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20190908 – An Elegant Defense

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MAIN IDEA:

The main idea here is to present contemporary understanding of immune system workings and humanize this discussion with real live example of 3 people who suffer from immunity system problems and one person who possess unusually powerful immune system, which allowed him to survive AIDs at the time before treatment was developed and the vast majority of infected people died.

DETAILS:

Part I: Lives in the Balance

  1. The Ties That Bind 2. Jason 3. Bob. 4. Linda and Merredith

In this part author discusses a little bit on the nature of immune system and then presents stories of four people: his friend Jason who suffered from cancer at middle age, Bob – gay man who survived AIDS, Linda – high power workaholic who encountered rheumatoid arthritis, which is autoimmune disease, and Merredith, who has genetic version of autoimmune disease.

 

Part II: The Immune System and the Festival of Life

  1. The Bird, Dog, Starfish, and Magic Bullet

Here author starts with the origins of immunology, which started in Italy first with discovery of chicken bursa by Fabricius ab Aquapendente
and then in 1622 with discovery of lymph circulation. The next step was in XIX century when Metchnikoff discovered phagocytes and developed theory of immunities, which was supplemented by work of Paul Ehrlich who discovered antigens.

  1. The Festival;

Here author describes what he calls festival of life: permanent movement of cells in the body and some processes used to fix the problems that periodically occur.

  1. Festival Crashers;

This is about all kind of challenges to this festival: Bacteria, Viruses, Parasites, and Cancers. Then author discusses how body’s immune system handles these challenges. The common problem of this handling is the difficulty of correct recognition between hostile and own healthy cells so that body would not attack the latter (autoimmune illnesses) and would not protect malignant cells (cancer). Here is how author describes his task: “ It is the story of scientific discovery. It goes like this, in brief: scientists got an idea about these things called T cells and B cells, started applying big conceptual knowledge through life-saving vaccines and transplants, and then these imaginative and innovative immunologists delved into the tiny fragments of the immune system, the cogs, and built a blueprint of the machine. They understood, as I’ll describe, what inflammation is about, and the molecules that make up our communications network. With each advance of science came another practical step, like building medicines by replicating our defense cells, and then would come another extraordinary scientific leap, like the discovery only a few years ago of a second immune system.

  1. The Mystery Organ

This starts with the story of tuberculosis patient who died shortly before discovery of antibiotics and whose sister became medical researcher who discovered thymus – the mystery organ strongly influencing work of immune system.

9 The B-Word

This is about discovery of two different immune cells that body produced- B-cells originating in bone marrow and generated antibodies, while T-cell went through thymus and could direct actions against disease.

  1. T Cells and B Cells

This is about functionality of B and T cells with nice picture of both:

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  1. Vaccines

This is brief, but important part describing how vaccines work. They present immune system with relatively weak cell form of enemy that allow it to develop response to this particular problem, so when real virus hit, the immune system already prepared to defeat it.

  1. The Infinity Machine

This is about big mystery of immune system – how it recognizes good cells vs. bad that needs to be attacked. Turned out that immune system has preset pieces of DNA ready to create antibodies for multitude of different invaders.

  1. Transplant

This chapter is about transplantation of organs that was very challenging process before medicine achieved good enough understanding of immune system to be able suppress it enough for body accept transplant, but not enough to leave it defenseless against infection.

14 The Immune System’s Fingerprint

This is an interesting chapter about uniqueness of immune system and its ability to sent chemical signals externally, based on MHC gene. Among other things it was discovered that close enough MHC repels people from each other, while different attracts, providing chance for increased diversity.

  1. Inflammation

This is another interesting and not trivial look at inflammation. Author links it to immune system and complex process of organism reaction to invasion with use of various more or less specialized killer cells: neutrophils, macrophages, and natural killer cells.

  1. Fever

This chapter is about discovery of a molecule that controls fever in the body – leukocytic pyrogen, even if it is present in miniscule quantities.

  1. Flash Gordon

This is about interferon (IFN) – a medicine that is based on dead virus. It prepares immune system to recognize DNA of virus in case of infection and attack it.

