Immune System Dysfunction

How the immune system normally works

The immune system has two linked parts:

• Innate immunity: fast, general defenses, including skin, neutrophils (white cells that eat bacteria), complement proteins and inflammation.
• Adaptive immunity: slower, targeted defenses. B cells make antibodies (immunoglobulins) and T cells kill infected cells and coordinate the response. Adaptive immunity creates memory, which is how vaccines work.

A healthy immune system attacks germs, tolerates the body's own tissues and harmless substances, and switches off inflammation when the threat has gone. Dysfunction happens when any of these steps fails.

The four main types of immune dysfunction

Several types can overlap. For example, many people with primary immunodeficiency also develop autoimmune conditions.

Immunodeficiency: a weak immune system

Primary (inborn)

Primary immunodeficiencies, now called inborn errors of immunity, are caused by genetic changes. There are more than 400 types. The most common in adults is common variable immunodeficiency (CVID), which causes low antibody levels. Severe combined immunodeficiency (SCID) affects babies and is now detected by newborn screening in all US states.

Secondary (acquired)

Far more common. Causes include:

• medicines: long-term steroids, chemotherapy, transplant drugs, biologic drugs for autoimmune disease
• infections: HIV, and temporarily after measles and other severe infections
• chronic illness: poorly controlled diabetes, kidney failure, cirrhosis, malnutrition
• blood cancers: chronic lymphocytic leukemia, myeloma, lymphoma
• removal of the spleen, aging, severe burns

Signs of a weak immune system

• infections that are more frequent, more severe or longer-lasting than usual
• infections with unusual germs (for example Pneumocystis pneumonia or widespread fungal infection)
• needing IV antibiotics to clear an infection
• recurrent abscesses in the skin or organs
• persistent thrush in the mouth after age 1
• poor growth in children

Autoimmunity: an immune system that attacks the body

The immune system loses tolerance and makes antibodies or T cells against the body's own tissues. More than 80 autoimmune disorders are known; together they affect around 1 in 12 Americans, most of them women. Early signs often include fatigue, low-grade fever, joint pain, rashes and swollen glands. See autoimmune disease for the early signs and tests.

Allergy: an overreactive immune system

In allergy, the immune system makes IgE antibodies against harmless substances such as pollen, foods, insect venom or medicines. Re-exposure triggers mast cells to release histamine. Reactions range from sneezing and hives to life-threatening anaphylaxis. Asthma and eczema share the same allergic tendency.

Autoinflammation

In autoinflammatory diseases, the innate immune system switches on inflammation without autoantibodies or infection. The hallmark is recurring fevers with rashes, joint or abdominal pain and high inflammation markers. See periodic fever syndromes.

How immune dysfunction is diagnosed

1. History: pattern and type of infections, family history, medicines, travel, vaccination.
2. Complete blood count with differential: white cell types, including neutrophils and lymphocytes.
3. Immunoglobulin levels: IgG, IgA, IgM and IgE.
4. Vaccine response: antibody levels before and after tetanus or pneumococcal vaccine show whether B cells work.
5. Lymphocyte subsets (flow cytometry), complement tests and neutrophil function tests.
6. HIV test.
7. Autoantibodies (ANA and disease-specific tests) and inflammation markers (CRP, ESR) for suspected autoimmunity.
8. Allergy tests: skin-prick tests or specific IgE blood tests.
9. Genetic testing for suspected inborn errors of immunity.

An allergist-immunologist or rheumatologist usually leads the workup.

Treatment

For immunodeficiency

• Prompt antibiotics for infections; sometimes preventive antibiotics
• Immunoglobulin replacement (IV or under the skin every 1 to 4 weeks) for antibody deficiencies
• Vaccination where safe; live vaccines are avoided in some types
• Stem cell transplant or gene therapy for severe forms such as SCID
• Treating the cause, such as HIV antiretroviral therapy or better diabetes control

For autoimmunity and autoinflammation

Medicines that calm the immune system: steroids, methotrexate, hydroxychloroquine, biologic drugs targeting specific immune signals (such as TNF or IL-1), and JAK inhibitors. These lower inflammation but can raise infection risk.

For allergy

Avoiding triggers, antihistamines, steroid nasal sprays and inhalers, epinephrine auto-injectors for anaphylaxis risk, and allergen immunotherapy (shots or tablets) to retrain the immune response.

Can you boost your immune system?

For people with a healthy immune system, there is no supplement that reliably "boosts" immunity. What helps is getting recommended vaccines, sleeping 7 to 9 hours, not smoking, keeping diabetes under control, staying active and correcting true deficiencies of vitamin D, zinc or protein. An immune system that is "overactive" (as in allergy or autoimmunity) does not need boosting.

Frequently asked questions

What are the signs of immune system dysfunction?

Signs depend on the type. A weak immune system causes frequent, severe or unusual infections. An overactive or misdirected one causes allergies, rashes, joint pain, fatigue and inflammation in organs. Recurrent unexplained fevers point to autoinflammation. Any persistent pattern should be checked with blood tests.

What causes a weak immune system?

The most common causes are medicines such as steroids, chemotherapy and transplant drugs, HIV, poorly controlled diabetes, kidney or liver failure, blood cancers, malnutrition, removal of the spleen and aging. Less commonly, genetic conditions called primary immunodeficiencies are responsible.

Is autoimmune disease a weak or strong immune system?

Neither, exactly. In autoimmune disease the immune system is misdirected: it attacks the body's own tissues. Some people with autoimmune disease also have weakened defenses against infection, partly from the disease itself and partly from the medicines used to treat it.

What blood test checks your immune system?

There is no single test. Doctors usually start with a complete blood count, immunoglobulin levels (IgG, IgA, IgM) and an HIV test. Vaccine antibody responses, lymphocyte subsets, complement and autoantibody tests are added depending on the pattern of symptoms.

How many infections a year is normal?

Healthy adults typically have 2 to 4 colds a year and young children 6 to 8 or more. Warning signs include 2 or more pneumonias in a year, 4 or more ear infections in a year in a child, infections needing IV antibiotics, or deep abscesses.