Immune system and hypersensitivity reactions Flashcards
What is the difference between innate and adaptive immune response?
Innate: ready for immediate action, relatively non-specific
Adaptive: slower in action, specific to particular pathogens
What are the events that occur in innate immunity?
- PAMPs, expressed on pathogen, trigger release of IL-1 and TNF-alpha from macrophages which act on endothelial cells tat express adhesion molecules
- Phagocytes adhere to endothelium whilst chemotaxis C5a, LTB4 IL-8, PAF are generated and released and attract neutrophils
- Phagocytes migrate towards bacteria
- Phagocytosis of bacteria- opsonins C3b, IgG mediate attachment to neutrophils
- Bacteria is killed and digested by granule enzymes and toxic O2 products
What are toll-like receptors?
Located on macrophages, they recognise PAMPs. TLR activation releases inhibition of NF-kappaB by IkappaB leading to production of cytokines and other inflammatory mediators.
What is an autoimmune disease?
They are caused when the immune system becomes directed against the own body’s tissues. The initial causative event is likely to be pathogen invasion, against which an immune attack is mounted, but which expresses a protein with sequence similar to endogenous proteins.
What are corticosteroids?
Released from the outer layer of the adrenal glands. (Glucocorticoids- endogenous steroids regulating glucose metabolism; corticosteroids include these and artificial steroids used in therapy). They produces anti-inflammatory effects by inhibiting or activating transcription of genes encoding proteins involved in regulating inflammation.
What drugs are used for short-term immunosuppression?
High-dose corticosteroids- severe side effects with long-term usage
Cyclophosphoamide- a prodrug which the active compound is released in the liver; alkylates DNA and so kills proliferating B,T cell. Severe side effects include hair loss, haemorrhagic cystitis, infertility.
How are mast cells activated?
They are activated by allergens by complement and by neuropeptides, they release a host of autacoids.
Where is histamine found?
Found in mast cells in tissues, basophils in blood, ECL cells of oxynic gland in stomach and histaminergic neurones in the CNS
What are the actions of histamine?
Contraction of smooth muscle in bronchi and gut; dilation of small arterioles mediated by NO production from endothelial cells; increased permeability of post-capillary venues via effects on endothelial cells; sensitises nerve endings leading to itching. Injections of histamine response elicits a classic triple response of Lewis: local redness, swelling and red flare from an axonal reflex releasing peptides from nerve endings. Involved in various allergic conditions such as hay fever, skin rashes and anaphylaxis.
What are some histamine H1 receptor antagonists?
Original antagonists- e.g. mepyramine, non selective, actions in CNS caused drowsiness
Second generation- e.g. terfenadine, more selective, could not cross BBB but had off-target cardiac effects (block of HERG ion channels leading to ventricular fibrillations torsades de pointes
Third generation- e.g. loratadine and fexofenadine, have less CNS action and no action on the heart; used widely
What is the difference between immediate and late hypersensitivity reactions?
Immediate: occurs in minutes, release of histamine, prostaglandins from mast cells
Late: 2-24 hours, release of cytokines from mast cells, neutrophils, lymphocytes, macrophages which migrate to the site of entry of the antigen
How can type I hypersensitivity reactions be treated?
- avoid allergen
- inject low-dose allergens to desensitise response
- ant-histamines
- corticosteroids
- cromolyn sodium: reduces mast cell activation
- leukotriene receptor antagonists
- adrenaline, used for emergency treatment of anaphylaxis, inhibits release of mediators from mast cells
What is a type II hypersensitivity reaction?
Reaction of the immune system against an antigen adsorbed to the surface of the body’s own cells, e.g. penicillin bound to RBC.The antigen can be a body protein. Antibodies (IgG and IgM) bind to foreign antigen. The Fc domains of these antibodies are recognised by natural killer cells and the cell bearing the foreign antigen is destroyed (antibody-dependent cell-mediated cytotoxicity/ADCC).
What is a type III hypersensitivity reaction?
Excess antigen leads to antigen-immune complexes which can accumulate in tissues, blood vessels etc. and initiate an inflammatory reaction
What are type IV hypersensitivity reactions?
Delayed reaction- takes days or weeks to develop, cell mediated. Activated T cells bind to and destroy target cells which are presenting an antigen.
