History of Allergy

The concept of allergy is relatively recent in the history of clinical medicine. Until the late 19th century allergy was not considered to be a medical discipline. In fact, the concept of hypersensitivity reactions to generally innocuous substances present in the environment had not yet been developed. Seasonal catarrh or “hay fever” was seen as toxic reactions to various plant products, and therapies were developed to neutralize these “toxins.”

In the early 20th century, scientific interest in allergy blossomed. Researchers began to explore the clinical reactions and mechanisms through which exposure to various substances in the environment produced symptoms. Challenge models were developed in which crude antigens from plant extracts were placed onto mucosal surfaces such as the nasal mucosa or conjunctiva, and responses were assessed related to these specific exposures. Researchers such as Noon began to quantify these responses and assess the degree of reactivity generated by various exposures. He related the degree of response to the robustness of the allergic sensitivity, and developed a rudimentary quantification scheme for measurement. He then applied this scheme to a specific treatment algorithm, and demonstrated in the 1920s that immunotherapy for inhalant allergy could be successfully implemented using these quantitative data.

Clinical interest in allergy developed steadily over the first half of the 20th century. Allergy practice flourished both in internal medicine and in otolaryngology, and numerous practice modalities were recommended during this time. Many papers and texts were written to promulgate treatment based on these various approaches. In addition, professional societies were founded within both medical specialties to further the practice of allergy and to foster communication of techniques and outcomes. These societies continue to the present day, and are very active and influential in the coordination of allergy care.

Despite a strong clinical interest in allergy and an active system of clinical practice, the causes of allergy were not well understood until the 1960s. During that period of time Johannson and Ishizaka independently isolated immunoglobulin E from the serum of allergy patients and demonstrated its primary role in clinical allergy. This development demonstrated the molecular basis of allergy and allowed both a rapid progression of the science related to allergy practice as well as the growth of standardized in vitro serum tests for specific IgE. These developments continued to foster a growth in clinical allergy practice, and led to the rapid influx of clinical and scientific research in the field of allergy-related immunology. These interests continue to the present day.

Allergy continues to be a prominent area of practice within clinical medicine, although the number of trained practitioners within medicine, pediatrics, and otolaryngology is relatively small in comparison to the number of physicians practicing other areas of medicine. In fact, practitioners of allergy account for only about 1% of the physicians practicing clinical medicine in the developed world, with a lesser number active in the developing world. Despite the large prevalence and impact of allergic diseases such as rhinitis, asthma, eczema, and urticaria, a small force of trained physicians is charged with care of the allergic patient.

It is the purpose of this textbook to review clinical allergy as it affects the diagnosis and treatment of the patient with allergic diseases. The text is meant to be clinically practical and of direct application for physicians and allied health personnel across medical specialties, both within the fields related to clinical allergy and in the primary care disciplines. It will provide the user with practical information on the assessment and management of patients with various allergic diseases, and will also discuss the pathophysiological and mechanistic bases for clinical practice. Allergic diseases remain a challenge for physicians and other health care professionals, and this textbook will attempt to address that clinical challenge in a practical and straightforward manner.

Prevalence of Allergic Diseases

In general, studies have suggested that allergic diseases, both respiratory and nonrespiratory, are steadily increasing in prevalence. This rise has been seen around the globe, not only in the west but also throughout the developing world. It has been estimated that 25% to 30% of the population in the western world are affected by allergic illnesses on a yearly basis, with a somewhat lower prevalence in the developing world. By a variety of indicators, the prevalence of allergic diseases such as rhinitis and asthma continue to grow steadily.¹

In order for patients to develop allergic hypersensitivity, and therefore to express allergic symptoms, they must have the genetic predisposition to respond in this manner. This predisposition to develop allergy is referred to as atopy. Individuals who are able to develop these allergic responses are said to be atopic. Atopy is genetically determined, with children of allergic parents more likely to develop allergy than children whose parents are not allergic. In fact, if both parents are allergic, the likelihood of an individual developing clinical allergy is greater than 50%.

