Lecture 31: Immunopathology - Hypersensitivity and Allergy

Question 1

What is type I hypersensitivity / what does this involve?

Answer 1

immediate hypersensitivity

Question 2

What is type II hypersensitivity / what does this involve?

Answer 2

antibody mediated

Question 3

What is type III hypersensitivity / what does this involve?

Answer 3

immune complex

Question 4

What is type IV hypersensitivity / what does this involve?

Answer 4

delayed type hypersensitivity

Question 5

What is allergy?

Answer 5

an immune-mediated inflammatory response to common environmental antigens that are otherwise harmless

Question 6

What is atopy?

Answer 6

the enhanced tendency to produce IgE in response to environmental antigens

Question 7

What are the tendencies of individuals with atopy?

Answer 7

have high levels of IgE (varies with condition)
large numbers of eosinophils
large numbers of IL-4 secreting Th2 cells

Question 8

What are common features of allergens?

Answer 8

individuals are repeatedly exposed via a mucosal route
very stable
high solubility in bodily fluids
introduced in very low doses

Question 9

What type of immune response do allergens induce?

Answer 9

a Th2 response

low dose, mucosal location

Question 10

What are the different types of allergic reactions (type I hypersensitivity)?

Answer 10

systemic anaphylaxis, allergy rhinitis (hay fever), asthma (acute, chronic) and food allergies

Question 11

What can type I hypersensitivity be separated into?

Answer 11

two phases which are sensitisation and response

Question 12

What are examples of local and systemic responses?

Answer 12

local: rhinitis, bronchoconstriction and conjunctivitis
systemic: anaphylaxis

Question 13

How does sensitisation occur?

Answer 13

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

Question 14

How does an allergic response occur?

Answer 14

allergen-specific IgE binds to mast cell; triggers mast cell degranulation

Question 15

What causes degranulation?

Answer 15

multivalent antigen cross-links bind IgE antibodies

Question 16

What does activation of mast cells result in?

Answer 16

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)

Question 17

What are the physiological effects of mast cell degranulation in the GI tract?

Answer 17

increased fluid secretion and peristalsis

diarrhea, vomiting

Question 18

What are the physiological effects of mast cell degranulation in the airways?

Answer 18

decreased diameter and increased mucus secretion

wheezing, coughing, phlegm

Question 19

What are the physiological effects of mast cell degranulation in the blood vessels?

Answer 19

increased blood flow and permeability

increased cell and protein, fluid in tissue, lymph flow and effector response

Question 20

What occurs during the immediate allergic response?

Answer 20

redness, vasodilation
soft swelling, leakage of plasma from venules
dependent upon IgE

Question 21

What causes the symptoms of the immediate response?

Answer 21

preformed mediators (histamines, etc) which are rapidly metabolised

Question 22

What occurs during the late allergic response?

Answer 22

hard swelling, accumulation of leukocytes
neutrophils, Th2 cells, eosinophils
occurs after 8-12 hours

Question 23

What causes the symptoms of the late response?

Answer 23

induced mediators (chemokines, cytokines, leukotrienes)

Question 24

What are the two outcomes of type II hypersensitivity?

Answer 24

injury due to activation of effector mechanisms or abnormal physiological response

Question 25

Activation of which effector mechanisms causes injury?

Answer 25

the complement cascade recruitment of inflammatory cells activation via Fc receptor

Question 26

What causes an abnormal physiological response?

Answer 26

binding to receptors or proteins interfering with function | activation or inhibition

Question 27

What is haemolytic disease of the newborn caused by?

Answer 27

preformed maternal IgG antibodies which react against the child's Rh antigens on their RBC’s in utero -> removal of RBC via complement activation

Question 28

How is haemolytic disease of the newborn treated?

Answer 28

providing anti-Rh antibodies to the mother within 24 hrs of delivery to remove fetal RBC's in maternal circulation

Question 29

When does type III hypersensitivity occur?

Answer 29

if complexes composed of self or foreign antigen are excessively produced, and inefficiently cleared

Question 30

What does the severity of type III hypersensitivity depend on?

Answer 30

depend on size and amount | depend on affinity and isotype of antibody

Question 31

What does the pathology of type III hypersensitivity depend upon?

Answer 31

where complexes are deposited e.g. cationic antigen complexes bind to blood vessels and kidney glomeruli (SLE)

Question 32

How are immune complexes removed?

Answer 32

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

Question 33

What happens when immune complexes are not cleared?

Answer 33

neutrophil activation / complement activation / mast cell degranulation increased blood vessel permeability / blood flow activation of platelets results in occlusion of vessels

Question 34

What is vasculitis caused by?

Answer 34

immune complex deposition in blood vessel walls

Question 35

What is glomerulonephritis caused by?

Answer 35

immune complex deposition in kidney basement membranes

Question 36

What is arthritis caused by?

Answer 36

immune complex deposition in joint synovium and vessels

Question 37

What are the mediators of type IV hypersensitivity?

Answer 37

heavy involvement of T cells (and macrophages) | classically CD4+ Th1 but sometimes CD8+ CTL

Question 38

What is type IV hypersensitivity elicited by?

Answer 38

microbial infection, intradermal injection of protein antigens or contact with chemicals (absorbed through skin)

Question 39

What occurs during type IV hypersensitivity sensitisation?

Answer 39

antigen penetrates the skin and is taken up by local antigen presenting cells -> dendritic cell primes T cell in lymph node

Question 40

What occurs during type IV hypersensitivity response?

Answer 40

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

Question 41

What is the purpose of a tuberculin skin test (Mantoux test)?

Answer 41

detects the presence of Mtb-specific CD4 T cells (an example of type IV hypersensitivity)