Lecture 8 (Anti-inflammatories 2)

Question 1

What cell does arthritis activate?

Answer 1

Macrophages

Question 2

What are the most important mediators involved in driving an immune response? (2)
What cells are they released by?

Answer 2

IL-1 (Interleukin1)
TNF-a

Released by macrophages

Question 3

How do immunosuppressant drugs effect inflammatory response?

Answer 3

Immunosuppressant drugs inhibit induction phase of inflammatory response

Question 4

How does cyclosporin inhibit the transcription of pro-inflammatory cytokines? (3)

Answer 4

-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)

Question 5

How do glucocorticoids inhibit transcription of pro-inflammatory cytokines?

Answer 5

-Act at level of genes transcription to limit transcription of pro-inflammatory cytokine synthesis
(effective at induction and effector phases of immune response)

Question 6

What are the advantages of new drugs with humanised monoclonal antibodies? (3)

Answer 6

-High affinity and selectivity for target
-Neutralise action of either soluble or membrane bound pro-inflammatory cytokines (soluble receptors)
-Long half life

Question 7

What are the two main Inflammatory Respiratory Diseases? (2)

Answer 7

-COPD (Chronic Obstructive Pulmonary Disease)
-Asthma

Question 8

How do you treat asthma?

Answer 8

So, we use anti-inflammatory agents (steroids) which we take in with inhalers

Question 9

What is asthma characterised by? (3)

Answer 9

-Inflammation of the airways
-Bronchial hyper-reactivity
-Reversible airways obstruction

Question 10

What happens in hay fever(allergic rhinitis)?
and where does it happen?

Answer 10

-Nasal congestion, sneezing, allergic conjunctivitis

-Allergen activates mast cells in nasal mucosa and conjunctivae

Question 11

Where does Allergic Asthma take place?

Answer 11

-Allergen activates mast cells in lower respiratory tract

Question 12

What happens in early and late phase reactions in allergic asthma? (2)

Answer 12

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

Question 13

What cell’s overactivity is associated with asthma?

Answer 13

Th2 cells
(activate mast cells)

Question 14

What are the key mediators of type 1 hypersensitivity reactions?

Answer 14

Mast cells

Question 15

What happens in type 1 hypersensitivity reactions? (4)

Answer 15

-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

Question 16

What happens when inflammatory mediators are released from mast cells after they interact with allergen? (6)

Answer 16

-Smooth muscle contraction
-Increased vascular permeability
-Mucous secretion
-Platelet activation
-Stimulation of nerve endings
-Recruitment and activation of eosinophils

Question 17

What is secreted in the early/immediate phase of asthma? (2)

Answer 17

Cytokines and Chemokines

Question 18

What do we use to treat the early phase of asthma response?

Answer 18

Histamines and prostaglandins

Question 19

What do we use to treat try late phase of asthma response?

Answer 19

We use glucocorticoids

Question 20

What pathology is associated with chronic inflammation of the airways? (5)

Answer 20

-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

Question 21

What side-effect does long-term steroid use have?

Answer 21

Cushing’s synondome

Question 22

What does MAB at the end of drug name mean?

Answer 22

Monoclonal antibody

Question 23

What do new therapies of asthma focus on inhibiting? (2)

Answer 23

-PGD synthase (synthesis prostaglandin D2 and acts on DP1 and DP2 receptors)
-Antagonists for DP1 and DP2 receptors

Question 24

Where is Prostaglandin D2 (PGD2) synthesised?

Answer 24

Mast cells

Question 25

How can we treat COPD?

Answer 25

We can try to slow down progression
-using B2 agonists, muscarinic antagonists, corticosteroids

Question 26

Why do early and late phases happen in respiratory allergy? (2)

Answer 26

-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

Question 27

Which cells lead to asthmatic effects?

Answer 27

Mast cells which line airways and mediators lead to asthma effects