Chapter 7

The nonspecific inflammatory response and the immune response act synergistically in defense against infection. Deficits in either process often result in increased susceptibility to attack by pathogenic microorganisms, manifested clinically as recurrent or intractable infection or as an opportunistic infection, ie, infection by a pathogen of low virulence that does not cause disease in a normal host.

### Deficiency of the Vascular Response

#### Diabetes Mellitus

In diabetes mellitus, involvement of small arterioles characterized by thickening of the basement membrane increases susceptibility to infection. These abnormal vessels may fail to dilate and do not show the normal changes in permeability associated with the acute inflammatory response.

#### Vascular Disease (Ischemia)

Severe arterial narrowing limits the amount of blood entering an injured area during acute inflammation and contributes to the decreased resistance to infection observed in older patients, in whom severe arterial narrowing due to atherosclerosis is common.

### Abnormal Neutrophil Function

#### Quantitative Disorders

Neutropenia (decreased numbers of neutrophils) due to any cause is associated with a defective cellular response in acute inflammation that leads to increased susceptibility to infection. A severe reduction in the peripheral blood neutrophil count (< 1000/μL) must occur before the risk of infection is significantly increased. The most common cause of neutropenia in clinical practice is cancer treatment utilizing cytotoxic drugs and radiation therapy (Chapter 26: Blood: III. the White Blood Cells).

#### Qualitative Disorders

Abnormal neutrophil function may be manifested as disorders of neutrophil motility. Intrinsic abnormalities that affect motility are rare and include lazy leukocyte syndrome, in which neutrophil emigration is abnormal, and Chédiak-Higashi syndrome, which is characterized by defective movement and degranulation of neutrophils associated with the presence of large cytoplasmic granular inclusions composed of greatly enlarged lysosomes. The condition is inherited as an autosomal recessive trait. Melanosomes also are abnormal, leading to partial albinism.

Neutrophil motility may also be impaired by lack of the CD11/CD18 cell adhesion complex, deficiency of complement components, or the presence of antineutrophil antibodies in rheumatoid arthritis.

#### Disorders of Phagocytosis

Abnormalities of phagocytosis may result from deficiency of opsonins, as occurs in hypogammaglobulinemia and complement factor 3 (C3) deficiency. Impaired degranulation occurs in Chédiak-Higashi syndrome and in use of antimalarial drugs and corticosteroids.

#### Disorders of Microbial Killing

##### Chronic Granulomatous Disease of Childhood

Chronic granulomatous disease occurs as an X-linked or autosomal recessive disorder characterized by decreased ability of neutrophils to produce hydrogen peroxide. The different forms of the disease are associated with different enzyme deficiencies that interfere with energy production at the cellular level.

The disease becomes manifest in the first few years of life, chiefly in males, and is characterized by recurrent infections of skin, lungs, bone, and lymph nodes. Patients are susceptible to diseases caused by organisms such as staphylococci and Serratia that produce catalase, which destroys the small amount of hydrogen peroxide produced in cells ...

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