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45 Cards in this Set

  • Front
  • Back

What is hypersensitivity?

First contact with antigen - immunologically primed

Further contactwith the antigen leads to a secondary reaction. If excessive, tissue damage.

What is different in hypersensitivity response?

•largequantities of the antigen




or the immune system response is increased.

Types

–Type IV dependent on T cell recognition. Delayedtype hypersensitivity




–TypesI, II, III and V depend on antigen-antibody reactions. Immediatetype reactions.

Type I


What is produced?


Which cells are induced?


Type of reaction

Production of IgEagainst innocuous antigens – induces mast cell activation, anaphylactic,immediate reaction

What triggers mast cell degranulation?

•IgE strongly bound to the plasma membrane bya high affinity receptor.
Source of IgE

· IgE produced by plasma cells in lymph nodes andby plasma cells at site of allergic reaction (mucosal tissue/skin)




· IgE predominantly located in tissues, tightlybound to surface of mast cells.

Cause ofanaphylaxis

· On subsequent exposure of Ag, contraction ofsmooth muscle and dilation of capillaries. Injection of penicillin or beestings.

What is Anaphylaxis?




How is it shown?

degranulationof mast cells by binding of Ag to IgG strongly bound to plasma membrane by highaffinity receptor - releases histamine (acting on H1 receptors onlocal blood vessels) and other mediators causing a rapid increase in vascularpermeability.




Show by injecting histamine to guinea pig.

What is Anaphylacticshock?




How is it controlled?

widespreadincrease in vascular permeability from massive release of histamine – largeloss of BP so shock with airways constriction.




Controlled with adrenalineinjection – reverses action of histamine.

involvement of penicillin

–highly reactive beta-lactam reacts with amino group on host proteins to formcovalent conjugates (haptens) with self-proteins provoking a TH2 response insome individuals – induces IgE synthesis. TH2 activate penicillin-binding Bcells to produce IgE against penicillin hapten.

Types of mast cells and location, expression

•mucosal - gut and lung mucos. •tryptase chymase




connective tissue - most other tissues including theperitoneal cavity and other connective tissues. These cells express Tryptase

Ratio of LTC4 : PGD 2 release

Mucosal25 : 1 (more LT)




Connective1:40 (more PG)

Mast cell receptor

· Both possess high affinity IgE receptor: alpha subunit binds to the Fc regionof IgE with v. high affinity. Beta and gammasubunits are involved in signal transduction. Found in cholesterol-rich lipidrafts.

What binds to mast cell receptors?

· Multivalent haptens bind to multiple IgEs boundto receptor – crosslinks IgE receptors which triggers secretion of inflammatorymediators.

Effect of receptor crosslinking?

· More receptors crosslinked together increasessensitivity of cells to Ag.

How do LTC4 and PGD2 work?

•G protein coupled receptors.

What is Atopy?

hyperallergic




predispositionto become IgE-sensitised to environmental allergens

Allergic rhinitis?




Prevalence, mechanism

· 10% of population, airborne allergensinteracting with sensitised MCs in conjunctivae and/or nasal mucosa.




· Activation of mucosal MCs beneath nasalepithelial by allergens – diffuse across the mucous membranes of nasal passages




· MC mediators cause local vasodilation andincreased capillary permeability

cause of Food allergies




Mechanism

· Allergen induced IgE crosslinking in upper/lowerGI tract – causes localised smooth muscle contraction and vasodilation.




· MC activation – may increase guy permeability toallergens.

When can Sensitisation to dietary allergens occur?

· inearly infancy through breastfeeding, with antigen passing into mother’s milk.

Atopic Dermatitis

· Allergic eczema – high serum IgE levels, Th2cells and eosinophils in infiltrate

Atopic allergy – treatment - first

· Avoidance – advised after sensitisation. Avoidcontact with potential allergens can be impractical;

Desensitisation treatment




How it works

· Desensitisation to Ag after identification ofallergen. Repeated subcutaneous injection of increasing doses of Ag – reduceseverity of type I reactions in SOME patients.






Appears to generate IgG reactionto Ag. IgG may compete to bind to allergen, blocking IgE binding.

Currentresearch

· produce modified recombinant known allergens.

Immunotherapyfor food allergies - best result so far

· Oral – best results so far, sublingual orepicutaneousSublingual allergen immunotherapy (SLIT) – lessrisk of severe systemic reactions than subcutaneous admin but not as effectiveas injections

Aims in Immunotherapy for food allergies

Aim was to boost synthesis of IgG “blocking” Abs –divert allergen from contact with tissue-bound IgE. Also, downregulation of IgEsynthesis. Alternatively, may induce regulatory T cells and switch from Th2 toTh2 cytokine production.

What is Desensitisation

· restore tolerance by reducing tendency to induceIgE production

Alternative therapy

vaccinationwith peptides derived from common allergens; induces Treg cells andproduction of IL-10. IgE-mediated response is not induced by peptide – tooshort to cross-link IgE

What is type II?

antibodydependent cytotoxic




•Bindingof an antibody to antigen on a cell surface may result in the destruction ofthe cell by phagocytosis




–Leadsto opsonisation of cell – leads to phagocytosis oractivation of complement (MAC)

Cause of MAC
With example


•May be due to adherence of the phagocyticcell to the Fc region of the antibody or via bound C3




–autoimmune thrombocytopaenic purpura

Type II - alternative killing method

•Targetcells coated with low concentrations of IgG may also be killed by antibody dependentcell-mediated cytotoxicity (ADCC)

Example of type II hypersensitivity in rbcs

Autoimmunehaemolytic anaemia

rbcs - only require one active complement siteto destroy the cells

What is type III?

(Immunecomplex mediated



•Occurs whenpatient is exposed to large quantities of antigen over a prolonged period




–antigen and antibody may react to forminsoluble complexes at fixed sites within the body

When does it occur

–may occur with persistent infections,autoimmune diseases or repeated exposure to an environmental antigen.

Effect of deposition ofantigen-antibody complexes

Complement


- release of C3a and C5a - activates mast cells and increasesvascular permeability


–releaseof chemotactic factors which leads to an influx of polymorphonuclear leukocytes


- full complement - MAC complex



What is Arthusreaction?

•Complexesdeposited in blood vessels may lead to platelet aggregation




–releasevasoactive amines (increased vascular permeability)




–mayform microthrombi, blocking capillaries which produces alocalised ischaemia.

What is Arthusreaction the basis of ?

•rheumatoid arthritis

What is type IV?

delayedtype - •Notdependent on antibody reactions




•Dependenton lymphoid cells –particularlyT-lymphocytes





What causes the response?

Tissue damage bymacrophage activation by Th1; eosinophils – Th2; CTLs

Type V

stimulatory




•formation of autoantibodies to cellsurface receptors on lymphocytes




–Some of these antibodies may inappropriatelyactivate the cells

Example of disease

–Gravesdisease

Innatehypersensitivity reactions

•Some infections induce toxic shocksyndrome




–characterised by hypotension, hypoxia, oliguria andmicrovascular abnormalities

Innatehypersensitivity reactions- Gram-negative

•Gram-negativebacteria can provoke septicaemia bythe action of lipopolysaccharide (LPS)

Explain the mechanism

· Endotoxin acts on macrophages and endothelialcells – excessive release of TNF, IL1 and IL6.

LPS can activate alternativecomplement pathway – activates platelets – disseminated intravascularcoagulation.

Innatehypersensitivity reactions- Gram-positive

S.aureus binds macrophages – induces TNFa synthesis;




–peptidoglycanin the cell wall can aggregate platelets




–Inaddition the staphylococcal enterotoxin is a superantigen