Cytokines Flashcards
Describe cytokines
- small, soluble proteins - peptides and glycoproteins
- intracellular messengers of the immune system
- most produced in response to signal
- bind to specific membrane receptors due to large size
Describe the family nomenclature of cytokines
- where spacing of certain cystine molecules are within cytokines
- CXC, CC, CX3C, XC
Describe chemokines
- subset of cytokines
- specialised function - chemoattractants
- mobilise immune cells to move to tissues or within tissues
Describe the family nomenclature of chemokines
- interleukin-1, 2 and 17 family
- interferon family
- transforming growth factor
- tumour necrosis factor
What are the different actions of cytokines?
- autocrine
- paracrine
- endocrine
- pleiotropic
- redundant
- synergistic
- antagonistic
Describe the autocrine action of cytokines
- act on the cells that secrete them
- e.g., action of IL-2 on T-Cells
Describe the paracrine action of cytokines
- act on nearby cells
- e.g., action of IFN during a viral infection
Describe the endocrine action of cytokines
- act on distant cells
- e.g., action of IL-1 in a systemic inflammatory response
Describe the pleiotropic action of cytokines
any given cytokine may have different biological effects on different target cells
Describe the redundant action of cytokines
two or more cytokines that mediate similar functions
Describe the synergistic action of cytokines
combined effect of 2 cytokines is greater than the additive effect of each alone
Describe the antagonistic action of cytokines
effects of one cytokine inhibit or offset the effects of another
Describe how non-specific cytokine function is prevented
- transient production
- short half-lives
- regulated receptor expression by target cells only after antigen activation
- soluble cytokine receptors
- antagonist cytokines
Describe soluble cytokine receptors
- can be ‘lost’ in diluted blood
- 5 major families
- receptors of different type may have same signal transduction action
What are the 5 major soluble cytokine receptor families
- class I cytokine receptors
- class II cytokine receptors
- immunoglobulin superfamily receptors
- TNF receptors
- chemokine receptors
Describe how cytokines are critical to different aspects of the immune system
- clear target for treatment
- enhance vaccination
- enhance pathogen clearance
- reduce pathology
- control hypersensitivity/autoimmune disease
- anti-cytokine therapy, part of immunotherapy
Describe immunotherapy
- introduction of immunological molecules e.g., cytokines
- inhibition of immunological molecules e.g., antibodies against cytokines
- modification of immunological molecules e.g., antibodies that activate immunological response
What are the different types of cytokine therapy?
- IFN alpha and beta
- IL-2
- Anti-IL-2R
- Anti-IL-6
Describe IFN-a and b cytokine therapy
- used for hepatitis B and C - viral infections
- combination with anti-viral drugs
- also used to treat multiple sclerosis, cancer
Describe IL-2 therapy
- cancer
- critical in T-Cell proliferation and activation
- in vivo or ex vivo application of IL-2 to lymphocytes
- stimulates and activates anti-tumour response
Describe Anti-IL-2R therapy
- critical in T-Cell proliferation and activation
- blocking antibody against IL-2R
- used in multiple sclerosis, transplantations
Describe Anti-IL-6 therapy
- Tocilizumab
- IL-6 pro-inflammatory cytokine, associated with poor covid-19 prognosis
- used in serious covid-19 patients, mixed results
What are the challenges of cytokine therapy?
- short half-lives - repeated treatments
- largely a local impact - high doses
- lots of side effects
- increased chance of infection
Give an example of anti-cytokine therapy
anti-TNF-alpha
Describe Rheumatoid Arthtitis
- hypersensitivity disease - III or IV
- inflammation and damage of capsule around joints, lung and heart membranes
- major cytokine involved is TNF-a
Describe TNF-a
- pro-inflammatory - activates macrophages
- produces within minutes of fever and swelling
- Golimumab, Adalimubab, Certolizumab
- all monoclonal antibodies against TNF-a
Describe how anti-TNF-a can be used to treat Rheumatoid Arthritis
- binds and blocks TNF-a
- decreases frequency and magnitude of symptoms
- increases physical function
Describe monoclonal anti-sera
- vaccinate target (TNF) into an animal to raise an antibody immune response
- isolate from the spleen plasma cells recognising different epitopes
