Lecture 8 (Anti-inflammatories 2) Flashcards
What cell does arthritis activate?
Macrophages
What are the most important mediators involved in driving an immune response? (2)
What cells are they released by?
IL-1 (Interleukin1)
TNF-a
Released by macrophages
How do immunosuppressant drugs effect inflammatory response?
Immunosuppressant drugs inhibit induction phase of inflammatory response
How does cyclosporin inhibit the transcription of pro-inflammatory cytokines? (3)
-Cyclospoporin inhibits II-2 synthesis so less proliferation of T-cells
-Binds to cyclophilin
-Then drug-immunophilin binds to calcinerurin and inhibits it (presents signalling/activation of transcription factors)
How do glucocorticoids inhibit transcription of pro-inflammatory cytokines?
-Act at level of genes transcription to limit transcription of pro-inflammatory cytokine synthesis
(effective at induction and effector phases of immune response)
What are the advantages of new drugs with humanised monoclonal antibodies? (3)
-High affinity and selectivity for target
-Neutralise action of either soluble or membrane bound pro-inflammatory cytokines (soluble receptors)
-Long half life
What are the two main Inflammatory Respiratory Diseases? (2)
-COPD (Chronic Obstructive Pulmonary Disease)
-Asthma
How do you treat asthma?
So, we use anti-inflammatory agents (steroids) which we take in with inhalers
What is asthma characterised by? (3)
-Inflammation of the airways
-Bronchial hyper-reactivity
-Reversible airways obstruction
What happens in hay fever(allergic rhinitis)?
and where does it happen?
-Nasal congestion, sneezing, allergic conjunctivitis
-Allergen activates mast cells in nasal mucosa and conjunctivae
Where does Allergic Asthma take place?
-Allergen activates mast cells in lower respiratory tract
What happens in early and late phase reactions in allergic asthma? (2)
Early - reversible airways obstruction, inflammation. Patient have increased numbers of mast cells in bronchi which mediate these effects
Late (50% patients) - Cytokines -> leukocyte infiltration (especially eosinophils) leading to inflammation, some patients develop chronic asthma (chronic inflammation, results in tissue damage and airway remodelling
What cell’s overactivity is associated with asthma?
Th2 cells
(activate mast cells)
What are the key mediators of type 1 hypersensitivity reactions?
Mast cells
What happens in type 1 hypersensitivity reactions? (4)
-When receptors are activated, there is release of histamine (occurs in seconds)
-Histamine binds to histamine receptors which are present in smooth muscle in lungs
-Mediators in addition of histamine, activation of receptors drives production of prostaglandins, drive bronchoconstriction
-They also lead to increased vascular permeability
Can also act on nerve endings to make you cough
What happens when inflammatory mediators are released from mast cells after they interact with allergen? (6)
-Smooth muscle contraction
-Increased vascular permeability
-Mucous secretion
-Platelet activation
-Stimulation of nerve endings
-Recruitment and activation of eosinophils
What is secreted in the early/immediate phase of asthma? (2)
Cytokines and Chemokines
What do we use to treat the early phase of asthma response?
Histamines and prostaglandins
What do we use to treat try late phase of asthma response?
We use glucocorticoids
What pathology is associated with chronic inflammation of the airways? (5)
-Clogged airways full of mucus to difficult to breathe
-Limited oxygen exchange due to limited volume
-Thickening of airways, growth of smooth muscle cells
-Other types of cells grow there which restrict flexibility of lungs
-More cells that produce mucus grow
What side-effect does long-term steroid use have?
Cushing’s synondome
What does MAB at the end of drug name mean?
Monoclonal antibody
What do new therapies of asthma focus on inhibiting? (2)
-PGD synthase (synthesis prostaglandin D2 and acts on DP1 and DP2 receptors)
-Antagonists for DP1 and DP2 receptors
Where is Prostaglandin D2 (PGD2) synthesised?
Mast cells
How can we treat COPD?
We can try to slow down progression
-using B2 agonists, muscarinic antagonists, corticosteroids
Why do early and late phases happen in respiratory allergy? (2)
-Early phase is due to mass cells secreting histamine
-Late phase reactions (some genetic component) are due to cytokines forcing inappropriate inflammatory response to take place
Which cells lead to asthmatic effects?
Mast cells which line airways and mediators lead to asthma effects
