The Degree of Immune Response Depends on Several Characteristics of the Antigen
The degree of immune response induced by an antigen is called antigenicity or immunogenicity. Understanding the characteristics of antigens that provoke a strong or weak immune response provides important insight into the body’s ability to combat invading antigens successfully.
Furthermore, this understanding is useful in designing a vaccine preparation with potent antigenicity. Characteristics that contribute to potent antigenicity include the following:1. Foreign versus self antigens. Antigens that are considered to be foreign to the host tend to be highly antigenic. For example, if a horse is injected separately with antigens that are derived from a dog or from its own tissues, the horse will mount a strong immune response to the dog antigens, but not to its own (self) tissues.
2. Size. The size of an antigen also influences the level of immune response. Large antigens enable better processing by antigen-presenting cells (e.g., macrophages, dendritic cells) and subsequent presentation of antigenic peptides to lymphocytes for induction of an immune response. Examples of large antigens include bacterial and insect toxins, viral capsids, surface proteins on protozoa and helminths, and venoms. At the other extreme, very small antigens (e.g., small synthetic antigens, endogenous hormones, pesticides, etc.) tend to be ineffective in provoking an immune response. Very small antigens are inherently incapable of inducing immune responses; however, when bound to a larger protein, they can be potent antigens. Such small compounds are referred to as haptens. A good example of a hapten is a poison ivy-derived chemical, urishiol1 which readily combines with many proteins (e.g., skin proteins) to induce a vigorous immune response.
3. Biochemical structure and complexity. In general, proteins tend to be more antigenic than lipids or carbohydrates.
Large size alone is insufficient to provoke a good immune response. For example, many sugars and lipids, even though large in size, are ineffective in inducing an immune response because they consist of simple repeating units (e.g., repeating sugars in starch), which lack complexity. Complex carbohydrates and lipids, on the other hand, as found in many microbes, are strong immunogens. Carbohydrates and lipids, when combined with protein to form glycoproteins and lipoproteins, respectively, have increased complexity and thus are good antigens.4. Stability and degradability. For immune cells to respond, stability of an antigen is an important feature. Flexible antigens, such as Aagellin in a bacterium, are poor immunogens. However, when stabilized and rendered less flexible, as done in vaccine preparations, Aagellin tends to be a potent immunogen. For an immune response to be initiated, the antigen ingested by phagocytic cells (e.g., macrophages) must be degraded and broken down into small peptides. Lymphocytes (T cells) will only respond to the peptides and not to large, native molecules. Antigens such as steel pins or plastic heart valves, even though large and complex, are inert and not degradable and thus are not good antigens.
Large, complex proteins (or lipoproteins or glycoproteins) that can be degraded and processed therefore tend to be excellent antigens. Other parameters that influence an individuaΓs ability to respond to antigens include genetics (e.g., major histocompatibility complex genes), endogenous biomolecules that regulate and modulate immune responses (e.g., hormones, neuropeptides), and the level and route of exposure of antigens.
An antibody that is induced in response to an antigen will specifically bind to the antigen. Any minor alteration of the antigen will negatively impact the antibody’s ability to bind to an antigen. Therefore» invading microbes often alter their antigens to prevent the binding of induced antibodies» thus avoiding immune attack.