Allergy And The Mechanisms Of Hypersentivity

Question 1

What is hyposensatvity?

Answer 1

An inappropriate immune response to non-infectious antigens that results in tissue damage and disease

Question 2

What are the four type of hypersensitivity?

Answer 2

Type 1- immediate hypersensitivity

Type 2 - cytotoxic hypersensitivity

Type 3 - serum. Sickness and Arthur’s reaction

Type 4 - 44delayed-type hypersensitivity, contact dermatitis

Question 3

What occurs in type 1 hypersensitivity (allergy)?

Answer 3

A immune reactant - IgE

Antigen - soluble antigen, eg. Allergen

Effector mechanism - mast cell activation and degranulation causing inflammation

Question 4

What are some examples of type 1 hypersensitivity?

Answer 4

Allergic rhinitis

Asthma

Anaphylaxis

Question 5

What is the prick test?

Answer 5

Test the allergic reaction by injection of antigen

And seeing what the immune response reacts to

Question 6

Wat is systemic anaphylaxis?

Answer 6

A progressive inflammation

Severe loss of function

Progressive anaphylactic shock

Question 7

What occurs in type 2 hypersenstivity?

Answer 7

Penicillin modifies rote is on human erythrocytes to create foreign epitopes - new areas antibodies can bind too.

Immune reactant - igG or anti drug antibodies directed at cell surface receptors

Antigen - drug ingested or a modified internal protein

Effector mechanism - antibody bound cells are cleared by complement + ffcgR+ cells such as macrophages - uncontrollable activation or blocking receptor function

Question 8

What are some examples of type 2 hypersensitivity?

Answer 8

Some drug allergies

• eg. Penicillin,
• eg. Graves’ disease ,
• eg. myasthenia gravis (antibodies block or destroy nicotinic acetylcholine receptors at the junction between the nerve and muscle
• eg haemolytic disease of newborn

Question 9

How can haemolytic disease of newborn occur?

Answer 9

1. During fetal erythrocytes leak into maternal blood father breakage of the embryonic chorion
2. Maternal B cells are activated by the Rh antigen an produce a large amount of antibodies
3. Rh antibody titer in mothers blood is elevated after first exposure
4. Rh antibodies are small enough to cross the embryonic chorion and attack the fetal erythrocytes

Question 10

What occurs in type 3 hypersensitivity (serum sickness)?

Answer 10

Immune reactant - igG

Antigen - soluble antigen

Effector mechanism - igG and soluble antigen form immune complexes, which are cleared by phagocytosis

Question 11

What are examples of type 3 hypersensitivity?

Answer 11

Arthur’s reaction following tetanus vaccination

Serum sickness

Farmers lung

Question 12

What occurs during Arthur’s reaction?

Answer 12

1. Local immune complex formation causes Activate mast cells to release inflammatory mediators
2. Inflammatory cells invade the site and blood vessels permeability and blood flow are increased
3. Platelets also accumulate, leading to occlusion of the small blood vessels, haemorrhage, and the appearance of purpura

Question 13

What is serum sickness?

Answer 13

Caused by large doses of soluble antigens (drugs)

IgG antibodies produced from small immune complexes with the antigen in excess

Immune complexes deposited in tissues

Tissue damage is caused by complement activation an the subsequent inflammatory responses

Question 14

What determines the pathology of type 3 hypersenstivity?

Answer 14

Antigen dose and route of delivery

Question 15

What occurs in type 4 hypersenstivity (delayed type)?

Answer 15

Immune reactant - Th1, Th2 (antigen specific)

Antigen - soluble antigen

Effector mechanism - eosinophil activation (Th2), macrophage activation (Th1)

Question 16

What are some examples of type 4 hypersensativity?

Answer 16

Tuberculin reaction

Allergic contact dermatitis

Question 17

Describe what happens in type 4 hypersenstivity

Answer 17

Antigen is injected into subcutaneous tissue and processed by local antigen presenting cells

Th1 effector cell recognises antigen and releases cytokines that act on vascular endothelium

Recruitment of phagocytes and plasm to site of antigen injection causes visible lesion

Question 18

What test s used to diagnose type 4 hypersensativity?

Answer 18

Mantoux test

Question 19

Define a allergy (type 1 hypersenstivity)

Answer 19

Disease following a response by the immune system to an otherwise innocuous antigen

Question 20

What is IgE?

Answer 20

First line f defence against worms

Bin FcR1 receptor on mast cells

Pre-arms mast cells to react when in the presence of antigen

Question 21

Describe the simple model of allergen specific IgE production

Answer 21

First exposure to pollen

IL-4 drives B cells to produce IgE in response to pollen antigens

Pollen specific IgE binds to mast cells

Question 22

What causes allergic sensitisation?

