What Happens When the Immune System Does Not Work Properly?

Sometimes a person’s immune system does not work properly. This can result from immune deficiencies present at birth; medications that suppress the immune system, like steroids; unnecessary or overzealous immune responses, such as allergies; or immune responses to one’s self, called autoimmunity. One of the amazing aspects of the immune system is that it is compensatory, meaning that when one part is weak or non-functional, typically another part can step in. Think of it like a trip to the grocery store. If you need to go to the store, but your tire is flat, you may go by another method of transportation — another motor vehicle, a bicycle or walking. The substitute may or may not be as efficient, but it still allows you to complete your task. The same is true of the cells and proteins of our immune system; most “jobs” of the immune system can be done by more than one part of the immune system although some parts are better at certain jobs than others.

This same feature that makes the immune system flexible also makes it difficult to study. This is why studies in the lab, and even in animals, still need to be repeated in people before we can be sure the findings apply. However, laboratory and animal studies remain important because they provide us with preliminary information that puts us in the best position to succeed when we complete studies in people.

All of this said, sometimes people still have conditions that alter their ability to respond to infections, so let’s take a look at a few and explore how the immune system works in these unique situations.

Immune deficiencies

Immune deficiencies can result from inherited or spontaneous genetic variations, from medications that suppress the immune system, or from infections that damage components of the immune system.

Genetic variations

A change to a person’s genes can result in the immune system lacking, or having non-functional, components. Most of these conditions are rare, but when they occur, a person is often diagnosed early in life because they experience a higher than average number of infections. More than 40 different deficiencies have been identified; a small number of examples include:

  • Severe combined immune deficiency (SCID), which results from problems with T cell development.
    • DiGeorge syndrome is a type of SCID, which results from improper T cell maturation.
  • X-linked agammaglobulinemia, which results in a lack of B cells.
  • Atypical hemolytic uremic syndrome, which is caused by a defect in certain immune-related proteins called complement. The result can be excessive swelling, and in some cases, the swelling can occur around the breathing tubes leading to suffocation.
  • Kostmann disease, also known as severe congenital neutropenia, which results in chronically low levels of the white blood cells known as neutrophils.
  • A group of periodic fever syndromes, which result from deficiencies in the pathway that controls inflammation, or swelling. Symptoms can include recurrent fevers, swelling or joint pain.


Medications like chemotherapies for cancer or immune suppressive medications for a variety of rheumatologic or allergic disorders.


Human immunodeficiency virus (HIV) is the most well-known example of a chronic immune system condition caused by an infection. HIV infects T cells, specifically a type of T cell called CD4+ T cells. This results in two issues. First, the immune response is severely compromised because, as described on the “Parts of the Immune System” page, T cells are the equivalent of police chiefs or sergeants, so the coordination of the immune response is hampered. The second issue is that as the immune system works to overcome the infection, it targets one of its own components.

HIV infections occur in phases that can be identified, in part, by a person’s CD4+ T cell count. Early in the infection, called the acute phase, CD4+ T cells decrease. The infected person may have influenza-like symptoms, but may not yet realize they are infected. However, if a person’s blood is tested during the acute phase, the virus can be detected at high levels. Initially, the T cell population rebounds, only to drop again over time. During this period, which can be short or last for years, the person is typically asymptomatic. Eventually, the CD4+ T cell population becomes so depleted that the individual starts to experience other, opportunistic, infections. This marks the beginning of the final phase, commonly known as acquired immune deficiency syndrome or AIDS, which eventually results in death. Often death is the result of one of these opportunistic infections.

Unnecessary or overzealous immune responses (e.g., allergies)

When our immune system responds to something that is not an infectious agent, it can cause symptoms of disease unnecessarily. Allergic reactions are associated with this type of immune response. Likewise, sometimes our immune systems overreact, overwhelming our body and often resulting in death.

