Drugs and the immune system Flashcards
What is an inflammatory reaction?
Events in the tissue in response to a pathogen or noxious substance
What is the initial innate immune response
Macrophages and dendritic cells
What are PAMPs?
Pathogen-associated molecular patterns
What are cytokines?
Protein/peptide mediators released by cells of the immune system during inflammation. Act locally by kinase-linked receptors.
Give two pro-inflammatory interleukins
- IL-1 (released from macrophages)
2. TNF-a (tumour necrosis factor
What does the Fc portion of an antibody do?
Activates complementation cascade and forms links to attach to neutrophils an macrophages. Binds to mast cells and basophils.
What does the autocrine effect lead to?
Cell-mediated Th-1 or antibody mediated responses
What does type one intermediate or anaphylactic hypersensitivity involve?
Histamine which acts on GPCRs, primarily fixed to IgE mast cells
What is type II cell-mediated complex hypersensitivity?
Where antibodies are reacting with soluble agents. Produces lupus erythematosus
What does type IV cell-mediated hypersensitivity involve?
T lymphocytes involved in transplant regection issues
What is histamine?
A basic amine synthesised from histidine by histidine decarboxylase. At the cellular level, there is a high concentration in mast cells and basophils.
When is histamine released?
- Receptor-mediated interaction with C3a and C5a of the complement system
- Interaction of antigen and IgE antibody
- Triggered by a release of intracellular Ca2+
- inhibition of release by a rise in cAMP e.g. B-adrenoreceptor agonists.
What are the 3 types of histamine receptors?
- 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.
Which histamine receptor do we want anti-histamines to react with?
H1
Name 3 histamine H1 antagonists
- Diphenhydramine
- Promethazine
- Cetrizine and terfenadine
What are eicosanoids?
Generated de novo fro phospholipids. Implicated in control of many physiological processes. Include prostanoids and leukotrienes.
what are the effects of prostanoids and leukotrienes?
- Vasodilation
- Potentiate the actions of histamine to increase vascular permeability.
- Potentiate the actions of bradykinin to produce pain.
- Production of fever.
What are cytokines?
peptides released from immune system cells. Act by autocrine and paracrine mechanisms on kinase-linked receptors.
Name 4 groups in the cytokine family.
- Interleukins
- Tumour necrosis factors
- Growth factors.
- Interferons
What are the main actions of NSAIDS?
Inhibition of cyclooxygenase and decrease in prostanoid synthesis.
- Analgesic (peripheral action)
- Anti-inflammatory
- Antipyretic
What do PGE1 and PGE2 respond to?
5-HT and brandykinin
What is the cause of an increase in body temperature during infection?
Hypothalamus being affected by PGE2 synthesis from IL-1
What does the decrease of COX-2 result in?
Decrease in the synthesis of PGE1 and PGE2 so:
- Reduction in vasodilation
- Reduced erythema
- Reduced local oedema.
What can ILB4 do?
Stimulate movement of other WBC to the site of infection - it is a chemotaxin
Give 6 general side-effects of using NSAIDs
- Damage to the GIT due to COX-1 inhibition
- Direct irritant action
- Renal disease from chronic use due to disturbance of PG-mediated blood flow
- Decreased activity in the uterus - can prolong labour
- Hypersensitivity reactions and potentially bone-marrow disturbance.
What are salicylates?
Aspirin, irreversible inhibitor of COX
What may aspirin cause in children?
Reye’s syndrome
What is paracetamol?
Irreversible inhibitor of COX inhibition. Less anti-inflammatory than aspirin. Can cause severe liver damage due to metabolite NAPQI
What do propionic acids include?
Ibuprofen and Naproxen (reversible COX inhibition)
Name 2 COX-2 drugs
- Celecoxib
2. Rofecoxib
How are adrenal steroids activated?
HPA axis
What do adrenal steroids include?
- Mineralocorticoids
2. Glucocorticoids
What are the two main functions of adrenal steroids?
- Resting state to facilitate hormonal actions
- Fight or flight response
Inhibiting both early and late stages of inflammation
Give 2 unwanted effects of using NSAIDs
- Suppression of response to infection
2. Suppression of natural corticosteriod synthesis by mimicry of feedback. Must be withdrawn slowly after chronic use.
