Allergy and Hypersensitivity Reactions export

What is a hypersensitivity reaction?

a state of altered reactivity in which the body reacts with an exaggerated immune repose to a foreign agent

What type of immune reactions are classified as hypersensitivity reactions?

inappropriate immune reactions classified as type I, II, III and IV reactions; these lead to inflammation and tissue destruction

What is a type I hypersensitivity reaction based in the Gell and Coomb's classification?

IgE-mediated reaction

most common hypersensitivity reaction

When do type I hypersensitivity reactions occur?

occurs rapidly in response to allergen (= antigen) so sometimes called 'immediate hypersensitivity'

What causes the pathological effects of type I hypersensitivity reactions?

caused by release fo inflammatory mediators (e.g. histamine) from mast cells and basophils

What are allergens?

innocuous antigens that initiate an unwanted IgE-mediated reaction

What are some inhaled materials that are allergens?

plant pollens

dander of domesticated animals

mols spores

faeces of very small animals (e.g. house dust mites)

What are some injected materials that are allergens?

insect venoms

vaccines drugs

therapeutic proteins

What are some ingested materials that are allergens?

food

orally administered drugs

What are some contacted materials that are allergens?

plant leaves

industrial products made from plants

synthetic chemicals in industrial products

metals

What do the pathological consequences of allergens depend upon?

route of entry of allergen

response can vary from mild irritation to severe life-threatening reactions

What are the different responses that occur from allergens?

systemic anaphylaxis

wheal and flare

allergic rhinitis

bronchial asthma

food allergy

What are some common allergens that causes systemic anaphylaxis?

drugs

serum

venom

peanuts

What is the route of entry for allergens in systemic anaphylaxis?

IV (either directly or following rapid absorption)

What is the response that occurs due to systemic anaphylaxis?

oedema

increased vascular permeability

tracheal occlusion

circulatory collapse

death

What are some common allergens that cause wheal and flare?

insect bites

allergy testing

What is the route of entry for allergens that cause wheal and flare?

subcutaneous

What is the response that occurs due to wheal and flare?

local increase in blood flow and vascular permeability

What are the common allergens that cause allergic rhinitis?

pollens

dust-mite faeces

What is the route of entry for allergens that cause allergic rhinitis?

inhaled

What is the response that occurs due to allergic rhinitis?

oedema of nasal mucosa

irritation of nasal mucosa

What are the common allergens that cause bronchial asthma?

pollens

dust-mite faeces

What is the route of entry for allergens that cause bronchial asthma?

inhaled

What is the response that occurs due to bronchial asthma?

bronchial constriction

increased mucosa production

airway inflammation

What are the common allergens that cause food allergy?

shellfish

milk

eggs

fish

wheat

What is the route of entry for allergens that cause food allergy?

oral

What is the response that occurs due to food allergy?

vomiting

diarrhoea

pruritus (= itching)

urticaria (= hives)

anaphylaxis

What parasites are IgE evolved to rid the body of?

metazoan parasites (e.g. ascaris, schistosoma)

Why have IgE evolved to rid the body of metazoan parasites?

as conventional effector immune functions are inadequate

How do IgE repsond to parasite antigens?

they 'arm' mast cells, eosinophils and basophils atoms respond to parasite antigens by binding high affinity Fc receptors

What is the role of IgE in type I reactions?

1) IgE-producing B cells are activated during sensitisation (= first exposure)

2) IgE binds to Fc receptor on mast cells or CD63 on basophils

3) IgE recognises allergen and neck exposure binds rapidly and causes immediate degranulation (= elicitation)

What is the course of a type I hypersensitivity reaction?

allergic reactions consist of immediate reaction followed hours later by late phase response

What is the immediate phase in a type I hypersensitivity reaction?

caused by direct effect of mast cell degranulation

What is the late phase in a type I hypersensitivity reaction?

caused by the continuous mediator production

vascular changes leading to oedema and immune cell recruitment

What are some examples of type I hypersensitivity reactions?

atopic eczema (dermatitis)

urticaria (hives)

systemic anaphylaxis

What is atopic eczema?

type I hypersensitivity reaction with an unknown aetiolgoy

has genetic predisposition (= atopic) and can accompany range of other allergies

What are some allergens that can cause atopic eczema?

