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Spirochete Infections

Key Points Human disease caused by spirochetes typically follows a clinical course that reflects three sequential phenomena: (1) early, local proliferation of the organisms at the site of introduction, (2) spirochetemia with systemic dissemination, and (3) persistence of small numbers of microbes at various, often immune, “privileged” sites. Direct detection of pathogenic spirochetes is sometimes possible by microbiologic culture, microscopy, or genomic amplification, but diagnosis more…

Mycotic Diseases

Key Points Opportunistic fungal pathogens have emerged as common causes of invasive disease in the compromised host. Histopathologic examination of deep tissue is a major means used for the rapid detection and recognition of fungal pathogens causing invasive infection. Micromorphologic and phenotypic methods continue to be the general processes used in the clinical laboratory for the identification of fungal pathogens in culture. Molecular methods have advanced…

Mycobacteria

Key Points The Mycobacterium tuberculosis complex is of public health importance because it is transmitted from person to person. The Mantoux skin test and interferon-γ release assays are useful for identifying persons with latent M. tuberculosis infection. For optimal detection of mycobacteria in clinical specimens, laboratories should use a fluorochrome stain and liquid culture system with a concomitant solid medium for culture. Nucleic acid amplification testing…

In Vitro Testing of Antimicrobial Agents

Key Points The minimum inhibitory concentration (MIC) is defined as the lowest concentration of antibiotic that inhibits the visible growth of an organism in vitro. It is distinguished from the breakpoint, which is the concentration of antibiotic that determines whether an isolate is categorized as susceptible, intermediate, or resistant. MIC values are determined by inhibitory methods in the laboratory, which include broth dilution, agar dilution, and gradient…

Medical Bacteriology

Key Points Bacteria can be categorized based on the Gram stain reaction (gram-positive or gram-negative), shape (cocci, bacilli, coccobacilli, spirochete), preferred atmosphere (aerobic, microaerophilic, anaerobic), and presence or absence of spores. They can be identified on the basis of key biochemical tests, antigenic components (e.g., cell wall antigens, toxins), and/or molecular features, including nucleic acid–based testing and proteomic detection. Among the gram-positive cocci, the most important…

Allergic Diseases

Key Points The prevalence of allergic disease, particularly food allergy, has increased in recent years throughout the world, especially in developed countries. Allergen-specific immunoglobulin E (IgE) antibody is the most important trigger molecule for allergic inflammation. Laboratory tests for IgE antibody that support a high likelihood of allergic disease are widely available and clinical practice guidelines advocate their use. A positive IgE antibody test result is…

Organ-Specific Autoimmune Diseases

Key Points Autoimmune disorders frequently affect the skin, gastrointestinal, and hepatobiliary systems; the kidney; the endocrine system; and the nervous system. The dominant clinical feature of organ-specific autoimmune disease is chronic inflammation, generally localized in a single organ specific for each individual disease. In organ-specific autoimmune diseases, an organ-specific, tissue-specific, or cell-specific autoantigen is targeted. Some autoantigens circulate, some are cell surface molecules, and some are…

Vasculitis

Key Points Vasculitis affects blood vessels of any type in any organ or tissue and causes diverse signs and symptoms of disease that overlap with many other diseases. Even if it is not the final diagnosis, vasculitis is often in the differential diagnosis in a patient with evidence of single organ or systemic inflammatory disease. Laboratory tests for vasculitis identify a specific etiologic factor or measure…

Clinical and Laboratory Evaluation of Systemic Autoimmune Rheumatic Diseases

Key Points Many types of autoantibodies to intracellular antigens are present in the various systemic autoimmune rheumatic diseases. Currently it is considered important not only to detect the presence and quantity of the intracellular autoantibody in the patient but also to identify its antigenic specificity. Past studies have shown that distinct diagnostic autoantibody profiles are observed in many of the systemic autoimmune rheumatic diseases. Some of…

Immunodeficiency Disorders

Key Points Primary immunodeficiencies are a group of disorders where the defect lies within the immune system; most of them are caused by single-gene defects. Because of the complexity of diagnosing a primary immunodeficiency, the cooperation of the clinician, the research scientist, and the clinical pathologist is required. A logical approach to the diagnosis of primary immunodeficiency disorders based on staged diagnostic testing or clinical picture…

