Hypersensitivities Flashcards
Type I hypersensitivity
IgE causes release of mediators from mast cells leading to hypersensitivity.
Type II hypersensitivity
Mediated by Abs that binds tissue Ags and cause complement-dependent tissue injury and disease.
Type III hypersensitivity
Mediated by Abs that bind circulating Ags to form immune complexes that deposit in vessels and cause complement-dependent injury to vessel wall (vasculitis). Can have ischemic affects.
Type IV hypersensitivity (AKA delayed type hypersensitivity)
Mediated by T cells and results from inflammation caused from cytokines produces by Th1 and Th17 cells OR killing of host cells by CD8+ cells.
Atopy
Genetic tendency to develop allergic diseases.
“Most important mediators of Type I hypersensitivity” (4)
Vasoactive amines (His)
Proteases
PGs
LKs
Histamine causes:
Dilation of small BVs and increases vascular permeability.
Proteases cause:
Damage to local tissues.
Prostaglandins cause:
Vascular dilation.
Leukotrienes cause:
Smooth muscle contraction.
Cytokines cause:
Local inflammation (late phase reaction).
Sequence of type I hypersensitivity (3)
- Production of IgE after activation of Th2 cells by primary exposure to Ag.
- Binding of IgE to Fc receptors of mast cells.
- Release of mediators by mast cells after secondary exposure to Ag and cross-linking of membrane-bound IgE by Ags.
Immediate reaction in type I hypersensitivity
Vascular and smooth muscle reaction to allergen that develops within minutes.
Late phase reaction in type II hypersensitivity
Inflammation infiltrate with lots of eosinophils, neutrophils and T cells. Develops 2-24 hrs after.
Allergen testing
Assess type I.
Inject allergens into ventral arm in dermis.
Positive reaction is redness and swelling within 20-30 min.
Allergen-SIT
Performed by giving increasing doses of allergen to induce T cell tolerance, increase threshold for mast cells and basophil reaction and decrease IgE mediated His release.
Treg cells have an important role in successful allergen-SIT.
Sequence of type II hypersensitivity
- Ab-Ag deposits in tissues.
- IgG and IgM activates classical pathway which recruits WBCs and causes inflammation.
- IgG binds to neutrophils and Mo FcRs and activate a proinflammatory response.
- ROS and lysosomal enzymes released cause damage to tissues.
Which complement byproducts recruit leukocytes in an effector mechanism of type II?
C3a and C5a.
Mechanism of Graves’ disease
Abs specific for cell receptors for hormones or NTs stimulate activity of TSH receptors EVEN in the absence of TSH causing hyperthyroidism (type II).
Mechanism of Myasthenia Gravis
Abs specific for cell receptors for NTs inhibit binding of Ach to AchR (type II).
Major mechanism of type II hypersensitivity
Classical pathway activation and recruitment of leukocytes.
In all of type II disorders, injury is caused by:
Complement-mediated and Fc-receptor-mediated inflammation.
Arthus reaction
Induced by subcutaneous administration of protein Ag to a previously immunized animal. It results in immune complexes at site of Ag injection and local vasculitis (type III).
Autoimmune diseases mediated by type IV hypersensitivity (3)
MS
RA
Type I DM
Crohn’s disease
Inflammatory disease w/ microbial component. Has an autoimmunity component and is likely caused by abherrant reactions to microflora.
PPD is what? And causes what?
Protein Ag of tuberculosis.
Elicits a DTH reaction called “tuberculin reaction).
Allergic contact dermatitis (ACD)
Caused by environmental exposure to external agents in contact with skin.
Type of type IV.
Most commonly from metals.
Can occur at any age.
TB granulomas contain (3)
Activated Mo.
Multinucleated giant cells.
Lymphocytes (primarilty T cells).
In some, there may be a central area of necrosis.
Formation of a granuloma
- T cells home to the tissues.
- Th1 cells and activated Mo lead to production of TGF.
- IFN-y and TNF further stimulate Mo.
4 Over the course of several days to weeks a mature granulama is formed.
SLE overview
Type III.
Presents with rashes, arthritis, glomerulonephritis.
Auto-Abs are found (mostly anti-DNA Abs), creating immune complexes and cause the symptoms.
RA overview
Type II/III
Inflammation of synovium and destruction of joint cartilage and bone.
Cells involved: Th1, Th17, activated B cells, plasma cells, Mo.
Pts often have circulating IgM/IgG that react with Fc of own IgG (auto-Abs).
Principles of Immunotherapy (6)
Anti-inflammatory agents (steroids) Depletion of cells and Abs Anti-cytokine therapy Inhibit cell-cell interaction and leukocyte migration. IV IgG Treg cell-based therapies
