Lecture 31: Immunopathology - Hypersensitivity and Allergy Flashcards
What is type I hypersensitivity / what does this involve?
immediate hypersensitivity
What is type II hypersensitivity / what does this involve?
antibody mediated
What is type III hypersensitivity / what does this involve?
immune complex
What is type IV hypersensitivity / what does this involve?
delayed type hypersensitivity
What is allergy?
an immune-mediated inflammatory response to common environmental antigens that are otherwise harmless
What is atopy?
the enhanced tendency to produce IgE in response to environmental antigens
What are the tendencies of individuals with atopy?
have high levels of IgE (varies with condition)
large numbers of eosinophils
large numbers of IL-4 secreting Th2 cells
What are common features of allergens?
individuals are repeatedly exposed via a mucosal route
very stable
high solubility in bodily fluids
introduced in very low doses
What type of immune response do allergens induce?
a Th2 response
low dose, mucosal location
What are the different types of allergic reactions (type I hypersensitivity)?
systemic anaphylaxis, allergy rhinitis (hay fever), asthma (acute, chronic) and food allergies
What can type I hypersensitivity be separated into?
two phases which are sensitisation and response
What are examples of local and systemic responses?
local: rhinitis, bronchoconstriction and conjunctivitis
systemic: anaphylaxis
How does sensitisation occur?
the allergen leaves occludin in tight junctions and enters mucosa -> DC primes T cell in lymph node -> plasma cell travels back to mucosa and produces allergen-specific IgE antibodies
How does an allergic response occur?
allergen-specific IgE binds to mast cell; triggers mast cell degranulation
What causes degranulation?
multivalent antigen cross-links bind IgE antibodies
What does activation of mast cells result in?
secretion of preformed mediators (histamine)
synthesis and secretion of lipid mediators (prostaglandins and leukotrienes)
synthesis and secretion of cytokines (IL-3, IL-4, IL-13, IL-5)
What are the physiological effects of mast cell degranulation in the GI tract?
increased fluid secretion and peristalsis
diarrhea, vomiting
What are the physiological effects of mast cell degranulation in the airways?
decreased diameter and increased mucus secretion
wheezing, coughing, phlegm
What are the physiological effects of mast cell degranulation in the blood vessels?
increased blood flow and permeability
increased cell and protein, fluid in tissue, lymph flow and effector response
What occurs during the immediate allergic response?
redness, vasodilation
soft swelling, leakage of plasma from venules
dependent upon IgE
What causes the symptoms of the immediate response?
preformed mediators (histamines, etc) which are rapidly metabolised
What occurs during the late allergic response?
hard swelling, accumulation of leukocytes
neutrophils, Th2 cells, eosinophils
occurs after 8-12 hours
What causes the symptoms of the late response?
induced mediators (chemokines, cytokines, leukotrienes)
What are the two outcomes of type II hypersensitivity?
injury due to activation of effector mechanisms or abnormal physiological response
Activation of which effector mechanisms causes injury?
the complement cascade
recruitment of inflammatory cells
activation via Fc receptor
What causes an abnormal physiological response?
binding to receptors or proteins interfering with function
activation or inhibition
What is haemolytic disease of the newborn caused by?
preformed maternal IgG antibodies which react against the child’s Rh antigens on their RBC’s in utero -> removal of RBC via complement activation
How is haemolytic disease of the newborn treated?
providing anti-Rh antibodies to the mother within 24 hrs of delivery to remove fetal RBC’s in maternal circulation
When does type III hypersensitivity occur?
if complexes composed of self or foreign antigen are excessively produced, and inefficiently cleared
What does the severity of type III hypersensitivity depend on?
depend on size and amount
depend on affinity and isotype of antibody
What does the pathology of type III hypersensitivity depend upon?
where complexes are deposited e.g. cationic antigen complexes bind to blood vessels and kidney glomeruli (SLE)
How are immune complexes removed?
small Ag:Ab complexes form in the circulation and activate complement -> many molecules of C3b are bound covalently to the complex -> bound C3b binds to CR1 on erythrocyte surfaces -> in the spleen and liver, phagocytic cells remove the immune complexes
What happens when immune complexes are not cleared?
neutrophil activation / complement activation / mast cell degranulation
increased blood vessel permeability / blood flow
activation of platelets results in occlusion of vessels
What is vasculitis caused by?
immune complex deposition in blood vessel walls
What is glomerulonephritis caused by?
immune complex deposition in kidney basement membranes
What is arthritis caused by?
immune complex deposition in joint synovium and vessels
What are the mediators of type IV hypersensitivity?
heavy involvement of T cells (and macrophages)
classically CD4+ Th1 but sometimes CD8+ CTL
What is type IV hypersensitivity elicited by?
microbial infection, intradermal injection of protein antigens or contact with chemicals (absorbed through skin)
What occurs during type IV hypersensitivity sensitisation?
antigen penetrates the skin and is taken up by local antigen presenting cells -> dendritic cell primes T cell in lymph node
What occurs during type IV hypersensitivity response?
re-exposure to antigen: Th1 recognises antigen and releases cytokines -> recruitment and activation of phagocytes and plasma to site of antigen exposure causes a visible lesion
What is the purpose of a tuberculin skin test (Mantoux test)?
detects the presence of Mtb-specific CD4 T cells (an example of type IV hypersensitivity)
