This is the second and updated version of the Textbook of Allergy for the Clinician. It is a unique book in the field of allergy. The uniqueness lies in the international character of the book with contributors representing both the East and West. This book represents the diversity of issues affecting patients in the specialty of allergy, asthma & immunology. There is some discussion of the basic mechanisms involved and extensive elaboration for the clinicians. This book will appeal to medical students, residents and fellows undergoing training as well as consultants in academic and clinical practice settings. The color plates, especially in the section on Aerobiology, will help in the interaction between the patient and consultant in identifying the plant or flora which is the causative factor. The differences and similarities between the Eastern and Western approaches in the practice of the specialty are being addressed for the first time in a book.
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Yes, you can access Textbook of Allergy for the Clinician by Pudupakkam K. Vedanthan, Harold S. Nelson, Shripad N. Agashe, PA Mahesh, Rohit Katial, Pudupakkam K. Vedanthan, Harold S. Nelson, Shripad N. Agashe, Rohit Katial, PA Mahesh in PDF and/or ePUB format, as well as other popular books in Medicine & Clinical Medicine. We have over one million books available in our catalogue for you to explore.
The immune system is composed of an adaptive immune system and an innate immune system. The adaptive immune system distinguishes itself from the innate system by the following features: (a) Specificity of antigen recognition, (b) Diversity of the antigen receptor repertoire, (c) Rapid clonal expansion, (d) Adaptiveness to the changing environment and (e) Immunological memory. The innate system lacks fine specificity, has limited diversity and rudimentary memory but manifests rapid engagement. Lymphocytes are the primary cells of adaptive immunity; they include T cells, B cells and NK cells. Each individual cell type will be described in this chapter.
Lymphoid cell generation
Generation of Antigen-specific Receptors: The growth of B and T cells from pluripotent stem cells requires successive differentiation through a series of stages that starts in the bone marrow and ends in the thymus (T cells) or peripheral lymphoid tissue (B cells) (Marrack et al. 2000, Carding et al. 2002, Calame 2001). During differentiation lymphocytes are able to recognize self and non-self antigens through the expression of antigen-specific receptors known as T Cell Receptors (TCR) and B Cell Receptors (BCR) (Nemazee 2000). TCRs are comprised of ab or gd subunits whereas BCRs are composed of membrane-bound immunoglobulins (Fig. 1.1). Approximately 90% of peripheral blood T cells are ab+ and the remainder cells are gd+, although the proportion of the latter reaches 25â30% in the gastrointestinal mucosa and skin.2 The generation of TCRs and BCRs creates an impressive repertoire in the order of > 1014 through combinatorial joining of V, D and J (b and d chains) or V and J (Fig. 1.2). Recombination is triggered by IL-7 and involves recombination-activating gene-1 and -2 (RAG-1 & -2) and a DNA repair enzyme (metallo-b-lactamase) encoded by the gene Artemis (Hesslein and Schatz 2001). The deficiency of the RAG enzymes, IL-7 receptor- and the Artemis gene product causes Severe Combined Immunodeficiency (SCID). A partial deficiency of RAG-1 & -2 causes Omenn syndrome. The BCR is capable of recognizing small and large peptides, in contrast, the TCR recognizes small stretches of linear peptides of 10â12 amino-acids in length.
Thymic Selection of T Cells: During the generation of antigen receptors, self MHC-reactive and non-reactive TCRs are generated (Hennecke and Wiley DC 2001).
T cells require signaling through the TCR for survival and proliferation; T cells that are unable to recognize self-MHC or have very low avidity TCRs for self-MHC die because of the lack of the TCR signal (death by neglect). T cells, which recognize self-MHC in conjunction with the self-peptide, are expanded (positive selection). Positively selected T cells with very high avidity for self-peptides (auto-reactive T cells) are killed (negative selection). Ninety-five percent of T cell precursors die due to negative selection/failing to express the appropriate TCR.
B cell precursors are not subjected to extensive deletions; self-reactive B cells undergo another round of receptor gene rearrangement (receptor editing) to replace an auto-reactive BCR with a normal BCR. In the early phase of differentiation, immature T cells express both CD4 and CD8 co-receptors (double-positive cells) (Sebzda et al. 1999, Germain 2002) CD4 T cells are selected through interaction with class II MHC molecules and CD8 T cells through interaction with class I MHC molecules.
Two tyrosine kinasesâLck (Lymphocyte-specific protein tyrosine kinase) and ZAP70 (zeta-associated protein 70) play a critical role in the selection of CD4 and CD8 T cells, respectively. Patients with congenital deficiency of Lck have severe combined immunodeficiency because of the failure of CD4 differentiation; ZAP70 deficiency results in a severe defect of CD8 T cell differentiation. A small fraction of T cells, mostly of gd subtype, is negative for both CD4 and CD8 (double negative) (Carding et al. 2002).
Immune surveillanceânaĂŻve lymphocyte
In order to increase the probability of antigen encounter, lymphocytes continuously circulate across various tissues. NaĂŻve T and B cells preferentially migrate to lymph nodes due to homing receptors L-selectin and CCR7 (Moser and Loetscher 2001). Their ligands, CCL19 and CCL21 are expressed on High Endothelial Venules (HEV) of lymph nodes.
Events following an antigen encounter
Antigen Presentation: Professional Antigen Presenting Cells (APC) are those that express high levels of class II MHC molecules and possess the capacity to internalize, process and present foreign antigens in the MHC groove. APC cells include Dendritic Cells (DC), B cells, monocytes/macrophages and their tissue counterparts. Immature DCs, residing in the peripheral tissue, phagocytose and process foreign antigens (Table 1.1) (Guermonprez et al. 2002). Pathogen-derived molecules and cytokines from inflamed tissue, trigger DC maturation, enhance antigen processing and expression of foreign-peptide-loaded MHC proteins. Mature DCs secrete cytokines and upregulate different co-stimulators and CCR7.
Table 1.1 Major histocompatibility complex molecules.
MHC I
MHC II
Genes
HLA-A, B, C
HLA-DP, DQ, DR
Structure
Transmembrane a chain bound to b2-microglobulin, only the a chain interacts with the peptide
Transmembrane a and b chain, both chains interact with the antigenic peptide
Presented peptide
Peptides derived from self/non-self intracellular proteins, e.g., viral peptides
Peptides derived from extracellular proteins, e.g., bacterial peptide
Mechanism of presentation
Intracellular proteins are degraded by the ubiquitin/proteasome pathway in the cytosol; transported by TAP to endoplastic reticulum and loaded onto MHC; the MHC/peptide complex translocates to the cell membrane
Extracellular proteins are endocytosed and degraded by lysosomal proteases; subsequently peptides-containing endosomes are fused to MHC-containing vesicles; peptides are loaded onto MHC and the complex translocates to the cell membrane
Presenting Cells
All nucleated cells, including APC
Antigen Presenting Cells (APC): dendritic cells, B cells, macrophages