Primary Immune Deficiencies (PIDs) can be defined as defects in the immune system.
No, that can’t be enough.
PIDs are defined as inherent defects in the immune system?
Nope. Still not good enough.
PIDs are defined as the susceptibility to rare pathogens?
We’ve known about PIDs atleast since the 1950s. We shed a tear at the John Travolta movie “The boy in the plastic bubble” (partly because of the movie but mostly because it had John Travolta). Indeed, Severe Combined Immunodeficiency (SCID) as described in the movie is the most well known of the PIDs. But is that all? Are PIDs simply the abcence of a functioning immune system?
The first PID described was Bruton’s agammaglobulinemia in the 50s.
No wait! The first PID to be described was Epidermodysplasia Verruciformis (insert length of name joke here) in 1922, although it was only officially classified and allowed to sit along with the cool kids at the PID table upon discovery of causal mutations in the immune response in the 2000s. Trust me, you’ve heard of this PID.
The Indonesian tree man. Source- www.whatsonxiamen.com
EV is caused by a severe susceptibility to common forms of human papillomavirus. The same stuff that causes tiny warts is us can grow unchecked in people with mutations in two genes present in the skin (skin!), resulting in uncontrolled growth of warts.
There are many misconceptions on what PIDs are, and whom they affect. For instance, once misconception is that defects in the immune system as we know it (T cells, B cells and macrophages) are responsible for PIDs. However, the above example showed that PIDs can occur when the immune system is normal, but defects in skin can result in susceptibility to certain infections.
Other misconceptions include PIDs being present only in infants and children. This is true for PIDs such as SCID, where severe deficiency in the immune system results in infections from the most common of pathogens, and hence death. However, people now realise that a previously under-appreciated number of PIDs do occur in adults; and sometimes can initiate suddenly during adulthood. Common Variable Immunodeficiency (CVID), which is characterised by decreased immunoglobulins and no memory B cells is the clinically most common PID known, with a frequency between 1:6000-1:10,000. Incomparison, breast cancer incidence rates in the US are around 13:10,000 (or about 1:1000).
Think PIDs are rare? Think again. The most common PID is Selective IgA Deficiency. How common is it? 1:600. However, the rest of the immune response is capable of handling the defects in IgA deficiency, and thus this PID is not as clinically prevalent. For all you know, you might be IgA deficient and not know about it!
PIDs are not defined by susceptibility to a host of pathogens that wouldn’t bother infecting our more immune competent brethren. Rather, certain PIDs have been identified that confer susceptibility to single pathogens. The above example of EV is one. Deficiency in our immune response to single pathogens such as Herpes have been identified, where these individuals lack functioning toll like receptors, and thus increased virus replication occurs in the central nervous system resulting in death. If these kids survive, then they are completely protected against reinfection by Herpes, as well as other infectious insults. There are those individuals who are increasingly susceptible to mycobacteria, including those in the vaccine strain BCG. Given the inherent variability of clinical phenotypes of PIDs, it has been impossible to define what a PID really is. The recent increase in classification of PIDs has been primarily due to a willingness of physicians to diagnose for these diseases, as well as improved detection techniques.
Casanova and Abel call PIDs “Experiments in Nature”. They argue that PIDs might not only be more common than previously thought, but might infact be the rule rather than the exception. A few hundred years ago, the life expectancy was about 40 years of age, with most people dying due to infectious diseases. Now the life expectancy in most parts of the world is around the 70s. Has our immune system developed in the past 100 years? Not really, but we have become cleaner. We only drink sterile water. We are more judicious of our waste disposal (rather than pooping in the city drinking water). We’ve developed antibiotics. We’ve developed better quarantine techniques. We have vaccines (although those who don’t use them should be prime candidates for the Darwin awards). What indeed could be happening is that we all might be immunodeficient. Perhaps to a common pathogen that is currently prevalent in countries we would never visit. Perhaps to an extinct pathogen. Or perhaps even to a pathogen that lies around us, but we were protected initially by a vaccine.
PIDs have had their uses to. PIDs are often due to genetic alterations in the immune system. Studying these individuals can teach us a lot about how the body has evolved to respond to pathogens. Just as researchers try to recreate nature and generate mutations in a mice to study a phenotype, so has nature played… nature (?) and created mutations in us.
That mouse is you. And nature’s watching. Source- http://blog.cd-writer.com
So the next time your friend says he doesn’t get sick because he has a strong immune system, introduce him to the ebola. Lets see how strong his immune response to that pathogen is :).
1) Laurent and Abel, 2004. Nature Reviews Immunology (4): 55-66.