Allergies and allergic reactions

Allergic responses are most closely associated with a type of immune system cell, called a mast cell. Mast cells can be found in large numbers just beneath our skin and the linings of our respiratory, digestive, and genital tracts. Their main role is to protect us from parasites, but they are more “famous” for their role in allergic reactions. When a mast cell is activated — either by a parasite or in the case of allergic reactions, by a non-infectious agent perceived to be a pathogen — it releases a chemical called histamine. Histamine causes inflammation, recruits white blood cells to the area, increases mucus production and blood flow, and may also cause muscular contraction in an attempt to expel the pathogen. Mast cells that line the respiratory and digestive systems are responsible for muscle contractions that cause coughing, sneezing, vomiting and diarrhea. Mast cells not only require a pathogen, but they also rely on linkages with IgE or IgG antibodies to activate an immune response.

The type of allergic response generated is characterized by the type of antibody the mast cell is associated with when it is activated:

Immediate hypersensitivity reactions involve IgE antibodies

These are the more common type of allergic reaction, causing conditions such as:

  • Allergies to environmental agents (e.g., pollens), foods and medications
  • Eczema
  • Anaphylactic reactions

Symptoms can be minor nuisances or require emergency intervention, such as shots of epinephrine or emergency medical interventions.

People can develop these types of reactions as a result of genetic predisposition or environmental exposures early in life. Some people wonder if allergies are so common because children are not exposed to enough infectious agents early in life; this is known as the “hygiene hypothesis.” However, the environmentally based contributors to the development of immediate hypersensitivity appear to be multifactorial and complex. Respiratory and gastrointestinal infections, pollution, diet, and tobacco smoke have all been considered as potentially affecting the development of these types of reactions.

These types of reactions typically occur within 30 minutes of exposure to an allergen.

Hypersensitivity reactions involving IgG antibodies

Hypersensitivity reactions can also be caused by involvement of IgG antibodies with mast cells. Although these reactions are caused by a different part of the immune system, the symptoms an affected person experiences may be similar. This type of reaction can occur:

  • After taking certain kinds of medications, such as penicillin.
  • In response to the introduction of large amounts of airborne pathogens, such as molds or dust, such as from working on a farm. This condition is known as farmer’s lung.
  • As a result of chronic viral or bacterial infections, such as damage to the liver resulting from a long-term viral infection or to the heart following a long-term, undetected bacterial infection.

Historically, when treatment with antibody preparations made from horse serum were more common, people might also have reactions of this nature and develop an illness referred to as “serum sickness.” As technology has improved, this illness has become less common.

These types of reactions typically occur one to two weeks after exposure to an allergen.

Reactions involving T cells

Reactions that involve T cells tend to appear less rapidly than those caused by mast cell activation, occurring over days. These can include:

  • Delayed hypersensitivity reactions resulting from exposure to proteins in insect venom or from the bacteria that causes tuberculosis.

    Scientists and clinicians use the reaction to tuberculosis proteins as a way of monitoring for exposure to the bacteria. The tuberculin, or Mantoux, test involves putting a small amount of one of the proteins under the skin and watching over a period of two to three days to see if a reaction occurs.
  • Allergic contact dermatitis results from exposure to chemicals or agents that result in a T cell response right below the surface of the skin, such reactions to poison ivy or some small metals, such as nickel.

These types of reactions typically occur one to two weeks after exposure to an allergen.

Cytokine storm

Anytime our immune system responds to a potential infection, some damage to normal tissues also occurs. The innate immune response is non-specific and fast-acting resulting in tissue damage, and the adaptive immune system targets cells that show evidence of being infected. Most often this damage is relatively minimal and other components of the immune response work to “restore order” in the infected area even as the battle rages.

However, if the tissue damage is severe, some pathogens may get into the bloodstream and infect other parts of the body. When an infection reaches the bloodstream, a person is said to have sepsis. The result is that immune responses are occurring in battles throughout the body.

Sometimes, this attack — coupled with the immune response to it — can become overwhelming leading to what has been coined a “cytokine storm.” When this happens, the immune response essentially destroys the ability of the body to carry on normal function. A person’s organs begin to stop functioning, and medical care may or may not be successful in gaining control of the situation. Scientists do not completely understand why certain pathogens seem to be more likely to induce this kind of an immune response, nor do they understand why some infected people are more likely to succumb to this type of immune response. One example of a time when this occurred with greater frequency was during the 2009 H1N1 pandemic. While some people became ill and recovered; others died as a result of an overzealous immune response. By studying these types of occurrences, scientists hope to learn more about how and why they occur in order to better respond to and prevent them in the future.

