Hypersensitivity (rudimentary) Flashcards
αβγδεμκλ↑↓
Type I hypersensitivity
IgE mediated
Initiation: 2-30 mins
~20-30% pop.
Ag induces cross-linking of pre-existing IgE bound to mast cells with release of vasoactive mediators:
- primary inflammatory mediators e.g histamine/ serotonin released by degranulation, increase vascular permeability& smooth muscle contraction
- secondary inflammatory mediators are synthesised e.g leukotrienes, prostaglandins, cytokines
Allergens are often
- proteases
- low molecular weight & highly soluble: diffuse readily into mucus
- generally stable, can survive as a dessicated particle.
- contain peptides that can bind MHC class II.
Low dose encountered by favour IL-4 producing Th2 responses.
Treatment: identification & avoidance of allergen, antihistamines, corticosteroids.
Type I hypersensitivity examples
Systemic anaphylaxis Local anaphylaxis Hay fever (allergic rhinitis) Asthma Eczema Penicillin allergy
Type II hypersensitivity
Antibody-mediated cytotoxic hypersensitivity.
Initiation: 5-8 hours
Ab (IgM or IgG) directed against cell surface antigens mediates cell destructon via ADCC or complement
Type II hypersensitivity examples
Blood transfusion reactions (ABO)
Rhesus reaction
Haemolytic disease of the newborn
Autoimmune haemolytic anaemia: destruction of RBCs
Thrombocytopenia: destruction of platelets.
Haemolytic anaemia & thrombocytopenia are uncommon side effects of e.g penicillin. Drug binds to the cell surface, making a novel epitope, & is a target for antibodies in a minority of individuals. Cell-bound antibody triggers clearance of the cell by
- tissue macrophages in the spleen (bear Fcγ receptors) or by complement lysis
Type III hypersensitivity
Immune-complex mediated hypersensitivity
Initiation: 2-8 hours
Cause: inability to clear immune complexes. Immune complexes arise from persistent infection of inhalation.
Ag-Ab complexes (immune complexes) deposited at various sites in tissues induce mast cell degranulation via low affinity FcγRIII, PMN are attracted & degranulation damages tissues. Complement is activated. Similar to Type I but with IgG.
Occurs when antigen is soluble & in high doses (low doses tend to produce IgE responses)
Type III hypersensitivity examples
- Arthus reaction (localised). Can be triggered in the skin of sensitised individuals who have IgG against the sensitising antigen.
- Serum sickness (used to result when high doses of horse serum used to treat pneumonia).
- Pigeon fanciers lung.
- Post infection complications such as arthritis & glomerulonephritis.
Type IV hypersensitivity
Cell-mediated hypersensitivity. ‘Delayed type’
Initiation: 24-72 hours
Memory TH1 cells release cytokines that recruit & activate macrophages
- Chemokines: recruit macrophages to site of antigen deposition
- IFNγ: Induces expression of vascular adhesion molecules. Activates macrophages, increasing release of inflammatory mediators.
- TFNα and TNFβ: cause local tissue destruction. Increase expression of adhesion molecules on local blood vessels
- IL-3/ GM-CSF: Stimulate monocyte production by bone marrow stem cells.
Amount of antigen required is generally 10-100x more than for antibody-mediated hypersensitivity.
Type IV hypersensitivity examples
Contact dermatitis. Contact hypersensitivity= cutaneous responses to haptens, which form stable complexes with host proteins. e.g poison ivy, metal salts.
Tubercular lesions (Nb Mantoux test for TB)
Testing sensitivity to antigens
Skin-prick test
‘Wheal and flare’ response appears at site of infection within a few minutes.
Wheal = swelling (edema)
Flare= erythema, from increased blood flow
Genetic susceptibility to Type I hypersensitivity
Having 2 susceptible parents doubles risk.
Atopic individuals
Have multiple allergies (Type I hypersensitivity), typically eczema & asthma.
Serum IgE is raised 10-100x normal level.
ABO blood grouping
Blood groups = polymorphic structures present on RBCs. Some of these structures are present only on RBCs, some on all tissue cells.
Molecules consist of a core H antigen.
O (null) allele is unmodified H antigen. Sugars may be attached to this core:
- A allele adds a terminal N-acetylgalactosamine
- B allele adds a terminal galactose
- AB indicates both modifications.
ABO blood group
= only histocompatibility alloantigen for which pre-existing antibody is present in naive, previously untransfused recipients.
Rhesus reaction
Type II hypersensitivity Blood incompatibility (different case to ABO) If mother is rhesus negative & child is rhesus positive, some Rh+ cells leak into the maternal circulation at birth- mother produces antibodies to Rhesus antigen. The IgG can cross the placenta & compromise the Rh+ baby.
Treatment/ avoidance:
- giving anti-Rh antibody to the mother before she reacts to her childs RBCs.
- antibody-mediated clearance & destruction of childs cells prevents initiation of immune response.
