Immunodeficiency (Weakened Immune System)

What immunodeficiency means

The immune system has several layers: the skin and mucous membranes, white blood cells such as neutrophils that swallow bacteria, B cells that make antibodies, T cells that coordinate the response and kill infected cells, and the complement proteins and spleen that clear germs from the blood. A defect in any layer leaves gaps in protection. The kind of infections someone gets often points to which part is missing.

Primary vs secondary immunodeficiency

Primary immunodeficiency

Primary immunodeficiency, now often called inborn errors of immunity, is caused by gene changes. More than 450 types are known. Examples include severe combined immunodeficiency (SCID), common variable immunodeficiency (CVID), X-linked agammaglobulinemia, DiGeorge syndrome and chronic granulomatous disease. Many appear in infancy, but CVID is often diagnosed in adults aged 20 to 40. Selective IgA deficiency is the most common and often causes no symptoms.

Secondary (acquired) immunodeficiency

This is much more common and develops in people born with normal immunity:

• Medicines: chemotherapy, long-term or high-dose steroids, transplant drugs, and biologic drugs for arthritis, psoriasis and inflammatory bowel disease.
• Infections: HIV destroys CD4 T cells. Untreated, it leads to AIDS. Measles can also suppress immunity for months.
• Cancers of the blood and immune system: leukemia, lymphoma and multiple myeloma.
• Chronic diseases: poorly controlled diabetes, chronic kidney disease, liver cirrhosis.
• Loss of the spleen: after surgery or from sickle cell disease.
• Malnutrition and protein loss through the gut or kidneys.
• Older age, which gradually weakens immune responses.

Signs of a weak immune system

• infections that are more frequent than expected, such as four or more ear infections or two or more pneumonias a year
• infections that are severe, need hospital care or intravenous antibiotics
• infections that do not clear with standard antibiotics
• infections with unusual germs, such as Pneumocystis pneumonia or certain fungi
• persistent thrush in the mouth after infancy
• recurrent deep skin or organ abscesses
• chronic diarrhea and weight loss
• in children, poor growth and weight gain
• autoimmune problems, such as low platelets or anemia, which are common in some primary immunodeficiencies

Frequent colds alone are usually not a sign of immunodeficiency. Young children in daycare can normally have 8 to 10 colds a year.

How it is diagnosed

1. History and exam: the pattern, frequency and type of infections, medicines, family history and growth.
2. Complete blood count with differential: counts neutrophils and lymphocytes.
3. Immunoglobulin levels: IgG, IgA and IgM.
4. Vaccine responses: antibody levels before and after tetanus or pneumococcal vaccines show whether B cells respond normally.
5. Lymphocyte subsets: flow cytometry counts T, B and natural killer cells.
6. HIV test, and tests for diabetes, kidney and liver disease.
7. Complement tests and neutrophil function tests when relevant.
8. Genetic testing to identify specific primary immunodeficiencies.

All US states screen newborns for SCID using a heel-prick blood test, so most affected babies are found before serious infections.

Treatment

Treat the cause

• antiretroviral therapy for HIV, which restores immune function in most people
• adjusting immunosuppressive medicines where possible
• controlling diabetes and treating blood cancers

Prevent infections

• Preventive antibiotics or antifungals: for example, to prevent Pneumocystis pneumonia in people with low T-cell counts.
• Immunoglobulin replacement: antibodies from donated plasma given into a vein every 3 to 4 weeks or under the skin weekly. It is standard for antibody deficiencies such as CVID and is also used in some blood cancers.
• Growth factors such as G-CSF to raise neutrophil counts after chemotherapy.

Cure in some primary types

• Stem cell (bone marrow) transplant: can cure SCID and several other severe primary immunodeficiencies, especially when done early.
• Gene therapy: approved or in trials for some types, such as ADA-SCID.

Treat infections early

People with immunodeficiency should have a low threshold for seeing a doctor. Many carry a written plan or an emergency letter explaining their condition.

Vaccines and everyday precautions

• Inactivated vaccines (flu shot, COVID-19, pneumococcal, shingles recombinant vaccine) are generally safe and recommended, though the response may be weaker.
• Live vaccines (MMR, chickenpox, yellow fever, nasal flu vaccine, oral typhoid) may be unsafe in significant immunodeficiency. Ask your specialist before any live vaccine.
• Household members should be fully vaccinated to protect you.
• Wash hands often, avoid close contact with people who are sick, and practice food safety: avoid unpasteurized dairy, undercooked meat and eggs, and raw sprouts.
• Take extra care with travel, gardening (wear gloves) and pet litter boxes.

Outlook

The outlook varies widely. Many secondary immunodeficiencies improve once the cause is treated or medicines are reduced. People with HIV on effective treatment have a near-normal life expectancy. Most people with antibody deficiencies live full lives on immunoglobulin replacement. Severe forms such as SCID are fatal in infancy without treatment but are often cured with early transplant.

Frequently asked questions

What are the signs of a weak immune system?

Signs include infections that are frequent, severe, long-lasting or need intravenous antibiotics, infections with unusual germs, persistent thrush, recurrent abscesses, chronic diarrhea and, in children, poor growth. Frequent minor colds alone, especially in young children, are usually normal.

What is the difference between primary and secondary immunodeficiency?

Primary immunodeficiency is caused by inherited gene changes and is often noticed in childhood. Secondary immunodeficiency is acquired later from causes such as chemotherapy, steroids, HIV, diabetes, kidney disease or blood cancers. Secondary forms are far more common and may improve when the cause is treated.

Can immunodeficiency be cured?

Some forms can. Treating HIV, stopping immune-suppressing medicines or recovering from chemotherapy can restore immunity. Stem cell transplant and gene therapy can cure SCID and some other primary types. Many inherited forms are lifelong but well controlled with immunoglobulin replacement and preventive antibiotics.

What does it mean to be immunocompromised?

It means your immune system is weakened enough that you are at higher risk of infections and of serious illness from them. It applies to people on chemotherapy, transplant drugs, high-dose steroids or certain biologics, and those with advanced HIV or primary immunodeficiency.

Can people with immunodeficiency get vaccines?

Yes, most inactivated vaccines are safe and recommended, including flu, COVID-19 and pneumococcal vaccines, although protection may be weaker. Live vaccines such as MMR and chickenpox may be unsafe in significant immunodeficiency, so check with your specialist first.