Type II hypersensitivity

Abstract: This chapter examines each of the four types of hypersensitivity (HS) in turn, describing the immune system mechanisms involved, the resulting clinical pathology, and the therapies available to those who experience these reactions. Type I hypersensitivity, known as allergy or atopy, is mediated by IgE antibody specific for antigens that are normally non-pathogenic (allergens), such as plant pollens. In an atopic individual exposed to allergen, B cells produce allergen-specific IgE, which binds to FcɛRs of mast cells, “arming” or “sensitizing” these cells. Re-exposure to the allergen immediately triggers the sensitized mast cells to degranulate and release soluble inflammatory mediators that cause local symptoms such as dermatitis, urticaria, asthma, and rhinitis. Anaphylaxis is a systemic atopic response that can be life-threatening and requires immediate epinephrine administration. Type II hypersensitivity responses are due to the direct antibody (Ab)-mediated cytotoxicity that occurs when IgG or IgM antibodies bind to antigenic epitopes on cells, triggering antibody-dependent cell-Mediated cytotoxicity (ADCC), complement activation, and phagocytosis. Targets include mobile cells such as red blood cells or neutrophils, and cells fixed in tissues such as keratinocytes or epithelial cells. In type III hypersensitivity, IgG or IgM antibodies in the circulation bind to antigen and form large, insoluble immune complexes. These complexes become lodged in narrow channels in the body, triggering inflammatory responses that damage underlying tissues. Type IV hypersensitivity, as exemplified by chronic “delayed-type” hypersensitivity (DTH) reactions, contact hypersensitivity, and hypersensitivity pneumonitis, is delayed in character and is primarily due to the reactivity of T helper 1 (Th1) cells and macrophages that infiltrate a site of antigen exposure and induce tissue damage.

Abstract: The immune system plays a crucial role in maintaining health and protecting the human body against microbial invasions. However, this same system can lead to exaggerated immune and inflammatory responses that result in adverse outcomes known as hypersensitivity reactions. There are four traditional classifications for hypersensitivity reactions, and these include Type I, Type II, Type III, and Type IV reactions: Type I hypersensitivity is also known as an immediate reaction and involves immunoglobulin E (IgE) mediated release of antibodies against the soluble antigen. This results in mast cell degranulation and release of histamine and other inflammatory mediators. Type II hypersensitivity is also known as cytotoxic reactions and engages IgG and IgM antibodies, leading to the complement system activation and cell damage or lysis. Type III hypersensitivity is also known as immune complex reactions and involves IgG, IgM, and sometimes IgA antibodies. The build-up of these immune complexes results in complement system activation, which leads to polymorphonuclear leukocytes (PMNs) chemotaxis and eventually causing tissue damage. Type IV hypersensitivity is also known as delayed-type and involves of T-cell-mediated reactions. T-cells or macrophages are activated as a result of cytokine release, leading to tissue damage. There has been a more recent classification introduced by Sell et al. that accounts for multiple components of the immune system and categorizes the reactions into seven parts. However, the focus of this article will be on the classic Type I hypersensitivity reactions.Type I hypersensitivities include atopic diseases, which are an exaggerated IgE mediated immune responses (i.e., allergic: asthma, rhinitis, conjunctivitis, and dermatitis), and allergic diseases, which are immune responses to foreign allergens (i.e., anaphylaxis, urticaria, angioedema, food, and drug allergies). The allergens that result in a type I hypersensitivity may be harmless (i.e., pollen, mites, or foods, drugs, etc.) or more hazardous such as insect venoms. The reaction may be manifested in different areas of the body and may result in instances such as: Nasal allergic rhinitis or hay fever Ocular allergic conjunctivitis, potentially due to seasonal allergens such as pollen or mold spores Dermatological hives, atopic eczema, or erythema Soft tissue angioedema Pulmonary reactions, such as allergic asthma or hypoxia Systemic reaction, which is a life-threatening medical emergency, and also known as anaphylaxis. There are certain risk factors that increase the risk of allergic diseases. These factors include geographical distribution, environmental risks such as pollution or socioeconomic status, genetic predisposition, or the “hygiene hypothesis”. The “hygiene hypothesis” suggests that our modern society practices of good hygiene and the lack of early exposure to many microbes or antigens may result in failures of the immune system functionality. As such, the hypothesis suggests that early exposure to a diverse range of microorganisms and antigens may actually lead to overall decreased rates of allergies, asthma, and other immune disorders.