Although more than 50 genetically determined immunodeficiency syndromes have been reported since 1952, defects in immunity were considered rare until acquired immunodeficiency syndrome (AIDS) emerged more than 30 years ago. This growing list of primary and secondary diseases now encompasses all major components of the immune system, including lymphocytes, phagocytic cells, and complement proteins.

Older children and adults with recurrent upper and lower respiratory tract infections and/or diarrhea, abscesses, sepsis, or meningitis should be evaluated for immunodeficiency. Before proceeding with laboratory testing, primary care providers need to rule out the following:

• Anatomic or physical causes (e.g., foreign bodies, indwelling catheters)

• Cancer

 • Connective tissue disease

• Diabetes

 • Renal disease

 Laboratory testing can then proceed with a complete blood cell (CBC) count, including a platelet count and erythrocyte sedimentation rate (ESR). These are among the most cost-effective screening tests. If the ESR is normal, chronic bacterial infection is unlikely. If the absolute neutrophil count is normal, congenital and acquired neutropenias and severe chemotactic defects are eliminated. If the absolute lymphocyte count is normal, the patient is not likely to have a severe T cell defect. The absolute lymphocyte count is the number of lymphocytes in the total white blood cell (WBC) population (Box 1).

Box1. Determination of Absolute Lymphocyte Count

Laboratory tests to screen for more common immunodeficiencies include immunoglobulin testing, complement testing, cell-mediated immunity testing, and the neutrophil function test. Additional laboratory testing should include a general metabolic panel to assess overall general health, HIV types 1 and 2, protein electrophoresis, sweat chloride, and pneumococcal antibody IgG titers pre- and postvaccine in patients with only recurrent sinopulmonary infections. Follow-up testing based on any initially abnormal results is presented in Tables 1 and 2. If all initial test results are normal, IL-1 receptor associated kinase-4 (IRAK-4) deficiency screening or a Toll like receptor function assay should be performed. If abnormal results are subsequently found, the diagnosis is an innate immune deficiency.

Table1. Next Steps in Laboratory Evaluation of Suspected Immunodeficiency

Table2. Next Steps in Evaluation of Suspected Immunodeficiency Based on Physical Findings

Cell-Mediated Immune System

Deficiencies of cell-mediated immunity are often suspected in individuals with recurrent viral, fungal, parasitic, and protozoal infections. Patients with AIDS exhibit some of the most severe manifestations of cell-mediated immunity.

One avenue of testing involves delayed hypersensitivity skin testing to determine the integrity of the patient’s cell-mediated immune response. More than 90% of normal adults will react to one of the following antigens within 48 hours after antigen exposure: Candida albicans, Trichophyton, tetanus toxoid, mumps, and streptokinase-streptodornase. Reactivity to histoplasmin or purified protein derivative (PPD) is positive in patients with active infection or previous exposure to histoplasmosis or tuberculosis, respectively; therefore these tests are not useful for the assessment of anergy.

The number of T lymphocytes, the primary effector cells in cell-mediated reactions, can be determined by several techniques. Previously, the gold standard was the E rosette technique (erythrocyte rosette formation), but the development of flow cytometry with MAbs has replaced this technique. Testing for the functionality of lymphocytes is just as important as a quantitative count of CD4+ and CD8+ cells.

The in vitro diagnostic test (IVD; see later, “Assessment of Cellular Immune Status”) is the newest approach to testing the functionality of T lymphocytes. It is important to recognize that CD4 counts do not always reflect the actual status of the patient’s immune system. ImmuKnow (Cylex, Columbia, Md) is the first U.S. Food and Drug Administration (FDA) approved immune function test. It is widely considered to be the gold standard of immune function testing.

The QuantiFERON-CMI kit (Cellestis, Valencia, Calif) is an in vitro assay for measuring cell-mediated immune functionality. The procedure is a single-step enzyme-linked immunosorbent assay (ELISA) to determine T cell responses by measuring IFN-γ levels in plasma. This is a specific marker cytokine for a cell-mediated or inflammatory immune response (e.g., bacterial, parasitic, or viral).

Research-Based Tests

 Various procedures are research-based, including a lymphocyte antigen and mitogen proliferation panel. This type of procedure measures cytokine production by mononuclear cells in response to mitogen stimulation by IL-1β types 6 and 8 and TNF-α. Another method includes flow cytometry and the enzyme-linked immunosorbent spot assay (ELISPOT). Flow cytometry can be used in conjunction with intracellular cytokine staining with 3H-thymidine to detect the T cell response to specific antigenic stimulation by multianalyte fluorescence detection. In addition, peptide–MHC complex tetramer or pentamer staining is used to quantify the number of T cells with a particular antigenic epitope based on the expression of a specific T cell receptor. A multiplex cytokine analysis (e.g., multiplex bead-based Luminex assay [Life Technologies, Grand Island, NY]) is being used to detect multiple cytokines in serum, plasma, or tissue culture supernatants.

Humoral System

 The humoral system can be screened for abnormalities by quantitating the concentrations of IgM, IgG, and IgA. An initial simple screening can be determined by the presence and titer of antibodies to type A and B red blood cell (RBC) antigens.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم الإعلام يشارك في الاجتماع التحضيري لمناقشة الخطة الإعلامية لزيارة عاشوراء

بحضور متوليها الشرعي.. العتبة العباسية المقدسة تواصل إقامة المجالس الحسينية لإحياء شهر المحرم

قسم الشؤون الفكرية يطلق برنامجه التبليغي في أكثر من 20 دولة إفريقية

شعبتا الخطابة النسوية والتوجيه الديني تواصلان إقامة المجالس الحسينية في مرقد أبي الفضل العباس (عليه السلام)

المزيد

الآخبار الصحية

دراسة تكشف علاقة خطيرة بين عمر الأم وصحة مولودها

دراسة تحذر.. اضطراب نوم بسيط قد يسبب الموت المبكر ؟

الاستحمام بالماء الساخن.. راحة مؤقتة وأضرار دائمة للبشرة

ماذا يحدث للجسم عند تخطي وجبة الإفطار؟

المزيد

الآخبار التكنلوجية

كيف تساعد الصيانة الوقائية في الحفاظ على كفاءة التكييف في سيارتك ؟

في ظاهرة غريبة حيرت العلماء.. كوكبنا قد يسجل أقصر يوم في التاريخ هذا الصيف!

السد الصيني العملاق يعيق دوران الأرض ويغيّر شكلها ؟

السعودية تطلق 10 تجارب علمية إلى محطة الفضاء الدولية

المزيد

مواضيع ذات صلة

Plasma Cell Biology

B Lymphocyte Subsets

Natural Killer and K-Type Lymphocytes

Antigen Recognition by T Cells

Antigen Processing and Antigen Presentation to T Cells

Cytotoxic T Lymphocytes

T Regulatory Lymphocytes

Helper T Lymphocytes

Sites of Lymphocyte Development

MONOCYTE-MACROPHAGE DISORDERS

Clinical Features of HIV Infection and AIDS

Pathogenesis of AIDS