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  1. Learn the common autoimmune diseases involving primarily the connective tissue.

  2. Understand the disorders associated with immune deficiencies and their underlying pathophysiology.

  3. Learn the diagnostic tests required to establish a diagnosis for autoimmune disorders and for immunodeficiency disorders.


The immune system is a tightly regulated network that incorporates both innate and adaptive pathways. The genes regulating the innate system are coded in the germ line. The innate immune system is not antigen specific. The cells and soluble factors of the innate system have pattern recognition receptors (PRRs, such as toll-like receptors) to common motifs on pathogens and altered self-motifs. The motifs on pathogens are called pathogen-associated molecular patterns (PAMPs). Altered self-antigens include danger-associated molecular patterns (DAMPs) as found in heat shock protein, and apoptosis-associated molecular patterns (AAMPs) as found in ds DNA, RNP, and histones. This response is rapid and there is no memory of the encounter.

The receptors on the T and B cells of the adaptive immune system are antigen or epitope specific and clonally variable, and their diversity is derived from gene recombination. The cells retain memory of the encounter and on subsequent engagement with that antigen, the cells exhibit more rapid and robust responses.

The immune network is tightly regulated by cells and cytokines, and a derangement in this immune homeostasis can result in immune response to self-antigens as in autoimmunity (failure of self-tolerance), or failure to recognize pathogens and eliminate them as occurs in immunodeficiency syndromes (failure of immunity). The following two groups of disorders are the focus of this chapter: the autoimmune diseases involving the connective tissue and the primary immunodeficiency diseases.

Diseases in which immune responses to self-antigens occur in the context of a genetic predisposition resulting in disease expression are called autoimmune diseases. Some involve organ-specific pathologic autoimmunity such as Hashimoto thyroiditis and celiac disease, and these are discussed in Chapters 22 and 15, respectively. The autoimmune disorders discussed in this chapter are systemic diseases with predominant involvement of the connective tissue, manifesting clinical features including inflammation of the joints, skin, muscles, and other soft tissues (see Tables 3–1 and 3–2 and Figure 3–1).

TABLE 3–1Systemic Autoimmune Diseases: Diseases Associated with Positive Test Results for Antinuclear Antibodies (ANA)

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