Allergic diseases occur throughout the lifespan, but often have their origins in childhood. Infants and young children are often sensitized to foods and other macromolecules absorbed through the gut, and develop a variety of hypersensitization symptoms such as colic and eczema. These sensitivities can be enhanced by maternal food allergies, and these allergies have been demonstrated to be transmitted placentally. Among these atopic children, exposure to aeroallergens over the first few years of life often causes additional sensitization, resulting in the development of upper respiratory allergy and the condition known as allergic rhinitis. Allergic rhinitis also has a very strong genetic predisposition, with up to two-thirds of children with both parents suffering from allergic rhinitis also demonstrating symptoms of this disease. Concurrent with the development of allergic rhinitis is a rise in IgE levels in children. As will be discussed later in this chapter, IgE is the immunoglobulin involved in the immune response, and levels of IgE become significant in allergic children after the age of 2 years. Allergic rhinitis is quite common in childhood, with studies suggesting that up to 40% of children may be diagnosed by their physician with allergic rhinitis by the age of 6 years.

In many children with allergic rhinitis, respiratory inflammation continues to worsen over time, not only affecting the upper airway but beginning to cause disease in the lower airway as well. Lower airway inflammation, referred to as asthma, is a common disease of both childhood and adulthood, with prevalence rates in the population of about 8% worldwide. Asthma is more common among patients with allergic rhinitis than among the general population, with allergic rhinitis patients demonstrating a threefold increase in the development of asthma over time. While not all asthma is atopic, and while early childhood asthma is associated with infectious causes such as respiratory syncitial virus, the major identifiable predisposing cause for asthma is allergic disease. In fact, some studies suggest that allergy may be present in most, if not all, patients with significant asthma.

This progression of allergic disease from food-mediated colic and eczema, to allergic rhinitis, and finally to asthma has been referred to as the allergic march, implying that allergic disease will continue to progress in a steady manner from early childhood into adulthood.² It is unclear at this time whether early aggressive intervention can prevent or blunt this progression of disease. It is clear, however, that this allergic march is common in many children with atopic disease.

Burden of Allergic Diseases

Allergic rhinitis, asthma, and other atopic diseases are not only characterized by bothersome symptoms, they also carry a significant burden to patient function and quality of life. While diseases such as allergic rhinitis are sometimes considered trivial by physicians and other health providers, they have great impact on the daily activities of the individuals who are symptomatic. In addition, other atopic diseases such as asthma not only impact quality of life and daytime function, but can be life threatening if not appropriately recognized and managed. For that reason, atopic diseases should be suspected given characteristic signs and symptoms and should be managed actively and effectively.

For example, allergic rhinitis has been demonstrated to affect a daytime function in both children and adults.^3,4 These studies suggest that over 90% of children and adults have noted disruption in their abilities to work productively in the workplace or in the school when their rhinitis is symptomatic. Nearly one in four of these adults and children have missed work or school due to their symptoms. These findings demonstrate that allergic rhinitis is not only bothersome in terms of its adverse symptoms, it will impact the ability of adults and children to perform the general activities of their daily living, such as work and school attendance. Similar findings have been reported in a number of studies.

In addition, in patients with allergic rhinitis, the presence of the disease impacts on other aspects of function. Children with allergic rhinitis learn less effectively than those without the disease.⁵ Adults and children with allergic rhinitis have difficulty falling asleep and staying asleep.⁶ Furthermore, many of the older treatments for allergic rhinitis, particularly the first-generation antihistamines such as diphenhydramine, further adversely affect quality of life and function through their sedating and anticholinergic side effects.⁷

While the effects of upper airway allergy on function and quality of life can be significant, the adverse effects of asthma are even more dramatic. Asthma is a disease that is often poorly treated, due to a variety of factors including poverty, delay in diagnosis, inappropriate treatment, and patient nonadherence. It affects sleep, learning, daytime function, and has a significant negative impact on quality of life. Asthma deaths continue to number around 180000 annually on a worldwide basis, with delay in diagnosis and inadequate treatment being primary driving factors.⁸

The impact of these chronic diseases is substantial in the population around the world. Awareness of the signs and symptoms of atopic diseases and knowledge about effective treatment methodologies for managing these diseases is often lacking. Only through continued vigilance and sensitivity to the role of atopy in chronic disease will intervention strategies improve and effective management of these illnesses be possible.

