Porth's Essentials of Pathophysiology, 4e

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Disorders of the Immune Response

C h a p t e r 1 6

Plasma cell

C

Plasma cell

IgA

IgG 1

IgM

C

Differ- entiation

Migration to

IgG 2

B lympho- cyte

Switching

Proliferation

Pre- B cell

Stem cell

Plasma cell

IgG

D

FIGURE 16-6. Stem cells to mature immunoglobulin- secreting plasma cells. Arrows indicate the stage of the maturation process that is interrupted in (A) transient hypogammaglobulinemia, (B) X-linked agammaglobulinemia, (C) common variable immunodeficiency, and (D) IgG subclass deficiency.

lymphoid tissue

IgG 3

Bone marrow

IgE

A,C

IgG 4

Plasma cell

IgD

B

C

Plasma cell

C

are susceptible to meningitis, recurrent otitis media, and sinopulmonary infections with organisms such as S. pneumoniae, H. influenzae type b, S. aureus, and Neisseria meningitidis. 33 The abnormal gene in X-linked agammaglobulinemia that maps to the long arm of the X chromosome has a role in all stages of B-cell development. Mutation in the gene results in an absence of mature circulating B cells and plasma cells. T lymphocytes, however, are normal in number and function. Most boys with the disorder remain asymptomatic until 6 to 9 months of age because of the presence of maternal antibodies. A clue to the presence of the disor- der is the failure of an infection to respond completely and promptly to antibiotic therapy. Diagnosis is based on demonstration of low or absent serum immuno- globulins. Therapy consists of prophylaxis with intrave- nous immunoglobulin (IVIG) and prompt antimicrobial therapy for suspected infections. The prognosis for this condition depends on the prompt recognition and treat- ment of infections. Chronic pulmonary disease is an ever-present danger. Common Variable Immunodeficiency. A similar dis- order of B-cell maturation is a condition called common variable immunodeficiency (CVID). In this syndrome, the terminal differentiation of mature B cells to plasma cells is blocked. 35,37,38 More than 80% of persons with this disorder have a normal number of B lymphocytes, but they fail to differentiate into antibody-secreting cells when the lymphocytes are presented with anti- gen. 38 Some persons may also have increased apopto- sis of helper T cells and decreased T-cell function and signaling. The symptomatology of CVID is similar to that of X-linked agammaglobulinemia (i.e., recurrent otitis

Transient Hypogammaglobulinemia of Infancy. During the first few months of life, infants are pro- tected from infection by IgG antibodies that have been transferred from the maternal circulation during fetal life. Immunoglobulin A (IgA), IgM, IgD, and IgE do not normally cross the placenta. The presence of ele- vated levels of IgA or IgM in the infant cord blood suggests premature antibody production in response to an intrauterine infection. An infant’s level of maternal IgG gradually declines over a period of approximately 6 months (see Chapter 15, Fig. 15-14). Concomitant with the loss of maternal antibody, the infant’s imma- ture humoral immune system begins to function, and between the ages of 1 and 2 years, the child’s antibody production reaches adult levels. Any abnormality that interferes with the production of immunoglobulin-producing plasma cells can produce a state of immunodeficiency. For example, certain infants may experience a delay in IgG production (IgM and IgA levels are normal) beyond 6 months of age. The total number and antigenic response of circulating B cells are normal, but the chemical communication between B and T cells that leads to clonal proliferation of antibody-pro- ducing plasma cells seems to be reduced. 35 This condi- tion is referred to as transient hypogammaglobulinemia of infancy. The result of this condition usually is lim- ited to repeated bouts of upper respiratory and middle ear infections. This condition usually resolves by 2 to 4 years of age. X-Linked Agammaglobulinemia. X-linked (Bruton) agammaglobulinemia is a recessive trait that almost exclusively affects boys, as they have only one X chromosome. 32–35,37,39 As the name implies, persons with this disorder have essentially undetectable lev- els of all serum immunoglobulins. Therefore, they