Hypersensitivity All Types
Hypersensitivity
Type I Hypersensitivity
Mechanism
Upon initial exposure to antigen, IgE antibodies are released from mature B cells (plasma cells).
These antibodies bind to mast cells (and basophils, not shown); the mast cells are now "sensitized."
Upon subsequent exposure to the same antigen, antigens bind to the antigens and cross-link them, leading to degranulation.
As a result, cytokines, membrane phospholipids, and granules are released form the mast cell.
Key mediators
Histamine, leukotrienes, prostaglandins, and platelet activating factor.
Recall that these are the mediators of acute inflammation, which, when excessive, cause damage to the tissues.
Manifestations
Early edema and erythema are often characterized by "wheal and flare" – the "wheal" is caused by vascular leakage and swelling; the "flare" is caused by vasodilation and reddening of the skin.
The later stage of type I hypersensitivity is characterized by eosinophilia in the effected tissues; chemokines released during degranulation and leukocyte activation attracts eosinophils, which release proteins that cause more tissue damage.
Anaphylaxis is a systemic and potentially fatal form of type I hypersensitivity; epinephrine is administered to reverse respiratory and cardiovascular effects.
Type II Hypersensitivity
Mechanisms
Example: transfusion reaction
Donor red blood cell have their own surface antigens.
Host IgG antibodies bind those antigens, which initiates the complement cascade.
As a result, a Membrane Attack Complex (MAC) forms and allows water influx into the red blood cell, causing lysis.
Manifestations
Blood cell destruction
Goodpasture's syndrome: damage to renal and lung tissue by anti-basement membrane antibodies.
Cellular dysfunction: antibodies that bind to cellular receptors, altering their activity.
For example, IgG antibodies can bind TSH receptors, with inhibitory OR stimulatory consequences, depending on their configuration.
Type III Hypersensitivity
Mechanism
When IgG-bound antigen deposits in tissues, complement and neutrophils are activated, with tissue destruction as a result.
Manifestations
Hypersensitivity pneumonitis, aka allergic alveolitis, is a local type III response to inhaled antigens; historically common in farmers who inhaled mold, fungi, and other environmental pathogens, it is increasingly common in office workers exposed to microorganisms in humidifiers and air conditioning systems.
Immune complexes activate complement in the alveoli, the site of gas exchange in the lungs. Then, local Arthus reactions thicken the lung interstitium, making gas exchange more difficult.
Serum sickness is a systemic example of a type III reaction.
It is induced by antibodies from other species. It is characterized by widespread effects, including rash, edema, joint pain, and fever.
Type IV Hypersensitivity
Mechanisms
In response to antigens, helper T cells release cytokines that recruit macrophages and neutrophils, which damage host tissues.
Cytotoxic cells directly damage host tissues via granzymes.
Manifestations
An example of helper T cell-mediated hypersensitivity is the tuberculin reaction test: a positive result, characterized by induration and erythema, indicates that an individual has been previously infected by M. tuberculosis.
An example of cytotoxic T cell-mediated hypersensitivity is contact dermatitis; in response to certain organic or metallic substances, such as poison ivy, cytotoxic T cells destroy host tissues and cause an itchy, red, vesicular rash.