  1. The Harmonious Way

This very brief chapter is about change in approach to immune system from perceiving it as defensive system that attacks intruders to understanding that it is kind of homeostatic mechanism that maintains overall cellular balance of the body reacting to violation of this balance in such way as to restore it.

19 Three Wise Men and the Monoclonal Antibody

This is about the research that developed process for isolating specific antibodies and produce them in volume. Such antibodies called monoclonal antibodies that could be potentially produced for any disease.

  1. A Second Immune system

This is the story of discovery of second signal system – innate immunity based on gene called Toll receptor that defines which cell attack and which should be not attacked. The understanding of immune reaction is now includes coordinated working of both: innate and adaptive immune systems. Here is brief description:

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Part III: Bob: 21. Sex Machine; 22. GRID;  23. The Phone Call; 24 CD4 and CD8; 5. Magic; 26. The Prime; Part IV: Linda and Merredith: 27. Linda; 28 The Wolf: 29. Invisible Evidence 30. Best of Both Worlds (Sort Of); 31. Merredith;

This part of the book follows stories of 3 people that author selected for the “human interest” part of the book.

  1. Should You Pick Your Nose? 33. Microbiome; 34. Stress; 35. Sleep;

The 3 chapters about factors impacting immune system. They discuss correspondingly: need to train immune system in real life, so too much sterility in life and too cautious approach to raising children puts people at risk of having poorly trained immune system, resulting in allergies and openness to infection; value of microbiome that surround human body and provides vital support for its functioning, so overuse of antibiotic and other suppressors of micro organism could be not just harmful, but deadly; Finally minimization of stress and optimization of amount and quality of sleep are important factors in maintaining immune system in good shape.

Part V: Jason 36. A Word About Cancer 37.Laughter and Tears

In these two chapters author once again returns to the story of his friend Jason and Jason’s struggle with cancer.

38 The Lazarus Mouse

Here author moves to discuss interaction of immune system with cancer, which is practically comes down to its failure to attack cancerous cells. The research found that it seems to be possible to remove the restriction that disrupt this process and prompt immune system to attack, consequently leading to possibility of developing qualitatively new method of cancer treatment.

  1. Wound Healing

Here author discusses process of wound healing and suggests that cancer related to this process when immune system react to cancer cells as a wound and start protecting it.

  1. Programmed Death

In this chapter author retells the story of antibody development that would prompt immune system attack cancer cells. Here is author’s description of how it was done:(For those interested in the details, Lonberg and his peers, in the late 1990s, were figuring out how to cause the T cell to receive its signal at CD28, which is the spot where the “go” signal is received, and not at CTLA-4, where the “stop” signal arrives. Both receive their signal from the molecule B7-1; if B7-1 binds to CTLA-4, the immune system stops, and if it binds to CD28, the attack goes forward. In some cancers, “CTLA-4 is hogging B7,” Lonberg said. So the goal was to “displace” B7-1 from the CTLA-4 so that CD28 could bind. They did this by creating an ultra-specific antibody to bind to CTLA-4. When the antibody bound to CTLA-4, it pried loose the B7-1. Now the brakes would have been turned off. The immune system could attack the tumor as if it were foreign and dangerous, not innocuous and self.)

  1. The Breakthrough 42. Jason Races Time 43. Shepherd of Death 44. Trials, Personal and Clinical 45. The Other Shoe Part VI: Homecoming 46. Bob 47. Linda 4S. Jan and Ron 49. Jason Down the White Tunnel; 50. Jason Rises; 51. Apollo 11; 52. Home; 53. Jasons Way; 54. The Meanings of Life; 55. The Meaning of Jason

These final chapters retells current state of four people used to illustrate the book: author’s friend Jason died, but others keep going, indicating increased level of knowledge and abilities of current medicine.

MY TAKE ON IT:

This book clearly improved my understanding of immune system, how it works, what is current level of understanding of this system, and what could be expected in reasonably near future. The human-interest story was in my view a bit out of place, but it is not that bad. Anyway, the information from this book indicates that humanity is getting closer and closer to real understanding of immune system workings and therefore closer to eliminating practically all diseases known to humanity, including not only auto-immune diseases and allergies, but also immune deficiency diseases such as all kinds of cancers. It would be very interesting to see the results.


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