Immunology - Hypersensitivity Reactions

Question 1

What are hypersensitivity reactions?

Answer 1

Immune response that results in bystander damage to self, usually an exaggeration of normal immune response

Question 2

What are the four types of hypersensitivity reactions?

Answer 2

Type I - immediate hypersensitivity

Type II - direct cell killing

Type III - immune complex mediated

Type IV - delayed type hypersensitivity

Question 3

Define allergy

Answer 3

IgE-mediated antibody response to external allergen

(Type I hypersensitivity)

Question 4

How quickly do type I hypersensitivity reactions occur?

Answer 4

minutes to 1-2 hours

Question 5

What may affect the threshold for allergic reaction?

Answer 5

cofactors such as exercise, alcohol and infection

Question 6

What are specific features of allergic disease?

Answer 6

asthma

urticaria

angioedema

allergic rhinitis

allergic conjunctivitis

diarrhoea and vomiting

anaphylaxis

Question 7

Which cells are involved in allergy?

Answer 7

B lymphoctes - recognise antigen, produce IgE

T lymphocytes - helper for B cells

Mast cells - release vasoactive substances

Question 8

Which substances are preformed in mast cells?

Answer 8

histamine

tryptase

heparin

Question 9

Which substances do mast cells synthesize on demand?

Answer 9

leukotrienes

prostaglandins

cytokines (including IL4, TNF)

Question 10

What is the function of mast cells?

Answer 10

defense against parasites

wound healing

Question 11

What role do mast cells play in the inflammatory cascade?

Answer 11

increase blood flow

increase vascular permeability

contraction of smooth muscle

increase secretions at mucosal surface

Question 12

How long do hives normally last?

Answer 12

appear within 1 hour

last 2-6 hours, occasionally 24 hours.

Question 13

What is angioedema?

Answer 13

Self-limited, localised swelling of subcutaneous tissues or mucous membranes

non-pitting oedema

often without clear demarkation

generally not itchy

Question 14

What are the clinical features of anaphylaxis?

Answer 14

Angioedema of lips and mucous membranes

Laryngeal obstruction, stridor

Hypotension

Wheeze

Itch of palms, soles of feet, genitalia

Flushing

Urticaria

Oral itching

Vomiting, diarrhoea, abdominal pain

Loss of consciousness

Death

Question 15

What are non allergic causes of mast cell degranulation?

Answer 15

Drugs: morphine & other opiates; aspirin and NSAIDS

Thyroid disease

Idiopathic

Physical urticaria - pressure & heat

Question 16

What is Samter’s triad?

Answer 16

Asthma

Nasal Polyps

Severe end of aspirin sensitivity spectrum

Question 17

What are the general features of allergic reaction?

Answer 17

Reaction occurs quickly

Responses are often consistent

Often associated with more than one organ system

Question 18

What are the investigations for allergy?

Answer 18

Skin prick tests

Quantitive IgE to putative allergen

Challenge test

Question 19

What investigation would you perform during an acute anaphylactic episode?

Answer 19

Serum mast cell typtase levels - evidence of mast cell degranulation

Question 20

What drugs need to be stopped for skin prick tests?

Answer 20

Antihistamines for 48 hours

Question 21

How does the sensitivity and specificity of IgE RAST test compare with that of skin prick testing?

Answer 21

70-70%

Question 22

What are common causes of elevated total IgE?

Answer 22

Allergic disorders

Vasculitis

Lymphoma

Drugs

Question 23

What are the pitfalls of measuring total IgE in allergy?

Answer 23

Many other causes of elevated IgE

Significant allergic disease can exist in absence of elevated IgE

Question 24

When does tryptase reach its peak concentration during anaphylaxis? When does it return to baseline?

Answer 24

Peak 1-2 hours

Baseline 6 hours

Question 25

How do adrenalin injection pens work in anaphylaxis?

Answer 25

β2-adrenoreceptors Constrict arterial smooth muscle - increases blood pressure, reduces vascular leakage Dilates bronchial smooth muscle

Question 26

What is immunotherapy?

Answer 26

Controlled exposure to increasing amounts of allergen

Question 27

What are the risks of immunotherapy?

Answer 27

Anaphylaxis

Question 28

What are the key features of Type II hypersensitivity reactions?

Answer 28

Antibody to cell surface antigens resulting in activation of complement antibody mediated phagocytosis

Question 29

What type of hypersensitivity reactions are transfusion reactions?

