Living without an Immune System
The average human comes into contact with millions of pathogens everyday, and that doesn’t even include the bacteria and viruses that already live in your lungs and intestines. But despite this, we rarely get sick. Especially when you compare the handful of times the average person gets sick to the number of pathogens we encounter everyday, it's clear that our immune systems are a key player in survival.
The most basic interpretation of the immune system is that it is a complex series of cells, tissue and organs that work together to defend the body against harmful foreign substances, or pathogens, whether it’s preventing them from entering the body in the first place or attacking them once they get inside. The interaction between these many complex components serve to keep the body healthy and well.
In order to identify abnormalities within the body, the immune system is able to recognize two types of signals: “danger” cues called danger-associated molecular patterns (DAMPs) that are usually released upon cell damage, and protein and molecules unique to pathogens called pathogen-associated molecular patterns (PAMPs). Both of these signals, when detected, are able to cause inflammation, the first step in immune system activation.1,2
Inflammation allows the recruitment of immune cells to the site of infection. Immune cells, and the immune system as a whole, has generally been split into two classes: innate and adaptive immunity. The innate immune system broadly recognizes pathogens and acts within hours of infection. PAMPs can be detected by phagocytes, innate immune system cells, which then consume the pathogen, or by proteins, which activate the complement system.3 The innate immune system is also responsible for priming the adaptive immune system to respond in case the infection is still unresolved. The adaptive immune system generally responds to infections within 5-7 days, and identifies molecular markers specific to the pathogen, which is then used as a recognition system. In addition to fighting the infection, it is also able to remember the pathogen and provide the body with long-term immunity against experienced diseases.4
However, despite the layers of physical, chemical and biological defenses the body is able to put up, sometimes, either something goes wrong, or the body is not able to fight off the attacker. One particularly instance is that of a small group of diseases called SCID, Severe Combined Immunodeficiency. SCID is a genetic condition where a child is born without a developed adaptive immune system. As a result, that child is extremely vulnerable to infection. This rare disease is estimated to occur in over 1 in 100,000 births. In families where parents are genetically related, this rate can increase to 1 in 5,000 births.5
Infections which are common and harmless in infants with normal immune systems can be quick to overwhelm that of a child with SCID.5 Children born with undetected or unmanaged cases would be subject to certain death from infection within the first year of life.6 The initial challenge is with diagnosis. Without cause for suspicion, prenatal infants may not be screened for the disease. Aditionally, the child appears healthy at birth, due to the presence of circulating maternal antibodies, from when the child was in the womb. It is only a few days later, following waning of these maternal antibodies, that affected infants develop frequent diarrhea, infections and other symptoms which typically lead to eventual wasting and failure to thrive.5
The case of David Phillip Vetter, the “Bubble Boy,” was slightly different. After his older brother died in infancy from SCID, his parents had been informed that there was a 50% chance their next baby boy would also have the disease. Nevertheless, David P. Vetter was conceived and the medical community began meticulous preparations for his birth. David was born into a sterile environment, and within 20 seconds of his birth, had been put into a specially designed plastic isolator “bubble.” In fact, he would remain in a completely sterile, plastic environment for the next 12 years of his life.7
Although the clinical manifestations of the various types of the disease are fairly uniform, they do have different causes.8 All are a result of the mutation in genes responsible for the production of T and B cells, which are key components of the adaptive immune system.
In some types of SCID both B and T cells, while others only have T-cell dysfunction. However, even when only T cells are affected, the manifestation of disease remains similar as T-cells are needed in order to signal and activate B-cells.9
David had an X-linked form of SCID, which accounts for 50% of all SCID cases. This form of SCID is characterized by an absence of mature T cells and natural killer cells, which is a type of white blood cell responsible for repressing diseases such as tumors or virus-infected cells. There is also an increased number of B cells. The issue is that early on, there is a block in the T cell differentiation pathway. It is due to a mutation in the IL2RG gene on the X chromosome. This gene is crucial to producing components on many interleukin (immune system-specific signalling proteins) receptors, which is crucial to the differentiation and activation of several types of immune cells. Without differentiation, these cells are unable to carry out recognize fight off pathogens, and essentially unable to perform their specific immune functions in the body.8 Without activation by the differentiated T cells, B cells are not able to generate antibodies against the pathogens, nor create memory cells to allow the body to recognize and mount a more effective attack against the same pathogen in the future.
Living with SCID has numerous risks. In addition to easy susceptibility by common pathogenic organisms, use of live vaccines which are harmless to normal children can cause life-threatening infections.
Even with transfusion during treatment, there is a risk of graft-versus-host disease (GVHD), which occurs when the donated T- cells in the bone marrow reject the host. These transplanted cells, which contain functional immune cells, recognize the host as foreign and attack the host’s body.10
With advancements to medicine, David was, at the age of 12, able to receive a bone marrow transplant from his older sister Katherine. However, complications meant that he had to be removed from his sterile environment for the second time in his life. He died 14 days later, due to a virus in his sister’s bone marrow that had gone undetected.7
A few decades later, bone marrow and stem-cell transplants have evolved. Combined with an increased tendency to include SCID in newborn screening, early detection and better treatment options have meant that currently, as many as 80% of SCID patients can be saved. Although David’s life and story is a unique one, it displays the prevailing challenges and choices families of children with rare genetic disorders face in order to give their child a chance at life.
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2. Niaid.nih.gov. Overview of the Immune System. 2016. Available at: http://www.niaid.nih.gov/topics/immuneSystem/Pages/overview.aspx.
3. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Innate Immunity. Garland Science. 2002. Available at: http://www.ncbi.nlm.nih.gov/books/NBK26846.
4. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. The Adaptive Immune System. Garland Science. 2002. Available at: http://www.ncbi.nlm.nih.gov/books/NBK21070/.
5. Brian T Kelly J. Screening for severe combined immunodeficiency in neonates. Clinical Epidemiology. 2013;5:363. doi:10.2147/CLEP.S48890.
6. Severe combined immunodeficiency. Genes and Disease. 2016. Available at: http://www.ncbi.nlm.nih.gov/books/NBK22254/pdf/Bookshelf_NBK22254.pdf.
7. Pbs.org. American Experience. The Boy In The Bubble. People & Events | PBS. 2016. Available at: http://www.pbs.org/wgbh/amex/bubble/peopleevents/p_vetter.html.
8. Fischer A. Severe combined immunodeficiencies (SCID). Clinical and Experimental Immunology. 2000;122(2):143-149. doi:10.1046/j.1365-2249.2000.01359.x.
9. Uptodate.com. Severe combined immunodeficiency (SCID): An overview. 2016. Available at: http://www.uptodate.com/contents/severe-combined-immunodeficiency-scid-an-overview.
10. Updated by: Yi-Bin Chen a. Graft-versus-host disease: MedlinePlus Medical Encyclopedia. Nlmnihgov. 2016. Available at: https://www.nlm.nih.gov/medlineplus/ency/article/001309.htm.
Cite This Article:
Zheng K., Chan G., Ho J. Living without an Immune System. Illustrated by A. Mir. Rare Disease Review. August 2017. DOI:10.13140/RG.2.2.17759.87200.