Answer 22

Exposure to allergen is critical

Role of pro-allergic dendritic cells and cytokines

Genetic predisposition to allergy

Question 23

What are features of inhaled allergen that may promote the priming of Th2 cels that drive IgE responses?

Answer 23

Protein

Enymatically active

Low dose

Low molecular weight

Highly soluble - readily elated from particle

Stable - allergen can survive in desiccated particle

Contains peptides that bind host MHC class 2 - required for T cell priming

Question 24

What makes a dendritic cell pro-allergic?

Answer 24

Not known

One candidate protein is RSLP - may switch DC to pro-allergic state

Question 25

What is the role of filaggrin in allergens?

Answer 25

Flaggrin links skin integrity and allergy Defective atopic dermatitis is greater and there are no flaggrin granules

Question 26

What is the structure of a resting mast cell?

Answer 26

Contains granules containing histamine and other inflammatory mediators

Question 27

What is the structure of a activated mast cell?

Answer 27

Multivalent antigen cross-inks bound IgE antibody, causing release of granule continents

Question 28

What mediates thee early and late phases of the allergic response?

Answer 28

Early educated by mast cells Late response educated by T cells

Question 29

What occurs during the acute allergic response?

Answer 29

Primary allergen exposure occurs and causes IgE production After second exposure

Question 30

What occurs during the chronic allergic reaction?

Answer 30

Primary allergen exposure occurs and causes IgE production After second exposure

Question 31

What are the effector mediators produced by mast cells in the early phase?

Answer 31

Histamine - increase vascular permeability and cause smooth muscle contraction Leuktrienes - increase vascular permeability and cause smooth uncle contraction and stimulates mucus secretion Prostaglandins - chemoattractants for T cells eosinophils and basophils

Question 32

What are the effector educators produced by mast cells in the late phase?

Answer 32

Cytokines - IL-4, IL-13 - promotes Th2 and IgE - TNF-a - promotes. Tissue inflammation

Question 33

What is the effect of mast cell activation in the GI tract?

Answer 33

Increased fluid secretion, increased peristalsis Expulsion of GI tract contents

Question 34

What is the effect of mast cell activation in the airways?

Answer 34

Decreased diameter, increased mucus secretion Congestion and blockage of airways Swelling and mucus secretion in nasal passages

Question 35

What is the effect of mast cell activation in blood vessels?

Answer 35

Increased blood flow, increased permiability Increased permeability Increased fluid in tissues means more flow of lymph to lymph nodes Increased cells and proteins in tissues means Increased effector response in tissues

Question 36

What are eosinophils?

Answer 36

Located in tissues Recruited to sites of allergic reactions Express FceRI upon activation

Question 37

What are the 2 effector functions of eosinophils?

Answer 37

1. Release toxic granule proteins and free radicals upon activation to kill parasites and cause tissue damage in allergic reactions 2. Synthesis no release prostaglandins, leukotrienes and cytokines in order to amplify the inflammatory response by activating epithelial cells and recruiting leukocytes

Question 38

What cels cause chronic allergic inflammation?

Answer 38

Th2

Question 39

What does the late phase of the IgE mediated allergic response depend on?

Answer 39

Allergen dose Continued synthesis and release of inflammatory mediators

Question 40

What is asthma?

Answer 40

A state of reversible bronchial hyper-reactvity resulting from persistent inflammatory process in response to stimuli in a genetically susceptible individual

Question 41

What are examples of non-atopic asthma?

Answer 41

Occupational Excerise induced Nocturnal asthma Post-bronchiolitic wheeze

Question 42

What are the characteristics of allergic asthma?

Answer 42

Episodes of wheezy breathing Narrowing of airways Rapid changes in airway obstruction Severity varies

Question 43

what occurs in the acute response of allergic asthma?

Answer 43

Occurs within seconds of allergen exposure Results in airway obstruction and breathing difficulties Caused by allergen-induced mast cell degranulation in the submucosa of airways

Question 44

What occurs in the chronic is response of allergic asthma?

Answer 44

Chronic inflammation of airways Caused by activation of eosinophils, neutrophils, T cells and other leukocytes Mediators released by these cells cause airway remodelling, permanent narrowing of the airways and further tissue damage

Question 45

What is the treatment of allergy in the clinic?

Answer 45

Steroids - act directly on DNA to increase transcription of anti-inflammatory mediators and decrease transcription of pro-inflammatory mediators Broncholators - reverse acute effect of allergy on airways Immunotherapy - reverses the sensitisation to allergen by means of tolerating exposure Inhibit effects of mediators on specific receptors - anti histamine Inhibit mast cell degranulation - mast cell stabiliser Inhibit synthesis of specific mediations - lypoxygenase inhibitors