2. Hypersensitivity Flashcards
define the term hypersensitivity
the antigen specific immune responses that are either inappropriate or excessive and result in harm to host
what are the 4 different types of hypersensitivity reaction?
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
what are the 2 phases involved in a hypersensitivity reaction?
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
summarise the pathophysiology of allergy
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.
describe the treatment options for type 1 hypersensitivity
- allergen desensitisation
- anti igE antibody
- antihistamine
- leukotriene receptor antagonists
- corticosteroids
summarise the pathophysiology of hypersensitivity type 2 reactions
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
give some examples of type 2 hypersensitivity reactions
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
describe the treatment options for type 2 hypersensitivity reactions
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
summarise the pathophysiology of type 3 hypersensitivity reactions
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
give some examples of type 3 hypersensitivity reactions
- rheumatoid arthritis (antigen = Fc portion of IgG)
- glomerulonephritis (bacterial endocarditis, hep B infection )
- systemic lupus erythematous (antigen = Ds DNA)
summarise the pathophysiology of type 4 hypersensitivity reactions
driven by lymphocytes and macrophages, TH1 T cells to endogenous and exogenous antigens
how do type 4 hypersensitivity respond to exogenous antigens?
- contact - epidermal infection, eg: nickel, diagnosed with patch testing
- tuberculin - tissue damage, eg: TB, leprosy
- granulomatous
how do type 4 hypersensitivity respond to endogenous antigens?
- insulin dependent diabetes melltius
- hashimoto’s thyroiditis
- rheumatoid arthritis
describe the treatment options for type 3 and 4 hypersensitivity reactions
anti-inflammatory drugs
monoclonal antibodies
in type 1 hypersensitivity reactions, what is the difference in how urticaria and angioedema are triggered?
location of mast cell activation-
epidermis - urticaria (histamine and leukotrienes/cytokines)
deep dermis - angioedema (histamine and bradykinin)
what does systemic mast cell activation result in and what is the treatment option available?
anaphylaxis = hypotension, CVS collapse, generalised urticaria, angioedema, breathing problems
what are some examples of exogenous antigens?
non infectious substances
infectious microbes
drugs
what are some examples of endogenous antigens?
infectious microbes
self antigens
what is involved in the complement pathway to cause tissue damage in type 2 hypersensitivity reactions?
cell lysis
neutrophil recruitment/activation (C3a/C5b)
opsonisation (C3b)
give an examples of a disease caused by type 2 hypersensitivity which is IgM mediated
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
give an example of a disease caused by type 2 hypersensitivity which is IgG mediated
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
why does a mismatch of ABO system rarely cause haemolytic disease of newborn?
as are IgM medaited which do not cross placenta
explain the immune mechanisms explaining the therapeutic benefit of RhoGam and explainw hen it can be adminstered
binds to D factor and causes the complement pathway to be activated causing less of anti-Rh antibodies
what are the three types of a possible allergens?
seasonal exposure - pollens
perennial exposure - house dust mite. fungal spores
accidental exposure - insect venom, medicines, chemicals, foods
what are the mechanisms involved in allergy?
adaptive - T helper 2, IgE
mast cell activation
what are the differences in developing and western countries in development of allergies?
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
define dysbiosis
the composition and functional alterations of microbiome
so loss of microbiome diversity
give examples of mast cell mediators
enzyme - tryptase
toxic mediator - histamine
cytokine - IL4, IL13, IL5
lipid mediator = Leukotrienes C4, D4, E4
