Hypersensitivity Reactions Flashcards
Type I: immediate-type Hypersensitivity Reactions
Antigen type: soluble antigen
Effector mechanism: Mast cell activation
Timing: Within minutes of exposure to allergen
Examples and results: pollen, pet dander, dust mite feces, food, and the wheal-and-flare result of allergy testing or bug bites; Anaphylaxis, urticaria, and allergic rhinitis
Process: An allergen enters the body and is picked up by an APC. The APC heads to the secondary lymphoid tissues and present the antigen to a T-cell. The T-cell produces TH2 cells, which the activate B-cells. The B-cells then initiate class switching to IgE antibodies. IgE antibodies bind to and are cross linked to the FcE receptors on mast cells. Type I hypersensitivities are initiated by mast cell degranulation upon IgE’s binding an antigen
NOTABLES:
No one is born with an effector response to any allergen. There must be an initial exposure to generate a primary immune response (without symptoms) followed by a second exposure that elicits the hypersensitivity response (with symptoms).
Allergens must be PROTEINS/proteins/proteases because they must be T-dependent antigens that can bind to MCH Class II molecules.
Effector Molecules of Mast Cells (Contents of Mast Cell Granules)
1) Tryptase, chymase, cathepsin G, carboxypeptides
2) Histamine and heparin
3) TNF-alpha
4) IL-4 and IL-13
5) IL-3, IL-5, and GM-CSF
6) Leukotrienes C4, D4, and E4
Enzymes from mast cells that remodel connective tissue matrix
tryptase, chymase, cathepsin G, and carboxypeptidases
Mast cell effector molecule that increase vascular permeability and cause smooth muscle contraction
histamine and heparin
Histamine is quite clinically important
Both of these are toxic to parasites
Cytokines that stimulate and amplify TH2-cell response
IL-4 and IL-13
Cytokines that promote eosinophil production and activation
IL-3, IL-5, and GM-CSF
Mast cell granules that cause smooth muscle contraction, increase vascular permeability, and cause mucous secretion
Leukotrienes C4, D4, and E4
Result of mast cell degranulation in GI tract
Increased fluid secretion and increased peristalsis, leading to vomiting and diarrhea (AKA explosion of allergen/parasite)
Result of mast cell degranulation in airways
Increased mucus secretion and decreased diameter of airway resulting in phlegm, sneezing, coughing, wheezing, and difficulty breathing
Result of mast cell degranulation in blood vessels: local
Increased blood flow and permeability, resulting in activation of vascular endothelium and the subsequent movement of fluids and proteins from vasculature into the inflamed tissue. Edema, inflammation, increased lymph flow and carriage of antigens to lymph nodes.
Result of systemic mast cell degranulation in circulation
The usual increased permeability and influx of fluid to tissues; swelling of tissues, including tongue; loss of BP and less O2 to tissues; anaphylactic shock and loss of consciousness.
Type II: Altered self hypersensitivity reactions
Antigen type: a) cell-associated antigen; b)cell-surface receptor
Effector mechanism: a) complement, phagocytes, and NK cells; b) antibody alters signaling
Timing: 4-12 hours
Examples and results: a) Penicillin-induced => rash and b) chronic urticaria
Process: Allergen-specific IgG antibodies initiate the reaction. The inflammatory response is mediated by complement cascades, phagocytes, and NK cells.
What happens when a patient has a hypersensitivity type II reaction to penicillin?
A patient has an infection and gets penicillin. Penicillin binds to and modifies surface determinants of RBCs. Macrophages have meanwhile up-regulated B7 and infection-control capabilities, so they bind RBCs and present them to naive T-cells. The effector T-cells provide second signal of activation to B-cells with specificity for altered RBCs. IgG antibodies bind/opsonize RBCs bound to penicillin. RBCs get coated with C3b and are either taken up by phagocytes or lysed by MAC complex.
Result: large-scale destruction of RBCs that does’t stop until all altered determinants have been recycled off the surface of RBCs.
Type III: Immune Complex Hypersensitivity Reactions
Antigen type: Soluble antigen
Effector mechanism: Complement and phagocytes
Timing: 1-2 hours
Examples and results: serum sickness and Arthus reaction
Process: An allergen is introduced to the tissues underlying the epithelium. IgG antibodies specific for the allergen bind it and activate the classical complement cascade. Anaphylatoxins from the cascade bind to C5a receptors on mast cells underlying the tissues, resulting in mast cell degranulation and inflammation. Macrophages and neutrophils also recognize the opsonized antigens and produce inflammatory mediators. If too many immune complexes accumulate and cannot be cleared, they deposit along vasculature, especially within the kidney glomeruli (glomeruli nephritis is irreversible!). Vasculitis in the brain and systemically can also result. These reactions can be life threatening because they progress to anaphylactic response. A patient presents like a septic shock patient.
NOTABLES:
Type II hypersensitivities often become type III.
Because C5a initiates systemic mast cell degranulation, this response can be life threatening, and patients present like a septic shock patient.
Most reactions occur after IV administration; those that are chronically inhaled are called “Farmer’s Lung”; those that result from inhalation of bird dropping antigens are called Pigeon Breeder’s Disease, Poultry Worker’s Lung, or Bird Breeder’s Disease.
Type of hypersensitivity caused by inhalation of antigens from bird droppings
Pigeon Breeder’s Disease, Poultry Worker’s Lung, or Bird Breeder’s Disease
