7 - Immunopathology

Question 1

Hypersensitivity

Answer 1

Inappropriate vigorous immune responses to antigens that pose little or no threat

Question 2

Autoimmunity

Answer 2

Directed against self antigens

Question 3

Immunodeficiency

Answer 3

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)

Question 4

Type I hypersensitivity

Answer 4

• 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

Question 5

Type II hypersensitivity

Answer 5

Antibody-mediated destruction of cells by IgG and IgM antibodies through complement activation, Antibody-dependant cellular cytotoxicity (ADCC) and Opsonisation

Question 6

Type III hypersensitivity

Answer 6

• 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

Question 7

Type IV hypersensitivity

Answer 7

• 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

Question 8

Symptoms of type I hypersensitivity

Answer 8

• Gastrointestinal tract: increased fluid secretion and peristalsis
• Eyes and airways: increased
  mucus secretion and decreased airway diameter
• Blood vessels: increased vascular permeability and vasodilation

Question 9

Type I hypersensitivity second exposure

Answer 9

• 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

Question 10

Immediate hypersensitivity

Answer 10

Mast cell degranulation begins within seconds of antigen binding

Question 11

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

Answer 11

Neutrophils, eosinophils, macrophages, monocytes and NK cells

Question 12

Antibody Dependent Cellular Cytotoxicity (ADCC)

Answer 12

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

Question 13

Two types of type II hypersensitivity

Answer 13

Haemolytic disease of the newborn and Myasthenia gravis

Question 14

Haemolytic disease of the newborn

Answer 14

• 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

Question 15

Effects of haemolytic disease of newborn on foetus

Answer 15

Tissue damage, enlargement of the liver, elevated bilirubin, petechial haemorrhaging

Question 16

Solution to haemolytic disease of newborn

Answer 16

• 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)

Question 17

Myasthenia gravis

Answer 17

• 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.

Question 18

Result of myasthenia gravis

Answer 18

• 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

Question 19

Diseases that are contributed to by immune complexes

Answer 19

Systemic lupus erythematosus, rheumatoid arthritis, meningitis and
malaria

Question 20

Immune complexes

Answer 20

• 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

Question 21

3 types of type IV hypersensitivity

Answer 21

• Delayed type hypersensitivity
• Contact hypersensitivity
• Celiac disease

Question 22

Type I diabetes

Answer 22

• 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

Question 23

Primary immunodeficiency

Answer 23

• Rare, inherited
• e.g. X-linked hyper-IgM syndrome caused by mutations in the CD40L gene

Question 24

Secondary immunodeficiency

Answer 24

• Immune system is compromised due to an external factor
• More frequent than primary
• e.g. Malnutrition, AIDS, cancer, age, immunosuppression