Immune Dysfunction

Immunopathology is the branch of pathology dealing with the immune system and its response to disease and infection. The immune system is a complex defense system that functions to protect the body from disease. A properly functioning immune system is finely tuned to rapidly respond to invading infectious agents while ignoring benign agents and substances. The immune system relies heavily on the lymphatic system, which is made up of organs and cells that store and circulate fluids involved in immune response. The primary function of the lymphatic system is the collection and transport of lymph, a colorless fluid that contains white blood cells, which help fight infection. Due to the complexities of the immune and lymphatic systems, errors can occur, leading the immune system to overreact or underreact to various internal or external agents.

The immune system consists of three lines of defense that are categorized into innate immune defenses and adaptive immune defenses. The innate immune system involves aspects of general defense that are not specifically targeted against any particular pathogen. The first line of immune defense and innate immunity involves barriers to entry into the body. The skin, epithelium, and mucus coatings all provide protection that prevents pathogens or chemicals from entering the body. The diverse array of microorganisms that natively live on and in the body without causing disease also provides a barrier that makes colonization more difficult for potential pathogens. Similarly, many tissues of the body that are exposed to the external environment produce general-purpose antibiotic enzymes, such as lysozyme, that fortify tissues from pathogen colonization. The second line of innate immune defense consists of immune cells that kill invading cells in a nontargeted manner. Granulocytes (white blood cells that contain secretory granules), macrophages, and natural killer cells are all nonspecific and capable of destroying any type of invading pathogen. In contrast, the adaptive immune system that makes up the third line of defense consists of a complex array of cell types that recognize and target specific pathogens with antibodies. B and T cell lymphocytes, which include such types as cytotoxic T cells, helper T cells, and regulatory T cells, are part of the adaptive immune system. B cells produce antibodies, proteins that can be secreted from or bound to the surface of B cells and recognize and bind to specific antigens, while T cells perform a variety of functions such as directly destroying pathogens or recruiting other cells involved in an adaptive immune response. The three lines of defense work in conjunction with each other, and at the same time. An individual with an underreactive immune system is in a state of immunodeficiency, and their system's ability to fend off infection is compromised. When immunodeficiency results from genetic or developmental defects, it is called primary immunodeficiency or inherited immunodeficiency. Primary immunodeficiency is the failure (due to genetic or developmental defects) of the immune system to adequately protect the body from infections and other health problems. One example of primary immunodeficiency is X-linked agammaglobulinemia, or XLA. XLA is a genetic disorder resulting in the inability to produce B cells (lymphocytes responsible for producing antibodies). Severe combined immunodeficiency disease (SCID) is the most serious form of primary immunodeficiency. SCID involves a severe developmental defect in both the body's B-lymphocyte system and its T-lymphocyte system and testing for this disease is mandatory in some states.

Secondary immunodeficiency, also called acquired immunodeficiency, is the failure of the immune system to adequately protect the body from infections and other health problems. Secondary immunodeficiency can result from various extrinsic factors, including poor nutrition and pathogens, or it can be drug-induced by immunosuppressive therapies. Protein-energy malnutrition, or malnutrition as a result of a diet with little to no protein, leads to atrophy of the primary lymphoid organs (bone marrow and thymus, producers of B and T cells, respectively). Pathogens, such as human immunodeficiency virus (HIV), specifically attack T cells in the host immune system. This may lead to acquired immune deficiency syndrome (AIDS). People taking medications such as azathioprine to treat autoimmune diseases, such as Crohn's disease or ulcerative colitis, may suffer a suppression in the production of their white blood cells.

Immune dysfunction can also result in overreactivity. An immune system that is overly active, or hypersensitive, responds to benign threats in an exaggerated manner. In autoimmune disorders the hypersensitive immune system perceives the body's own tissues as a threat. Examples of autoimmune disorders include rheumatoid arthritis, type I diabetes mellitus, multiple sclerosis, and inflammatory bowel disease (Crohn's disease or ulcerative colitis). The immune system can also overreact to external agents in the environment, such as pet dander, plant oils (such as poison ivy and poison sumac), and pollen. A hypersensitive reaction, regardless of the inciting agent, can result in damage to a host's own tissues. It is often unknown why one individual develops hypersensitivity and another does not. People may have a genetic predisposition to developing allergies. Individuals with family members that have allergies are more likely to develop them. Some people also have atopy, a genetic predisposition to developing type I hypersensitivity.