Drugs and the immune system

Question 1

What is an inflammatory reaction?

Answer 1

Events in the tissue in response to a pathogen or noxious substance

Question 2

What is the initial innate immune response

Answer 2

Macrophages and dendritic cells

Question 3

What are PAMPs?

Answer 3

Pathogen-associated molecular patterns

Question 4

What are cytokines?

Answer 4

Protein/peptide mediators released by cells of the immune system during inflammation. Act locally by kinase-linked receptors.

Question 5

Give two pro-inflammatory interleukins

Answer 5

1. IL-1 (released from macrophages)

2. TNF-a (tumour necrosis factor

Question 6

What does the Fc portion of an antibody do?

Answer 6

Activates complementation cascade and forms links to attach to neutrophils an macrophages. Binds to mast cells and basophils.

Question 7

What does the autocrine effect lead to?

Answer 7

Cell-mediated Th-1 or antibody mediated responses

Question 8

What does type one intermediate or anaphylactic hypersensitivity involve?

Answer 8

Histamine which acts on GPCRs, primarily fixed to IgE mast cells

Question 9

What is type II cell-mediated complex hypersensitivity?

Answer 9

Where antibodies are reacting with soluble agents. Produces lupus erythematosus

Question 10

What does type IV cell-mediated hypersensitivity involve?

Answer 10

T lymphocytes involved in transplant regection issues

Question 11

What is histamine?

Answer 11

A basic amine synthesised from histidine by histidine decarboxylase. At the cellular level, there is a high concentration in mast cells and basophils.

Question 12

When is histamine released?

Answer 12

1. Receptor-mediated interaction with C3a and C5a of the complement system
2. Interaction of antigen and IgE antibody
3. Triggered by a release of intracellular Ca2+
4. inhibition of release by a rise in cAMP e.g. B-adrenoreceptor agonists.

Question 13

What are the 3 types of histamine receptors?

Answer 13

• H1, vascular permeability, contraction of smooth muscle and vasodilation.
• H2, stimulation of gastric acid secretion. Increase cardiac rate and force.
• H3, Presynaptic sites, inhibit neurotransmitter release.

Question 14

Which histamine receptor do we want anti-histamines to react with?

Answer 14

H1

Question 15

Name 3 histamine H1 antagonists

Answer 15

1. Diphenhydramine
2. Promethazine
3. Cetrizine and terfenadine

Question 16

What are eicosanoids?

Answer 16

Generated de novo fro phospholipids. Implicated in control of many physiological processes. Include prostanoids and leukotrienes.

Question 17

what are the effects of prostanoids and leukotrienes?

Answer 17

• Vasodilation
• Potentiate the actions of histamine to increase vascular permeability.
• Potentiate the actions of bradykinin to produce pain.
• Production of fever.

Question 18

What are cytokines?

Answer 18

peptides released from immune system cells. Act by autocrine and paracrine mechanisms on kinase-linked receptors.

Question 19

Name 4 groups in the cytokine family.

Answer 19

1. Interleukins
2. Tumour necrosis factors
3. Growth factors.
4. Interferons

Question 20

What are the main actions of NSAIDS?

Answer 20

Inhibition of cyclooxygenase and decrease in prostanoid synthesis.

1. Analgesic (peripheral action)
2. Anti-inflammatory
3. Antipyretic

Question 21

What do PGE1 and PGE2 respond to?

Answer 21

5-HT and brandykinin

Question 22

What is the cause of an increase in body temperature during infection?

Answer 22

Hypothalamus being affected by PGE2 synthesis from IL-1

Question 23

What does the decrease of COX-2 result in?

Answer 23

Decrease in the synthesis of PGE1 and PGE2 so:

1. Reduction in vasodilation
2. Reduced erythema
3. Reduced local oedema.

Question 24

What can ILB4 do?

Answer 24

Stimulate movement of other WBC to the site of infection - it is a chemotaxin

Question 25

Give 6 general side-effects of using NSAIDs

Answer 25

1. Damage to the GIT due to COX-1 inhibition 2. Direct irritant action 3. Renal disease from chronic use due to disturbance of PG-mediated blood flow 4. Decreased activity in the uterus - can prolong labour 5. Hypersensitivity reactions and potentially bone-marrow disturbance.

Question 26

What are salicylates?

Answer 26

Aspirin, irreversible inhibitor of COX

Question 27

What may aspirin cause in children?

Answer 27

Reye's syndrome

Question 28

What is paracetamol?

Answer 28

Irreversible inhibitor of COX inhibition. Less anti-inflammatory than aspirin. Can cause severe liver damage due to metabolite NAPQI

Question 29

What do propionic acids include?

Answer 29

Ibuprofen and Naproxen (reversible COX inhibition)

Question 30

Name 2 COX-2 drugs

Answer 30

1. Celecoxib | 2. Rofecoxib

Question 31

How are adrenal steroids activated?

Answer 31

HPA axis

Question 32

What do adrenal steroids include?

Answer 32

1. Mineralocorticoids | 2. Glucocorticoids

Question 33

What are the two main functions of adrenal steroids?

Answer 33

1. Resting state to facilitate hormonal actions 2. Fight or flight response Inhibiting both early and late stages of inflammation

Question 34

Give 2 unwanted effects of using NSAIDs

Answer 34

1. Suppression of response to infection | 2. Suppression of natural corticosteriod synthesis by mimicry of feedback. Must be withdrawn slowly after chronic use.