L24: Hypersensitivity Flashcards
What are the 4 types of hypersensitive reactions?
→Type 1: immediate hypersensitivity
→Type 2: cytotoxic hypersensitivity
→Type 3: serum sickness and Arthus reaction
→Type 4: delayed-type hypersensitivity, contact dermatitis
Describe Type I allergy reaction
→Initial exposure to the antigen causes the priming of Th2 cells, and their release of IL-4 causes the B cells to switch their production of IgM to IgE antibodies which are antigen-specific
→IgE antibodies bind tomast cellsand basophils, sensitising them to the antigen
→When the antigen enters the body again, it cross links theIgEbound to the sensitised cells, causing the release of preformed mediators
What should be included in a skin prick test?
→positive control
→negative control
What does Type 2 hypersensitivity reactions respond to?
→altered components of human cells
Give 4 example of a type 2 hypersensitivity
→penicillin modifies proteins on human erythrocytes to create foreign epitopes
→Grave’s disease
→myasthenia gravis-Antibodies block or destroynicotinic acetylcholine receptorsat thejunction between the nerve and muscle
→– Hemolytic disease of the newborn
Describe type 2 cytotoxic hypersensitivity
→Antibodies binding to cells can activate the complement system, leading to degranulation ofneutrophils
→Antibody-bound cells are cleared by:
FcgR+ cells such as macrophages
What is a special case of Type 2 response?
→involves IgG antibodies directed at cell-surface receptors
→ these antibodies disrupt the normal functions of the receptor by either:
→ uncontrollable activation or blocking receptor function
Describe haemolytic disease of the newborn
during birth, Rh+ fetal erythrocytes leak into maternal blood after chorion breaks
→maternal B cells are activated by Rh antigen and produce anti-Rh antibodies
→Rh antibody titre in mother’s blood
→Rh antibodies are small enough to cross the chorion and attach the foetal erythrocytes in second pregnancy
Describe Type 3 response
→IgG and soluble antigen form immune complexes eg complement which causes tissue damage
→activation of Fc-gammaR3 on mast cells induces their degranulation
→Immune complexes are cleared by phagocytes
Give examples of Type 3 response
→diptheria/tetanus vaccination
→antivenom
→farmer’s lungs
What is a difference between Type 2 and 3 reponse?
→Type 2= antigens are cell bound
→Type 3= antigens are soluble
Describe delayed-type hypersensitivity
→Th1 mediated response
→release IFN-gamma to activate macrophage
→production of chemokines, cytokines, cytotoxins
Th2 mediated:
soluble antigen
→Th2 activate eosinophil via IL-4,5, eotaxin
→production of enzymes and cytokines
Give examples of Th1 and Th2 mediated Type 4 reponse
→Th1= Tuberculin reaction
→Th2= Allergic contact
dermatitis
Give example of Type 4 reponse
→Mantoux test
→strong Th1 immune
Where does IgE bind?
→high affinity receptor of FcεR1 receptor on mast cells also oesoniphils
How do Bcells inform class switching?
→Th2 cells produce Il4 and IL13 which informs Bcell to switch to IgE
What might high dose exposure lead to?
→tolerance
What are the features of inhaled allergens that promotes Th2 priming?
→proteins- only proteins induce T-cell response →enzymatically active →low dose →low molecular weight so can diffuse →highly soluble →stable →binds to MHC-2
What is filaggrin?
→links skin integrity and allergy
What happens when filaggrin is defective?
→atopic dermatitis is greater
Which protein may make dendritic cells pro-allergic?
→TSLP
→TH2 signalling molecule
Describe mast cell activation
→antigen cross links bound IgE antibody, causing release of granule contents
→IgE produced upon first exposure
What is early phase allergic response?
→mast cells
What is late phase response mediated by?
→mediated by T cells
→recruit other cells by cytokine release
→Potentiate further responses
