitutive
- IL-8, CCL2, fractalkine, SDF1
Chemoattraction: Cytokines and Chemokines
Process?
Recognizing and activation by pathogens or PAMPs, macros in tissue release cytokines and chemokines
- IL-1 and TNFa make endothelial cells express cellular adhesion molecules (CAMs)
- Chemokines recruit leukocytes to the site
Cytokines: Innate and Adaptive Bridge - IL6
IL-6
IL-6 produced by both lymphoid and nonlymphoid cells
- IL-1 triggers secretion of IL-6
- IL-6 affects inflammation, acute phase reactions, activation states of B and T cells
- Stimulates B cells to proliferate and differentiate into plasma cells
- Induce CD4+ T cells to make more pro and anti-inflammatory cytokines
Cytokines: In the Adaptive Immune System
Mostly made by T cells, directly affects function of T and B cells (more than in innate)
Cytokine: IL-2 in Adaptive Immunity
T-cell growth factor
- Both T and B cells, lytic activity in NK cells
- Can also activate proliferation of Th2 cells
IL-7 is another cytokine that can induce proliferation, helps with survival of memory
Cytokines: Adaptive Immunity - Helper T Cells
Four main subclasses: TH1, TH2, TH17, T-regulatory
- TCR recognizes antigen, clonal expansion occurs
- Differentiation into subclasses is influenced by cytokines
CD4+ TH1 vs. TH2
And Functions
- TH1: protects against intracellular pathogens
- TH2: interleukins, help B cells produe antibodies against extracellular pathogens
TH1 Cells: IFN-y
TH1 cytokines make IFN-y: affects RNA expression levels of many genes
- Regulation/activation of many cells
- Stimulates antigen presentation by MHC I and II molecules
- Is a type II IFN: invovlved in regulation of cell function
TH2 Cells: IL-4
TH2 cells: antibody-mediated immunity, B cell activation and class switching
IL-4 regulates TH2 immune activities
- Expressed on lymphocytes and nonhematopoietic cell types,
- Neutralizes IgG
- Production of IgE
- Suppression of macrophage
- Eosinophil activation
Importance of TH1 vs. TH2
Leprosy- bacteria that live in macrophages, two forms
Tuberculoid: induces cell mediated response (TH1), form granulomas and clear bacteria from macrophage
Lepromatous: produces humoral response (TH2), bacteria cannot be controlled, systemic disease
Immune Suppression Regulatory Cells (Tregs)
What are they and what do they produc
T cells, key role in establshing peripheral tolerance to self-antigens, allergens, tumor/transplant antigens, and infectious agents
- Inhibits immune response by direct contact or by cytokines
Produces: IL-10 and TGF-beta
Tregs: Transforming Growth Factor Beta (TGF-b)
What it does
Induces antiproliferatve activity
- Regulator of cell growth, apoptosis, migration, inflammatory response
- Down regulates inflammatory response when no longer needed
- Foxp3 produced by TGF-b, causes Tregs to suppress other T cells
Anti-inflammatory cytokine
Tregs: IL-10
Anti-inflammatory, suppressive on TH1 cells
- Inhibits antigen presentation and stimulates CD8+ T cells
- Antagonist to IFN-y, down regulator of immune response
TH1 Cytokines
- IFN-y
- IL-2
- TNF-b
- Chemokines
- TNF-a
- IL-3
TH2 Cytokines
- TNF-a
- IL-3
- IL-4
- IL-5
- IL-6
- IL-10
TH1 Function Overview
- Macrophage activation
- Neutrophil activation
- Complement-binding and opsonizing antibodies
more innate immunity
TH2 Functions Overview
- Total antibody production
- IgE production
- Eosinophil/mast cell production/activation
- Neutralizing IgG
- Suppress macrophages
more adaptive immunity/regulation
