Immune deficiencies

Transient physiologic hypogammaglobulinemia occurs in infants between the ages of approximately 3 and 6 months. Although infants born with adult levels of placentally transferred IgG, a low level of IgG results from:

1. The disappearance of maternal antibody which has a half life of 22-28 days

2. The infants low early rate of synthesis of secretable immunoglobulins

B. Congenital agammaglobulinemia (Bruton’s disease) is a sex-linked (male) disorder that affects infants between the ages of 5 and 6 months. These patients have an apparently normal thymus and CMI.

1. Clinical features include:

a) Recurrent pyogenic infections

b) digestive tract disorders

2. Cause—may occur in the transition from pre-B to B cells and involves the loss of a tyrosine kinase gene. The pre-B cells are normal

3. Diagnosis is made by noting the absence of tonsils (on examination), germinal centers (on lymph node biopsy), and B cells (on peripheral smear) Serum immunoglobulins levels of less that 10% also suggest the disease.

4. Treatment—passive transfer of adult serum immunoglobulin can be administered prophylactically to diminish infections.

C. Dysgammaglobulinemia. Patients of varying age present with a selective immunoglobulin class deficiency.

1. Diagnosis—Most patients have decreased IgA levels with 1:600-800 of those patients having levels of less than 5mg/dl

2. Immunologic features include:

a) Loss of mucosal surface protection

b) Failure of IgA bearing cells to differentiate into secreting plasma cells, although their numbers are normal

c) increased susceptibility to autoimmune disease

D. Congenital thymic aplasia (DiGeorge syndrome) is characterized by hypocalcemia, tetany and an absence of T cells

1. Cause—Not hereditary. It is caused by unknown intrauterine injury to the third and fourth pharyngeal pouches that occurs between the third and sixth weeks of gestation

2. Clinical Features:

a) Thymus and parotid glands are not developed

b) Depressed CMI permits opportunistic infections (Candida, Pneumocystis, viruses)

c) Apparently normal germinal centers, plasma cells, and serum immunoglobulin

3. Treatment—These patients die early

a) Vaccination with live vaccines (measles) is contraindicated

b) The transplantation of fetal thymic tissue is experimental and may be complicated by a graft-versus-host reaction.

E. Chronic mucocutaneous candidiasis is a highly specific T cell disorder that is characterized by an absence of immunity to Candida. Patients have apparently normal T cell absolute numbers and functions. Approximately 50% of patients with this disorder also have endocrine dysfunctions (hypothyroidism)

F. Wiskott-Aldrich syndrome is a sex-linked (male) disorder occurring mainly in children. The syndrome has three main features 1) thrombocytopenia (bleeding), eczema, and recurrent infections. An increased incidence of lymphoreticular malignancies or lymphomas occurs.

1. Immunologic features include:

a) Depressed CMI and a low serum IgM level, but normal IgG and IgA levels

b) Poor response to bacterial capsular polysaccharide antigens.

2. Cause—May be an absence of specific glycoprotein receptors on T cells and platelets.

3. Treatment—Bone marrow transplantation may be effective

G. Severe combined immunodeficiency disease (SCID) is a rare disorder characterized by a genetic defect in stem cells that results in the absence of the thymus gland and t and b cells. Affected children are extremely susceptible to infections and have a very short life span.

1. Immunologic features—A deficiency in the enzyme adenosine deaminase (ADA) occurs in 50% of patients. This deficiency results in the accumulation of toxic deoxyadenosine triphosphate (DATP), which inhibits ribonucleotide reductase and prevents DNA synthesis. A mutation in the g chain of the IL-2 receptor gene is found in other patients with SCID

2. Treatment—Gene therapy with ADA is experimental

H. Chronic granulomatous disease (CGD) results from a genetic defect in the nicotimamide adenine dinucleotide phosphate (NADPH) oxidase system in neutrophils. Patients are susceptible to infections by age 2 years, especially organisms of low virulence.

1. Immunologic features—Neutrophils bactericidal activity (respiratory burst) is defective because of depressed NADPH oxidase, superoxide dismutase activity and decreased hydrogen peroxide levels

2. Diagnosis is based on failure of neutrophils and macrophages to reduce a nitroblue tetrazolium dye

3. Treatment with IFN-g has been successful

I. Absence of spleen can be due to surgical removal after a trauma, treatment of certain hematologic diseases or as a result of infarction in sickle cell disease.

1. Increased susceptibility to encapsulated organisms such as Streptococcus pneumoniae

2. The spleen is required for induction of protective humoral immune responses to the thymus-independent capsular polysaccharide antigens of such organisms.

Tags: immune, immunity, immunology, globulin, antigen, antibody, disease, sex-linked, thymus, capsule, polysaccharide

Category: Pathology Notes