Comorbidities of Allergic Diseases

Allergic diseases can be expressed in many different organ systems. While respiratory allergies are the most common group of allergic illnesses, allergic reactions can affect the eyes, the skin, and the gastrointestinal tract. These various allergic responses can be triggered by a wide variety of substances, which can be inhaled, ingested, injected, or contacted directly onto a mucosal surface. In addition, these allergic responses can be immediate in onset or delayed, and can be brief in duration or prolonged.

The majority of allergic diseases affect the upper and lower respiratory tracts. Respiratory illnesses that have a very direct allergic pathogenesis include allergic rhinitis and asthma. Other respiratory illnesses such as otitis media and acute and chronic rhinosinusitis have significant elements of allergy, at least in the expression of their symptoms, and perhaps in their pathogenesis as well (Figure 1.1). Among patients with allergic rhinitis, both adults and children, there is a greater prevalence of these other allergic illnesses than in the nonallergic population. In addition, among patients with allergic rhinitis, there is a higher likelihood of the development of rhinosinusitis, asthma, and otitis media than in patients who do not have allergic rhinitis. For that reason, the presence of allergy must be considered in any individual who presents with chronic respiratory symptoms, either upper or lower.

Figure 1.1 Comorbid allergic diseases.

Over the past decade, an awareness of the close interrelationship between upper and lower airway inflammatory diseases has been appreciated. Due to similarities in epithelial cells and membranes, inflammatory mediators, and pathophysiological mechanisms, the entire airway has been conceptualized as a unified system. It has been observed that diseases that affect one portion of this airway system will often affect other respiratory sites as well. This observation has led to a model described as the “unified airway model,” also known as the model of “one airway, one disease.”^9,10 Allergic rhinitis and asthma, therefore, are considered diseases along a pathophysiological spectrum, whose mechanisms exert similar influences in discrete portions of a unified airway system. This model has been useful conceptually, in explaining many observations of concurrent inflammation in both the upper and lower airway.

In 2000, the World Health Organization brought together an international panel of experts to examine the association between upper and lower airway inflammatory diseases. This panel issued a consensus document known as the ARIA document (Allergic Rhinitis and its Impact on Asthma). In the ARIA guidelines, the close association between allergic rhinitis and asthma was detailed, with specific recommendations for treatment of these coexisting diseases. The document stated “The upper and lower airways may be considered as a unique entity influenced by a common, evolving inflammatory process, which may be sustained and amplified by interconnected mechanisms.” In addition, it went on to argue that “When considering a diagnosis of rhinitis or asthma, an evaluation of both the upper and lower airways should be made.”¹¹

Despite this common existence of allergic diseases, both in allergic rhinitis and asthma as well as in related illnesses, the diagnosis of allergy is seldom entertained. Many clinicians fail to consider a diagnosis of allergy among patients with chronic respiratory illnesses or other types of chronic inflammation. Patients will rarely present to the clinician with the complaint of “allergies,” unless they have what are considered classic seasonal allergic symptoms such as sneezing. In order for clinicians to diagnosis a patient with an allergic disease, and for them to initiate appropriate treatment based on that diagnosis, they first must be vigilant and open to the possibility of allergy being present. This level of clinical suspicion is critical among physicians and other health care personnel and should be reinforced and encouraged.

In order to better appreciate the range of allergic diseases, an understanding of the basic and clinical science involved in these illnesses is important. An appreciation for and working knowledge of these areas is vital for the clinician in clinically assessing the patient, reaching an appropriate diagnosis, and formulating and carrying out an effective treatment plan.

Basic Immunology

The primary function of the immune system is to guard against invasion of the host organism by foreign substances. It is composed of a number of interrelated elements, including cells and soluble mediators, which work as an integrated unit in defending the body from injury. These factors utilize a variety of mechanisms to regulate immune function and to protect against: (1) invasion from external pathogens such as viruses, bacteria, and parasites, and (2) malignant transformation of cells. The immune system has evolved over many thousands of years and is highly efficient and effective in the human species.

