IV - Type II, III, IV Hypersensitivity Disorders Flashcards
Breifly describe the key features of Type II hypersensitivity.
Antibodies produced by the cell immune response bind to antigens on the patient’s own cell surfaces.
Briefly describe the pathophysiology of Type II hypersensitivity reactions.
IgG and IgM antibody bind to a cell surface antigen, resulting in activation of complement, causing cell lysis and opsonisation (antibody mediated phagocytosis).
What are the four key roles of complement in the immune system?
- Complement punches holes in bacterial membranes, causing DIRECT KILLING of encapsulated bacteria.
- CHEMOTAXIS - stimulates migration of macrophages and neutrophils to the site of inflammation.
- OPSONISATION - enhances phagocytosis by macrophages and neutrophils.
- SOLUBILISATION - of immune complexes.
Discuss transfusion reactions with respect to type II hypersensitivity.
Pathophysiology
Symptoms
Target = donor red cells.
Anti-blood group antibodies bind to the surface of circulating donor erythrocytes.
This forms and antigen - antibody complex, which activated complement and stimulated phagocytosis.
Symptoms may begin after only 1ml transfusion and include: pyrexia & rigors; tachycardia & tachypnoea; hypotension & dizziness; headaches; may be fatal.
Give examples of type II hypersensitivity reactions in the following systems: Kidney Nervous system Endocrine system Skin
Kidney - Goodpasture’s syndrome - antibodies bind to glomerular basement membrane.
Nervous - Guillain barre syndrome - antibodies bind to peripheral glycoprotein
Endocrine - Graves disease - antibodies bind to TSH receptor
Skin - Pemphigus vulgaris - antibodies bind to epithelial cement
How could you prove that the disease is mediated by autoantibodies?
Demonstrate that serum causes disease when transferred into another host. Diseases which may be transferred to the neonate: myasthenia gravis, idiopathic thrombocytopaenic purpura, Rhesus disease.
Describe the two options for management of Type II hypersensitivity.
- Plasmepheresis - plasma is removed from the blood and replaced with that of a donor with the aim of removing the pathogenic antibody.
However, rebound antibody production limits efficacy of plasmapheresis. - Immunosuppression - patient is given an immunosuppressive agent which switches off B cell production of the antibody.
Describe Type III hypersensitivity.
Circulating antigens and autoantibodies join together to form immune complexes, which are deposited into the small vessels, resulting in complement activation. This causes infiltrates of macrophages and neutrophils.
Give examples of local Type III hypersensitivity.
Farmer’s lung - inhaled fungal particles stimulate response.
Bird fancier’s lung.
Malt worker’s lung.
Cheese worker’s lung.
Describe acute hypersensitivity pneumonitis.
Pathophysiology
Symptoms
Immune complexes are deposited in the walls of the alveoli and bronchioles. This causes wheezing and malaise after 4-8 hours of exposure to antigen.
Describe systemic lupus erythematosus.
Pathophysiology
Diagnosis
Management
SYSTEMIC type III hypersensitivity.
Antibodies are produced against the contents of the cell nuclei and form immune complexes which are deposited in small vessels in the skin, joints & kidneys.
Symptoms - fever, renal impairment, vasculitis skin rash, arthralgias.
Diagnosis is specific IgG to putative antigen e.g. anti-DNA binding antibodies in SLE.
Management - avoidance; corticosteroids (decrease inflammation); immunosuppression (decrease production of antibody).
Describe type IV hypersensitivity - delayed Type Hypersensitivity.
Pathophgysiology
T CELL MEDIATED HYPERSENSITIVITY.
Initial sensitisation to antigen generated “primed” T cells, and subsequent exposure activates these.
There is recruitment of macrophages, other lymphocytes, and neutrophils. .
CD4+ cels orchestrate the response and form granulomas; CD8+ cells mediate direct killing.
Give examples of AUTOIMMUNE diseases associated with Type IV hypersensitivity reactions.
Type 1 diabetes
Psoriasis
Rheumatoid arthritis
Give examples of NON-AUTOIMMUNE diseases associated with Type IV hypersensitivity reactions.
Nickel hypersensitivity Tuberculosis Leprosy Sarcoidosis Cellular rejection of solid organ transplant
Describe Sarcoidosis Brief description What organs does it affect? Aetiology? Pathophysiology? Management?
A rare condition that causes small patches of rad and swollen tissue , called granulomas to develop in the organs of the body. It usually affects the lungs and skin.
It has an unknown aetiology.
Underlying pathophysiology is Type IV delayed hypersensitivity response to unknown antigen.
Management is watchful waiting; NSAIDS for acute onset of disease; systemic corticosteroids to block T cell & macrophage activation.
