Anaphylatoxins are small, potent molecules that are fragments of larger proteins, acting as messengers in the body’s immune system. They orchestrate immune responses, protecting the body from infections and contributing to various inflammatory processes. Understanding these molecules clarifies how the body responds to threats and how these responses can sometimes lead to disease.
How the Body Creates Anaphylatoxins
The body produces anaphylatoxins as part of the complement system, a complex network of proteins within the innate immune system. This system acts as a first line of defense against invading pathogens and damaged cells. When activated, the complement system initiates a cascade of reactions, leading to the cleavage of specific complement proteins.
The main complement proteins involved in generating anaphylatoxins are C3, C4, and C5. Enzymes known as convertases cleave these larger proteins into smaller fragments. For instance, C3 is cleaved into C3a and C3b, C4 into C4a and C4b, and C5 into C5a and C5b. The “a” fragments—C3a, C4a, and C5a—are the anaphylatoxins, which are then released to perform various biological functions. The generation of these fragments occurs through three primary pathways of complement activation: the classical, alternative, and lectin pathways.
The Many Roles of Anaphylatoxins in the Body
Anaphylatoxins perform several functions crucial for a healthy immune response. They promote inflammation, a natural process designed to protect tissues from injury or infection. These molecules act as signaling agents, drawing immune cells to areas where they are needed, a process called chemotaxis.
Anaphylatoxins, particularly C3a and C5a, attract various types of immune cells, including neutrophils, eosinophils, macrophages, basophils, and mast cells, to sites of infection or tissue damage. Once at the site, these cells help to neutralize threats and clear away cellular debris.
Anaphylatoxins also influence blood vessel dynamics, causing vasodilation and increasing vascular permeability. This allows immune cells and fluid to more easily exit the bloodstream and enter the affected tissues, facilitating the immune response.
These molecules also trigger the degranulation of mast cells and basophils. This is the release of stored substances, such as histamine, from these immune cells. Histamine further contributes to the inflammatory response by promoting vasodilation and increasing vascular permeability.
Anaphylatoxins and Health Conditions
While anaphylatoxins are beneficial in regulated immune responses, their uncontrolled activity can contribute to various health issues. Their name, “anaphylatoxin,” reflects their capacity to induce anaphylaxis, a severe allergic reaction. In anaphylaxis, C3a, C4a, and C5a trigger widespread mast cell and basophil degranulation, leading to symptoms like rapid vasodilation, increased vascular permeability, and smooth muscle contraction in the airways.
Anaphylatoxins also play a significant role in sepsis, a condition resulting from the body’s overwhelming response to an infection. In septic patients, elevated levels of C3a and C5a contribute to excessive inflammation and organ dysfunction, which can lead to multi-organ failure.
Furthermore, these molecules are implicated in Acute Respiratory Distress Syndrome (ARDS), a severe lung condition where fluid builds up in the air sacs. C5a, for example, can lead to the activation and accumulation of neutrophils in the lungs, contributing to lung injury. Dysregulation of anaphylatoxins is also linked to other inflammatory and autoimmune diseases, such as allergic asthma, rheumatoid arthritis, and lupus. In these conditions, persistent or inappropriate activation of anaphylatoxins can promote chronic inflammation and contribute to tissue damage.