soaps and detergents

house dust-mites

pet fur

pollen

bacterial and fungal antigens

What does the allergen have to pass through to cause atopic eczema?

has to pass through physical barrier of epidermis

What is a predisposing factor that can affect how allergens cause atopic eczema?

mutations in the genes maintaining barrier function

What is a common symptom of atopic eczema?

pruritus which facilitates allergens breach of epithelial barrier

What is the pathogenesis of atopic eczema affected by?

conditions which affect barrier function

e.g. cold and dry weather, dampness, stress, sweating, hormonal changes

What is urticaria?

presents differently to eczema with red, swollen itchy wheals (=hives)

self-limiting condition that usually settle down within a few mins to a few days

What are some allergens that cause urticaria?

pollen and plants

chemical

latex

insect bites and stings

some medications

What is acute urticaria?

when the rash clears completely within 6 weeks

What is chronic urticaria?

may not be an allergy but signs of autoimmune condition

What is systemic anaphylaxis?

caused by allergens that reach the bloodstream and activate mast cells throughout the body

What is anaphylactic shock in terms of cells?

mass degranulation

What are the 3 potentially fatal reactions associated with systemic anaphylaxis?

1) laryngeal oedema --> suffocation

2) bronchiole constriction --> suffocation

3) peripheral oedema --> hypotension and heart attack

Why does penicillin have the potential to cause anaphylaxis?

in some individuals, penicillin-peptide complexes initiate an IgE response that has the potential to cause anaphylaxis

How can penicillin bind with peptide to form the complexes that induce anaphylaxis in some individuals?

beta lactam ring in penicillin can react with amino groups on proteins therefore attaching to carrier proteins (= hapten)

What different tests can be done to test for allergies?

skin prick test

blood test

patch test

food challenge

What is a skin prick test?

first test to be done when looking for an allergen; results within 20 mins

is when the skin is trucked with a tiny amount of the suspected allergen

the skin around the prick will become itchy, red and a wheal will appear

What is a blood test when looking for a suspected allergy?

specific IgE test that measures blood IgE levels in response to allergen

What is a patch test when looking for a suspected allergy?

tests a skin reaction is due to contact with specific allergen

small amount of allergen added to metal discs taped to skin for 20 mins and reactions monitored

What is the food challenge when looking for a suspected allergy?

diagnose food allergy by subject gradually given increasing amounts of the suspected food to which they are allergic to and their reason monitored

has to be conducted in an ITU setting due to danger to pt.

can only test one food at each appointment

What are the different treatments for type I hypersensitivity reactions?

drugs

immunological treatment

What are some classes of drugs that can be used to treat type I hypersensitivity reactions?

antihistamines (= compete with histamine for receptors)

hydrocortisone (= block histamine synthesis)

cromoglycate (= stabilises mast cells and stops histamine release)

epinephrine (= best immediate treatment for anaphylactic shock to reverse effects of mast cell granules, short duration)

When should epinephrine be used?

before calling 999

in anaphylaxis cases a biphasic effect in 4-20% of cases

What is the biphasic response that occurs?

1) recurrences several hours after resolution of the initial symptoms

2) observe pt. for up to 12hrs after apparent recovery from initial episode

What occurs when epinephrine stimulates adrenoreceptors?

increases peripheral vascular resistance

improves BP and coronary perfusion

reduces angioedema

causes bronchodilation

increases intracellular cAMP in mast cells and reduced release of inflammatory mediators

What are type II hypersensitivity reactions according to Gell and Coomb's classification?

non-IgE mediated (cytotoxic) reactions that involve activation of complement by IgE or IgM binding to antigenic cell (= cell surface antigens)

What makes type II hypersensitivity reactions cytotoxic reactions?

cell is lysed by:

1) membrane attack complex formation --> complement

2) Ig-dependent cell mediated toxicity --> NK cells

What are some examples of conditions where it is type II antibodies abasing cell-surface or matrix antigens?

autoimmune haemolytic anaemia

autoimmune thrombocytopenic purpura

goodpasture's syndrome

pemphigus vulgaris

acute rheumatic fever

What autoantigen causes autoimmune haemolytic anaemia?