The immune system is adaptive yet specific. It is able to respond to a wide variety of environmental challenges, and to do so in a way that is specifically directed toward the type and magnitude of the assault. It is programmed by exposure to foreign invaders, and has memory for those specific invaders that allows it to respond with robustness and immediacy to additional challenges.

The term “immune” is derived from the Latin word immunitas that refers to the specific exemption that was granted to Roman senators in their state duties. This concept is carried forward into today’s legal system, where witnesses can be given immunity from prosecution for cooperating with a criminal investigation. In health and disease, the immune system is designed to provide this same exemption or protection through preventing or limiting the effects of the disease on the organism. The immune system has a number of properties, which are detailed in Box 1.1.

Immune System Components

The immune system is composed of both cellular and molecular components that are involved in various regulatory and effector functions. The molecular components of the immune system include specific agents, such as antibodies and antigens, and nonspecific agents, such as cytokines. These two components work in a coordinated manner in controlling and facilitating the immune response.

▪ Cellular Components of the Immune System

All of the cells of the immune system are derived from pluripotent stem cells in the bone marrow. During hematopoiesis, these cells will develop along two cells lines: lymphoid and myeloid. The lymphoid lineage will differentiate into three types of discrete immune cells: B lymphocytes, T lymphocytes, and NK (natural killer) cells. These cells are involved in all aspects of the immune response. The myeloid lineage, in contrast, will differentiate into all the other blood cells, including erythrocytes, platelets, neutrophils, eosinophils, basophils, monocytes, and mast cells (Box 1.3). With the exception of the erythrocytes and platelets, the remaining cells are referred to as leukocytes.

BOX 1.3 Cellular components of the immune system (leukocytes)

Lymphoid cells

B lymphocytes

T lymphocytes

NK cells

Myeloid cells

Monocytes

Macrophages

Dendritic cells

Antigen-processing cells

Granulocytes

Neutrophils

Eosinophils

Basophils

Mast cells

Lymphocytes

Lymphocytes are derived from the pluripotent stem cells in the bone marrow. They are then differentiated by passage through the thymus (T lymphocytes) or will mature in the bone marrow directly (B lymphocytes). Lymphocytes are the only cells that are capable of recognizing specific epitopes of antigens, and are therefore responsive for the specificity of the immune system. Lymphocytes account for 20% of circulating leukocytes. Lymphocytes are classified according to markers present on their surfaces, according to a system known as clusters of differentiation (CD). In addition, T lymphocytes also contain T-cell antigen receptors, or TCRs. B cells and T cells have similar structures, yet differ in their functions and mechanisms of action.

T cells function as critical regulatory inflammatory cells involved in the control of the immune response. All T cells contain the CD3 surface marker, which can be used to differentiate T cells from other lymphocytes. T cells can be further segregated into two specific classes: T-helper cells and T-suppressor cells. T-helper cells are distinguished by having CD4 surface markers, while T-suppressor cells have CD8 surface markers. Both cells lines contain T-cell receptors.

T-helper cells are further divided into two populations: T-helper-1 (Th1) cells and T-helper-2 (Th2) cells. Th1 cells respond primarily to invasion by microbial pathogens, and elaborate specific Th1 cytokines, including interleukin (IL)-2, IL-3, and interferon (IFN)-gamma. They mediate cytotoxicity and local inflammatory responses. Th2 cells, by contrast, are more involved in the humoral response, and are the primary T cell population involved in allergy and atopy. Th2 cells elaborate different cytokines, referred to as Th2 cytokines, including IL-4, IL-5, IL-6, IL-10, and IL-13. These cytokines are involved in shifting the immune response toward the Th2 orientation, and in shifting the production of antibody toward immunoglobulin (Ig) E, the antibody primarily responsible for the allergic response (Figure 1.2).

Figure 1.2 Cytokine profiles and induction of Th subsets.

