The immune system is the body’s defense against infection and disease. It is made up of a complex network of cells, tissues, and organs that work together to protect the body. Testing the immune system involves looking at the different components and functions to determine if the system is working properly.
Complete Blood Count
A complete blood count (CBC) is often one of the first tests used to evaluate the immune system. This common blood test measures the levels of white blood cells, red blood cells, and platelets in the blood. White blood cells, or leukocytes, are part of the immune system. The CBC provides important numbers and percentages for the different types of white blood cells, including:
- Lymphocytes: T cells, B cells, and natural killer cells
- Monocytes
- Granulocytes: Neutrophils, eosinophils, and basophils
These numbers provide valuable insight into the status of the immune system. For example, a low white blood cell count (leukopenia) may indicate an immune deficiency, while an elevated count (leukocytosis) may signal an infection or inflammatory disease. The CBC results help identify abnormalities or potential problems with immunity.
Immunoglobulins
Immunoglobulins, also called antibodies, are Y-shaped proteins produced by plasma cells. They are a critical part of the humoral immune response. There are five classes of immunoglobulins: IgG, IgA, IgM, IgD, and IgE. The levels of these immunoglobulins in the blood can be measured through a simple blood test.
IgG antibodies make up about 80% of all immunoglobulins. Low levels of IgG may indicate an immunodeficiency. IgA and IgM levels may be elevated during an infection. Checking immunoglobulin levels helps assess both short-term and long-term immune status.
Lymphocyte Subsets
As noted above, lymphocytes are a type of white blood cell integral to immune response. Lymphocytes consist of T cells, B cells, and natural killer cells. Each of these lymphocyte subsets performs different protective functions. Flow cytometry can be used to measure the levels and ratios of lymphocyte subsets in the blood.
CD4 cells or T-helper cells coordinate immune response. The CD4 count is a common test for immunocompetence in HIV/AIDS patients. CD8 cells or cytotoxic T cells directly attack infected or cancerous cells. An inverted CD4:CD8 ratio may indicate an immune disorder. Natural killer cell and B cell numbers provide additional lymphocyte information.
Immunophenotyping
Immunophenotyping examines the proteins expressed on the surface of immune cells through the use of antibodies. Flow cytometry and cell sorting techniques allow identification and enumeration of cell populations based on these surface proteins or “markers”. Age-related changes in cell marker expression can indicate weakened immunity. Immunophenotyping also helps identify abnormal cells associated with blood cancers like leukemia and lymphoma.
Proliferation Assays
Lymphocyte proliferation assays measure the ability of T cells to multiply in response to mitogens or antigens. Blood samples are cultured with agents that stimulate T cell activation and proliferation. Greater proliferation indicates greater immune responsiveness. Lower proliferation may signal an underlying immunodeficiency affecting cellular immunity.
The proliferative capacity of lymphocytes tends to decrease with age. Factors like stress and nutrition can also impact lymphocyte proliferation. This functional assay provides valuable information about immune competence beyond just cell counts.
Vaccine Titer Tests
Testing antibody titers for certain vaccine-preventable diseases can help assess immune memory. While most routine childhood vaccines like measles, mumps, and rubella (MMR) confer long-lasting immunity, the immunity for some other diseases can wane over time. Titer tests measure antibodies to a specific antigen in the bloodstream.
An antibody titer is reported as a ratio, such as 1:20. A higher number indicates more antibodies and increased immunity. Titer tests are commonly used to check for immunity to diseases like varicella, hepatitis B, and some serotypes of pneumococcal pneumonia. Low titers may indicate the need for a booster vaccine.
Delayed Hypersensitivity Skin Tests
Delayed hypersensitivity skin tests evaluate cell-mediated immunity. They involve injecting a small amount of antigen into the skin and measuring the localized immune reaction or induration. Common antigens used include Candida albicans, tetanus toxoid, tuberculin, and trichophyton.
After 48-72 hours, the area is checked for swelling at the injection site. A positive test means the body demonstrated immune memory and mounted a response. Lack of reaction often signals some degree of cellular immune dysfunction. However, weakened immunity to skin test antigens does not always correlate with susceptibility to associated diseases.
Total Immunoglobulin E
Immunoglobulin E (IgE) is involved in allergic reactions. Measuring total IgE levels in the blood can help diagnose allergies and immune problems linked to allergy or mast cell disorders. Elevated IgE may indicate allergies, asthma, eczema, or parasitic infections. Very high IgE levels are associated with hyper-IgE syndrome, a primary immunodeficiency.
Complement Testing
The complement system consists of various plasma proteins that enhance antibody function. Complement aids in killing pathogens, inflammation, and removal of immune complexes. Complement deficiencies are associated with recurrent infections. Total complement activity (CH50) and individual complement components like C3 and C4 can be measured by blood tests.
Dihydrorhodamine (DHR) Test
The DHR test assesses neutrophil oxidative burst activity. Neutrophils are the most abundant type of white blood cell and an essential part of the innate immune response. They help destroy engulfed bacteria through oxygen-dependent mechanisms like oxidative burst.
