Week 5 Flashcards
What are ROS components?
Reactive oxygen species
Where are IgA antibodies found?
In mucous, saliva, tears and breast milk.
What do IgA antibodies protect against?
Pathogens
Where are IgD antibodies found?
Part of the B cell receptors.
What are the main function of IgD antibodies?
Activate basophil and mast cells.
What are IgE antibodies responsible for?
Allergic reactions.
Where are IgG antibodies secreted from ?
Plasma cells in the blood.
Can IgG antibodies cross the placenta?
Yes
Where are IgM antibodies found?
Attached to the surface of B cells or in the blood.
What is the onset time of type 1 hypersensitivity?
5-15 minutes
What antibodies mediate type 1 hypersensitivity?
IgE
What hypersensitivity type are most allergic reactions?
1
What causes an allergy?
There is a genetic component to an allergy where the individual has certain genes that make their T cells more hypersensitive to certain antigens.
How do type 1 allergens enter the body?
They are breathed or taken in.
Contact with the skin.
What is an allergen?
An antigen that causes an allergic reaction.
What are the symptoms of type 1 hypersensitivity?
Rhinitis Conjunctivitis Hives Angiodema Asthama Anaphylaxis
What is angiodema?
Swelling of deeper layers of the skin caused by a build-up of fluid.
How many times do you need to be exposed to an allergen to become allergic?
2
On the first exposure you become sensitive and on the second you can have more severe reactions.
What are the possible treatments for type 1 hypersensitivity reactions?
Adrenaline
Antihistamines
Corticosteroids
What are some of the clinical features of asthma?
- Reversible generalised airway obstruction.
- Chronic Episodic wheeze.
- Bronchial hyperresponsivness.
- Bronchial irritability cough.
- Mucus production.
- Breathlessness
- Chest tightness
- Reduced variable peak flow.
Outline how Asthma is treated.
- Beta-1 Agonist drugs can be required by inhalation.
- Inhalation of a steroid of a low-moderate dose.
- Long acting Beta-2 agonists and Leukotriene agonists may be inhaled in high doses if needed.
- Oral steroids.
How do beta-2 agonists and leukotriene antagonists work to treat asthma?
They block the degranulation of receptors that activation constriction of airways.
What are the symptoms of Rhinitis?
Sneezing Rhinnorehoea Itchy nose and eyes Nasal blockage and Sinusitis Loss of smell and taste
What is the common name for Rhinitis?
Hay-fever
How is allergic Rhinitis treated?
Anti-histamines
Nasal steroids
Cromoglycate
What type of Rhinitis patients is Cromoglycate given to and why?
Children to help the eyes.
What is anaphylactic shock?
A severe generalised allergic reaction which is uncommon but can be fatal.
What are the clinical symptoms of anaphylactic shock?
- Generalised degranulation of IgE sensitised mast cells.
- Cardiovascular effects such as vasodilation and cardiovascular collapse.
- Respiratory effects such as bronchospasm and laryngeal oedema.
- Skin effects such as vasodilation, erythema, urticarial and angioedema.
- GI effects such as vomiting an diarrhoea.
What is Erythema?
Redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries.
What is Urticarial ?
Hives
What is Angioedema?
An area of swelling of the lower layer of skin and tissue just under the skin or mucous membranes
What are the symptoms of anaphylactic shock?
- Itchiness around the mouth and lips.
- Swelling of the lips and throat.
- Wheezing
- Chest tightness
- Dyspnoea
- Faintness
- Collapsing
- Diarrhoea
- Vomiting
What is Dyspnoea ?
Difficulty with breathing.
What type of sensitivity is type 2 hypersensitivity?
Cytotoxic
Outline what type 2 hypersensitivity is
Antibody mediated destruction of healthy cells by central tolerance.
What is the central tolerance that occurs in type 2 hypersensitivity?
Immune cells that are self-reactive are destroyed and this leads to autoimmunity.
What are the possible mechanisms of type 2 hypersensitivity ?
-Complement - cytotoxic.
Intrinsic antigen MAC - cytotoxic.
-Complement opsonisation - cytotoxic.
-Antibody dependent cell mediated cytotoxicity.
-Antibody-mediate cellular destruction - non-cytotoxic.
Outline the Cytotoxic complement mechanism of type 2 hypersensitivity.
- Penicillin binds to red blood cells, IgG against penicillin binds and forms a complex.
- C1 binds to Fc portion of Ab.
