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By the American Diabetes Association Classification, Type 1A Diabetes is the immune-mediated form of diabetes, while Type 1B represents nonimmune-mediated forms of diabetes with beta-cell destruction leading to absolute insulin deficiency (1  ). There are additional forms of insulin-dependent diabetes with defined etiologies (˵Other Specific Types of Diabetes:″ genetic, hormonal, and environmental). Finally, type 2 diabetes is, overall, the most common form of diabetes and is characterized by insulin resistance and less beta-cell loss. Even in children, it is important to identify individuals who do not have type 1A diabetes with estimates that approximately 1.5% of children presenting with diabetes have monogenic forms of diabetes. Several monogenetic forms of diabetes are reported to be better treated with sulfonylurea therapy than insulin (e.g., mutations of the ATP-sensitive beta cell selective potassium channels and HNF-1alpha mutations) (2  ), and diabetes due to glucokinase mutations require no therapy at all. Approximately, one half of permanent neonatal diabetes is due to either mutations of the proinsulin gene that leads to beta-cell loss (similar to the Akita mouse (3  )) or Kir6.2/SUR1 mutations (4  ). [ABSTRACT FROM AUTHOR]

The NOD mouse model of type 1A (immune-mediated) diabetes and genetic derivatives of this strain are probably the most extensively studied autoimmune animal models (1–4  ). NOD mice spontaneously develop insulitis. This is followed in the great majority of female mice by sufficient beta-cell destruction to result in overt diabetes and approximately 50% of male mice develop diabetes. Insulitis develops between 4 and 8 weeks and over a prolonged period of time increasing numbers of mice develop severe hyperglycemia. In addition, the mice develop sialitis and other autoimmune disorders, such as thyroiditis, retinitis, and autoimmune neuropathy, depending upon the genetic backgrounds (5–7  ). Multiple derivatives of the NOD model (congenic strains of mice with specific mutations and transgenes) are available from repositories at the Jackson Laboratories and Taconic and from individual investigators. There is no doubt that type 1A diabetes is the result of T cell-mediated destruction of beta cells with genetic mutations and therapies that eliminate (e.g., Rag and SCID mutations) T cells preventing disease and ability to transfer the disease with autoreactive T cells. [ABSTRACT FROM AUTHOR]

This book on immunoendocrinology deals primarily with -autoimmune disorders. The study of endocrine autoimmune diseases has played a prominent role in advancing the understanding of autoimmunity including creation of the first models of induced autoimmune disease (1), demonstration that autoimmunity can cause human pathology (2), and characterization of remarkable syndromes linking multiple autoimmune diseases, as well as the first discovery of genes contributing to multiple diseases such mutations of the AIRE (Autoimmune Regulator) gene (3  ) of APS-1 (Autoimmune Polyendocrine Syndrome) and a specific polymorphism (R620W) of the PTPN22 gene associated with type 1 diabetes and rheumatoid arthritis (4, 5  ). Autoimmunity can be driven primarily by autoantibodies (e.g., targeting of the TSH-receptor by antibodies in Graves΄ disease) or predominantly by T cells (e.g., Type 1A diabetes), but in general, both humoral and cellular autoimmunity occur together. Autoimmune endocrine disorders may affect single organs, a few organs, or many organs. Regardless of the number of organs affected, the underlying autoimmune disease mechanisms are similar with potential variation in the probability of loss of tolerance. In general, persons suffering from rare single organ-specific autoimmune diseases tend to develop multi-organ autoimmunity over time. [ABSTRACT FROM AUTHOR]

