A Functional Overview of the Immune System and Immune Components

Chapter 1 establishes a foundation to appreciate how components of the immune system work together to protect against development of clinical disease. The basic systems and cells involved in immune responses are presented as a general overview of functional immunity. Components and systems presented include concepts of innate (always present) and adaptive (inducible and specific) responses, myeloid and lymphoid cells, and an introduction to immune anatomy.

Keywords

Innate immunity; adaptive immunity; myeloid; lymphoid; lymphocyte; lymphoid organs; cluster of differentiation (CD)

Chapter Focus: To establish a foundation to appreciate how components of the immune system work together to protect against development of clinical disease. The basic systems and cells involved in immune responses will be presented to give a general overview of functional immunity. Components and systems will be defined to allow an understanding of concepts of innate (always present) and adaptive (inducible and specific) responses, and how these responses interact with one another to form the basis for protection against disease.

Immune Homeostasis

A functional immune system offers constant surveillance of ourselves in relationship to the world. It confers a balanced state of health through effective elimination of infectious agents (bacteria, viruses, fungi, and parasites) and through control of malignancies. Indeed, the immune system has evolved to allow cells and organs to interact with the environment to protect against harmful invaders. At the same time, mechanisms are in place for tolerance toward the naturally occurring microbiome (microbial and viral agents) that reside within us in symbiotic ways. Taken together, these responses represent a balance of components that ward off development of clinical disease.

Self vs. Non-Self

Discrimination between “self” and “non-self” is considered the chief function of the immune system. We are under constant assault by invaders. Our bodies represent prime substrates for organisms to grow and reside, with an abundance of nutrients, warmth, and protection from the outside elements. The immune system is basically a series of obstacles to limit and inhibit pathogen entry and then attack and destroy those organisms once they enter the body. The immune response is exquisitely designed to recognize these invaders as “foreign.” In fact, the major feature that renders our immune system so effective is its ability to distinguish our body’s own cells (“self”) from that which it considers foreign (termed “non-self”). Each one of our cells carries specific tags, or molecular markers, that label it as “self.” These markers are important, as they not only determine what is unique about us, but they also distinguish one person from another.

Almost anything and everything that registers as “non-self” will trigger an immune response. An intricate system of molecular communication and cellular interactions allows immune components to function in concert to combat disease-causing organisms. The foreign agent (microbe, virus, parasite, etc.), or any part of it that can be specifically recognized, is called an antigen. Simply put, an antigen is defined as any substance that can be recognized by the immune system. Major classes of antigens include proteins, carbohydrates, lipids, and nucleic acids. If an antigen is of high complexity and weight, it can trigger full immune activity and become immunogenic.

The ability to distinguish our own cells from the outside world is critical in maintaining functional protection. If this ability is lost, e.g., when “self” tissue is seen as foreign, then our immune system launches an aggressive response against our own tissues. This is what happens during autoimmunity, where destruction of “self” leads to clinical disease.

The immune system maintains a balance of responsiveness. Too little a response is ineffective, while too aggressive a response can lead to targeted destruction of bystander tissues. Both scenarios are equally as devastating and may result in clinical disease. The regulation of immune function and overall immuno-homeostasis is under control of multiple factors that include genetic components and environmental cues. The intensity and duration of response must be sufficient to protect against invading pathogens, with prompt and specific downregulation when the foreign material (the antigen) is no longer present. The clinical state that arises when immune responses are not properly regulated is termed hypersensitivity; a state of excessive or inappropriate responses leads to disease. As one might imagine, hypersensitivity can occur in many different forms, depending upon which arm of the immune system is dysregulated.

Innate and Adaptive Immunity

The immune system is loosely divided into two major functional categories termed innate and adaptive immunity. Innate immune mechanisms provide the first line of defense from infectious disease (Table 1.1). The innate immune components are present from birth and consist of components available prior to the onset of infection. These defensive components include both physical barriers and biochemical factors. Defensive innate mechanisms may be anatomic (skin, mucous membranes), physiologic (temperature, low pH, chemical mediators), phagocytic (digestion of microorganisms), or inflammatory (vascular fluid leakage).

Innate mechanisms are particularly powerful at limiting infections. However, once the infectious agent is established inside the body, a more focused set of reactive molecules and cellular components are required to specifically combat the organism. An intricate system of molecular communication and cellular contact allows components of the innate immune group to trigger cells involved in adaptive immunity. In essence, both innate and adaptive components must function in concert to combat and control disease.

The adaptive (also called “acquired”) immune response accounts for specificity in recognition of foreign antigenic substances. It is critical to understand that specificity of the adaptive immune response lies within two distinct subsets of white blood cells, called lymphocytes. Lymphocyte recognition of unique shapes associated with foreign antigens is accomplished by functional receptors residing on their cellular surface. Key elements of the acquired immune responses are compared to innate functional elements, as listed in Table 1.2.

The adaptive...