Answer 29

Type II Anti-blood group antibodies bind to surface of circulating donor erythrocytes

Question 30

What are the features of immediate haemolytic transfusion reaction?

Answer 30

Overwhelming systemic response occuring after only 1ml blood transfused Pyrexia and rigors tachycardia/tachypnoea hypotension/dizziness headaches, chest or lumbar pain May be fatal

Question 31

Give some examples of Type II hypersensitivity.

Answer 31

Transfusion reactions Autoimmune haemolytic anaemia Idiopathic thrombocytopaenic purpura Goodpasture's syndrome (kidney) Myasthenia gravis (nervous system) Guillan Barre (nervous system) Grave's disease (TSH receptor - hyperthyroidism) Pemphigus vulgaris (skin)

Question 32

What is the management for type II hypersensitivity?

Answer 32

Plasmapheresis (limited by rebound antibody production) Immunosuppression (switch of B cell production of antibody)

Question 33

What causes Type III hypersensitvity reactions?

Answer 33

Deposition of antigen-antibody immune complexes in small vessels causing complement activation and infiltration of macrophages and neutrophils

Question 34

What are the clinical features of acute hypersensitivity pneumonitis (type III)?

Answer 34

wheezing and malaise, 4-8 hours after exposure Dry cough, pyrexia, breathlessness Examination often normal Cell accumulation and inflammation within alveoli

Question 35

What type of hypersensitivity reaction is Systemic Lupus Erythematous?

Answer 35

Systemic Type III Antibodies produced against contents of cell nuclei Immune complexes deposited in small vessels in skin, joints, kidneys Complement activation, recruitement of immune cells.

Question 36

How are Type III hypersensitivity reactions diagnosed?

Answer 36

Specific IgG to putative antigen Complement

Question 37

How are Type III hypersensitivity reactions managed?

Answer 37

Avoidance Corticosteroids to reduce inflammation Immunosuppression to decrease antibody production

Question 38

What are the anti-inflammatory effects of corticosteroids?

Answer 38

Inhibits Phospholipase A2 - blocks formation of inflammatory mediators: Prostaglandin formation Platelet Activating Factor Arachidonic Acid

Question 39

What is the effect of corticosteroids on phagocytes?

Answer 39

Decreased expression of adhesion molecules on endothelium - transient increase in neutrophil counts because they don't leave the bloodstream for the tissues Decreased release of proteolytic enzymes

Question 40

What are the effects of corticosteroids on the number of circulating lymphocytes?

Answer 40

Decreased numbers of lymphocytes because: lymphocytes are sequestered in lymphoid tissue and spleen high dose is cytotoxic to lymphocytes

Question 41

How is the function of lymphocytes blocked by corticosteroids?

Answer 41

Inhibition of cytokine expression Inhibiting of antigen-induced T cell proliferation Decreased antibody production by plasma cells

Question 42

What are the metabolic side effects of corticosteroids?

Answer 42

diabetes central obesity protein catabolism (muscle wasting) lipid abnormalities adrenal suppression

Question 43

What are the non-metabolic effects of corticosteroids?

Answer 43

Cataracts Glaucoma Peptic ulceration Pancreatitis Osteoporosis Hirsutism Acne Moon face

Question 44

How is Type IV hypersensitivity mediated?

Answer 44

T cells Primed T cells are produced by initial sensitization to antigen Subsequent exposure activates previously primed T cells causing recruitment of macrophages, lymphocytes, neutrophils Inflammatory cascade Granuloma

Question 45

Give examples of autoimmune Type IV hypersensitivity reactions.

Answer 45

Type I diabetes Psoriasis Rheumatoid Arthritis

Question 46

Give examples of non-autoimmune Type IV hypersensitivity.

Answer 46

Nickel hypersensitivity Tuberculosis Leprosy Sarcoidosis Cellular rejection of solid organ transplant

Question 47

What is characteristic of sarcoidosis?

Answer 47

Granuloma formation Multi system disease

Question 48

How is sarcoidosis managed?

Answer 48

Watchful waiting - many patient have spontaneous remission NSAIDS (acute onset) Systemic corticosteroids

Question 49

Which occupational diseases are characterised by Type IV hypersensitivity and granuloma formation?

Answer 49

Beryllosis Silicosis Other dust diseases

Question 50

What type of hypersensitivity reaction is the chronic stage of hypersensitivity pneumonitis?

Answer 50

Type IV