Rh blood group antigens, I antigen

What us the consequence of autoimmune haemolytic anaemia?

destruction of RBCs by complement and FcR+ phagocytes causing anaemia

What else can causes haemolytic anaemia?

autoimmune haemolytic anaemia

blood group incompatibility

penicillin

What is the autoantigen that causes autoimmune thrombocytopenic purpura?

platelet integrin GpIIIn:IIIa

What is the response to the autoantigen that causes autoimmune thrombocytopenic purpura?

abnormal bleeding

What is the autoantigen that causes Goodpasture's Syndrome?

non-collagenous domain of basement membrane collagen type IV

What is the response caused by the autoantigen that causes Goodpasture's Syndrome?

glomerulonephritis

pulmonary haemorrhage

What is the autoantigen that causes pemphigus vulgaris?

epidermal catherin

What is the response to the autoantigen that causes pemphigus vulgaris?

blistering of the skin

What is the autoantigen that causes acute rheumatic fever?

streptococcal cell-wall antigens

antibodies cross-react with cardiac muscle

What is the response to the autoantigen that causes acute rheumatic fever?

arthritis

myocarditis

late scarring of heart valves

What are type III hypersensitivity reactions according to the Gell and Coomb's classification?

non-IgE mediated (immune comple) reactions

What antibodies are mainly involved in type III hypersensitivity reactions?

involve mainly IgG responses

What is the pathogenesis of type III hypersensitivity reactions characterised by?

the formation of immune complexes (= antigen-antibody aggregates)

involves reactions against soluble antigens circulating in the serum

What can the immune complexes cause in type III hypersensitivity reactions?

can activate complement

can activate macrophages

resulting in inflammatory response leading to tissue injury

What are some examples of type III hypersensitivity reactions?

serum sickness

Arthus reaction

oral erythema multiforme (EM)

What are some examples of type III immune complex diseases?

mixed essential cryoglobulinemia

rheumatoid arhritis

What autoantigen causes mixed essential cryoglobulinaemia?

rheumatoid factor IgG complexes (with or without hepatitis C antigen)

What is the response caused by the autoantigen responsible for mixed essential cryoglobulinemia?

systemic vasculitis

What is the autoantigen that causes rheumatoid arthritis and the response it causes?

rheumatoid factpr IgG complexes

causes arthritis

What is Arthus reaction?

antigen-antibody (IgG) complexes deposited in localised tissues (low levels locally) therefore causing localised vasculitis response

intradermal injection of antigen (= insect bite) or vaccination

What happens in the immune system when an Arthus reaction is triggered?

complement activation and mast cell sensitisation via Fc receptors

activates phagocytes and localised inflammatory response which can cause blood vessel occlusion due to accumulation of platelets

What is serum sickness?

a systemic Arthus reaction due to large quantities of injected antigen (e.g. injected foreign serum proteins)

What are the symptoms of serum sickness?

vasculitis

rash

fever

joint swelling/pain

What causes the symptoms of serum sickness?

antigen-antibody complexes circulars and lodge in many different tissues

What is the disease onset of serum sickness characterised by?

initial increase in Ig against foreign serum proteins

leads to immune complex formation and deposition in tissues

Why is serum sickness a self-limiting disease?

as complexes can be cleared

What drug can cause a serum sickness reaction?

penicillin

What is oral erythema mutliforme?

crusty blistering of oral mucosa caused by deposition of immune complexes (IgM) in the microvasculature of the oral mucous membrane

What else can cause oral erythema multiforme other than deposition of immune complexes?

hypersensitivity to drugs

What drugs can cause hypersensitivity leading to oral erythema multiforme?

co-trimoxazole is used to treat UTIs or lower RTIs; adverse reactions occur in ~1-3% of population

What are type IV hypersensitivity reactions according to the Gell and Coomb's classification?

non-IgE mediated (cell mediated) reactions directed by pro-inflammatory mediators release by antigen-specific T cells

What are some examples of type IV hypersensitivity reactions?

T1DM

RA

MS

Crohn's Disease

psoriasis

What is the autoantigen that causes T1DM and the response it causes?

pancreatic beta-cell antigen that causes beta-cell destruction

What is the autoantigen that causes RA and the response it causes?

unknown synovial joint antigen that causes joint inflammation and destruction

What are the autoantigen that causes MS and the response it causes?

myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein

causes brain invasion by CD4 T cells, muscle weakness, and other neurological symptoms

What is the autoantigen that causes Crohn's disease and the response it causes?

antigens of intestinal microbiota that cause regional intestinal inflammation and scarring