Chapter Summary

Autoimmunity occurs when the body’s immune system mistakenly attacks its own cells, tissues, or organs. To understand this condition, it important to understand the components and mechanisms of a functional immune system. Autoimmune conditions may be caused by a combination of environmental and genetic factors, which may trigger an autoimmune attack. Autoimmune attacks can lead to numerous autoimmune diseases, as well as other conditions with an autoimmune component (but are not considered primarily autoimmune diseases).

Pathogens are present in our environment, entering our bodies through food, water, surfaces, and air. Mammalian immune systems have evolved to detect and combat these threats using a complex network of specialized immune cells. Features of the immune system, such as pathogen identification, specific response, amplification, retreat, and remembrance are essential for survival of infectious diseases.

The innate immune system serves as a first responder to pathogenic threats. Innate immunity includes both physical and chemical barriers as well as molecular attack. The innate immune system responds with inflammation, phagocytosis, cytokine release, destruction by NK cells, and/or the complement system. When innate mechanisms are insufficient to clear a pathogen, the adaptive immune response is mobilized.

The adaptive immune response is slower-acting, longer-lasting, and more specific than the innate response. APCs display antigens via MHC molecules to complementary naive T cells and, in response, the T cells differentiate and proliferate, becoming T_H cells or CTLs. Immunologic memory can persist after a primary exposure to a pathogen. If re-exposure occurs, the adaptive immune response can proliferate without input from the innate immune system.

Antibodies (immunoglobulins) are secreted from plasma cells and mediate the humoral immune system. There are five antibody classes which determines its mechanism of action and production site, but does not control its binding specificity. Antibodies bind antigens via variable domains and can either neutralize pathogens, mark them for phagocytosis, or activate the complement cascade.

Immune disruptions can manifest as either an insufficient immune response or a response to non-pathogenic entities. Immunodeficiency increases an individual’s susceptibility to infections and even some cancers. Hypersensitivities are misdirected responses to harmless foreign particles (allergy) or host factors (autoimmunity).

Celiac disease is characterized by an autoimmune response triggered by the consumption of gluten, a protein that is found in food products containing wheat, barley, and rye. Gluten is incompletely digested into gliadin in the small intestine, and through binding to immunoglobulins, it is falsely presented to MHC II and inflammatory cytokines are produced. The current recommendation for celiac disease treatment is following a strict gluten free diet (GFD), which in most cases removes all symptoms.

Rheumatoid arthritis is a chronic inflammatory autoimmune disorder affecting the joints. It primarily affects the synovial joints, but can also affect the skin, lungs, and other organ systems. Because synovial joints are metabolically active, the synovial membrane has many blood vessels and lymphatics running through them, which makes them more vulnerable to autoimmune dysfunction. Rheumatoid arthritis is a progressive condition, but can be treated through anti-inflammatory or immunosuppressant drugs.

Vitiligo is a skin condition defined by localized patches of depigmentation of the skin, irises, and hair. There are two main types of the disease: non-segmental and segmental vitiligo. Non-segmental is an autoimmune condition and makes up ~85% of all vitiligo cases, while segmental vitiligo is far less common and is not autoimmune. Vitiligo treatment, although not necessary, includes cosmetic coverup, skin grafting/bleaching, and topical immune suppressants

Graves’ disease is an autoimmune disorder that causes hyperthyroidism, resulting in excess release of thyroid hormones. Graves’ is a type II hypersensitivity reaction, and is most common in middle aged women, smokers, and people who experience high levels of stress. The three main symptoms of Graves’ disease include hyperthyroidism, ophthalmopathy, and dermopathy. Treatment includes beta blockers, anti-thyroid drugs, and in extreme cases, thyroid destruction or removal.

Systemic lupus erythematosus (SLE) is an autoimmune condition that can affect many organs and tissues, but most frequently the skin. SLE autoimmune reaction includes the activation of the complement system and is classified as a type III hypersensitivity reaction. Sex hormones play an important role in the very uneven distribution of SLE in women of child-rearing age compared to men. Treatment is aimed at avoiding environmental triggers during remittance, and immunosuppression during flares.

Credits

Authors: Morgan Alford (UBC) and Dylan Mann (UBC)