The Major Histocompatibility Complex And Disease

Key Points The major histocompatibility complex (MHC) genomic region contains many genes with immune-related functions, including the human leukocyte antigen (HLA) genes. Identification of genes within the MHC has increased the possibility of defining the genetic basis of immunity. The clustering of immune-related genes in the MHC region may not be coincidental and may be the result of evolutionary forces joining genes with similar functions. The…

Human Leukocyte Antigen: The Major Histocompatibility Complex of Humans

Key Points The major histocompatibility complex (MHC) is one of the most diverse and polymorphic genetic systems in humans. It consists of human leukocyte antigen (HLA) class I molecules (HLA-A, -B, and -C) and class II molecules (which include HLA-DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, -DPA1, and -DPB1). In total, there are over 20,000 unique HLA alleles. MHC genes are closely linked and segregate into offspring…

Mediators of Inflammation: Cytokines and Adhesion Molecules

Key Points Cytokines are soluble proteins released by cells to facilitate communication and interaction between cells, to modulate the immune response, to direct cell differentiation, and to orchestrate associated inflammatory and reparative activities. Adhesion molecules are complex cell surface glycoproteins that mediate cellular interactions, such as cell migration during embryogenesis, wound healing, and the inflammatory response. Cytokines Cytokines coordinate multiple biological processes, including embryonic development, nonspecific…

Mediators of Inflammation: Complement

Key Points The complement system is a group of circulating proteins that promote inflammation and host defense. Unregulated tissue damage is a possible complication of complement activation; a large variety of circulating and membrane-bound proteins exist to regulate complement activity. Complement component C3 is the central convergence point for all complement activation pathways. It is frequently necessary to measure serum complement levels to track disease activity.…

Laboratory Evaluation Of Immunoglobulin Function And Humoral Immunity

Key Points Five different classes of antibody are known—immunoglobulin (Ig) M, IgG, IgA, IgD, and IgE—each with a distinct heavy chain. Two different light-chain types have been identified: κ and λ. Antigens react with antibodies at the Fab region, which contains variable regions of both heavy and light chains. The Fc region on the heavy chains determines what other proteins will bind to the antibody (e.g.,…

Laboratory Evaluation of The Cellular Immune System

KEY POINTS Humoral immune tests assess production of specific antibody responses to past or recent infections, and cellular immune assays measure current immune responses. The immune system changes with age and nutritional status. Differences in immune responses of test subjects associated with immaturity, immunosenescence, or malnutrition should be taken into account when evaluating the results of specific tests. Primary immunodeficiency may be associated with an increased…

Immunoassays And Immunochemistry

Key Points Antigens can have a wide variety of types of chemical composition such as proteins, carbohydrates, and lipids. They can range in size from very small molecules, such as hormones, to very large ones on viral or bacterial particles. Antibodies can be polyclonal as in an immune response with somewhat broad specificity. Monoclonal antibodies are developed from cloned hybridomas; thus, they have very high specificity…

Overview of the Immune System and Immunologic Disorders

Key Points The immune system consists of cellular and humoral components that defend the body against invading microorganisms. Deficiency of individual factors of the immune system can leave an individual susceptible to different infections. The lymphoid cells of the immune system are composed of T cells that act directly against foreign antigens and B cells that differentiate into immunoglobulin (Ig)-secreting plasma cells capable of synthesizing immunoglobulins…

Antithrombotic Therapy

Key Points Warfarin has historically been the most commonly used oral anticoagulant. It is a vitamin K antagonist and blocks γ-carboxylation of a series of glutamic acid residues during the synthesis of factors II, VII, IX, and X, and proteins C and S. The resulting decreased functionality of the coagulation factors leads to prolongation of prothrombin time (PT), which is monitored as the international normalized ratio,…

Laboratory Approach to Thrombotic Risk

Key Points Several regulatory mechanisms have evolved to limit the extent of clot formation after coagulation is triggered. Under normal conditions, these allow hemostasis to be achieved while preventing the growth of a hemostatic plug into an intravascular thrombus. Among these regulatory systems are the antithrombin mechanism, the protein C–protein S system, the fibrinolytic system, and the tissue factor pathway inhibitor mechanism. Deficiencies of the major…