Immune responses against one’s self (autoimmunity)

One of the most important aspects of immunity is the ability to distinguish a “foreign” invader from one’s own cells and tissues; otherwise, our immune system would attack our own bodies. This capability is called tolerance.

The opposite of tolerance is autoimmunity, or an immune response to some part of one’s self. Three different aspects of autoimmunity may contribute to whether or not an individual develops such a disease:

  1. If you recall from the previous section (“Parts of the Immune System”), cells called lymphocytes can become B cells or T cells. During this process, they “rearrange” some of their genes. This genetic rearrangement is necessary for providing the immune system with the ability to respond to the literally billions of different antigens that we come into contact with during our lives. Inevitably, some of these genetic rearrangements create combinations that would “recognize” part of ourselves as foreign. Typically, when this happens, protective mechanisms in the immune system, realize what has happened and those cells are destroyed, thereby preventing them from causing any problems. However, sometimes the protective mechanism fails, resulting in autoimmunity.
  2. In some people, a variation in a part of the gene that does not rearrange makes a person more susceptible to autoimmunity. This type of susceptibility can be inherited or can result from a spontaneous change during fetal development. In some autoimmune diseases, a pregnant woman’s affected antibodies can cross the placenta, and the baby can also be affected. One example is Graves’ disease.
  3. Finally, some people live their entire lives with a susceptibility described above and never develop the associated autoimmune disorder. This provides evidence for the role of environment. In some autoimmune diseases, scientists understand what environmental trigger causes the disease to develop, but for others, they do not. One example is the development of rheumatic fever following a bout of strep throat or scarlet fever.

The diseases that result from autoimmunity differ based on what part of a person’s body is targeted by the errant immune response. In some cases, only a single organ is affected, such as type 1 diabetes which affects the pancreas. However, in other situations, the immune response is targeted to a protein or part of the body that is not localized in one place, causing widespread symptoms, such as in the case of rheumatoid arthritis.

Autoimmunity also becomes important in situations of blood transfusions, tissue grafting and organ transplantation. In these situations, if the tissues are not from the person who is receiving them, doctors and scientists need to figure out ways to trick a person’s immune system. If the immune system is activated, it will attack the foreign tissue. This is called rejection. Rejection can causing new, and typically, chronic symptoms.

Autoimmunity and medical interventions

Blood transfusions

In the case of blood transfusions, the types of cells that are transferred typically do not elicit immune responses. If a person needs repeated transfusions of platelets, the cells that help our blood clot, the blood needs to be more closely matched, but generally speaking, blood transfusions do not present an issue if they match at the level of blood type.

Tissue grafting

Skin grafting is a common example of tissue grafting. The easiest is taking skin from the same person to put elsewhere on the body, called an autograft, because rejection is not a concern. Likewise, if the skin is taken from someone who is genetically identical, called a syngeneic graft, concerns about rejection are also minimal. However, in the situation of an allograft, where the individuals are not genetically related, rejection is more common.

Organ transplantation

Like tissue grafting, the more genetically similar the donor is to the recipient, the less likely the recipient’s immune system will reject the organ. Due to improvements in matching donors and recipients and the use of powerful anti-rejection medications, this field has progressed since its beginning. Unfortunately, anti-rejection medications need to be used for the remainder of a person’s life and sometimes the side effects can be difficult, so scientists and clinicians are continuing to work toward better understanding and addressing issues related to these types of procedures. In addition, sometimes the same disease that harmed the person’s organ originally also attacks the transplanted organ.

Reviewed on September 03, 2019

Materials in this section are updated as new information and vaccines become available. The Vaccine Education Center staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family's personal health. You should not use it to replace any relationship with a physician or other qualified healthcare professional. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult your physician or, in serious cases, seek immediate assistance from emergency personnel.