Immunodominant Major Histocompatibility Complex class I (MHC I)- associated epitopes suppress T-cell responses against cryptic epitopes. That is, when confronted with complex antigens, CD8+ T cells respond to only a few ˵immunodominant″ epitopes and neglect other ˵cryptic″ peptides that would otherwise be immunogenic when presented alone. Immunodominant epitopes are better immunogens than cryptic epitopes. Compared with T cells specific for cryptic epitopes, CD8+ T cells that recognize immunodominant epitopes interact with their antigen with higher avidity, are primed after a shorter duration of antigen presentation, expand more swiftly and extensively, and generate more potent effector function. Furthermore, by curtailing the duration of Ag presentation [through deletion or exhaustion of antigen presenting cells (APCs)], immunodominant CD8+ effector T cells selectively impair priming against cryptic epitopes. Immunodominance results in one major advantage and one potential drawback: that is, immunodominance favors expansion of the fittest effector T cells but may enhance the risk of immune escape by antigen-loss variants. Targeting immunodominant epitopes is probably crucial not only for success of immune responses against pathogens but also in cancer immunotherapy. Indeed, CD8+ T cells targeted to immunodominant but not cryptic minor histocompatibility antigens can eradicate leukemia and melanoma in mice. In this chapter, I will review the current state-of-the-art regarding T-cell immunodominance and discuss key elements of ongoing and future research in this area. [ABSTRACT FROM AUTHOR]

The article discusses the processes to physiologic and histologic changes in the pulp to the attempts of the tissue at repair. It highlights the presence B lymphocytes, dendritic cells and macrophages, which expressed the surface proteins' type II major histocompatibility complex (MHC), in the response of pulp to toxins and bacteria. It explores the different response of odontoblasts to the toxins produced by gram-negative and gram-positive bacteria.

The entry presents information on major histocompatibility complex (MHC) I antigen presentation. It refers to the process by which antigen-presenting cells express foreign antigen complexed with MHC class I molecules on their cell surface for recognition by lymphocytes. It discusses protein processing by the proteasome and its regulators.

The article presents an encyclopedia entry for autoimmune disease, animal models. It discusses on the use of animals for the evaluation of etiologic agents, influences of chemical exposure and therapeutic efficacy for autoimmune diseases. These genetically predisposed models are used to determine mild to severe syndromes that spontaneously develop, usually due to mutations in major histocompatibility complex, cell surface receptor or cytokine genes.

The article presents an encyclopedia entry about antigen presentation via major histocompatibility complex (MHC) Class II molecules. The term major histocompatibility complex refers to a genetic region with multiple gone loci that is responsible for the acute rejection of transplanted allogeneic tissue. Different MHC region react to different transplant rejection and class II molecules are those that are essential in cell mediated immune responses.

A definition of the term "HLA Class I" is presented. It is the acronym for human leukocyte antigen, a term for major histocompatibility (MHC) in human. MHC is a complex of genes that encode MHC molecules that are required for antigen presentation. presentation. The major histocompatibility system was first discovered in the search for polymorphic antigens to match for transplantation.

The article provides information on hapten. It was introduced by Karl Landsteiner in the 1920s to define low molecular weight chemical reagents which will not induce immune responses. Carriers that are foreign to the immunized individuals result in antibodies and T cells directed against the attached hapten as well as the carrier protein. For many hapten-specific T cells the carrier peptides mainly serve to anchor and position the hapten moiety on the MHC surface.

The entry explains major histocompatibility complex (MHC) restriction. Because of the nature of α β T cell receptor, the characteristic of T lymphocytes when they are bound to a particular allelic form of a MHC molecule, is to recognize foreign peptides. Both the CD4+ and CD8+recognize peptides presented by MHC class molecules. T cell activation would be abolished by the exchange of the peptide and a different MHC molecule.

A definition of the term "hapten" is presented. It refers to a non-immunogenic compound of low relative molecular mass which becomes immunogenic after conjugation with a carrier protein or cell and so induces an immune response. It mentions that the binding of a hapten to a protein allows presentation of the hapten in the peptic-binding groove of MHC molecules.

This entry provides information on the term "T Helper 1 Cytokines," of Th1. CD4 T cells produce cytokines such as IFN-∝ and IL-2, which are autocrine and paracrine signaling molecules, in response to major histocompatibility complex class II antigen stimulation, and stimulate growth and activation of immunocytes and other inflammatory cells.

