Hypersensitivities Flashcards
Type I hypersensitivity reactions are mediated by
IgE and results from the actions of mediators by mast cells
Type II hypersensitivity reactions are mediated by
Abs that bind tissue Ags and cause complement dependent tissue injury and disease
Type III hypersensitivity reactions are mediated by
Circulating Ag-Ab complexes which deposit in vessels and cause complement dependent injury in the vessel wall (vasculitis)
Type IV hypersensitivity reactions are mediated by
T cells and results from inflammation caused by cytokines produced by CD4+ Th1 and Th17 cells, macrophages, or killing of host cells by CD8+ CTLs
What happens in the initial allergen encounter in type I hypersensitivity reactions?
Th2 and IL-4
Adaptive immune response by B cells that mature into plasma cells to make IgE to that allergen
What unique property does IgE have?
It enters the circulation and is rapidly bound by FcRe (CD23) on mast cells in the tissues
What occurs during the subsequent allergen encounter during a type I hypersensitivity reaction?
Cross linking causes mast cell degranulation that releases vasoactive amines, cytokines/chemokines and lipids
What are the important mediators of type I hypersensitivity reactions?
Histamine, proteases, prostaglandins, leukotrienes and cytokines
What role does histamine play during type I hypersensitivity reactions?
The major amine that causes dilation of small vessels and increases vascular permeability
What role do proteases play during type I reactions?
May cause local tissue damage
What role do prostaglandins have during type I reactions?
Cause vascular dilation
What role do leukotrienes play in type I reactions?
Stimulate prolonged smooth muscle contraction
Describe immediate phase of type I reactions
Characterized by vasodilation, congestion and edema
Describe the late phase of type I reactions
Develops 2-24 hours later
Characterized by an inflammatory rich in eosinophils, neutrophils and T cells
What are the aims of allergen SIT?
To induce peripheral T cell tolerance to allergens
To increase the thresholds for mast cell and basophil activation by allergens
To decrease IgE mediated histamine released by mast cells
What is penicillin induced anemia?
Type II hypersensitivity reaction
The drug binds directly to the RBC surface and induces an anti drug Ab
These conditions improve when the drug is discontinued
Describe Quinidine induced anemia
Type II hypersensitivity reaction
Auto Abs form immune complexes with the drug
The ICs can bind to the erythrocyte surface through CR1
Tx may require immunosuppression and/or plasmapheresis to remove the ICs
Describe methyldopa induced anemia
Type II hypersensitivity reaction
This drug induces an anti drug Ab that cross reacts with an Rh Ag
Tx may require immunosuppression and/or plasmapheresis to remove the auto Abs
List type II hypersensitivity reaction diseases
Autoimmune hemolytic anemia, autoimmune thrombocytopenic purpura, goodpasture’s syndrome, Grave’s disease (hyperthyroidism), Myasthenia gravis, pemphigus vulgaris, pernicious anemia and rheumatic fever
What is hemolytic disease of newborn?
During delivery of the first pregnancy, Rh antigens enter the mother’s circulation through breaks in the placenta -> mother makes anti-Rh Abs -> mother has anti-Rh Abs -> anti-Rh Abs cross the placenta and destroy fetal blood cells of the subsequent pregnancy
How can HDN be prevented?
By immunotherapy with anti-(anti-Rh) at around week 28 of pregnancy
Which diseases are associated with type III hypersensitivity reactions?
SLE, polyarteritis nodosa, post-streptococcal glomerulonephritis, serum sickness, arthus reaction
What causes the tissue injury seen in type IV hypersensitivity reactions?
Caused by inflammation induced by cytokines that are produced mainly by CD4+ T cells (Th1 and Th17 cells), macrophages and/or by killing of host cells by CD8+ CTLs
Autoimmune disease mediated by type IV hypersensitivity reactions include
Multiple sclerosis, rheumatoid arthritis and type 1 DM
Inflammatory disease with a microbial component associated with type IV hypersensitivity reactions
Crohn’s disease (IBD) is likely caused by the aberrant reactions to intestine microflora which have an autoimmunity component
The other diseases like tuberculosis are caused by reactions to microbial Ags
