Porth's Essentials of Pathophysiology, 4e

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Infection and Immunity

U N I T 4

CHART 16-1   Probable Autoimmune Disease* Systemic Mixed connective tissue disease Polymyositis-dermatomyositis Rheumatoid arthritis Scleroderma Sjögren syndrome Systemic lupus erythematosus Blood Autoimmune hemolytic anemia Autoimmune neutropenia and lymphopenia Idiopathic thrombocytopenic purpura Other Organs Acute idiopathic polyneuritis Atrophic gastritis and pernicious anemia

SUMMARY CONCEPTS (continued)

Autoimmune Disease Autoimmune diseases represent a group of disorders that are caused by a breakdown in the ability of the immune system to differentiate between self- and nonself-antigens. They can affect almost any cell or tis- sue in the body. Some autoimmune disorders, such as Hashimoto thyroiditis, are tissue specific, whereas oth- ers, such as SLE, affect multiple organs and systems. Chart 16-1 lists some of the common autoimmune dis- eases. Many of these disorders are discussed elsewhere in this book. ImmunologicTolerance To function properly, the immune system must be able to differentiate foreign antigens from self-antigens in a process called self-tolerance. 1–3 It is the HLAs into recipients who are immunologically compromised. Three basic requirements are necessary for GVHD to develop: (1) the transplant must have a functional cellular immune component, (2) the recipient tissue must bear antigens foreign to the donor tissue, and (3) recipient immunity must be compromised to the point that it cannot destroy the transplanted cells. ■■ Destruction of the cells or tissues of the graft can result from direct action of the recipient’s cytotoxicT cells, fromT-cell–generated cytokines and a delayed hypersensitivity reaction, or from antibodies generated against antigens in the graft. ■■ Hyperacute rejection occurs almost immediately after transplantation and is caused by existing recipient antibodies to graft antigens that initiate a type III, Arthus-type hypersensitivity reaction in the blood vessels of the graft. Acute rejection occurs within the first few weeks or months after transplantation and occurs when graft tissue or blood vessels are damaged by alloreactiveT cells or antibodies. Chronic rejection occurs over a prolonged period and is caused byT-cell–generated cytokines that damage blood vessels, causing ischemic damage to graft tissue. ■■ Graft-versus-host disease (GVHD), which occurs most often following bone marrow transplantation, develops when immunologically competent cells or precursors are transplanted

Autoimmune adrenalitis Goodpasture syndrome Hashimoto thyroiditis Type 1 diabetes mellitus Myasthenia gravis Premature gonadal (ovarian) failure

Primary biliary cirrhosis Sympathetic ophthalmia Temporal arteritis

Thyrotoxicosis (Graves disease) Crohn disease, ulcerative colitis

*Examples are not inclusive.

encoded by MHC genes that serve as recognition markers of self and nonself for the immune system (see Chapter 15). To elicit an immune response, an antigen must first be processed by an antigen-pre- senting cell (APC), such as a macrophage, which then presents the antigenic determinants along with an MHC II molecule to a CD4 + helper T cell. The dual recognition of the MHC–antigen complex by the T-cell receptor (TCR) of the CD4 + helper T cell acts like a security check. Similar recognition checks occur between CD8 + cytotoxic T cells and the MHC I–antigen complex of tissue cells that have been targeted for elimination. A number of chemical messengers (e.g., interleukins) and costimulatory signals are essen- tial to the activation of immune responses and the preservation of self-tolerance. Several mechanisms have been postulated to explain the tolerant state, including central tolerance and peripheral tolerance. 1,2,20–23 Central tolerance refers to the elimination of self-reactive T cells and B cells in the central lymphoid organs (i.e., the thymus for T cells and the bone marrow for B cells). Peripheral tolerance derives from the deletion or inactivation of autoreactive T cells or B cells that escaped elimination in the central lymphoid organs. Anergy represents the state of immu- nologic tolerance to specific antigens. It may take the form of diminished immediate hypersensitivity, delayed- type hypersensitivity, or both.