Overview of immunological diseases Flashcards
Immune system may fail to control infection
Pathogen factors (evasion mechanisms)
Host factors (immunodeficiency)
Immune system may cause disease directly
Failure of tolerance (e.g. allergy/ autoimmunity)
Immune system inappropriately activated for unknown reasons (e.g. IBD) or for reasons known but poorly understood (e.g. asbestosis or cigarette smoke)
Gell and Coombes hypersensitivity reactions type 1-4
Classify immunologically mediated diseases
Refers to mechanisms of disease when the immune system is inappropriately activated
Type 1
Mechanism: IgE . antibody directed against allergen triggers mast cell degranulation
e.g. seasonal rhinitis, cat allergy
Type 2
Mechanism: a pathogenic antibody directly causes diseases
e.g. autoimmune haemolysis
Type 3
Mechanism: antibody antigen complex mediated disease
e.g. serum sickness, systemic lupus, erythematosis
Type 4
Mechanism: inflammation directly mediated by T cells
e.g. contact dermatitis, tuberculin reaction
Type 1 hypersensitivity: IgE mediated allergy
B cells class switch to IgE antibody, secreted IgE is picked up by tissue mast cells and circulating basophils
Cross linking of allergen specific IgE antibodies by allergen activates the mast cell
Mast cell rapidly degranulates releasing histamine, tryptase and other pre-formed mediators
Pharmacological effects of histamine lead to symptoms in the affected organ
In health, believed to assist with parasite immunity
Type 2 hypersensitivity: AB blood system and transfusion medicine
Refers to pathology directly mediated by antibodies
Mismatch blood transfusion reactions are an example
IgM antibodies against AB antigens develop during first year of life
Antibodies are an example of isoantibodies
Type 2 hypersensitivity: haemolytic disease of the newborn
Major blood group system is ABO
D antigen (rhesus) us a secondary classification
Majority of the population are D+
Mother may be sensitised by exposure to fetal red cells during pregnancy
- parturition
- trauma
Antibodies may cause disease in subsequent pregnancies
Haemolytic disease of the newborn
Autoimmune haemolysis highly deleterious to fetus
- growth retardation, CV failure, hydrops fetalis, neurotoxicity from high bilirubin levels
Rhesus negative mothers with rhesus + partner are given anti-D IgG during pregnancy
Binds to fetal red cells entering circulation, fetal red cells then desstroyed, preventing sensitisation
Risk of maternal sensitisation reduced from 16% to 0.1%
Type 3 hypersensitivity
Describes disease caused by complexes of antibody and antigen
Such complexes area a normal phenomenon
- usually soluble, removed in spleen
In some situations they become insoluble and cause disease
- large quantity of antigen
- large quantity of antibody
- interaction between the two is very strong
- complexes are of the correct size
Local immune complex disease
Painful lesions in the fingertip pulp due to deposition of circulating immune complexes
May be seen in infective endocarditis
May be seen in other diseases with immune complex deposition
Type 3 hypersensitivity: serum sickness
A generalised transient immune complex mediated syndrome
Mainly results from injection of certain immunogenic drugs or anti-sera produced in animals e.g. after snake evenomation
- rash
- fever
- arthritis
- glomerulonephritis
Type 3 hypersensitivity: hypersensitivity pneumonitis
Extrinsic allergic alveolitis
Patient becomes sensitised to an environmental antigen by repeated exposure, producing large quantities of IgG antibodies
Immune complexes form in the lung upon re-exposure causing shortness of breath and cough
- mould spores in hay
- pigeon feathers and stool
Initially transient, lung scarring with repeated exposure