In the DHR assay, a blood sample is mixed with bacteria and DHR, which fluoresces in response to oxidative metabolites. Decreased fluorescence indicates impaired neutrophil function. DHR testing is used to evaluate patients with recurrent infections or suspected chronic granulomatous disease.
Leukocyte Adhesion Deficiency Testing
Leukocyte adhesion deficiency (LAD) is a rare primary immunodeficiency affecting leukocyte migration. Neutrophils cannot adhere and move from blood vessels into tissues due to defects in adhesion molecules. This leaves patients vulnerable to bacterial infections, impaired wound healing, and periodontitis.
Specialized flow cytometry testing detects abnormalities in adhesion molecule expression that confirm LAD diagnosis. Genetic testing can further identify the specific mutation involved.
Natural Killer Cell Testing
Natural killer (NK) cells provide early, nonspecific immune defense against viruses and tumor cells. NK cell numbers and functional assays can be assessed when NK deficiency is suspected. Flow cytometry enumerates NK cells as a percentage of lymphocytes. Cytotoxicity assays measure ability to kill target cell lines.
Low NK levels or activity may warrant genetic testing for rare disorders like NK deficiency. Impaired NK function is also associated with chronic fatigue syndrome.
Toll-like Receptor Function
Toll-like receptors (TLRs) are pattern recognition receptors that activate innate immune response. Each TLR detects specific microbial components. TLR signaling triggers production of cytokines and anti-microbial factors. Blood samples can be stimulated with TLR-specific ligands to evaluate responsiveness.
Defects in TLR function are linked to increased susceptibility to bacterial, fungal, and viral pathogens. Certain TLR polymorphisms may dampen immune activation and reduce TLR-mediated inflammation.
White Blood Cell Production Tests
The bone marrow continuously produces diverse white blood cells for the immune system. Problems with WBC development and maturation can lead to immunodeficiency. Bone marrow aspiration and biopsy allow microscopic examination of cellularity and cell morphology.
Other blood tests measure serum levels of IgM and IgE, vitamin B12, and iron to uncover potential deficiencies impairing hematopoiesis. Cytogenetic analysis of bone marrow helps detect genetic abnormalities in myeloid cells.
Blood Chemistry Profile
A blood chemistry panel provides vital health information by measuring levels of key proteins, enzymes, and biomarkers. Immunoglobulins, albumin, electrolytes, glucose, liver enzymes, and lipid profiles provide snapshot of overall health status. Normal values indicate good health and nutrition to support proper immune function.
Electrolyte imbalances, vitamin deficiencies, endocrine disorders, and liver or kidney dysfunction can weaken immunity. Blood chemistry results may spur further immune testing or prompt treatments to bolster immune fitness.
Cytokine Testing
Cytokines are immune signaling proteins produced by white blood cells and other cells. Pro-inflammatory cytokines like interleukin-1, interleukin-6, and tumor necrosis factor alpha enhance early immune response. Anti-inflammatory cytokines like IL-4 and IL-10 counteract this response. Cytokine dysregulation is linked to autoimmunity, inflammation, and immunosuppression. Cytokine levels can be measured in blood samples.
HLA Genotyping
Human leukocyte antigens (HLAs) are proteins expressed on most nucleated cells. The genes for these antigens are the most polymorphic in the human genome. HLA typing detects genetic variations that define a person’s tissue type. This data is used for organ transplant matching and may inform treatment options for autoimmune diseases.
DNA Sequencing
Advances in genetic sequencing have enabled discovery of many primary immunodeficiency diseases (PIDs). Next generation sequencing like whole exome sequencing analyzes the protein coding regions of the genome. Targeted gene panels sequence subsets of known PID genes. Genetic testing provides definitive PID diagnosis and helps guide treatment.
Summary of Common Immune System Tests
| Test | Measures |
|---|---|
| Complete blood count | White blood cells, lymphocytes, granulocytes |
| Immunoglobulins | IgG, IgA, IgM, IgE |
| Lymphocyte subsets | CD4, CD8, NK cells |
| Immunophenotyping | Cell surface proteins |
| Proliferation assays | Lymphocyte activation |
| Vaccine titers | Immune memory |
| Skin tests | Delayed hypersensitivity |
| Complement testing | Total complement, C3, C4 |
| DHR | Neutrophil function |
| Leukocyte adhesion | Adhesion defects |
| Toll-like receptors | Innate activation |
| Cytokines | Immune messengers |
| HLA typing | Genetic markers |
| Genetic testing | DNA mutations |
Conclusion
The immune system is complex and multifaceted. There are many different tests that provide information about the status and function of the immune system. A single test rarely gives the complete picture. Instead, physicians will often order a panel of blood tests, functional assays, genetic analysis, and imaging to thoroughly evaluate immune health. Common assessments include blood counts, immunoglobulins, lymphocyte subsets, cytokine levels, and proliferation assays. Skin testing for delayed hypersensitivity also continues to be a useful immune measure. Advanced genetic tools enable greater understanding of inherited immunodeficiencies. The results of these tests help detect deficiencies, abnormalities, and mechanisms that can lead to recurrent infections, autoimmunity, inflammation, and immune-related conditions.