(Reproduced with permission from Holgate ST. Allergy, 2nd edn, p 271, figure 17.13. Published by Mosby–Elsevier Inc. ©2001.)

T-suppressor cells are involved in regulation of the immune response. They are responsible for feedback regulation in keeping the immune response from escalating out of control. They do not play a significant role in the pathogenesis of allergic disease.

B lymphocytes are responsible for maintaining memory for antigen exposure, and for the secretion and elaboration of specific antibodies. Naïve mature B cells are able to express only nonspecific IgM and IgD, but after activation are programmed to produce specific immunoglobulins, IgA, IgG, and IgE. On direct interaction with T cells, cell-to-cell contact initiates differentiation of the B cell specific for a single antigen. The B cell then will further differentiate into either a B memory cell, which will be vigilant for subsequent antigen exposure, or into a plasma cell, which will produce large amounts of specific immunoglobulin.

Null cells are lymphocytes without surface markers. They do not secrete immunoglobulins, and are involved in the surveillance of cells for malignant transformation and viral infection.

Mononuclear cells

The mononuclear phagocyte system has two specific functions: phagocytosis of foreign material and processing and presentation of antigens to T cells by antigen-presenting cells. Phagocytosis is important in nonspecific clearance of foreign antigens. Antigen presentation is critical to the specific functions of the immune system in surveillance, memory, amplification, and antibody production.

Antigen-presenting cells (APCs) are specialized macrophages that are able to recognize foreign substances as antigen and process that antigen by enzymatic degradation. They are found in the skin, lymph nodes, and spleen. The APCs then process the antigen, placing relevant fragments onto their surfaces in conjunction with major histocompatibility complexes (MHC) I and II. They then present these complexes to T-helper cells through interaction with the T-cell receptors (TCRs). This interaction then activates the T cell, which can then proceed with initiation of the immune response through interactions with B cells and elaboration of cytokines.

Granulocytes

There are four types of granulocytes that are cellular components of the immune system: neutrophils, eosinophils, basophils, and mast cells. Neutrophils are the most commonly occurring and prevalent class of granulocyte, accounting for 95% of the total pool of circulating granulocytes. They are multilobulated cells that are drawn to sites of inflammation by cytokines. They engulf pathogens, destroying them with proteolytic enzymes. These enzymes are contained in cytoplasmic granules that are released on contact with bacteria or other pathogens.

Eosinophils are bilobed cells that account for 2–5% of circulating granulocytes in the nonallergic individual. This proportion is often elevated in allergic patients. Eosinophils are present only briefly in the circulation, with a serum half-life of only about 8 hours. Eosinophils mature under control of IL-5, which also is responsible for their chemotaxis and decrease in apoptosis. Eosinophils contain secretory granules that contain several proteolytic enzymes, including major basic protein (MBP) and eosinophilic cationic protein (ECP). These proteins are involved in defense against parasitic organisms and are cytotoxic, but are also capable of being bacteriocidal. Eosinophils are present in abundance in tissues with a mucosal interface, including respiratory, gastrointestinal, and genitourinary tracts. Eosinophils are key cells involved in atopy and the allergic response, and are present in abundance in diseases such as asthma and allergic rhinitis, as well as in chronic rhinosinusitis. Release of MBP and ECP from eosinophils causes host cell injury, leading to epithelial damage, ciliary dysfunction, and airway hyperreactivity.

Mast cells and basophils are virtually indistinguishable microscopically and functionally, and differ in that mast cells remain positioned in tissues while basophils are present in the circulation. Basophils account for less than 1% of circulating granulocytes. Both mast cells and basophils contain metachromatic granules containing inflammatory mediators, primarily histamine. Both mast cells and basophils are involved in the allergic response, and bind IgE molecules to their surfaces. With exposure to appropriate antigens, cross-linking of adjacent IgE molecules results in a series of biochemical events that leads to degranulation of these cells and release of inflammatory mediators into the tissues and systemic circulation. This event is responsible for the immediate hypersensitivity response, which is the primary mechanism involved in the triggering of allergic symptoms among atopic patients. This mechanism of triggering and release will be discussed more fully under mechanisms of immune response.

