1.1 Introduction

Most practicing clinicians are not necessarily skilled immunologists on the latest benchtop research. Immunology is one of the subjects that has been taught to medical students and, while important, it doesn’t seem applicable in day-to-day clinical practice. However, having knowledge of the basic mechanisms involved in allergic disorders is helpful in fully understanding how treatments for these diseases work and how to maximize the benefits for the patients. In this chapter a brief review of the immunology behind type I immunoglobulin E (IgE)-mediated hypersensitivity has been described in simple terms.

1.2 Hypersensitivity Reactions

There are several different types of hypersensitivity reactions. This book deals primarily with type I IgE-mediated hypersensitivity reactions, the cause of “allergies.” As implied, these reactions start very quickly (hence, the “immediate” nature of them) and the primary immunoglobulin (i.e., antibody) involved is IgE.

1.3 Adaptive Immunity

The immune system can be divided into two basic parts—the innate immune system and the adaptive immune system. The innate immune system comprises a network of barrier, enzymatic and cellular defenses that protect the body from invaders by using mechanisms that do not change or alter, regardless of what pathogens are attacking the body. The adaptive immune system comprises cellular and humoral defenses (immunoglobulins, proteins, and chemical signals) that do change or alter with the nature of the invading pathogen. It also has “memory” and its responses generally become more robust with repeated exposure to the same infection.

1.4 Adaptive Immune Responses

The adaptive immune system can respond in different ways, but it can be divided into two different types of responses based on the type of T-helper (T_h) cell involved. T_h1 responses are geared toward defense against intracellular invaders, while T_h2 responses are meant to defend against extracellular pathogens and parasites. Before progressing further, let’s review the different cells that play a role in allergic disorders and their treatments.

1.5 The Major Players

Antigen presenting cells (APCs): A class of cells that begin the allergic reaction. These types of cells include dendritic cells, Langerhans cells, and other cells. When APCs come into contact with some unknown pathogen, they swallow it up, chop it up into tiny pieces, and then present those tiny pieces on their surface to show to other cells, saying, “Hey! Do you know what this is? Have you seen this before?”

T-cells: A class of white blood cells. T-cells come in different varieties, and each variety has its own roles and responsibilities within the immune system. In this chapter, only certain T-cell types will be discussed. An APC usually shows its goods to some type of T-cells in the earlier stages of infection.

T helper cells: A class of T-cells and the most important cell type in the adaptive immune system. These cells help direct other cells to make antibodies, attack infected cells, or release chemical messages. They may help activate one part of the immune system and/or suppress another. These cells direct B-cells to produce different types of antibodies.

B cells: A class of white blood cells that produce Ig. While they can function as APCs, making antibodies is pretty much what they do. T-cells send signals to B-cells to produce a specific class of antibodies.

Immunoglobulins: These cells are also known as antibodies. They comprise five different varieties: IgG, IgM, IgA, IgD, and IgE. These are proteins made by B-cells that bind to a wide range of molecules and “flag” these things for the immune system. When an antibody binds to something, Igs tell the immune system, “Hey, pay attention to this! Do something with it!”

T helper type 1 cells (T_h1): A type of T_h cell responsible for defending against intracellular bacteria, viruses, and other infections. T_h1 cells send signals to B cells and direct them to produce IgG. When overactivated or not working correctly, this arm of the immune system can lead to autoimmune diseases.

T helper type 2 cells (T_h2): A type of T_h cell responsible for defending against extracellular parasites and other infections. T_h2 cells send signals to B-cells and direct them to make IgE. When overactivated or not working correctly, this arm of the immune system leads to allergic disorders and type I IgE-mediated hypersensitivity. When you think of T_h2, think “achoo.”

T regulatory cells (T_reg): A type of T-cell that, when working correctly, keeps the other T-cells in check, especially the T_h cells. It keeps them from getting too worked up about things, saying, “Relax, take a chill pill.” These cells play an important role in the development of tolerance and in immunotherapy.

Mast cells: These white blood cells live in the body’s tissues. They are essentially little floating bags of histamine and other chemical mediators. They bind IgE to their surface and when triggered, release histamine and other inflammatory mediators that cause the typical wheal and flare response (itching, redness, swelling).

Basophils: These white blood cells float in the bloodstream and are similar to, but not the same as, mast cells. They too are little floating bags of histamine and other chemical mediators. They bind IgE as well and participate in allergic diseases and anaphylaxis.

Eosinophils: A class of white blood cells that could be known as the “worm killers,” due to their role in fighting extracellular parasites. They are also little floating bags of preformed chemical mediators and they migrate from the blood into a variety of organs and tissues. They play a role in allergic disorders and asthma as well.