Marcel F. Jonkman - Autoimmune Bullous Diseases: Text and Review
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This book provides obligatory study material on courses on autoimmune bullous diseases. Residents and researchers in dermatology and adjacent disciplines can use the book as a quick reference guide when dealing with these patients. The book contains protocols and follows international guidelines. Currently there is no quick primer on Autoimmune Bullous Diseases for dermatologists who wish to learn the subtleties of diagnosis and management of this group of mucocutaneous diseases. Since mucous membranes are also included the following medical disciplines might be interested too: oral medicine and stomatology, ENT, ophthalmology, gynaecology, gastro-enterology. The Center for Blistering Diseases in Groningen has organized since the year 2000 an annual course on Bullous Diseases for dermatologists and pathologists. The staff is selected from the faculty. The course is interactive and problem-oriented. The proposed book would represent the documented practical knowledge of the staff on these diseases. The information should be clear and practical with examples and questions for self-assessment.
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Part I
Immunology and Diagnostic Tests
Immunology and Diagnostic Tests
Springer International Publishing Switzerland 2016
Marcel F. Jonkman (ed.) Autoimmune Bullous Diseases 10.1007/978-3-319-23754-1_11. Basic Principles of the Immune System and Autoimmunity
Gilles F. H. Diercks 1 and Philip M. Kluin 1
(1)
Departments of Pathology and Medical Biology, Center for Blistering Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Gilles F. H. Diercks
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Keywords
Immune system Autoimmunity Pemphigus PemphigoidLearning Objectives
After studying this chapter, you should know:
- The difference between the innate and adaptive immune system
- The functions of antigen presenting cells, B and T lymphocytes
- Causes of autoimmunity and types of hypersensitivity with emphasis on pemphigoid and pemphigus
The Immune System: A Short Introduction
Two Systems: The Innate and Adaptive System
The immune system is composed of two closely collaborative systems, an innate and an adaptive system (Fig. ). 
Fig. 1.1
An overview of the innate and adaptive immune system (Reprinted by permission from Macmillan Publishers Ltd: Dranoff [], Copyright 2004)
< The immune system is composed of an innate and an adaptive system >
These systems are activated as the first barriers of defense, mucosa and skin, are breached. The innate immune system is a constitutive present system that can act rapidly to eradicate microbes.
< The innate system is a quick response system >
The primary cells of the innate immune system are macrophages, granulocytes, natural killer (NK) cells, and dendritic cells, but other cells like epithelial cells can also be part of it. For instance, macrophages and granulocytes are capable of phagocytosis of microorganisms by endocytosis. Pathogen-associated molecules are present on microbes and recognized by cells of the innate system by binding to Toll-like receptors. In particular these cells are effective against bacteria, whereas NK cells are used to fight viruses. They do this in an indirect way by recognizing and killing virally infected host cells. Besides the cellular response, many proteins play an important part in the innate immune system, e.g., chemokines, interleukins, interferon, and tumor necrosis factor. Binding of microbial antigens will therefore not only induce phagocytosis but also release of cytokines, which will result in an inflammatory response. Apart from these proteins, the complement system constitutes an important part of the immune system. This system can be activated directly by a microorganism itself or indirectly by binding to antibodies produced by the adaptive immune system. Eventually proteins of the complement system promote phagocytosis and inflammation.
The Adaptive System in More Detail
Next to the innate system is the adaptive immunity that can be divided in a humoral and cellular system (Fig. ). 
Fig. 1.2
The principle classes of lymphocytes and their functions in adaptive immunity (Reprinted with permission from: Kumar et al. [], Copyright Elsevier 2010]
< The adaptive immune system is divided in a humoral and cellular system and is an antigen-specific system >
By definition the adaptive immunity is a learning system that has to be trained. In consequence the start will be slow, but once trained, the responses will also be quite fast. In contrast to the innate system, this system is antigen specific and by that more effective. An antigen as part of a microorganism or own cells, most frequently represents a protein, but it is good to know that it also can be a carbohydrate, lipid, or DNA, all being capable of inducing an antibody response.
Lymphocytes bear antigen receptors on their surface and can, on basis of these receptors, be divided into B lymphocytes and T lymphocytes. These receptors are called the B cell receptor (BCR) or cell surface immunoglobulin in B lymphocytes and the T cell receptor (TCR) in T lymphocytes.
< B and T lymphocytes are the main constituents of the adaptive immune system >
B lymphocytes originate directly from and also undergo some steps of maturation with assembly of the BCR within the bone marrow, whereas T lymphocytes start in the bone marrow but the assembly of their TCR takes place in the thymus (Fig. ). After recognizing an antigen by the BCR in the peripheral lymphoid tissues such as a lymph node, B lymphocytes are activated and altered into plasma cells and large quantities of antibody are processed and secreted by these specific B cells. These antibodies have the same antigen-binding site as the BCR that first recognized the antigen. Antibodies can inactivate an antigen, e.g., a microorganism by complement binding or aid in phagocytosis of this microorganism, the latter called opsonization. This entire process is thus called humoral immunity. 
Fig. 1.3
The origin and fate of B and T lymphocytes (Reprinted by permission from Macmillan Publishers Ltd: Gitlin and Nussenzweig []. Copyright January 2015)
T cells are part of the cellular immunity, which basically is important in eliminating intracellular microorganisms, mainly viruses. In contrast to the BCR, the T-cell receptor can only recognize small fragments of proteins (peptide) that are presented on the surface of the infected cell by major histocompatibility complex (MHC) molecules, also called human leukocyte antigens (HLAs). Thus microorganisms first have to be degraded before they can be recognized by the system. MHC molecules are divided into class I and class II molecules. Class I molecules are present on all nucleated cells and platelets. Only a physical combination of an antigen-peptide within a specific MHC-I-class molecule can be recognized by the T cell receptor. This activation transforms this particular T cell into a cytotoxic T cell capable of killing virally infected cells by inducing apoptosis.
MHC-II-class molecules are only expressed on certain cells of the immune system, in particular dendritic cells, macrophages, and B lymphocytes, together called antigen-presenting cells. These cells can present antigen-peptides in conjunction with MHC-II molecules to T-helper cells. These antigens are derived from degraded microorganisms that are phagocytized by the antigen-presenting cells. In addition, these T-helper cells can secrete numerous cytokines, thereby inducing activation of macrophages, stimulating B cells to produce antibodies but also cytotoxic T cells to do their work. T-helper cells can therefore functionally be divided into Th1 cells, stimulating a cytotoxic T cell response; Th2 cells, involved in the humoral immune response; and different subsets of regulatory T cells, involved in controlling these processes.
< T lymphocytes can be divided in cytotoxic T cells and T-helper cells >
Importantly the interaction between the antigen-presenting cells and the T cells with interaction between HLA molecule TCRs is helped by many other receptors and ligands on these cells, generally called costimulatory molecules.
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