▪ Molecular Components of the Immune System

A variety of soluble mediators are involved in the triggering and control of the immune reaction. These mediators include the classes of antibodies and cytokines, both of which are protein molecules that serve discrete functions within the immune system. The effects of these soluble mediators are responsible for the portion of the immune reaction known as humoral immunity.

Immunoglobulins

Immunoglobulins are glycoproteins that are produced by B cells in response to antigenic stimulation. They are the primary immune effectors and are responsible for specificity of the immune response. Five classes of immunoglobulins have been described, and these are classified as IgG, IgM, IgA, IgD, and IgE (Figure 1.3). The basic structure of the immunoglobulin molecule is similar among these five classes, and consists of four protein chains linked by disulfide bonds in the configuration of a “Y.” The base of this Y-shaped molecule is referred to as the Fc portion, which is responsible for binding to cell surfaces, and the arms of the molecule, referred to as the Fab portion, are freely exposed to the microenvironment to allow binding to specific antigens and activation of cellular immune mechanisms. Antibodies are produced by activated B cells after they are transformed into plasma cells. These plasma cells are programmed to produce one specific type of immunoglobulin, and are efficient in secreting large amounts of these antibodies rapidly.

Figure 1.3 Domain structure of different antibody classes.

(Reproduced with permission from Holgate ST. Allergy, 2nd edn, p 245, figure 16.4. Published by Mosby–Elsevier Inc. ©2001.)

IgG

The most common immunoglobulin in the human is IgG. It accounts for 70–75% of all immunoglobulin found in human serum. It is the major antigen involved in the secondary immune response. Its primary function is to eliminate various harmful foreign invaders, including viruses, bacteria, and toxic substances. IgG crosses the placenta and confers short-term immunity to newborn infants. The serum half-life of IgG is about 3 weeks. Four subclasses of IgG have been identified, referred to as IgG1, IgG2, IgG3, and IgG4. IgG4 is of special interest as levels of this specific immunoglobulin are noted to rise with successful allergy immunotherapy. For that reason, IgG4 is often referred to as blocking antibody.

IgM

IgM is a large protein molecule that is responsible for the primary immune response. It is present rapidly upon the body’s initial exposure to an antigen, and is effective as a first line of defense for bacterial invasion. IgM is present in the serum as a pentamer, which makes it a large antibody. It is therefore largely confined to the intravascular space. IgM functions through activation of complement and destruction of foreign antigen.

IgA

IgA is the primary antibody found in body secretions and at mucosal surfaces. It is secreted into various body fluids, and is found in high amounts in saliva and tears. IgA exists as a monomer in the serum, but when secreted is bound into a dimer. It is produced in interstitial plasma cells and transported actively into secretions. It is of primary importance in mucosal immunity.

IgD

IgD is present in small amounts in the serum, accounting for less than 1% of the body’s total immunoglobulin. It is predominantly bound to the surfaces of B cells, and is thought to be involved in antigen-triggered lymphocyte differentiation. Its precise function, however, remains poorly understood.

IgE

IgE is the immunoglobulin that is involved in the allergic response. It was the last of the five classes of immunoglobulins to be identified, with its precise description unknown until the 1960s. IgE is present in very small amounts in the serum, accounting for less than 0.001% of the total circulating immunoglobulin pool. Its half-life in the serum is only about 2 days, while it can remain bound on the surface of mast cells for up to 3 months. It is primarily bound to mast cells and basophils, with only a small portion of IgE free within the circulation. Its primary function within in the immune system is felt to be in protection from parasitic infections. It has also been suggested as one mediator involved in cancer surveillance. It is responsible for memory and specificity in the allergic response, and is elevated in patients with allergic diseases.

Cytokines

Cytokines are small regulatory polypeptides that are responsible for communication among cells of the immune system. They are potent messengers that are produced by many types of nucleated cells, including lymphocytes, macrophages, epithelial cells, endothelial cells, and fibroblasts. The cytokines that are produced specifically by lymphocytes have also been referred to as lymphokines, and those that act specifically between white blood cells are known as interleukins. Other classes of cytokines include interferon, tumor necrosis factor (TNF), and colony stimulating factor (CSF).

