Hypersensitivity Flashcards
Which type of hypersensitivity reaction is responsible for most allergic reactions?
Type I Hypersensitivity
Give five examples of clinical manifestations of type I hypersensitivity
Allergic rhinoconjunctivitis Asthma Eczema/urticaria Food allergy Anaphylaxis
What mediates type I hypersensitivity?
IgE antibodies
Also: mast cells, basophils, eosinophils, T-helper2 cells
Which type of hypersensitivity reaction is responsible for most tissue-specific cytotoxic reactions?
Type II Hypersensitivity
Give four examples of type II hypersensitivity reactions
Haemolytic reaction following blood transfusion (ABO, Rhesus incompatibility)
Haemolytic disease of the newborn
Hyperacute graft rejection
Organ-specific autoimmune disease
Give four autoimmune diseases that are caused by type II hypersensitivity reaction
Graves disease
Myasthenia gravis
Goodpasture’s syndrome
Pemphigus (skin blisters)
What mediates type II hypersensitivity reactions?
IgG or IgM antibodies
Which type of hypersensitivity reaction involves the abnormal deposition of formed antibody-antigen complexes in tissues?
Type III Hypersensitivity
Give six examples of diseases caused by type III hypersensitivity
Systemic Lupus Erythematosus
Serum sickness
Extrinsic allergic alveolitis (e.g. farmer’s lung)
Chronic infection (e.g. leprosy, malaria)
Post-strep glomerulonephritis
Tumours
What are the main mediators of type III hypersensitivity?
Antibodies
- immune complexes involving soluble antigens
Which type of hypersensitivity reaction takes at least 48 hours to manifest itself?
Type IV Hypersensitivity
- aka delayed hypersensitivity
Give five examples of diseases caused by type IV hypersensitivity
Mycobacteria infection (tuberculosis) Type 1 Diabetes Mellitus Multiple sclerosis Rheumatoid arthritis Contact dermatitis
What mediates type IV hypersensitivity?
T-helper cells Th1 and Th17
Also the cytokines secreted by Th cells
What type of antigens trigger type IV hypersensitivity reactions?
Haptens (low molecular weight agent)
+ Carrier (host protein that attaches to the hapten to provide sufficient antigenic bulk)
What are the three phases of a type I hypersensitivity reaction?
- sensitisation
2a. early phase response
2b. late phase response
Describe the sensitisation process in type I hypersensitivity
Phagocyte in periphery picks up an unrecognised allergen, becomes an APC and goes to the lymph node
Th2 cell in lymph node does not recognise the antigen
Th2 cell activated against the allergen and produces interleukins
IL-4 activates B-cells which produce IgE against the allergen
- IgE primes mast cells against the allergen
IL-5 activates eosinophils
Which mediators are involved in the response phases of type I hypersensitivity?
Early response: - preformed mast cell mediators (histamine, proteases) Late response: - newly synthesised mediators - Th2 cytokines - eosinophil mediators
Describe the pathophysiology of type II hypersensitivity
B-cells are pathologically self-reactive - produce IgG/IgM antibodies which bind to antigens on host cell surfaces
Antigen-antibody complex activates complement
Degranulation of neutrophils and formation of MAC cause cell lysis
What is the MAC?
Membrane Attack Complex
- forms transmembrane channels which disrupt the cell membrane of target cells, leading to cell lysis and death
Describe the pathophysiology of type III hypersensitivity
Excessive/abnormal immune complex formation (due to problems with the antigens and/or host response)
Complement activation and recruitment/activation of inflammatory cells by immune complexes
Inflammation causes tissue damage
What antigen and host-response factors contribute towards type III hypersensitivity?
Antigen
- chronic persistence of antigen
- abnormal Ag/Ab ration
- abnormal rate of Ag/Ab formation
Host response
- Antibody defects
- Complement defects
- Fc or phagocyte defects
How does the pathophysiology of type IV hypersensitivity differ to that of type I?
Different ligand bonds form during sensitisation
- CD28 and B7 ligand bonds form in type IV
T-helper1 cells involved in type IV, T-helper2 cells involved in type I
Type IV also involves cytotoxic T cells
How to Tc cells cause cell death in type IV hypersensitivity?
Release perforin which damages the cell surface
Describe the pathophysiology of type IV hypersensitivity
Macrophages become APCs and secrete IL-12, which stimulates the proliferation of further CD4+ Th1 cells.
CD4+ T cells secrete IL-2 and interferon gamma,
- IL-2 induces the further release of other Th1 cytokines
- IFN-gamma stimulates macrophages
How is type I hypersensitivity diagnosed?
History/examination
Skin-prick test
RAST test (IgE level)
Other lab tests
What are the treatment options for type I hypersensitivity?
Education and allergen avoidance Antihistamines Sodium cromoglycate Steroids Leukotriene antagonists Desensitisation immunoglobulins Adrenaline for anaphylaxis
How is type II hypersensitivity managed?
Prevention: - cross match blood - tissue typing - detection of RhD in pregnancy Immune suppression in autoimmune disease and transplant rejection
How is type III hypersensitivity diagnosed?
Clinical features
Tissue biopsy
Circulating immune complex tests
Precipitating antibody tests
What are the treatment options for type III hypersensitivity?
Antigen elimination (infection, tumour)
Removal of immune complexes
Immunosuppressive therapy
What are the management options for type IV hypersensitivity?
Prevention/avoidance of contact with allergen
Antimicrobial therapy (if required)
Anti-inflammatory drugs e.g. corticosteroids
Immunosuppressive drugs
Other immune modifiers e.g. monoclonal antibodies
Describe the pathophysiology of contact dermatitis
Type IV hypersensitivity reaction:
Haptens cross stratum corneum
Langerhans cells present to TH1 cells
TNF alfa and IL 1, 13 and 18 produced by TH1
LCs become differentiated Dendritic cells presenting allergenic epitope and multiply
More aggressive response 2nd time
