Drugs and the Immune System I Flashcards
What are 5 cardinal signs of inflammation?
- Heat
- Redness
- Swelling
- Pain
- Loss of function
What is inflammation?
Localised process by which cells and fluid accumulate in irritated tissues, and usually tend to protect them from further injury
Describe innate immunity
- 1st line of defence
- Checks most potential pathogens
- Breach of system result in activation of adaptive immune system
Describe adaptive immunity
- Specific reaction to infectious agent
- Eradicate the agent
- T cells recognise antigen displayed
- Capacity to remember infectious agent
Describe the initial sensitisation of the innate immune system
- Pathogens are recognised by epithelial cells and macrophages
- Pro-inflammatory cytokines released
- Cytokines active inflammatory cells
Name 2 pro-inflammatory cytokines released by epithelial cells during
- TNF-α
2. IL-1
Name 2 types of inflammatory cells activated by cytokines
- Neutrophils
2. Mast cells
Describe the initial sensitisation of the adaptive immune system
- Antigen presenting cells present to lymphocytes and natural killer cells
- IL-2 produced leading to clonal expansion of activated T lymphocytes
- Further mediators activate anti-inflammatory macrophages, cytotoxic T cells and B lymphocytes
Name 3 cell types which provide communication between adaptive and innate immunity
- Natural killer cells
- Lymphoid cells
- Mast cells
Name 2 sources of chemical mediators of inflammation
- Cellular
2. Plasma derived from liver
What are 2 types of cellular chemical mediators of inflammation?
- Synthesised
2. Preformed
Name 5 types of synthesised cellular chemical mediators of inflammation
- Prostaglandins
- Leukotrienes
- Cytokines (IL-1, IL-2, TNF-α)
- Nitric Oxide
- Platelet Activation Factors (PAFs)
Name 3 preformed cellular chemical mediators of inflammation
- Histamine
- Serotonin
- Lysosomal Enzymes
What type of cellular chemical mediator of inflammation does not cause vascular leakage?
Cytokines
What 3 types of cellular chemical mediator of inflammation cause chemotaxis?
- Leukotrienes
- PAFs
- Cytokines
Name 2 types of activation which can occur from plasma derived chemical mediators of inflammation
- Hageman Factor activation
2. Complement activation
Name 2 systems which are part of Hageman Factor activation
- Kinin system e.g. bradykinin
2. Coagulation / Fibrinolysis system
Name 4 chemical mediators during complement activation
- C3a
- C3b
- C5a
- C5b-9
What is the function of C3b chemical mediator?
Opsonisation
Which mediator of the complement activation does not cause vascular leakage or chemotaxis?
C3b
Name 4 ways drugs can modify the immune response
- Modulation of antigen processing (suppression)
- Enhancement of suppression of T cell function
- Modification of B cell responses and antibody production
- Interference with production / release of mediators or their effects (suppression / enhancement)
Name 2 main aims of treating inflammation
- Relief of pain
2. Stop tissue damage
Name 6 classes of drugs used to combat inflammation
- Histamine / Antihistamine
- Cytokines / Biologicals
- Immunosuppressive
- NSAIDs
- Steroidal Anti-Inflammatory Drugs
- Diseases Modifying Drugs
What is the chemical name for histamine?
Aminoethylimidazole
Name 4 places histamine is naturally found
- Plants
- Venoms / Stings
- Bacteria and certain fungi
- Throughout the human body
What enzyme is responsible for the synthesis of histamine?
Histidine decarboxylase (HDC)
How many types of histamine receptors are there?
4
Describe the gene location for H₁ receptor
Chromosome 3
Describe the gene location for H₂ receptor
Chromosome 5
Describe the gene location for H₃ receptor
Chromosome 20
Describe the gene location for H₄ receptor
Chromosome 18
What is the general function of H₁ receptors?
Rapid, short-lived vascular response, increasing vasodilatation, vascular permeability and hypotension
Describe the immune response to stimulated H₁ receptors
Pro-inflammatory, increasing the release of histamine and other mediators and chemotaxis of eosinophils and neutrophils
Describe the CNS response to stimulated H₁ receptors
Affect sleep, food intake, memory and learning
What is the general function of H₂ receptors?
Slower, sustained vascular response, increasing bronchodilatation and vascular permeability
Describe the immune response to stimulated H₂ receptors
Anti-inflammatory, decreasing chemotaxis of eosinophils and neurtophils
Describe the CNS response to stimulated H₂ receptors
Neuroendocrine
What is the general function of H₃ receptors?
Prevents excessive bronchoconstriction
Describe the immune response to stimulated H₃ receptors
Pro-inflammatory
Describe the CNS response to stimulated H₃ receptors
Decrease in histamine, dopamine, serotonin, noradrenaline and acetylcholine release
What is the the general function of H₄ receptors?
Differentiation of myeloblasts and promyelocytes
Describe the immune response to stimulated H₄ receptors
Increases calcium influx in human eosinophil cells and increases eosinophil and mast cell chemotaxis
Name the major effect of histamine on H₁ receptors
Allergic inflammation
Name the major effect of histamine on H₂ receptors
Gastric acid secretion
Name the major effect of histamine on H₃ receptors
Neurotransmission
Name the major effect of histamine on H₄ receptors
Immunomodulation
Name 2 types of cells where histamine is stored
- Mast cells
2. Basophils
How is histamine released from mast cells?
Degranulation
Describe 4 types of hypersensitivity reactions
- Type I - Immediate allergic reaction requiring sensitisation
- Type II - Cytotoxic involving antibodies with tissue damage
- Type III - Immune complex mediated with tissue damage
- Type IV - Delayed and cell mediated involving T lymphocytes
What is the triple response to histamine injection?
- Reddening
- Flare
- Wheal
How do antihistamines function?
Competitively antagonize histamine at the receptor, thereby decreasing the availability of the receptors for histamine
Name 2 H₄ receptor antagonists currently under development
- Seliforant
2. Adriforant
What is the potential use for seliforant?
Acute unilateral vestibulopathy
What is the potential use for adriforant?
Severe atopic dermatitis
Name a H₃ receptor antagonist
Pitolisant
What is the clinical use of pitolisant?
Treatment of narcolepsy with or without cataplexy
Name 4 H₂ receptor antagonist drugs
- Cimetidine
- Ranitidine
- Nizatidine
- Lafutidine
Name 4 H₁ receptor antagonist drugs
- Chlorphenamine
- Promethazine
- Terfenadine
- Cetirizine
Name 3 clinical benefits when H₁ receptor antagonist drugs antagonize the receptor
- Reduce vasodilatation
- Reduce capillary permeability
- Reduce flare and itch response
Describe the ADME of H₁ receptor antagonist drugs
- Well absorbed from GIT
- Distributed through whole body
- Metabolised by the liver
Name 3 uses of H₁ receptor antagonists
- Topical application to relieve itching
- Prophylaxis and treatment of allergic conditions e.g. rhinitis
- Common cold remedies
Name 4 adverse effects of H₁ receptor antagonists
- Sedation (enhanced by alcohol)
- Stimulation (phenindamine)
- Cardiac problems are possible
- Xerostomia
Name 2 dental applications of H₁ receptor antagonists
- Sedative (promethazine)
2. Allergic lesions on face and mouth