Food Allergy - GIT Permeability, Antigen Entry, Immune Complexes

Von Pirquet first described serum sickness, the prototype of Immune Complex disease in 1925. Any food protein entering the circulation in sufficient quantity can produce symptom patterns resembling serum sickness.

If antigens make it into the blood stream, they combine with circulating antibodies to produce circulating immune complexes (CICs). BIN cells interact with CICs, triggering immune reactions with the release of symptom-producing mediators. Serum sickness manifests as a systemic illness, typically evolving over a period of 7-10 days. Manifestations include general malaise, fever, flushing, sweating, hives, swelling, bruising, aching in joints and muscles, progressing in the worst case to inflammatory disease in target organs with protein in the urine from kidney damage. Aleve Online

Food-enriched blood, coming from the gastrointestinal tract, goes through the liver where most immune-complexes are removed. If circulating complexes pass the liver filter, they may cause disturbances in many organs. The other path of absorption of molecules from the GIT is through lymphatic drainage. The lymph channels flow together to form the thoracic duct, a flimsy vessel which drains its contents into the subclavian vein. This pathway may direct antigenic molecules directly to the lungs where food antigens may excite asthmatic attacks, bronchitis, or more serious and enigmatic inflammatory lung diseases. The combination of antibody with antigen in the blood stream is a circulating immune complex (CIC).

CICs have the general form of: Antigen---Antibody

CICs may simply be removed from the circulation by macrophages or they may trigger a cascade of events which lead to multiple symptoms, and possibly tissue damage:

CICs ---> Mediator release ---> Symptoms

Mediators + Immune cells ---> Inflammation

CIC's activate complement, a circulating system of 25 proteins which interact to produce a variety of defensive molecular weapons. CIC's may not cause tissue injury unless access to tissue spaces is increased by leakiness of blood vessels, allowing influx of CIC's and cells. CIC's may not cause tissue injury unless vascular permeability is increased - allowing influx of CIC's and cells. The complement system modulates and amplifies the biological effects of CIC's.

The main function of the complement cascade is to assemble a drilling rig made of proteins attached to a cell wall and then to drill holes in the cell wall, allowing its contents to flow out. Complement intends to punch enough holes in a cell to kill it. If the attacked cell is a bacteria threatening to invade your private parts, your are happy with complement activity. If these drilling rigs are punching holes in your own cell walls, you will not be so happy. This sort of complement misadventure does occur. Like most immune attack systems, complement has go and stop mechanisms.

We can say that complement system modulates and amplifies the biological effects of CIC's. Once activated the complement cascades through a series of changes, producing powerful effects including anaphylaxis and blood cell damage. At the same time, certain complement products are essential to clear CIC's and to stop the cascade of cell damage. Individuals with deficiencies of complement proteins are at greater risk of developing immune-complex disease.

CIC's leave capillaries to trigger inflammatory events in target tissues. A classic model of complex-induced pathology is the Arthus reaction, which appears 3-6 hours after antigen challenge and involves large insoluble (Type 3) complexes with complement (C3b) passing through vessel walls to excite inflammatory responses in target tissues. The Arthrus reaction can be prevented by depleting C3 with Cobra venom.