5 Causes of Immunosuppression

AIDS and High-Dose Steroids Can Cause Immunosuppression

Stem Cell Transplant

Recently, due to the introduction of new immunosuppressant drugs as well as an increase in the number of organ transplants, we've seen more people who are immunosuppressed or living with impaired immunity.

The immune system is the collection of all the cells, tissues, and organs that helps the body stave off infection. Without an intact immune system, a person falls prey to the outside world.

More potent immunosuppressant medication regimens, however, are only one reason why people become immunosuppressed or immunocompromised.

Verily, other bad things can disrupt the immune system, too, including AIDS and inherited diseases.

What Is the Immune System?

Your immune system exists to prevent or vitiate infection. The cells and pathways of the immune system are complex and diverse and suffuse all parts of the body.

Here are the different components of the immune system:

  • The bone marrow is where all the fun begins. The bone marrow contains stem cells that go on to become a variety of immune cells (B cells, T cells, lymphocytes, and so forth).
  • Not only is the skin the first line of defense against insults from the outside world, but certain layers of the skin (like the dermis) are also rich in immune cells. Furthermore, the skin also produces antimicrobial proteins.
  • There are lots of immune cells in the bloodstream. In fact, blood tests are used to monitor immunity.
  • The lymphatic system is replete with immune cells. The lymphatic system hooks up the bloodstream with tissues located throughout the body and serves as a highway for the transport of immune cells. These immune cells converge in the lymph nodes. Within the lymph nodes, the immune response is activated when microbes are detected.
  • A key immune cell type that allows us to adapt to threats posed by infection is the T-cell. Although T-cells are first produced in the bone marrow, they go on to mature in the thymus.
  • People do live without spleens (asplenia is medical jargon for lack of a spleen or splenic function). However, the spleen helps to prepare the body for infection, and people without spleens are more prone to develop infection with certain pathogens like meningococci (think meningitis), Streptococcus pneumoniae (think pneumonia) and Haemophilus influenzae, or H. influenza. Please note that despite its name, H. influenza doesn't cause the flu and instead causes respiratory infection in children. The spleen acts as the body's filter, and patches of immune cells in the spleen monitor blood for signs of infection. If infection is present, the spleen activates an immune response.
  • Like the skin, mucosal tissue, such as that found lining the gastrointestinal and respiratory tracts, is also a first-line of defense that prevents germs from gaining entrance to the body. As such, mucosal tissue is rich in immune cells.

Net State of Immunosuppression

Suppression of the immune system depends on several factors. In the aggregate, a person's net state of immunosuppression is appraised after considering the following variables:

  • type of immunosuppression (secondary to medication or illness)
  • duration of immunosuppression
  • intensity of immunosuppression
  • dosage and types of immunosuppressant agents or drugs
  • innate immunodeficiencies (inherited diseases that mess with the immune system)
  • anatomic factors leading to breakdown (such as impaired lymphatic drainage secondary to surgery or radiation)
  • infection (think HIV or CMV)

Immunosuppression Resulting from Medications

Lots of medications undermine the immune system. These immunosuppressant drugs may disrupt several layers of immune response or target individual types of immune cells.

 

Here are 3 medications that can disrupt the immune system:

  • Corticosteroids. These medications are prescribed for a variety of autoimmune, allergy, and inflammatory conditions, such as rheumatoid arthritis, inflammatory bowel disease, asthma, and atopy. During the short-term, these medications interfere with immune cell function. Specifically, corticosteroids deplete numbers of lymphocytes and monocytes as well as suppress phagocyte migration and function. Longer-term effects of these medications include skin thinning and impaired soft tissue repair, both of which can further exacerbate immunosuppression. People who are on high dosages of steroids are more susceptible to infection with a variety of organisms, such as Pneumocystis jirovecii, which causes deadly Pneumocystis pneumonia, as well as Strongyloides, which is also potentially deadly and caused by roundworms. Additionally, people with weakened immune systems secondary to steroid use are at risk of reactivation of tuberculosis or other latent infections.
  • Rituximab. This monoclonal antibody to CD20 is used to treat non-Hodgkin lymphoma, rheumatoid arthritis, and chronic lymphocytic leukemia. During clinical trials, rituximab wasn't linked to an increased risk of infection. Ever since rituximab has been on the market, however, there have been individual (anecdotal) reports linking rituximab administration to such rare illnesses as progressive multifocal leukoencephalopathy, which is caused by JC virus, and pure red cell aplasia, which is associated with parvovirus infection. Furthermore, immunosuppression secondary to rutiximab administration can lead to reactivation of hepatitis B infection.

  • Tumor Necrosis Factor-Alpha (TNF-α) Inhibitors. These medications are cytokines; cytokines are usually produced by immune cells. TNF-α inhibitors include drugs like infliximab, certolizumab pegol, and monoclonal antibodies and are used to treat autoimmune conditions like rheumatoid arthritis and Crohn's disease. Of note, immunsuppression resulting from administration of these drugs opens the door to infection with Listeria monocytogenes, a foodborne pathogen which can cause fetal death in pregnant women.

