IMMUNOLOGY- Hypersensitivity Reactions and Histamines Flashcards
What type of hypersensitivty reaction is Myaesthenia Gravis and Grave’s disease?
Type V (antibody dependent cell mediated cytotoxicity)
What is the systemic effect of leukotrienes? (3)
- Bronchoconstriction
- Vasoconstriction
- Increase vascular permeability
–> involved in allergic reactions and inflammation
Where is histamine metabolised and excreted?
metabolised in the liver by histaminase, excreted in the urine
Which type of hypersensitivity reactions does histamine modulate?
Typically Type I hypersensitivity (through H1 receptors)
Where are H1 receptors found? What type of hypersensitivity do they modulate?
Found in bronchial muscle and in the CNS.
Modulate Type 1 hypersensitivity reaction
How are H1 receptors activiated? What type of receptor are they?
G couple protein receptor :
Cetrizine –> activation of phospholipase C –> activation which increases intracellular calcium –> increased vascular permeability and arteriolar dilatation –> smooth muscle contraction, bronchospasm and CNS arousal.
Where are H2 receptors found? How are they activated?
Found in stomach, heart and uterus
Cimetidine –> stimulates adenylyl cyclase and cAMP –> pepsin and gastric acid secrtion –> increased myocardial stroke volume.
Where are H3 receptors found?
Expressed in CNS and mediate neurotransmitter release.
What is the difference between H1 anti-histamines and H2 antihistamines?
H1 antihistamines prevent smooth muscle contraction and vascular permeability caused by histamine, they have a
1) Anti-emetic effect
2) Sedative effect
3) Anti-cholinergic effect
H2 antihistamines decrease gastric acid secretion and inhibit cytochrome p450.
What is the mechanism of action of a mast cell stabiliser?
Inhibits release of histamine and slow-releasing substance of analyphaxis (SRS-A) from mast cells by stabilising their membranes –> they are ineffective once mast cells have degranulated
What hypersensitivity reactions are macrophages involved in?
Type 4 hypersensitivity reactions
Langhan’s giant cells are involved in what type of hypersensitivity reaction?
Type 4 hypersensitivity reaction
What is the pathological mechanism behind type 1 hypersensitivity reaction? What are the different phases?
PHASE I: SENSITISATION
pulmonary APCs and langerhan APCs on skin –> present to naive CD4 T-cells to produce IL-4, IL-5, IL-13.
IL-4 acts on B lymphocytes –> CLASS SWITCHING (IL-4 makes B-cells switch class of antibodies to IgE)
IgE attaches to mast cells and basophils (the FCER1 receptor) .
PHASE II: REACTION
Allergen enters body –> IgE recognise these allergens to signal mast cells to release chemical mediators –> ALLERGY/IgE CROSS-LINKING.
IMMEDIATE REACTION PHASE (minutes)
–> mast cell degranulation and release of pre-formed chemical mediators in mast cells such as histamine, serotonin, heparin, tryptase, chymase, ATP and lysosomal enzymes
–> histamine –> vasodilation and increased capillary permeability –> delivery of more inflammatory cells and oedema –> OEDEMA, ERYTHEMA AND WARMTH.
–> depolarises nerve endings for itching and pain.
LATE REACTION PHASE (hours)
–> conversion of phospholipids on mast cell membranes to arachidonic acid (via PLA2) –> leukotrienes (C4, D4, E4) and prostaglandins (D2) release.
leukotrienes C4, D4, E4 –> vasodilation, increased permeability and smooth muscle spasm
Leukotriene B4 and IL-5 (produced by mast cells) –> chemotaxis of eosinophils and neutrophils
IL-5 most potent activator for eosinophils
What is the type 2 hypersensitivity reaction?
What is the difference between intrinsic and extrinsic antigens?
ACID
***TYPE 2 - C - Cytotoxic, Cmooth. (linear deposition)
*
Antibody-mediated autoimmune dysfunction caused by IgG (or IgM) –> complement activation and NK cell activation.
INTRINSIC ANTIGENS
- protein antigens on cell membranes (RH antigen on RBCs, GP2B3A on platelets) –> autoimmune anaemias and thrombocytopaenias.
- protein antigens in the matrix between cells - goodpasture’s syndrome (basement membrane) and pemphigus vulgaris
- receptor antigens of cell (hormone receptors, myaesthenia gravis (Type 5)
EXTRINSIC ANTIGENS
1. blood-transfusion reaction - antibodies destroys transfused RBCs leading to transfusion reaction
- drug reactions - drug metabolites deposit on surface of cells, recognised by antibodies and attack which leads to damage of cells where these metabolites/antigens are deposited
What is the mechanism of type 2 hypersensitivity reaction? (3)
***TYPE 2 - C - Cytotoxic, Cmooth.
- opsonisation and phagocytosis
- complement activation
- antibody mediated cellular cytotoxicity (myaesthenia gravis) - antibodies block receptor for ACh –> muscle weakness and paralysis
What is the mechanism of type 3 hypersensitivity?
What are the 3 phases?
SLE
PHASE 1: immune complex formation
- antigens released into circulation (eg SLE) –> antibody activation and formation of antigen-antibody complexes
- eg UV radiation breaks down DNA, DNA antigens escape into circulation and formation of antigen-antigen complexes
PHASE 2: immune complex deposition
- immune complexes are deposited in small blood vessels, glomeruli of kidneys, synovial membrane of joints, pleura, pericardium
- preferentially deposited here due to very small blood vessels in these tissues and high filtration pressures
PHASE 3: inflammation and injury
- neutrophil chemotaxis and degranulation
- complement system activation
- C3A activates histamine
- C5A is chemoattractant
- these complexes adhere to cell surface firmily, so phagocytose attempts are unsuccessful –> release of lyosomal enzymes –> cell damage, inflammation and auto-cell damage.
Which diseases are associated with Type-4 hypersensitivity reaction?
- Contact dermatitis
- Granulomatous diseases (TB, sarcoid, cat-scrach disease)
- Rheumatoid arthritis
- Crohn’s Disease
- Multiple Sclerosis
- Type I Diabetes
macrophages cannot kill / remove target antigen completely, and so surround these antigens forming epitheloid like cells and get surrounded to form a GRANULOMA.
ACID (Delayed type 4) - Delayed, Diabetes, Dermatitis, Diagnose TB
What is the mechanism of type 4 hypersensitivity (CD8 mediated)?
T-cell mediated cytolysis - T-cells destroy APC cells directly (dendritic cells)
CD8 kill virally infected cells via performins and granzymes
What is the summary table for the hypersensitivity reactions?