- C1 activates the complement cascade and chemotactic factors are released which attract Neutrophils.
- Neutrophils degranulate and release MPO which kills cells.
Outline the Cytotoxic intrinsic antigen MAC method of type 2 hypersensitivity.
Activation of complement leading to C5b and C6-9 combining to form a membrane attack complex.
MAC penetrates the membrane causing lysis.
Outline the mechanism of cytotoxic complement opsonisation method of type 2 hypersensitivity.
IgG coats red blood cells which are then bound by C3b. This causes opsonisation.
The Ab-Ag complex is filtered in the spleen.
The phagocyte will bind to either Fc of Ab or to the C3b and phagocytose the cell.
Outline the cytotoxic antibody dependent method of type 2 hypersensitivity
Natural killer cells recognise the Fc tail of antibody complex and releases toxin granules such as perforin.
Holes are opened in the cell and enzymes such as grantees and granulysisn enter the cell and cause apoptotic death.
In the non-cytotoxic mechanism of type 2 hypersensitivity, how is hypersensitivity caused?
Cell death does not occur but oral cellular functioning is affected.
What is affected in the type 2 hypersensitivity reaction to cause Myaesthenia Gravis?
Acetylcholine Ab receptors affected.
What is affected in the type 2 hypersensitivity reaction to cause Glomerulonephritis ?
Anti-glomerular basement membrane is affected.
What is affected in the type 2 hypersensitivity reaction to cause Pemphigus Vulgaris.
Antibody is cemented to epithelial cells.
How is type 2 hypersensitivity treated?
Immunosuppressants.
Plasma exchange.
Splenectomy.
IV globulin.
Why are spleens often enlarged in people with type 2 hypersensitivity?
They are filled with immune debris.
What mediates type 3 immune complexes ?
Immune complexes.
What cells cause type 4 hypersensitivity?
CD8+ and CD4+ T cells
How does immune pathology occur?
- Macrophages / Eosinophil/ CLT activation.
- Th1 release cytokines which cause inflammation and tissue damage. This an be chronic if persistent.
- Days after exposure.
- Memory Th1 against delayed-type hypersensitivity antigens made by dendritic cells in sensitisation activates macrophages.
- Secondary contact causes Th1 memory cells to be activated and produce IFN-g, TNFs, IL2, Chemokine and GM-CSF.
What is the purpose of TNFs in immune pathology?
inflammation
What is the purpose of IL2 in immune pathology?
Activates cytotoxic T lymphocytes
What is the purpose of Cytokines in immune pathology?
Macrophage recruitment
What is the purpose of GM-CSF in immune pathology?
Monocyte and macrophage increased numbers
What type of hypersensitivity reaction causes dermatitis?
4
What causes type 4 hyper-sensitisation sensitisation?
Memory Th1 cells against DTH antigens are generated by dendritic cells. These Th1 cells activate macrophages and trigger an inflammatory response
What type of hyper sensitisation reaction is type 4 ?
Delayed
Give some Delayed Hypersensitivity responses
Chronic graft rejection Coeliac disease Contact hypersensitivity Tuberculosis Asthma Rhinitis Eczema
What are the 3 types of delayed hypersensitivity reaction?
Th1
Cytotoxic
Th2
What are the different mechanisms of delayed hypersensitivey reaction?
Transient / persistent Ag
T-cell activation of macrophages
How is anaphylactic shock investigated and diagnosed?
Skin prick test
RAST
Total IgE
Lung function checking
How is Anaphylaxis treated?
EpiPen kit
Immunotherapy
How does an EpiPen work to treat anaphylaxis?
Shuts down immune responses instantly.
What is the main cause of a lot of the events in anaphylaxis?
Tryptase
Wha is the purpose of in vitro blood testing?
Serological test for the determination of total IgE and allergen specific IgE.
What are the 1st generation serology tests?
Radioimmunoassay
PRIST
RAST
Why are 1st generation serology tests not used anymore?
Risks with radioactive sources and issues with disposing of these.
What are second generation serology tests?
Development of PRIST and RAST:
Florescent assay on a solid phase matrix.
What solid phase matrix is used in second generation serology testing?
Cellulose sponge
Outline how a 2nd generation serology test is done.
A balance mixture of relevant inhalant antigens are coupled with an immunoCAP. This reacts with the specific IgE in the patient serum sample.
After washing away non-specific IgE enzyme-labelled antibodies against IgE are added to form a complex.
