Page 1291 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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Assessment of Functional Immune

Responses in Lymphocytes

Roshini Sarah Abraham

The immune response is mediated by a complex network of induction of FOXP3 in conventional naïve T cells imparts
cells, soluble and membrane-bound biological mediators and suppressive function in vitro and in vivo, resulting in the genera-
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receptors interacting within the context of specific tissues and tion of induced-regulatory (iTreg) T cells. Besides producing
organs to protect against pathogens. Although the immune system antibodies to neutralize pathogens as well as presenting antigen
has been broadly divided into innate and adaptive components, to T cells, B cells also exert immunomodulatory control of the
there is considerable overlap and interaction between the two, immune response, primarily via interleukin (IL)-10 production.
despite the highly specialized functions and kinetics of each in IL-10–producing B cells, classified as regulatory B (Breg) cells,
the immune response. T and B cells form the pillar of the adaptive play an important role in immune homeostasis and in protection
immune response, whereas natural killer (NK) cells are the effector against autoimmune responses and inflammatory damage. Breg
lymphocytes of the innate immune response. There are approxi- cells, in addition to producing IL-10, secrete other cytokines
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mately 2 × 10 lymphocytes in the body, and typically the response that act on other effector T-cell subsets, Tregs, APCs such as
to a foreign antigen is in the context of initial activation of innate dendritic cells (DCs), and macrophages.
immune components. T cells recognize antigen primarily in the NK cells are considered to be innate immune effector cells,
context of antigen-specific T-cell receptors (TCRs) and specific but they straddle the threshold of innate and adaptive immunity.
peptides presented by molecules of the major histocompatibility NK cells are directly involved in cytotoxicity and cytokine secretion
complex (MHC), either class I or class II (Chapters 5 and 6). T upon activation, but they also function indirectly by regulating
cells are also capable of responding nonspecifically to polyclonal APC and the effector T-cells’ response. NK cell activation is
stimulators, such as mitogens (in vitro) or superantigens (in controlled by synergistic signals from activating and inhibitory
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vivo) that do not initiate an antigen-specific proliferative response. receptors. The characteristics, responses, and assays to measure
T cells upon activation also produce cytokines that are crucial the activity and function of each of these subsets are described
to their effector functions including activating B cells and inducing in detail in the sections below.
antibody production, promoting differentiation of cytotoxic T
cells, activating macrophages, and promoting activation and T-CELL RESPONSE
migration of inflammatory cells. Cytokines play a role in the
induction of the T-cell response when produced by antigen- T cells form the cellular arm of the adaptive immune response,
presenting cells (APCs) at the time of antigen recognition. B and each T cell has unique specificity derived from the presence
cells recognize antigen directly via the B-cell receptor (involving of a functional, antigen-recognizing receptor on the cell surface.
surface immunoglobulin) and produce antibodies with help from Naïve T cells derived from the thymus can migrate through the
T cells (T-dependent antigens) or from the innate immune system peripheral circulation and secondary lymphoid tissues (spleen
(T-independent antigens). More recently, the granularity of the and lymph nodes), but they cannot effectively participate in the
antibody response has been further delineated, and T-dependent immune response to pathogens. To do so, naïve T cells must
antibody responses are divided into type 1, with help provided undergo a defined process of cellular activation, which involves
by T-follicular helper cells (Tfhs), and type 2, with help provided recognition of antigen by the TCR in the context of MHC
by NKTfh cells. Similarly, T-independent responses are classified molecules. The majority of circulating T cells express the α/β
into three groups: type 1, induced by recognition of microbial TCR, whereas a smaller proportion of cells express the γ/δ TCR.
antigens by the Toll-like receptors (TLRs) in the absence of On the surface of the T cell, the TCR associates with the CD3
Bruton’s tyrosine kinase (BTK); type 2, which requires the presence complex, comprised of four distinct subunits (γ, δ, ε, and ζ);
of BTK; and type 3, which has neutrophil B-helper cells. 1,2 the cytosolic components of the CD3 complex are involved in
Regulatory (Treg) cells have been shown to play a critical role the intracellular propagation of signals after ligation of the TCR.
in the control of both physiological and pathological immune Besides the CD3 complex, the TCR also clusters with a CD4 or
responses in a variety of contexts (Chapter 18). Treg cells exert CD8 coreceptor, depending on the type of T cell; CD4 T cells
a direct inhibitory effect on the development of autoimmune recognize antigen (Ag) in the context of MHC class II, whereas
disease because their absence leads to the development of a severe CD8 T cells recognize antigen presented on MHC class I. The
phenotype, as manifested by the FOXP3 deficiency, IPEX first signal or “cognate” signal, which is recognition of peptide-
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(immune dysfunction/polyendocrinopathy/enteropathy/X-linked) MHC complex by the TCR, results in actin-mediated reorganiza-
(Chapter 35). Treg cells can suppress the proliferation of antigen- tion of the cytoskeleton in both the T cell and APC to form the
stimulated naïve T cells, as demonstrated by in vitro studies, and immunological synapse (Fig. 93.1). The synapse consists of the

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