7 - Immunopathology Flashcards
Hypersensitivity
Inappropriate vigorous immune responses to antigens that pose little or no threat
Autoimmunity
Directed against self antigens
Immunodeficiency
Detected clinically by a history of recurrent infection with the same or similar pathogens, including opportunistic pathogens (low pathogenicity). May be primary (congenital) or secondary (acquired)
Type I hypersensitivity
- Allergies
- Mediated by IgE antibodies, with mast cell activation the major final effector
- Individual had to become sensitised to the allergen by producing IgE antibodies against it
- Subsequent exposure leads to symptoms
Type II hypersensitivity
Antibody-mediated destruction of cells by IgG and IgM antibodies through complement activation, Antibody-dependant cellular cytotoxicity (ADCC) and Opsonisation
Type III hypersensitivity
- Immune complexes are formed when antibody
binds with antigen and are usually removed by
macrophages after complement activation - Persisting immune complexes can be deposited
in blood vessels and in a range of tissues and
organs; and cause inflammation – vasculitis,
glomerulonephritis, arthritis
Type IV hypersensitivity
- Delayed type
- excessive T cell activation
- Hypersensitivity reactions are mediated by T cells (primarily Th1 subtypes, but also Th17 and CD8)
- Antigens are processed and presented to T cells by APCs (sensitization). This is followed by an effector phase upon re-exposure to the antigen
Symptoms of type I hypersensitivity
- Gastrointestinal tract: increased fluid secretion and peristalsis
- Eyes and airways: increased
mucus secretion and decreased airway diameter - Blood vessels: increased vascular permeability and vasodilation
Type I hypersensitivity second exposure
- A second exposure to the allergen leads to cross-linking of the IgE bound to mast cells via FcεRI
- Mast cell degranulation occur, and the release of active mediators such as histamine, heparin and proteases
Immediate hypersensitivity
Mast cell degranulation begins within seconds of antigen binding
In type II hypersensitivity, which cells possess a cell surface receptor which binds to the Fc region of IG bound to the antigen in question
Neutrophils, eosinophils, macrophages, monocytes and NK cells
Antibody Dependent Cellular Cytotoxicity (ADCC)
FcγRIII in NK cells binds to IgG antibodies attached to the surface of a cell, leading NK cell to discharge its granule proteins into the cell, killing it
Two types of type II hypersensitivity
Haemolytic disease of the newborn and Myasthenia gravis
Haemolytic disease of the newborn
- Red blood cells from a RhD positive foetus leak into maternal circulation during birth and stimulate an immune response if mother is RhD negative
- Could be problem in subsequent pregnancies after the first as maternal anti Rh antibodies cross placenta
Effects of haemolytic disease of newborn on foetus
Tissue damage, enlargement of the liver, elevated bilirubin, petechial haemorrhaging
Solution to haemolytic disease of newborn
- Antibodies against Rh antigen can be administered at 28 weeks of first gestation and within 24-48 hours after the first delivery
- These antibodies will bind to foetal red blood cells that have entered the mother’s circulation, facilitating their clearance before B cells activation (therefore, no
memory cells to be activated in subsequent pregnancies)
Myasthenia gravis
- Normally acetylcholine released from motor neurons at the neuromuscular junction binds to acetylcholine receptors on skeletal muscle cells, triggering muscle contraction
- In myasthenia gravis, autoantibodies against the α chain of the nicotinic acetylcholine receptor (present on skeletal muscle cells), can block neuromuscular transmission
- The antibodies are believed to drive the internalisation and intracellular degradation of acetylcholine receptors.
Result of myasthenia gravis
- Patients develop potentially fatal progressive weakness as a result of their autoimmune disease
- As the number of receptors on the muscle is decreased, the muscle becomes less responsive to acetylcholine
Diseases that are contributed to by immune complexes
Systemic lupus erythematosus, rheumatoid arthritis, meningitis and
malaria
Immune complexes
- Formed when antibody
binds with antigen and are usually removed by
macrophages after complement activation - Persisting immune complexes can be deposited
in blood vessels and in a range of tissues and
organ and cause inflammation
3 types of type IV hypersensitivity
- Delayed type hypersensitivity
- Contact hypersensitivity
- Celiac disease
Type I diabetes
- Autoimmune attack against insulin-producing
cells (beta cells) of the islets of Langerhans in
the pancreas - Develops in children or young adults, but it
can appear at any age - Characterised by increased
blood glucose levels (hyperglycaemia)
-Patients have dependence on daily insulin administration
Primary immunodeficiency
- Rare, inherited
- e.g. X-linked hyper-IgM syndrome caused by mutations in the CD40L gene
Secondary immunodeficiency
- Immune system is compromised due to an external factor
- More frequent than primary
- e.g. Malnutrition, AIDS, cancer, age, immunosuppression
