The term “immunogenic” describes the ability of a substance, known as an immunogen, to provoke a response from the immune system. An immunogen acts as a trigger, initiating a series of defensive actions when recognized as a foreign entity. The intensity of this reaction is also part of what defines a substance’s immunogenicity.
This immune reaction can be intentional, as with vaccines, or undesirable, such as a response to a therapeutic drug. Understanding this process is necessary for developing safe and effective medical treatments.
Factors Determining Immunogenicity
A primary factor in immunogenicity is the degree to which a substance is recognized as foreign. The immune system distinguishes between its own “self” molecules and foreign “non-self” molecules, reacting strongly to substances that are significantly different from the body’s own components. For instance, a cow protein injected into a rabbit will cause an immune response because it is foreign, while the same protein injected into another cow will not.
Molecular size plays a significant part, as larger molecules are more immunogenic than smaller ones. Substances with a molecular weight greater than 10,000 daltons are potent immunogens, while smaller molecules may not initiate a response on their own.
The chemical makeup and complexity of a substance are also influential. Proteins, with their complex three-dimensional structures and varied amino acid sequences, are highly immunogenic. In contrast, simple, repetitive polymers like plastics or certain starches are less likely to provoke the immune system because they lack unique features for it to recognize.
For a substance to provoke a response, it must be degradable. Specialized antigen-presenting cells (APCs) must be able to engulf, break down, and present fragments of the substance to other immune cells. If a substance cannot be processed by APCs, it is unlikely to initiate an adaptive immune response, making this a required step for most protein-based immunogens.
The Body’s Reaction to an Immunogen
When an immunogen enters the body, it sets off a coordinated sequence of events called the adaptive immune response. This response is highly specific to the invading substance and involves specialized white blood cells called lymphocytes, namely T cells and B cells.
The process begins when antigen-presenting cells (APCs), such as macrophages or dendritic cells, encounter the immunogen. They engulf it and break it down into smaller pieces called antigens.
These APCs display the antigen fragments on their surface using molecules called the major histocompatibility complex (MHC). This antigen-MHC complex acts as a signal to a specific type of T cell, known as a helper T cell. When a helper T cell recognizes the presented antigen, it becomes activated and begins to orchestrate a broader immune attack.
Activated helper T cells then stimulate B cells, which also have receptors that can bind directly to the immunogen. When a B cell is activated by both the immunogen and a helper T cell, it multiplies and differentiates. Some of these B cells become plasma cells, which are antibody factories.
Plasma cells produce and secrete large quantities of antibodies, which are proteins that specifically match the antigen. These antibodies circulate throughout the body, binding to any remaining immunogens. This binding can neutralize the threat directly or mark it for destruction by other immune cells.
Other activated B cells and T cells develop into memory cells. These cells provide long-term immunity. If the same immunogen is encountered again, the immune system can mount a much faster and stronger response.
The Role of Immunogenicity in Medicine
In medicine, immunogenic properties are both harnessed and contended with. Vaccines are a prime example of desirable immunogenicity, introducing a controlled immunogen like a weakened virus or a fragment of a pathogen into the body. This safely provokes an immune response, generating protective antibodies and the long-term immunity provided by memory cells, preparing the body for future infections.
Conversely, immunogenicity can be an unwanted complication with biologic drugs, such as monoclonal antibodies. These medicines are complex proteins designed to target specific molecules involved in disease. The body can recognize them as foreign and mount an immune response, producing anti-drug antibodies (ADAs) that neutralize the medication, reduce its effectiveness, or cause adverse reactions.
Immunogenicity also helps explain allergies, which are misdirected immune responses to normally harmless substances. In an allergic person, common allergens like pollen or certain food proteins are identified as dangerous immunogens. This mistaken identity triggers an immune reaction, leading to the release of chemicals that cause allergy symptoms.
Immunogenicity Versus Antigenicity
The terms immunogenicity and antigenicity describe distinct, though related, properties. Antigenicity is the ability of a substance, an antigen, to bind to the products of an immune response, like antibodies or T-cell receptors. Immunogenicity is the ability to provoke and initiate that response in the first place.
A simple way to understand the distinction is that all immunogenic substances are also antigenic, but the reverse is not always true. An immunogen must both trigger a response and bind to the resulting antibodies or cells, whereas an antigen only needs to be able to bind.
A hapten provides a clear example of this difference. A hapten is a small molecule that is antigenic—it can bind to an antibody—but is not immunogenic on its own due to its small size. However, if a hapten attaches to a larger carrier protein, the combined molecule can become immunogenic. The hapten-carrier complex is large enough to be recognized as foreign, triggering an immune response that creates antibodies specific to the hapten.