Immune Deficiency (Weakened Immune System)

What immune deficiency means

The immune system has several arms that work together:

• Antibodies (B cells) fight bacteria such as those that cause pneumonia, sinusitis and ear infections.
• T cells control viruses, fungi and organisms that live inside cells, such as tuberculosis.
• Neutrophils (a type of white blood cell) clear bacteria and fungi at wounds and in the blood.
• Complement proteins help destroy bacteria, including meningococcus.
• The spleen filters bacteria from the blood.

A weakness in one arm leads to a typical pattern of infections. People with low antibodies get repeated chest and sinus infections. People with low T cells get severe viral infections, thrush and unusual lung infections. People with low neutrophils get bacterial and fungal blood infections.

Primary vs secondary immune deficiency

Inherited forms are covered in detail on primary immunodeficiency. For the general medical overview, see immunodeficiency.

Common causes of a weakened immune system

Medicines

• Chemotherapy, which can cause neutropenia about 7 to 14 days after each cycle
• Corticosteroids such as prednisone, especially at higher doses taken for several weeks
• Transplant anti-rejection drugs after an organ transplant
• Biologic and targeted drugs for rheumatoid arthritis, psoriasis, inflammatory bowel disease and multiple sclerosis, such as TNF inhibitors and B-cell depleting drugs
• Methotrexate, azathioprine and other immune-suppressing drugs

Diseases

• HIV: destroys CD4 T cells. Without treatment it progresses to AIDS. Effective treatment restores immunity for most people.
• Blood cancers: leukemia, lymphoma and multiple myeloma disturb normal immune cells and antibodies.
• Diabetes, especially when poorly controlled, impairs neutrophils and wound healing.
• Chronic kidney or liver disease.
• No working spleen: after removal, or from sickle cell disease, raising the risk of overwhelming bacterial infection.
• Protein loss: severe burns, nephrotic syndrome or protein-losing gut conditions.

Other factors

• Malnutrition and deficiencies of protein, zinc or vitamins
• Older age: immune responses and vaccine responses weaken gradually
• Pregnancy: mild changes that make some infections, such as flu and listeria, more serious
• Heavy alcohol use

Signs of a weak immune system

Everyone catches colds; a young child may have 6 to 8 a year. What suggests immune deficiency is infections that are:

• frequent: for example, frequent infections such as several pneumonias or sinus infections a year
• severe: needing hospital care or intravenous antibiotics
• persistent: not clearing with usual treatment
• unusual: caused by germs that rarely affect healthy people, such as Pneumocystis pneumonia, or a fungal infection in the mouth or lungs
• in unusual places: abscesses in the liver or brain, or bone infections

Other clues include poor growth in children, chronic diarrhea, weight loss, slow wound healing, and autoimmune problems such as low platelets, which often accompany antibody deficiencies.

How immune deficiency is diagnosed

1. History: the pattern and type of infections, medicines, family history, travel and sexual history.
2. Complete blood count with differential: looks for low neutrophils or lymphocytes.
3. HIV test: recommended for anyone with recurrent or unusual infections.
4. Antibody (immunoglobulin) levels: IgG, IgA and IgM, plus vaccine response tests to see whether you make antibodies after a vaccine.
5. Lymphocyte subsets: counts of T, B and NK cells.
6. Other tests as needed: blood sugar, kidney and liver function, complement levels, neutrophil function tests and genetic testing.

Treatment and protection

Treat or reduce the cause

Control blood sugar, start HIV treatment, adjust immune-suppressing medicines where possible, and treat cancer or malnutrition.

Prevent infections

• Vaccines: inactivated vaccines (flu, COVID-19, pneumococcal, shingles recombinant vaccine, hepatitis B) are recommended for most immunocompromised people. Live vaccines such as MMR, chickenpox and yellow fever are usually avoided when immunity is significantly weakened. Close contacts should be vaccinated too.
• Preventive medicines: some people take daily antibiotics, antivirals or antifungals, such as trimethoprim-sulfamethoxazole to prevent Pneumocystis pneumonia.
• Immunoglobulin replacement: antibody infusions into a vein or under the skin every 1 to 4 weeks for people who cannot make antibodies.
• Growth factors to speed white cell recovery after some chemotherapy.
• Stem cell transplant or gene therapy for some severe inherited forms.

Everyday precautions

• Wash hands often, and avoid close contact with people who are sick.
• Follow food safety rules: avoid unpasteurized dairy, raw or undercooked meat, eggs and seafood, and deli meats unless heated.
• Have a plan for fever: know who to call and whether to go straight to the ER.
• Ask early about antiviral treatment for flu or COVID-19, which works best within the first days of symptoms.

Frequently asked questions

What are the signs of a weakened immune system?

Infections that are frequent, severe, slow to clear or caused by unusual germs are the main signs. Examples include repeated pneumonias or sinus infections, infections needing IV antibiotics, recurrent thrush in adults, slow wound healing and chronic diarrhea. Occasional colds and stomach bugs are normal.

What is the most common cause of immune deficiency?

Acquired, or secondary, immune deficiency is far more common than inherited forms. Medicines such as chemotherapy, steroids and transplant drugs are the most frequent causes, followed by diseases such as diabetes, blood cancers, HIV and chronic kidney disease, and by malnutrition and older age.

What does immunocompromised mean?

Immunocompromised means your immune system is weakened enough that you are more likely to get infections or to get seriously ill from them. People on chemotherapy, transplant drugs or high-dose steroids, and people with untreated HIV or some blood cancers, are commonly described this way.

Can immune deficiency be cured?

Secondary immune deficiency often improves when the cause is treated or a medicine is stopped. HIV treatment restores much of immune function. Some inherited forms can be cured with stem cell transplant or gene therapy, while others are managed lifelong with antibody replacement and preventive medicines.

Can people with immune deficiency get vaccines?

Yes. Inactivated vaccines such as flu, COVID-19, pneumococcal and shingles recombinant vaccine are safe and recommended, though they may work less well. Live vaccines are usually avoided when the immune system is significantly weakened. Your specialist will advise on timing around treatment.