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Complex communication occurs via what two chemical substances?
- Cell surface molecules
Why are cytokines master regulators of the immune system?
- Critical for lymphocyte development
- Regulate innate & adaptive immunity
- Can make you sick
What type of cells produce many cytokines?
Many cell types, including non-immune cells
What are the cytokine nomenclature?
- Interleukins (IL)
- Colony-Stimulating Factors
- Growth Factors
What cell produce monokines?
monocytes (rarely used)
What cell produce Lymphokines?
What cell produces interleukins & what do they control?
- Produced by many cell types
- Control viral infections
What are colony-stimulating factors responsible for?
Maturation of leukocytes
What do chemokines control?
Control migration of leukocytes
What are growth factors responsible for?
Stem cell differentiation
What are the properties of cytokines?
- Low molecular weight (<30kd) proteins or glycoproteins i.e. small
- Synthesized in active & inactive forms
- Rapid secretion
- Secretion is brief & self-limiting- burst of cytokines released when need - short 1/2 life
- Active @ low conc. - high infinity receptor
How does cellular communication via cytokine occur?
- A stimulus is required
- The target cell must have cytokine receptors on the cell surface
- Induces gene activation (signal transduction)
What do autocrine do?
Affect the secretory cell itself
What do Paracrine do?
Target only cells nearby
What do Endocrine do?
Travel through blood to reach distant cell
What is the function of pleitropic?
Have multiple effects & affects multiple cell types
What is the function of redundant?
Several cytokines that perform the same function
What is the function of synergistic?
Combined effect --> sum of the individual effects
What is the function of antagonistic?
What are the target cells and effects of pleiotropic?
- B cell - Activation, proliferation, differentiation
- Thymocyte - Proliferation
- Mast cell - Proliferation
What is the cytokine involved in pleiotropic?
What is the target cell and effect of redundancy?
B cell - Proliferation
What are the cytokines involved in redundancy?
What is the target cell and effect of synergy?
B cell - Induces class switch to IgE
What are the cytokines involved in synergy?
IL-4 + IL-5
What is the target cell and effect of antagonism?
B cell - Block class switch to IgE & induced by IL-4
What are the cytokines involved in antagonism?
What are the function of cytokines?
- Direct effector functions: e.g. kill infectious agents/tumor cells
- Induce inflammatory responses
- Regulate hematopoiesis & immune responses
- Induce process of wound healing
- Communicate w/ nervous (neuronal) & hormonal (endocrine) systems
- Can be cause of some diseases (over or deficient production)
What are the cytokine families?
- Tumor necrosis factor (TNF)
What is hematopoietin?
Bone marrow cells + others
What is interferon?
Anti-viral & active immune system
What is chemokine?
What is tumor necrosis factor (TNF)?
What are the properties of cytokine receptors?
- High affinity receptors
- Often multi-chain complexes
What are the 5 groups of receptor families?
- Class I cytokine receptors
- Immunoglobin super family receptors
- Chemokine receptors
- Class II cytokine receptors
- Tumor necrosis factor receptors
Cytokine + receptor =
What is signal transduction?
- Movement of signals from outside the cell to inside
- Involves numerous, ordered, intracellular events
- Reaches nucleus & changes DNA
- Changes program of genes expressed
- Usually rapid - milliseconds
- small stimulus = large response
How is the immune reaction controlled by cytokines?
It is mediated by the release of pro-inflammatory & anti-inflammatory cytokines
What do CD4+ helper T cells differentiate to?
What cytokines do Th1 produce and what do they aid in?
- Produce IFHγ, IL-2 etc.
- Aid is cell mediated immunity
What cytokines do Th2 produce and what do they aid in?
- Produce IL-4, IL-5 etc.
- Aid in antibody production
What does chronic Th1 stimulate?
- Chronic inflammation
- Autoimmune disease e.g. type 1 diabetes, multiple sclerosis, Crohn's disease
Chronic inflammation & autoimmune diseases promotes Th1 because...
- pro-inflammatory (TNF, IL-1, IL-6 etc)
- Respond to intracellular pathogens
What does chronic Th2 stimulate?
- Failure to respond to infection
Allergy and failure to respond to infection promotes Th2 because...
- produce antibody
- respond to parasites
What is cytokine storm?
- Inappropriate (exaggerated) immune response
- Over-activated immune response e.g. graft versus host disease (GVHD), avian influenza, smallpox
- Rapid proliferation & highly activated immune cells
- Systemic release of >150 inflammatory mediators (cytokines, oxygen free radicals & coagulation factors) Especially TNFα & IL-6