Page 29 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPter 1 The Human Immune Response 15

intracellular bacteria, and tumor cells. These responses involve
the production of inflammatory cytokines by CD4 Th1 cells, as
well as the direct cytolytic activity of CD8 CTLs. In contrast,
host defenses to most antigens encountered primarily in the
extracellular milieu are largely dependent on humoral mechanisms
(antibody and complement) for antigen neutralization, precipita-
tion, or opsonization and subsequent destruction by phagocytes.
Targets of antibody-mediated immunity include extracellular
virus particles, bacteria, and toxins (or other foreign proteins).
It is worth reiterating, however, that induction of an effective
antibody response (including isotype switching) and development
of immunological memory (resulting from B-cell clonal expansion
and B memory cell differentiation) require antigen activation
not only of specific B cells but also CD4 T cells, particularly of
the Th2 type. Additionally, antibacterial and antifungal responses
that involve prominent responses by neutrophils require CD4
T cells of the Th17 type.

KeY ConCePtS
Characteristic Infections Associated With Immune
Deficiency Syndromes
Deficiencies of t Cell–Mediated Immunity
• Mucocutaneous fungal infections, especially Candida albicans FIG 1.4 Leg of a 16-year-old patient with chronic mucocutaneous
• Systemic (deep) fungal infections candidiasis as a consequence of a congenital T-cell deficiency
• Systemic infection with attenuated viruses (e.g., live viral vaccines) associated with hypoparathyroidism and adrenal insufficiency.
• Infection with viruses of usually low pathogenicity (e.g.,
cytomegalovirus)
• Pneumocystis jiroveci pneumonia
onstrations that the pathogenesis of various familial forms
antibody Deficiencies of chronic mucocutaneous candidiasis reflects deficiency of
• Infections by encapsulated bacteria (e.g., Streptococcus spp., Hae- IL-17–mediated immunity. 61
mophilus influenza)
• Recurrent pneumonia, bronchitis, sinusitis, otitis media However, patients with defects in antibody synthesis or
• Giardia lamblia enteritis phagocytic cell function are characteristically afflicted with
recurrent infections with pyogenic bacteria, particularly gram-
Phagocyte Deficiencies positive organisms. And patients with inherited defects in synthesis
• Infection by gram-positive bacteria (e.g., staphylococci, of terminal complement components have increased susceptibility
streptococci) to infection with species of Neisseria.
• Gram-negative sepsis In recent years, immunology has entered the lay lexicon, largely
• Systemic fungal infections (e.g., Candida spp., Aspergillus spp.) as a result of the HIV pandemic. People throughout the world
are now aware of the tragic consequences of immune deficiency.
adhesion Molecule Deficiencies The remarkable progress in understanding this disease, however,
• Infections with pyogenic bacteria (especially staphylococci)
• Cutaneous and subcutaneous abscesses depended substantially on earlier studies of relatively rare patients
with primary immunodeficiency syndromes, more recent accelera-
Complement Component Deficiencies tion due to progress in genomic definition of their molecular
• C3 deficiency: Infections with encapsulated bacteria basis. Similarly, cure of patients with primary immunodeficiencies
• Deficiency of terminal components: infections with gram-negative by cellular reconstitution, particularly bone marrow or stem cell
bacteria, especially Neisseria spp. transplantation (Chapter 82), presaged recent progress in
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correction of such diseases by gene replacement therapy (Chapter
85). The “present” of clinical immunology is, indeed, bright. But
Finally, clinical “experiments of nature” have proven particu- its future potential to impact prevention and treatment of many
larly instructive in our efforts to understand the role of specific challenging diseases, including cancer (Chapter 77), through
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components of the immune system in overall host defenses specific analysis of genetic mutations and enhancement or sup-
(Chapter 37). The importance of T cell–mediated immunity in pression of global or antigen-specific immune responses and
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host defenses to intracellular parasites, fungi (Fig. 1.4), and viruses check-point inhibition is even more exciting to contemplate.
is emphasized by the remarkable susceptibility of patients with A few approaches are broadly hinted at here, and it is hoped
T cell–deficiency to pathogenic organisms, such as Pneumocystis that readers will enjoy considering such “perspectives” throughout
jiroveci and Candida albicans, and by the fact that utilizing the book and, given the nature of the immune system, it is also
attenuated live virus vaccines in such patients can lead to devastat- hoped will challenge themselves to transform a particular author’s
ing disseminated infections. Indeed, the relationship between views to new and different clinical settings.
susceptibility to particular potential pathogens and specific Studies in experimental animals, especially murine studies,
immunological deficiencies is nicely illustrated by recent dem- have been critical to our understanding of molecular aspects of