Allergy

Question 1

What is type 1 hypersensitivity?

Answer 1

IgE-mediated mast cell degranulation. Implicated in asthma, eczema and hayfever; common allergies. Basophils are also implicated.

Question 2

What is allergy marching?

Answer 2

When a single allergy arises, other types of allergies arise. Generally allergies develop early in life and can persist.

Question 3

What is the main antibody implicated in T1H?

Answer 3

IgE; least dominant antibody in circulation (100ng/ml) useful against parasitic worm infections.

Question 4

How is IgE half life extended?

Answer 4

It is protected by proteolytic degradation when bound to mast cells. Hyper-IgE syndrome (rare - primary immunodeficiency) with defective IFNgamma production, therefore increases IL-4

Question 5

How is class switching to IgE mediated?

Answer 5

by IL-4 and IL-13 from Th2 cells inhibited by IGN gamma from Th1 cells.

Question 6

Why can IgE bind to mast/ basophils?

Answer 6

They have high affinity Fc(epsilon) receptor; allergen (antigen) bounds to fab, Fac bound to FcR; cross linking between FcR. This causes degranulation of mast cells and basophils; releasing inflammatory mediators; histamine serotonin from stored granules. Also causes synthesis of TNFalpha, protaglandins and leukotrienes.

Question 7

What is a major cause of allergies?

Answer 7

Dermatophagoides pteryonyssinusm; house dust mite whose faeces are allergenic

Question 8

How are allergies diagnosed?

Answer 8

History is taken and skin patch test however a positive response does not mean allergic.

Question 9

Describe an allergy response.

Answer 9

An immediate IgE-mediated response over 1 hour, frequently followed by late phase response occurring 5-12 hours later associated with infiltration by CD4 helper T cell, monocytes and eosinophils.

Question 10

What is the most common chronic disease of children in the West?

Answer 10

Asthma; 2000 deaths/ year in UK. Multifactorial disease; IgE genes and production, and environment.

Question 11

What is the aetiology of allergies?

Answer 11

Thought to be caused by early contact to allergen in the first four months in genetically predisposed infants. May be caused by exposure prior to adequate levels of mucosal IgA. Disruption of mucosal surface barrier.

Question 12

What are the treatments of allergies?

Answer 12

Allergen avoidance,
Pharmacotherapy (corticosteroids, to suppress transcription of proinflammatory genes. Sodium chromoglycate can also be used which blocks mediator release from mast cells. Anti-histamines used. Montelukast; leukotriene receptor antagonist.
Immunotherapy: repeated dose allergen injection or sublingual (SLIT = sublingual immunotherapy. Omalizumab - anti-IgE mAb, decreases igE and Fc(epsilon) receptor inhibtor, a monoclonal antibody

Question 13

What are Type II hypersensitivities?

Answer 13

Cytotoxic antibody against cell surface antigens implicated in haemolytic disease of the foetus and newborn (erythroblastosis foetalis)
Transfusion reactions
Transplant rejection
Characterised by ADCC

Question 14

What is the fundamental principle of haemolytic disease of the newborn?

Answer 14

ADCC

Question 15

What are type III hypersensitivities?

Answer 15

Immune complex mediated; SLE, post-streptococcal glomerular nephritis, serum sickness. Results in inflammatory response; complement activation.

Question 16

What is glomerular nephritis?

Answer 16

anti-nuclear antibodies which get trapped in glomeruli

Question 17

What is serum sickness?

Answer 17

Injection of foreign proteins; snake anti-venom which has been cultured in another mammalian species such as the horse.

Question 18

What are type IV hypersensitivities?

Answer 18

They are fundamentally different to the other three types; they have delayed type T cell mediated. such as tuberculin skin reaction to mycobacterial antigens and contact dermatitis to nickel or poison ivy.

Question 19

How are type IV mediated?

Answer 19

Sensitisation of T cells producing cytokines activating macrophages, differentiate into epithelioid cell, macrophages can fuse together and fuse Giant cells; granuloma in organ tissues.

Question 20

Do innate hypersensitivity reactions exist?

Answer 20

Yes; overzealous innate responses. Can be caused by infections with S. aureus or S. pyogenes which can provoke toxic shock syndrome; excessive release of TNF, IL-1 and IL-6.
Acute respiratory distress syndome associated with G-ve bacteria; LPS provokes massive invasion of the lung by neutrophils.