Page 18 - Clinical Immunology_ Principles and Practice ( PDFDrive )

4 Part one Principles of Immune Response

Granulocytes
TABLE 1.1 Features of Innate and
adaptive Immune Systems Polymorphonuclear leukocytes (granulocytes) are classified by
light microscopy into four types. By far the most abundant in
Distinguishing Features the peripheral circulation are neutrophils, which are principal
Innate Immunity adaptive Immunity effector cells linking the innate and adaptive responses by virtue
Germ line-encoded receptors Clonally variable receptors generated of their expression of surface receptors for antibody and comple-
targeting pathogen somatically by rearrangement of ment (Chapter 21). They are phagocytic cells that ingest, kill,
molecular patterns gene elements and degrade microbes and other targets of an immune attack
Does not require Consequence of B- and/or T-cell within specialized cytoplasmic vacuoles that contain potent
immunization activation
Limited memory Immunological memory well antimicrobial enzymes and oxidative pathways. The phagocytic
developed activity of neutrophils is promoted by their surface display of
Includes physical barriers to Antibody and cytotoxic T cells receptors for antibody molecules (specifically the Fc portion of
pathogen immunoglobulin G [IgG] molecules) (Chapter 15) and activated
complement proteins (particularly the C3b component) (Chapter
Common Features 21). Neutrophils are the predominant cell type in acute inflam-
Cytokines and chemokines matory infiltrates and are the primary effector cells in immune
Complement cascade responses to pyogenic bacteria (Chapter 27).
Phagocytic cells Eosinophils (Chapter 24) and basophils (Chapter 23) are the
Natural killer (NK) cells
“Natural” antibodies other circulating forms of granulocytes. A close relative of the
basophil, but derived from distinct bone marrow precursors, is
the tissue mast cell, which does not circulate in blood. Eosinophils,
RNA; and bacterial and viral unmethylated CpG DNA. CLR are basophils, and mast cells are important in defenses against
particularly important in antifungal innate immunity but also multicellular pathogens, particularly helminths (Chapter 31).
have important roles in defenses against bacteria, viruses, and Their defensive functions are not based on phagocytic capabilities
parasites. They comprise a large family that commonly recognizes but, rather, on their ability to discharge potent biological media-
microbe-specific carbohydrate ligands or structurally similar tors from their storage granules into the cellular microenviron-
lectin-like domains. Cytoplasmic PRRs include RIG-1–like ment. This process, termed degranulation, can be triggered by
receptors (RLRs) and nucleotide oligomerization domain (NOD)- antigen-specific IgE molecules that bind to basophils and mast
like receptors (NLRs). RLRs are involved in recognition of viruses cells via high-affinity receptors for the Fc portion of IgE (FcεR)
through interaction with intracytoplasmic viral double-stranded on their surfaces. In addition to providing a mechanism for
RNA (dsRNA), and NLRs recognize bacterial peptidoglycan anthelmintic host defenses and certain antibacterial responses,
motifs. 4 this is also the principal mechanism involved in acute (IgE-
Cells of the innate immune system are commonly triggered mediated) allergic reactions (Chapters 41–49).
through activation of the NF-κB transcription factor via the
MyD88 signaling pathway, thereby inducing an inflammatory Lymphocytes
response using mechanisms that are broadly shared with those Three broad categories of lymphocytes are identified on the basis
of the adaptive immune system. These include activation of of display of particular surface molecules: B cells, T cells, and
various types of innate lymphoid cells (e.g., natural killer [NK] innate lymphoid cells; each of these categories can be further
cells), which are characterized by absence of clonally expressed subdivided according to specific function and display of distinguish-
receptors for specific antigen (see below), activation of granu- ing cell surface molecules (Chapter 2). All lymphocytes differentiate
locytes and other phagocytes, the secretion of inflammatory from common lymphoid stem cells in bone marrow. B cells create
cytokines and chemokines, and interactions of the many par- their immunoglobulin receptors in bone marrow and differentiate
ticipants in the complement cascade. Additionally, activation of into antibody-producing cells in the periphery (Chapter 7). T-cell
cells of innate immunity that also act as APCs for the adaptive precursors move from bone marrow to the thymus (or, in some
immune system results in upregulation of membrane molecules cases, to extrathymic tissue compartments), where they complete
(e.g., CD80, CD86) that provide the second signal, along with their differentiation and selection (Chapter 8).
the T-cell receptor (TCR) for antigen, necessary for induction T cells and B cells are the heart of immune recognition, a
of antigen-specific T cells. 5 property reflecting their clonally specific cell surface receptors
Finally, because recognition of pathogens by the innate immune for antigen (Chapter 4). The TCR is a heterodimeric integral
system relies on germline encoded, nonrearranged receptors held membrane molecule expressed exclusively by T lymphocytes.
in common by the specific cell type, innate immunity is more B-cell receptors for antigen (BCRs) are membrane immuno-
rapidly responsive. It can initiate in minutes to hours and generally globulin (mIg) molecules of the same antigenic specificity that
precedes development of a primary adaptive immune response the cell and its terminally differentiated progeny, plasma cells,
by at least several days. will secrete as soluble antibodies. Memory B cells and nondividing,
long-lived plasma cells may account substantially for persistence
CELLS OF THE IMMUNE SYSTEM of antibody responses (including production of autoantibodies)
over many years. 6
The major cellular constituents of both innate and adaptive Receptors for “antigen” on the third class of lymphocytes,
immunity originate in bone marrow, where they differentiate innate lymphoid cells (ILCs), are not clonally expressed. ILCs
from multipotent hematopoietic stem cells (HSCs) along several are subdivided into three major groups according to the cytokines
pathways to become granulocytes, lymphocytes, and APCs that they produce (e.g., group 1 ILCs, including NK cells, produce
7
(Chapter 2). interferon-γ [IFN-γ] and tumor necrosis factor [TNF]). ILCs