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POST TIME: 16 April, 2019 11:20:18 AM
The body’s immune system
The human body is host to many organisms over a lifetime. Some are dangerous to health (pathogens), some are benign
Mohammed Abul Kalam, PhD

The body’s immune system

Scientists love analogies. They use them continually to communicate our scientific approaches and discoveries. As a medical social scientist, it strikes me that many of our recurring analogies for a healthy, functioning immune system promotes excellent behaviour traits. In this regard, we should all aim to be a little more like the cells of our immune system and emulate these characteristics in our lives and workplaces.
Human beings are large, complex, multicellular, multi-organ systems. We reproduce slowly and rely on a breadth of mechanisms that allow us to control the myriad of rapidly replicating, simple life forms that have evolved to live in or on us. The system of defence is referred to collectively as immunity.
The immune system is divided into two interactive spheres, the much older “innate” sphere, and the more recently evolved “adaptive” sphere. A primary challenge for the very specifically targeted cells that form the basis of adaptive immunity is to distinguish “self” (our own body cells and tissues) from “non-self” – the foreign invaders. When that goes wrong, we can develop autoimmune diseases such as multiple sclerosis or rheumatoid arthritis.
The human body is host to many organisms over a lifetime. Some are dangerous to health (pathogens), some are benign, and some are necessary for proper functioning. Most of the genetic material we carry around with us is “non-self”: principally harmless bacteria (called “commensals”) that live in the gastrointestinal tract.

The greatest numbers of viruses we carry around are the “bacteriophages”, which infect the commensal bacteria in our gut. Not all “phages” are, however, benign. For example, the toxin that causes human diphtheria is encoded in the genome of a bacteriophage.

There’s also a spectrum of viruses that persistently infect our body tissues. The most familiar are herpes viruses, like those that cause cold sores (H. simplex) and shingles (H. zoster). Both viruses hide out in the nervous system and are normally under immune control. They re-emerge to cause problems as a consequence of tissue stress (such as a sunburnt lip) or as immunity declines with age (shingles).

Our innate and adaptive immune systems:The innate system ranges from processes as basic as phagocytosis (ingestion of bacteria), to molecules like the interferons produced by any virus-infected cell that can limit replication. Such innate systems are found right across the evolutionary spectrum and don’t target specific pathogens.

The much younger adaptive immune system is what we stimulate with vaccines. A property of small white blood cells calledlymphocytes; it divides broadly into two lineages: the B cells and T cells. These bear the extraordinarily diverse and very specific immunoglobulin (Ig) and T cell receptor (TCR) recognition molecules that detect invading pathogens (bacteria, virus, fungi and so on).

The immunoglobulins bind to “non-self” (foreign) proteins called “antigens”, while the T cellare specifically targeted to “self” transplantation molecules.

The assassins of the immune system are then switched on; the killer T cells that eliminate virus-infected (or cancer) cells. Also activated are the “helper” T cells that secrete various molecules to “help” both the B cells and killer T cells differentiate and do their work.

How does our immune system learn and remember?All lymphocyte responses work by massive cell division in the lymph nodes (the “glands” in our neck that swell when we get a sore throat). This process is started by small numbers of “naive” B and T cells that haven’t encountered the invader before, and only stops when the foreign invader is eliminated. The B cells differentiate into large protein-secreting cells called plasma cells, which produce the protective antibodies (immunoglobulins) that circulate for years in our blood.

Most of the T cells die off after they’ve done their job, but some survive so they can remember how to target specific invaders. They can be rapidly recalled to their “killer” or “helper” functions. During development, T cells mature in a way that depends on both positive and negative feedback. This occurs in the thymus, an organ found in the front of your chest.As they mature, T cells are exposed to a process of trial and error, and take on board criticism and advice in equal measure, to ensure they are “trained” to respond appropriately to what they “see” when they leave the thymus.

Importantly, this process is balanced, and T cells must receive both positive and negative feedback to mature appropriately – too much of either on its own is not enough.In the diverse team of the immune system, cells can be both the student and the teacher. This occurs during immune responses with intense cross-talk between dendritic cells, T cells and B cells. In this supportive environment, multiple rounds of feedback allow B cells to gain a tighter grip on infections, tailoring antibodies specifically towards each pathogen.

Our immune system knows that context is important – it doesn’t rely on a “one-size–fits-all” approach to resolve all infections. This allows the cells of our immune system to perfectly respond to different types of pathogens: such as viruses, fungi, bacteria and helminthes (worms).

Importantly, our immune system needs to carefully control attack responses to get rid of danger. Being too heavy handed leaves us with collateral tissue damage, such as is seen allergy and asthma. Conversely, weak responses lead to immunodeficiencies, chronic infection or cancer.

When we are overworked and poorly rested, we don’t function at our peak. The same is true for our immune cells. An overworked immune cell is commonly referred to as being “chronically exhausted”. In this state, T cells are no longer effective at attacking tumor or virus-infected cells. They are lethargic and inefficient, much like us when we overdo it. For T cells, this switch to exhaustion helps ensure a balanced response and avoids collateral damage. However, viruses and cancers exploit this weakness in immune responses by deliberately promoting exhaustion.

The rapidly advancing field of immunotherapy has tackled this limitation in our immune system head-on to create new cancer therapeutics. These therapies release cells of their exhaustion, refresh them, so they become effective once more.

This therapeutic avenue is like a self-care day spa for our T cells. It revives them, renewing their determination and efficiency. The cornerstone of our adaptive immune system is the ability to remember our past infections. In doing so, it can respond faster and in a more targeted manner when we encounter the same pathogen multiple times.

Quite literally, if it doesn’t kill you, it makes your immune system stronger. Vaccines exploit this modus operandi, providing immune cells with the memories without the risk of infection.

While life might not have the shortcuts provided by vaccines, certainly taking time to reflect and learn after challenges can allow us to find better, faster solutions to future problems. The immune system protects us from the constant onslaught of viruses, bacteria and other types of pathogens we encounter throughout life. It also remembers past infections so it can fight them off more easily the next time we encounter them.

But the immune system can sometimes misbehave. It can start attacking its own proteins, rather than the infection, causing autoimmunity. Or, it can effectively respond to one variant of a virus, but then is unable to stop another variant of the virus. This is termed the original antigenic sin (OAS). OAS occurs when the initial successful immune response blocks an effective response when the person is next exposed to the virus. This can have potentially devastating consequences for illnesses such as the mosquito-borne-dengue..

There are around 400 million dengue infections worldwide each year and no vaccine is available. Reinfection of someone who has been exposed to dengue previously can result in life-threatening hemorrhagic fever. OAS is also thought to limit our immune responses to the highly variable influenza virus, increasing the chance of pandemics.

When a virus enters the body, a race begins between responding immune cells and the infecting pathogen. The pathogen replicates and finds a target cell or organ that will allow it to thrive. So, the effectiveness of a response depends on the immune system winning the race to clear the pathogen before it causes irreversible damage to the body.

Immune cells called “B cells” make antibodies. A pathogen such as a virus is a large molecule with different components, called antigens. When a B cell recognises an antigen, it is activated and interacts with other immune cells to receive directions.

How can we avoid OAS?We need to train our immune system to be more flexible and produce antibodies that can adapt when viruses try to evade the immune system.

To this end, researchers are designing vaccines to respond to multiple variants of pathogens. This has shown promising results and may be the way forward to overcome OAS for potentially life-threatening viruses such as dengue.

The writer is  former Head, Department of Medical Sociology,

Institute of Epidemiology, Disease Control & Research (IEDCR)

Dhaka, Bangladesh E-mail: med_sociology_iedcr@yahoo.com