2. Hypersensitivity

Question 1

define the term hypersensitivity

Answer 1

the antigen specific immune responses that are either inappropriate or excessive and result in harm to host

Question 2

what are the 4 different types of hypersensitivity reaction?

Answer 2

Type 1: Immediate (5 mins) = allergy
Type 2: 5-12hours = antibody mediated (membrane bound)
Type 3: 3-8 hours = immune complex mediated (soluble antigen)
Type 4: Delayed (24-72 hours) = cell mediated

Question 3

what are the 2 phases involved in a hypersensitivity reaction?

Answer 3

sensitisation phase = initial exposure to the antigen, activating APC’s and memory effector cells
effector phase = re exposure to the antigens, activation of memory cells

Question 4

summarise the pathophysiology of allergy

Answer 4

its an abnormal adaptive response to allergen leading to the activation of TH2 T helper cells, IL-4, IL5, IL13 rekease and IgE production and mast cell activation. upon first exposure (sensitisation), a TH2 response is intitiated and allergen specific IgE produced which binds to mast cells via the FcRεRI. Upon repeated exposure to the antigen the allergen will crosslink with 2 IgE and activate the mast cells causing degranulation resulting in tissue reaction.

Question 5

describe the treatment options for type 1 hypersensitivity

Answer 5

• allergen desensitisation
• anti igE antibody
• antihistamine
• leukotriene receptor antagonists
• corticosteroids

Question 6

summarise the pathophysiology of hypersensitivity type 2 reactions

Answer 6

the antibody(IgG or IgM) binds with cell surface antigen (eg: exogenous- blood group antigens, rhesus D antigens, endogenous - self antigens) to activate compliment resulting in cell and organ damage

Question 7

give some examples of type 2 hypersensitivity reactions

Answer 7

haemolytic transfusion reactions
haemolytic disease of the newborn
myasthenia gravis
grave's disease
autoimmune haemolytic anaemia (warm and cold)
immune thrombocytopenia purpura
goodpasture's syndrome

Question 8

describe the treatment options for type 2 hypersensitivity reactions

Answer 8

cell tissue damage -
anti inflammatory drugs - complement activation
plasmaspheresis - circulating antibodie and inflammtroy mediators filtered and replaced
splenectomy - opsonisation/phagocytosis
intravenous immunoglobulins - blockage of Fc receptor

physiological damage -
correct metabolism - antithyroid drugs in grave’s
replacement therapy - prydisostigmine in myasthenia gravis

Question 9

summarise the pathophysiology of type 3 hypersensitivity reactions

Answer 9

soluble antibody antigen complex forms causing immune complex to be deposited resulting in damage and disease development
- depends on complex size, host response, local tissue factors
the peristence of the immunocomplex and deposition drives the disease, commonly at jointsq, skin, small vessels and kidney
1. immune complexes depositied in tissues
2. complement activation
3. neutrophil chemotaxis
4. neutrophil adherence and degranulation

Question 10

give some examples of type 3 hypersensitivity reactions

Answer 10

• rheumatoid arthritis (antigen = Fc portion of IgG)
• glomerulonephritis (bacterial endocarditis, hep B infection )
• systemic lupus erythematous (antigen = Ds DNA)

Question 11

summarise the pathophysiology of type 4 hypersensitivity reactions

Answer 11

driven by lymphocytes and macrophages, TH1 T cells to endogenous and exogenous antigens

Question 12

how do type 4 hypersensitivity respond to exogenous antigens?

Answer 12

1. contact - epidermal infection, eg: nickel, diagnosed with patch testing
2. tuberculin - tissue damage, eg: TB, leprosy
3. granulomatous

Question 13

how do type 4 hypersensitivity respond to endogenous antigens?

Answer 13

1. insulin dependent diabetes melltius
2. hashimoto’s thyroiditis
3. rheumatoid arthritis

Question 14

describe the treatment options for type 3 and 4 hypersensitivity reactions

Answer 14

anti-inflammatory drugs

monoclonal antibodies

Question 15

in type 1 hypersensitivity reactions, what is the difference in how urticaria and angioedema are triggered?

Answer 15

location of mast cell activation-
epidermis - urticaria (histamine and leukotrienes/cytokines)
deep dermis - angioedema (histamine and bradykinin)

Question 16

what does systemic mast cell activation result in and what is the treatment option available?

Answer 16

anaphylaxis = hypotension, CVS collapse, generalised urticaria, angioedema, breathing problems

Question 17

what are some examples of exogenous antigens?

Answer 17

non infectious substances
infectious microbes
drugs

Question 18

what are some examples of endogenous antigens?

Answer 18

infectious microbes

self antigens

Question 19

what is involved in the complement pathway to cause tissue damage in type 2 hypersensitivity reactions?

Answer 19

cell lysis
neutrophil recruitment/activation (C3a/C5b)
opsonisation (C3b)

Question 20

give an examples of a disease caused by type 2 hypersensitivity which is IgM mediated

Answer 20

haemolytic transfusion reaction - life threatening
due to incompatibility in rhesus D antigens or ABO so the donor’s red blood cells are destroyed by the recipient’s immune system

Question 21

give an example of a disease caused by type 2 hypersensitivity which is IgG mediated

Answer 21

haemolytic disease of the newborn
where Rh antigens from the foetus enter the maternal blood and so the mother produces anti-Rh antibodies
but when pregnant again, anti Rh can cross the placenta and damage foetus’ RBC’s

Question 22

why does a mismatch of ABO system rarely cause haemolytic disease of newborn?

Answer 22

as are IgM medaited which do not cross placenta

Question 23

explain the immune mechanisms explaining the therapeutic benefit of RhoGam and explainw hen it can be adminstered

Answer 23

binds to D factor and causes the complement pathway to be activated causing less of anti-Rh antibodies

Question 24

what are the three types of a possible allergens?

Answer 24

seasonal exposure - pollens
perennial exposure - house dust mite. fungal spores
accidental exposure - insect venom, medicines, chemicals, foods

Question 25

what are the mechanisms involved in allergy?

Answer 25

adaptive - T helper 2, IgE

mast cell activation

Question 26

what are the differences in developing and western countries in development of allergies?

Answer 26

developing - large families, rural homes, livestock, variable microflora, low antiobiotic use, high helminth burden, poor sanitisation causing a TH1 response = generally more exposed so less allergic
western - small families, affluent, stable microflora, high antibiotic use, low or absent helminth burden, good sanitisation causing a TH2 response = generally more allergic esp atopy (due to dysbiosis of the microbiome)

ie: hygiene hypothesis

Question 27

define dysbiosis

Answer 27

the composition and functional alterations of microbiome

so loss of microbiome diversity

Question 28

give examples of mast cell mediators

Answer 28

enzyme - tryptase
toxic mediator - histamine
cytokine - IL4, IL13, IL5
lipid mediator = Leukotrienes C4, D4, E4