A definition of the term "T cell antigen-specific receptor" is presented. Peptides of thymus-dependent antigens are recognized by the antigen-specific receptor when presented by class I and II molecules that are encoded in the histocompatibility complex. Antigen-processing and antigen-presenting cells generate the peptides.

The entry explains a mismatched or matched organ. It refers to the determination of the exact major histocompatibility complex (MHC) haplotype by a patient and by an organ donor that allows the transplantation of organs that express the same MHC alleles found for the patient.

The entry offers information on major histocompatibility complex (MHC) tetramers. These soluble tetramers are a biotechnological reagent produced in the laboratory to analyze the specificity of antigen receptors expressed by T cells. Tetramers combined with fluorochromes can be used for cytofluorometric analysis.

A definition of the term "major histocompatibility complex class II molecule" is presented. It refers to cell surface molecules that participate in antigen presentation to CD4+ T helper cells.

A definition of the term "MHC antigen presentation" is presented. It refers to antigen presentation by which cells express antigen bound to major histocompatibility complex molecules on their cell surface for recognition by T lymphocytes.

A definition of the term "Major Histocompatibility Complex Molecules" is presented. It refers to heterodimeric membrane proteins, encoded by the large genetic locus identified as major histocompatibility complex, that serve as peptide display molecules for recognition by T lymphocytes.

An entry for "Langerhans cells" is presented. It refers to the bone-marrow derived cells with dendritic morphology expressing a CD1 protein marker in humans. The cells are responsible for the expression of major histocompatibility complex antigen. Langerhans cells are active in presenting antigen to T cells.

A definition of the term "Human Leukocyte Antigens" is presented. Human Leukocyte Antigens or HLA summarizes the human major histocompatibility complex or transplantation antigens. Genes are found in the HLA locus on chromosome 6 of humans. The HLA is composed of a platform of eight antiparallel beta sheets and two antiparallel alpha sheets.

The article presents an encyclopedia entry for coreceptor of the T cell receptor (TCR), where the cluster of differentiation (CD) 4 or CD8 stabilize the TCR interaction with the major histocompatibility complex-peptide complex and through the intracellularly bound kinase p56lck they contribute to CD3 signalling.

A definition of the term "antigen-presenting cell" is presented. It refers to the cells that can process protein antigens into peptides and express them on the surface for T cells stimulation. Such peptides are presented as a complex with class I or II major histocompatibility complex molecules. The processes involved in the T cell activation are discussed.

A definition of the term alloreactive is presented. It refers to the stimulation of T cells by major histocompatibility complex molecules other than those expressed on self.

A definition of the term "superantigen" is presented. This term refers to a bacterial or viral protein that links major histocompatibility complex molecules (MHC) and T-cell receptors through simultaneous interaction with the constant domains of MHC class II molecules and of T-cell receptor β-chains.

A definition of the term "major histocompatibility complex" (MHC) is presented. It refers to a complex of genes coding for a family of cell surface proteins. Its molecules bind peptide fragments of foreign proteins and present them to T-lymphocytes. The human HMC is known as human leukocyte antigens while the murine MHC as H-2 complex.

The article presents an encyclopedia entry for cytotoxic T-cells or cytolytic T-cells (CTL), which refers to effector cells of the immune system that carry the CD8 surface marker. It has the ability to recognize autologous cells expressing foreign antigens. Major histocompatibility complex-1 has a role in the recognition process.

A definition of the term "MHC," which refers to the major histocompatibility complex, is presented.

A definition of the term "HLA" or human leukocyte antigen, which is a term used for major histocompatibility complex in human.

A definition of the term "Haplotype" is presented. The term refers to a linked set of alleles associated with one parental genome. Basically, it is the particular combination of alleles in a defined region of some chromosome, in effect the genotype in miniature. The term was originally used to describe combinations of major histocompatibility complex alleles. Now, it is used to describe particular combinations of restriction fragment length polymorphisms or microsatellite alleles.