Page 397 - Clinical Immunology_ Principles and Practice ( PDFDrive )

378 PARt tHREE Host Defenses to Infectious Agents

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because of its potential for dual use. Infection can be spread Bartonella
to humans via contaminated animals or tick bites. This gram- Bartonella spp. represent gram-negative facultative intracellular
negative bacterium survives in macrophages and primarily causes pathogens transmitted by insect vectors, such as fleas, sandflies,
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acute pneumonia as well as skin sores, with subsequent involve- and mosquitoes. The most clinically relevant species are B.
ment of lymph nodes. henselae, B. quintana, and B. bacilliformis. B. henselae causes cat
scratch disease (CSD) resulting in local lymphadenopathy in the
Nongranulomatous Infections lymph node draining the scratch site accompanied by fever,
Legionnaires’ Disease or Legionellosis headache, and splenomegaly. Oculoglandular involvement
Legionnaires’ disease is caused by Legionella pneumophila, an (Parinaud syndrome), encephalopathy, neuroretinitis, or osteo-
environmental bacterium that persists within amoeba living in myelitis can occur, albeit in rare cases. In immunosuppressed
water reservoirs (e.g., air-cooling systems), from where it is spread patients, bacillary angiomatosis and peliosis can occur, character-
aerogenically. Infection is exacerbated by a compromised immune ized by pseudotumoral proliferation of endothelial cells. Bacteria
status. Characteristically, Legionnaires’ disease presents as atypical persist within erythrocytes with the intracellular location provid-
pneumonia associated with general symptoms and is complicated ing a protective niche.
by extrapulmonary infection, renal failure, and lung abscesses.
Cases of Legionnaires’ disease in the United States increased GRANULOMA PATHOLOGY AS HALLMARK OF
from 0.39 to 1.36 per 100 000 people from 2000 to 2011. 13
INTRACELLULAR BACTERIAL INFECTION
Chlamydial Urethritis, Cervicitis, and Conjunctivitis
C. trachomatis serovars D–K enter and persist in epithelial cells KEY CONCEPtS
of the urogenital tract, causing cervicitis and urethritis. In women, Balance of Protection and Host Pathology
infertility can develop as a result of chronic or recurrent infection. in Granulomas
In neonates, congenital infection during birth may result in
conjunctivitis and pneumonia. Urogenital infections by chla- Macrophage activation results in bacterial death (protective)
mydiae occur worldwide and are now considered the most Intracellular bacterial killing by “killer molecules” from T cells
(protective)
common sexually transmitted bacterial disease, with an estimated Lysis of infected macrophages by T cells results in release of bacteria
100 million new infections occurring annually. 14 and killing by more effective effector cells (protective) or bacterial
dissemination (pathogenic)
Trachoma Development of central necrosis in granulomas results in death of tissue
Smear infections of the eye with C. trachomatis serovars A, and bacteria (protective/pathogenic)
B, and C cause inclusion conjunctivitis. As a consequence of Fibrotic encapsulation of granuloma results in containment of infection
(protective)
multiple chronic infections and of the resulting immune response, Overexuberant tissue fibrosis and necrosis (pathogenic)
scars develop that eventually injure the cornea, leading to tra- Liquefaction of central necrotic tissue in granulomas results in bacterial
choma. Approximately 84 million people are infected with C. replication, cavity formation, and transmission of bacteria (pathogenic
trachomatis worldwide, 7.6 million of whom suffer from visual and contagious)
impairment. 15
A characteristic feature of many infections caused by intracellular
Chlamydia Pneumoniae bacteria is the eventual need for tissue remodeling by the host at
C. pneumoniae (formerly known as C. trachomatis TWAR strain) the site of infection. Granulomas are the result of an inability to
is the cause of mild respiratory disease in young adults and may rapidly clear host tissue of intracellular bacteria and represent a
cause serious infections in older, more debilitated patients. fascinating site of the host–pathogen interface (Fig. 26.1). The
Atypical pneumonia may also be caused by Chlamydia psittaci, longevity of the granuloma depends directly on the continuous
although this zoonosis, transmitted by birds, is relatively rare. presence of the microbial pathogen, and the lesion generally
disappears after its sterile eradication. Granulomas form the focus
Typhus of the coordinated cross-talk between different types of T cells,
Rickettsia prowazekii, R. typhi, and R. tsutsugamushi cause diseases B cells, and infected and uninfected mononuclear phagocytes
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of varying severity. They are transmitted by arthropods and (MPs) and dendritic cells (DCs). Even if the immune system fails
infect vascular endothelial cells at the site of an insect bite or to completely eliminate bacteria inside the granuloma, the latter
scratch, causing skin reactions. Subsequently, pathogens are performs a protective function by containing microbes within
disseminated to the central organs, and more general symptoms distinct foci and preventing their dissemination. At the same
develop. Globally, typhus is of minor importance. time, the granuloma can be detrimental to the host because it
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can interfere with physiological organ functions. More detailed
Rocky Mountain Spotted Fever, Ehrlichiosis study of cellular phenotype within granulomas is starting to
Rocky Mountain spotted fever is caused by Rickettsia rickettsii. establish how cellular differentiation is orchestrated and how
Infection of the vascular endothelium leads to systemic symptoms the granuloma develops.
and skin manifestations that may be followed by shock and Granulomatous lesions are generally initiated by nonspecific
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neurological complications. Worldwide, this disease, as well as inflammatory signals mediated by bacterial products, chemokines,
Mediterranean spotted fever caused by Rickettsia conorii, is of and proinflammatory cytokines that are produced by endothelial
minor importance; as is probably Ehrlichiosis, a newly emerging cells and MPs at the site of infection. Inflammatory phagocytes
zoonosis transmitted by ticks and caused by various Ehrlichia (of both monocytic and granulocytic origin) are attracted to
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spp., mainly E. chaffeensis. Disease manifestations include the site of microbial replication, and an infiltrative, sometimes
generalized symptoms, such as fever and muscle pain. exudative, lesion develops. Following the accumulation and