Immunosuppression Resulting from Asplenia

Surgical removal of the spleen is called "splenectomy." There are many reasons why a person may have her spleen removed, including cancer, trauma, and blood disorders (like refractory idiopathic thrombotic purpura). The medical term "asplenia" not only refers to the removal of the spleen by means of splenectomy but also the loss of splenic function secondary to conditions like sickle cell anemia.

People with asplenia are at increased risk of infection with encapsulated organisms, such as Streptococcus pneumoniae, Haemophilus influenzae, and some forms of Neisseria meningitides. In these people, a deadly infection can set in quickly — especially in the case of sepsis or blood infection. Sepsis is more common among people who have splenectomy secondary to cancer (malignancy) than it is among people who have their spleens removed after an accident (trauma). Of note, risk of infection with encapsulated organisms is greatest during the first few years following a splenectomy. 

Immunosuppression After Transplant

There are 2 types of transplants: stem cell transplants and solid organ transplants. Both of these types of transplants cause immunosuppression.

Stem cell transplants were once referred to as bone marrow transplants because stem cells, or undifferentiated cells capable of producing all types blood cells, were once harvested only from the bone marrow. Due to advances in medicine, we are now able to filter stem cells from the blood. Stem cell transplant is performed as treatment for certain types of blood cancers, including acute lymphocytic leukemia, Typically, people with these illnesses have already been exposed to intensive cancer treatments and are thus already immunosuppressed.

Solid organ transplants refer to transplants of organs like the heart, kidney, or liver. People who receive solid organ transplants often need lifelong treatment with immunosuppressant medications to decrease the risk of rejection.

During the first month of recovery from an organ transplant, a transplant recipient is most susceptible to infection related to the surgery itself. Common infections during this period include urinary tract infections, skin infections, and would infections. Between months 2 and 6 after surgery, transplant recipients are at risk for opportunistic infections as well as reactivation of herpes virus or other latent infections. Six months after transplant and beyond, recipients are most susceptible to community-acquired infections like those caused by encapsulated organisms (think Streptococcus pneumoniae and Haemophilus influenzae).

Immunosuppression Caused by Innate Immunodeficiency

Sometimes people inherit genetic diseases that result in a weakened immune system. Many of these primary immunodeficiencies are rare and diagnosed at an early age, such as severe combined immunodeficiency and chronic granulomatous disease. However, common variable immunodeficiency (CVID) is more common and presents in adolescence and young adulthood.

With CVID, the immune cells fail to produce immunoglobulins necessary to mount an immune response. Consequently, people with CVID are more likely to suffer from respiratory infections as well as infections of the gut like Giardia lamblia

The treatment of CVID is complicated and requires specialist care in part because people with this condition don't respond to immunization and instead require an infusion of immunoglobulin in a hospital setting.

Immunosuppression Caused by Infection

Immunosuppression not only results in increased risk of infection but can also be caused by certain infections. For example, cytomegalovirus (CMV), which usually results in either no symptoms or mononucleosis-type symptoms in people with normal immune systems, can further disturb the immune system in those who are already immunosuppressed. Specifically, CMV messes with T cells, which are actively involved in the immune response.

Another type of infection that can result in immunosuppression is HIV (human immunodeficiency virus). The progression of HIV to AIDS is marked by severe immunocompromise. This immunocompromise happens when HIV kills off a large number of helper T cells — CD4 and CD8 cells — which are necessary to mount an immune response. Once enough of these cells have been killed off, a person becomes susceptible to a number of scary opportunistic infections, including the following: 

  • Candidiasis
  • Coccidioidomycosis
  • Cryptococcosis
  • Cytomegalovirus disease
  • Encephalopathy, HIV-related
  • Herpes simplex
  • Histoplasmosis
  • Kaposi's sarcoma
  • Tuberculosis
  • Pneumocystis carinii pneumonia
  • Toxoplasmosis of brain

Please understand that not all people with HIV are immunosuppressed, or have AIDS. Fortunately, advances in medicine have made the treatment of HIV infection much more effective. Nowadays, people who vigilantly commit to antiretroviral therapy can live long lives without developing AIDS.

Summary

To a large extent, increased frequency of immunosuppression among the American population is a sign of progress. Thanks to advances in research, we now have better immunosuppressant drugs which can treat an increasingly diverse number of conditions. Furthermore, we're also doing more organ transplants which also result in immunosuppression.

Conversely, advances in medicine also have the potential to decrease the frequency of immunosuppression among members of the general population. Specifically, people with HIV who vigilantly adhere to their antiretroviral regimens can live long and happy lives sans immunosuppression. Unfortunately, however, despite advances in HIV treatment, only 3 of 10 Americans have their HIV under control.

Sources:

Hammond SP, Baden LR. Chapter 198. Infections of the Immunocompromised Host. In: McKean SC, Ross JJ, Dressler DD, Brotman DJ, Ginsberg JS. eds. Principles and Practice of Hospital Medicine. New York, NY: McGraw-Hill; 2012. Accessed April 12, 2016.

Nayeri U, Thung S. Chapter 15. Congenital Fetal Infections. In: DeCherney AH, Nathan L, Laufer N, Roman AS. eds. CURRENT Diagnosis & Treatment: Obstetrics & Gynecology, 11e. New York, NY: McGraw-Hill; 2013. Accessed April 13, 2016.

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