Of major interest in the immune response is the class of cytokines known as interleukins. These chemical mediators serve to direct and control the immune response through intercellular communication. They act specifically at IL receptors on cells and have specific functions in the immune response. For example, IL-4 is responsible for isotype switching, signaling plasma cells to shift their production of immunoglobulin from IgG to IgE. IL-5 is responsible for growth and proliferation of B cells and for eosinophil maturation and chemotaxis. A more complete list of interleukins and their functions is found in Box 1.4.

BOX 1.4 Interleukins and their functions

IL-1 Proinflammatory, stimulates immune response, involved in sepsis

IL-2 Promotes growth and proliferation of lymphocytes

IL-3 Promotes proliferation of stem cells and differentiation

IL-4 Responsible for isotype switching in allergic disease

IL-5 Promotes growth of B cells and eosinophil maturation and chemotaxis

IL-6 Proinflammatory, promotes B-cell growth

IL-8 Promotes neutrophil maturation, activation, and chemotaxis

IL-10 Inhibits cytokine synthesis and T-cell proliferation

IL-12 Promotes interferon production and null cell activation

IL-13 Involved in B-cell maturation and differentiation

IL-18 Promotes cell-mediated immunity

Complement

Complement refers to a series of protein molecules that function in a coordinated cascade in response to antigenic stimulation. It is involved in both specific and nonspecific immunity. Its role is to augment immune function. Complement is activated through antigen stimulation and under direction of immune cells. The complement pathway consists of a series of protein molecules that each act as catalysts for a series of proinflammatory events, resulting in an amplified response to antigen stimulation. Through lysis of target cells, enhancement of antibody function, and preparation of antigen molecules for phagocytosis (opsonization), complement is effective in eliminating potentially harmful assaults on the body from foreign organisms or intrinsic immune complexes.

Types of Immune Hypersensitivity Reactions

While the immune response is usually appropriate and targeted to the level and type of challenge, it is possible for that response to become inappropriate, or for an immune reaction, once initiated, to continue without adequate cessation. In addition, agents that should ordinarily not be recognized as harmful antigens can sometimes be mistaken by the immune system as harmful and can initiate an inappropriate immune response. In those cases, this immune response can be injurious to the host and can result in significant morbidity and even mortality. These poorly controlled or overexuberant responses of the immune system are referred to as hypersensitivity reactions. These hypersensitivity reactions have often been classified into four specific types of responses, although other authors have argued that several more responses may be present. These four classes of hypersensitivity responses, described by Gell and Coombs, are presented in Table 1.1 and will be discussed below.

TABLE 1.1 Hypersensitivity reactions

Summary of Immunology

The immune system is the body’s major line of defense in the protection of the organism from foreign antigens. It functions as a coordinated unit in surveillance and is vigilant to the introduction of harmful organisms. It generally functions efficiently and effectively, and is accurate and appropriate in its responses.

At times, however, the immune system will respond to antigens that ordinarily would not stimulate an immune response, and may do so in such a way that it causes significant symptomatology and morbidity. This process underlies the allergic response and the development of atopic diseases such as allergic rhinitis, atopic dermatitis, and asthma. The allergic reaction, therefore, consists of a complex interaction of a number of different components of the immune system, resulting in the expression of various symptoms.

It is important to understand the nature of the immune response, in health and in allergic disease, in order to better conceptualize how allergy affects the individual and the mechanisms through which the clinician can intercede in managing that disease. This understanding forms the basis for therapies of allergic illnesses, including environmental control measures, pharmacotherapy, and immunotherapy.

Conclusion

Allergic diseases are a common group of illnesses that are increasing in prevalence and importance around the world. While allergic diseases can be effectively managed using a variety of treatment approaches, they are often underrecognized, and therefore remain undiagnosed. Only with increased awareness of allergic diseases and with heightened sensitivity to the role of allergy in many common medical illnesses will medical therapy be successful in decreasing the burden of this group of common illnesses.