After incubation, unbound enzyme-labelled anti-IgE is washed away and the bound complex is then incubated with a developing agent.
After stopping the reaction, the fluorescence of the eluate is measure. The response of a serum sample is compared to the response of the reference serum.
What are the benefits of 2nd generation serology tests ?
Useful for identifying atopic sensitisation, especially at a young age.
The CAP contains allergens to egg, milk, fish, wheat, soy and peanut.
Can use more than one type of allergen which is highly effective.
Qualitative tests are reported as positive or negative.
What are 3rd generation serology tests?
Fully automated systems that are very specific and sensitive. They have new calibration schemes.
what type of results do 3rd generation serology tests give?
Quantitative
What are the benefits of 3rd generation serology tests over 2nd?
Faster
Greater range of allergen specificities.
More accurate.
How does an allergen induced mediator release assay wok?
Allergen cross linking of IgE on the surface of basophils induces the release of mediators; Histamine release assay and LTC4 assay.
Heparinised whole body is incubated with increasing concentrations of anti-IgE or allergen. Following the stimuli, supernatants are collected and assayed for level of mediator release.
How do basophil activation assays work?
?Flow cytometry is used to detect externally expressed CD63 on the surface of activated basophils.
How is serum tryptase used to indicate allergies?
Tryptase is contained within the mast cells. Mast cells degranulate upon hypersensitivity reaction. The plasma tryptase concentration reflects the clinical severity of the reaction and the reaction mechanism. Enzyme immunoassay is used to detect Tryptase
What is a skin prick test and why is it carried out?
Allergen is introduced into the epidermis of the skin by a small lancet. If the patient has specific IgE to that antigen, it will induce mast cell degranulation.
If there is a positive result, there will be a flare up at the site after 15 minutes.
What are the positives of carrying out a skin prick test?
Quick
Easy to perform
Easy to control
How are intradermal tests used to detect allergies?
A small amount of allergen is injected under the skin.
After 15 minutes signs of reaction will appear.
What are the positives of intradermal testing for an allergy?
More sensitive than a skin prick test.
What are the negatives of intradermal testing of an allergy?
Can only test for one allergy.
What is patch testing used for?
To detect T cell responses to an allergen.
How does a patch test cause an allergic response.
Putting antigen on the skin which promotes the Langerhans cells to migrate to the local draining lymph node to present to antigen-specific T cells. Clonal expansion will then be caused and T cells will return to the site of antigen presentation.
What are the indications for a patch test to be carried out?
Eczema where contact allergy suspected.
Chronic hand or foot eczema.
Eczema failing to respond to a treatment.
Perineal inflammation.
Why is oral allergy syndrome not carried out frequently?
Can trigger an anaphylactic shock.
What is pollen-food allergy syndrome?
One allergy which causes another. A type of pollen allergy causes a food allergy for e.g.
What causes difference in the prevalence of food contact hypersensitivity syndrome?
Type of sensitisation and cross-reactivity patterns.
Different geographical locations.
Name some cross-reactive allergens.
Profilins
Allegerns homologis to pathogenesis.
Lipid transfer proteins.
What does birch-pollen have a cross allergen reactivity with?
Apple Cherry Pear Celery Carrot
How is oral allergy syndrome diagnosed?
In Vitro slgE testing.
In vitro SPT or nasal provocation tests.
How can you confirm sensitisation to plant foods in question in terms of cross allergies?
Prick to prick procedure or oral food challenges.
How are oral allergy syndromes managed?
Avoid relevant foods.
Specific immunotherapy to pollen allergens.
Tolerate cooked foods.
Anti-histamines
When may tolerating cooked foods not be appropriate for oral allergy syndrome patients?
If patients have systemic reactions or exacerbations of angioedema.
How do anti-histamines work against oral allergy syndromes?
They can reduce symptoms but no resolves the issue and should not be taken prior to food intake. They can sometimes make the systemic reaction worse which is dangerous.
What are symptoms of oral allergy syndrome?
- Pruritis
- Erythema
- Angioedema of the lips, lips or soft pallette after contact on the oral cavity with plant derived foods.
What is Prutitis?
Pruritus or itch is defined as an unpleasant sensation of the skin that provokes the urge to scratch.
When do oral allergy syndrome symptoms occur?
During or shortly after eating raw or uncooked pollen-related foods.
How does cooking foods reduce oral-allergy syndrome symptoms?
Thermal processing and exposure to GI proteases denatures allergens tertiary structure an abolishes their IgE binding capacity.
