Hypersensitivity Flashcards
Describe each type of hypersensitivity reaction
Type 1 - immediate (IgE)
Type 2 - cell-bound antigen (IgG, IgM)
Type 3 - immune complex (IgG)
Type 4 - delayed (T-cells)
What exposures can cause hypersensitivity?
o Infectious agents
o Environmental substances
o Self-antigens
How can influenza viruses cause hypersensitivity?
Damages epithelial cells in the respiratory tract which may trigger high levels of cytokine secretion. The cytokines attract leukocytes to the lungs and trigger vascular changes that lead to hypotension and coagulation
In severe influenza, inflammatory cytokines also spill out into the systemic circulation, causing ill effects in remote parts of the body, such as the brain
How can dust cause hypersensitivity and what are the antibodies associated with asthma and farmers lung?
- Dust triggers responses because it is able to enter the lower extremities of the respiratory tract, an area rich in adaptive immune response cells
- Dust can mimic parasites and may stimulate an antibody response
Asthma and rhinitis - IgE immediate hypersensitivity
Farmers lung - IgG
What are the adaptive and innate immune system mediators involved in each hypersensitivity reaction?
Type 1 - immediate
Adaptive - IgE
Innate - mast cells, eosinophils
Type 2 - cell-bound antigen
Adaptive - IgG, IgM
Innate - compliment, phagocytes
Type 3 - immune complex
Adaptive - IgG
Innate - compliment, neutrophils
Type 4 - delayed
Adaptive - T-cells
Innate - macrophages
Describe Type 1 hypersensitivity
Mast cells and eosinophils, IgE
The effects are felt within minutes of exposure
Immediate hypersensitivity, allergy
B cells produce it when co-stimulated with IL-4 (secreted by TH2 cells)
Atopy (allergy)
How is IgE secreted?
B cells produce it when co-stimulated with IL-4 (secreted by TH2 cells)
What are allergens?
Antigens that trigger allergic reactions
Peanut allergy is the most common cause of severe allergic reactions - ARA h2 protein
Multiple food allergies - ARA h8
What are degranulating cells?
Release of mediators that cause allergic symptoms
Mast cells are resident in many tissues
Eosinophils migrate to tissues where type I hypersensitivity reaction is
Mast cells initiate allergic symptoms after allergen and IgE interact
Mast cells have receptors for IgE and FcEµRI (also IgE)
Describe anaphylaxis
Low BP
Angioedema
Airway obstruction
Caused by mast cells producing prostaglandins and leukotrienes. The result is vasodilation and increased vascular permeability. Shift of fluids from the vascular to the extra-vascular space resulting in a fall in vascular tone and severe drop in blood pressure
Describe allergic rhinitis
Inhaled allergens stimulate mast cells in the nasal mucosa and subsequent vasodilation and oedema in the nose causes nasal stuffiness and sneezing
Leukotrienes increase mucus secretion, which causes the discharge characteristic of allergic rhinitis
Describe asthma
Increased mucus secretion in asthma and contributes to the airflow obstruction
In the lungs, leukotrienes cause smooth muscle contraction, which has the most dramatic effects on airflow reduction
The symptoms improve after an hour or so as the immediate response dies down
Several hours after the acute episode, the airflow in the bronchi may deteriorate again, reflecting the migration of leukocytes into the bronchi in response to chemokines
The late phase may last several hours
How is allergy treated?
Beta-agonists - Mimic the effects of the sympathetic nervous system and work mainly by preventing smooth bronchial muscle contraction in asthma
Epinephrine (adrenaline) - Stimulates adrenergic receptors, decreases vascular permeability, increases blood pressure, and reverses airway obstruction
Antihistamines - block specific histamine receptors and have an important role in allergies that affect the skin, nose, and mucus membranes
Specific receptor antagonists - block the effects of leukotrienes e.g. montelukast LTRA
Corticosteroids - can prevent the immediate hypersensitivity reaction, the late phase, and chronic allergic inflammation
Describe type 2 hypersensitivity
IgG or IgM reacting with antigen present on the surface of cells leading to tissue damage
The bound Ig interacts with complement or with Fc receptor on macrophages
Opsonisation of target cells
Immune mediated haemolysis
Takes several hours
Drug-induced haemolysis
How does the body form anti-A and B antigens against blood?
A and B blood group antigens are oligosaccharides on the surface of RBCs
Similar to molecules expressed by bacteria
Antibodies recognize A and B
Anti-A and Anti-B are IgM antibodies naturally occurring
Individuals with O group have both antibodies from birth regardless of exposure
Antibodies produced against these antigens can cause type II hypersensitivity
How does alloimmune haemolysis occur?
Rhesus negative mother has rhesus positive baby
During labour, the foetal blood miss with the mother
The mother produces IgG antibodies
Thus, if the mother is pregnant with another rhesus positive baby, the antibodies will leak across the placenta and attack the baby’s RBCs
The baby has no effect on the mother as she has antibodies
How can autoimmune haemolysis occur?
Autoimmune haemolytic anaemia could be induced by infections or drugs
Part of a systematic autoimmune disease (SLE)
Autoantibodies produces by malignant B cells
What is Goodpasture syndrome?
IgG autoantibodies bind a glycoprotein in the basement membrane of the lung and glomeruli
Anti–basement membrane antibody activates complement, which can trigger an inflammatory response
Describe type 3 hypersensitivity
Immune complex disease, IgG
Immune complexes of antigen and antibody form and cause damage at the site of production or circulate and cause damage elsewhere
Immune complexes take some time to form and to initiate tissue damage
(ANTIBODY+ANTIGEN)
How do immune complexes form and how are they usually disposed of?
At low levels of antibody, each antigen molecule binds several immunoglobulin molecules
When antibody and antigen levels are approximately equal, or antibody levels are slightly in excess, large complexes can form
Complement breaks down large complexes
Complement Receptor 1 (CR1) transfers Complexes to Phagocytes
What happens when the complement fails to remove the complex?
Activation of the innate immune system
How can immune complexes affect the kidney?
Glomerulonephritis
a) Nephrotic syndrome (protein leaks into urine) with gradual development of renal failure
b) Nephritis with rapid onset renal failure, blood and protein in the urine and hypertension
(farmer’s lung is also type 3)
Describe type 4 hypersensitivity
The slowest form of hypersensitivity is that mediated by T cells
This can take 2 to 3 days to develop
How are type 4 reactions initiated and what are the consequences?
Delayed hypersensitivity reactions are initiated when tissue macrophages recognise danger signals and initiate an inflammatory response
Dendritic cells loaded with antigen migrate to local lymph nodes, where they present antigen to T cells
Specific T-cell clones proliferate in response to antigens, which migrate to the site of inflammation
Tumour necrosis factor (TNF) is secreted by both macrophages and T cells and stimulates much of the damage in delayed hypersensitivity
(dendritic cells = antigen-presenting cells)
