Page 17 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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The Human Immune Response

Robert R. Rich, David D. Chaplin

Clinical immunology is a medical subspecialty largely focused Adaptive and Innate Immunity
on a specific physiological process, inflammation, which is essential Immune responses are traditionally classified as adaptive (also
to good health, particularly in defense against pathogenic organ- termed acquired or specific) and innate (or nonspecific) (Table
isms, recovery from injury, and containment of neoplasms. But 1.1). The adaptive immune system, present uniquely in species
inflammation, mediated by the cells and soluble products of the of the phylum Chordata, is specialized for development of an
immune system, is also a powerful contributor to the pathogenesis inflammatory response based on recognition of specific “foreign”
of diseases that affect virtually every organ system. A consequent macromolecules that are predominantly, but not exclusively,
challenge for clinical immunologists, both clinicians and basic proteins, peptides, and carbohydrates. The vast majority of
scientists, is to reduce a dizzying array of disease descriptions chordate species are vertebrates, and this book addresses adaptive
to systematic understanding of pathogenic mechanisms, facilitat- immunity of that subphylum. Its primary effectors are antibodies,
ing translation of fundamental concepts and new discoveries B lymphocytes, T lymphocytes, and antigen-presenting cells
into more effective disease prevention or treatment. (APCs). T and B lymphocytes express surface antigen receptors
This introductory chapter is directed to nonimmunologist that are clonally specific as a consequence of receptor–gene
clinicians and researchers. It is structured as an introduction rearrangements. Expansion of clones of lymphocytes specific
to the interacting elements of the human immune system and for any particular antigen is induced by antigen encounter and
their disordered functions in diseases. The subtleties, including consequent activation and proliferation, thereby constituting the
immunological or molecular genetic jargon unavoidably used, basis of immunological memory.
are described in detail in the chapters that follow. Innate immune responses are phylogenetically far more ancient,
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being widely represented in multicellular phyla. Rather than
THE HOST–MICROBE INTERACTION being based on exquisitely specific recognition of a diverse array
of macromolecules (i.e., antigens), they are focused on recognition
The vertebrate immune system is a product of eons of evolution- of common molecular signatures of microbial organisms that
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ary relationships between rapidly evolving microbial organisms are not present in vertebrates. Among these structures, which
and their much less rapidly reproducing, and hence less adaptable, are termed pathogen-associated molecular patterns (PAMPs) or
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hosts. In general, the relationship is mutually beneficial, each danger-associated molecular patterns (DAMPs), are bacterial
providing nutrients and other materials essential to the well-being cell wall constituents, such as mannose-rich oligosaccharides,
of their partner—the host and its microbiome (Chapter 14). lipopolysaccharides, peptidoglycans, and several nucleic acid
Occasionally, however, a normally beneficial relationship becomes variants, including double-stranded RNA and unmethylated CpG
pathological, as pathogenic microbes overwhelm the microbiome, DNA. For both innate and adaptive immunity responses, defense
invading host tissues and resulting in host morbidity or even effector mechanisms can require either direct cell-to-cell contact
death. Because the vertebrate host cannot win a battle with or the activity of cytokines and chemokines, which are hormone-
microbial invaders by rapid mutation and selection, the immune like soluble molecules that act in the cellular microenvironment
system employs a strategy of complexity and redundancy, which (cell-mediated immunity). Most immune responses include
involves both the individual organism and its collective popula- participation of both modes of response. 2-4
tion. Reflecting plasticity of the response, specific defenses differ, The elements of innate immunity are diverse (Chapter 3).
depending on the nature of the infectious agent and its point They include physical barriers to pathogen invasion (e.g., skin,
of entry and distribution within the body. Regardless of the mucous membranes, cilia, and mucus), as well as an array of
defense mechanism, an intended outcome is destruction or cellular and soluble factors that can be activated by secreted or
neutralization of the invading organism. A secondary consequence, cell surface products of the pathogen, including PAMPs. Recogni-
however, can be collateral damage to host cells. These cells can tion of PAMPs by cells in innate immunity, which also commonly
be targeted for damage because they are sites of microbial resi- function as APCs to the lymphocytes of adaptive immunity, is
dence and replication, or they can be damaged as “innocent via cell membrane or cytoplasmic receptors known as pattern
bystanders.” Depending on the site and severity of the host’s recognition receptors (PRRs). PRRs can be either membrane
defensive response, it may be accompanied by local and/or bound or cytoplasmic. Membrane-bound PRRs include Toll-like
systemic symptoms and signs of inflammation, which may lead receptors (TLRs) and C-type lectin receptors (CLRs). Humans
to long-lasting tissue dysfunction as a result of tissue remodeling express 10 distinct TLRs, which recognize (among others) specific
and partial repair. bacterial glycolipids, lipopolysaccharide; viral single-stranded

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