The Underlying Truth about the Activation of the Immune System

The Discovery of Tumor Necrosis Factor and its Relation to Rheumatoid Arthritis


The Immune System

Our immune system is comprised of various structures and organisms that work in harmony to fight and prevent infection. There are 2 parts to our immune system, the innate immune system and the adaptive immune system:

Innate Immune System: The bodies first line of defense, immediately preventing the spread of pathogens in the body. The innate immune system is made up of macrophages, neutrophils, lysosomes and, natural killer (NK) cells.

Adaptive Immune System: The bodies second immune defense system, developing slowly after exposure to an initial infection. As a result, the immune system is “trained” and capable of recognizing many specific components or antigens from the pathogen.

Dr. Bruce Beutler:

Dr Beutler began his research through the isolation of a Tumor Necrosis Factor (TNF), a protein that caused necrosis or death in certain tumor cell lines in vitro.

In using recombinant DNA to inhibit the effects of TNF, he proved that this protein could cause severe inflammation in the body. He then discovered that the effects of TNF were also in relation to Lipopolysaccharides (LPS).

Septic Shock Following an Ulcerative Colitis Flare

LPS is known to be associated with liver damage and neurological degeneration.

It was revealed that a protein called Toll-like receptor 4 (TLR4) immediately recognizes LPS and helps mitigate the severity of its effects. However, through a study on mice, he determined that a mutated TLR4 caused high quantities of LPS to be released into the bloodstream causing major organ failure, also known as sepsis in the body.

Dr, Jules Hoffmann

(A) The Toll pathway in the fruit fly. (B) The Toll-like Receptor (TLR) 4 pathway in the mouse

Dr Jules Hoffmann, studied the immune response in fruit flies (Drosophila). He discovered an intracellular pathway that was responsible for encoding antifungal peptides.

It was later revealed that the “toll-like” pathways serve as microbial sensor, signaling the presence of a pathogenic microorganism. This then would stimulate the production of antimicrobial peptides that would destroy the pathogens.

What Now?

Understanding the Toll-like receptors was a big steppingstone for the medical community. This concept further illustrated a key component of the innate immune system and how detection of microbial infections trigger an immediate host defense response.

Through further research on TNF, scientists have hypothesized a potential treatment for patients with rheumatoid arthritis. This condition is known to cause joint tenderness and swelling, along with bone erosion and joint deformity, commonly found in the hands, feet, and knees.

Experiments on mice revealed that anti-TNF antibodies produced positive effects and decreased swelling in patients with rheumatoid arthritis and other inflammatory diseases.


Other Toll-like receptors such as TLR2, TLR4, and TLR9 are undergoing clinical evaluation for the treatment of sepsis, cancer, and other inflammatory diseases.

Hopefully, with the current studies and improvements of technology, we can find better treatment plans for those suffering with life threatening conditions.

Important Vocabulary


Natural Killer Cells: responsible for the elimination of cells under physiological stress (tumor cells and virus infected cells).

T-cells/B-cells: Work together to recognize foreign substances called antigens.

Cytotoxic T-cells: recognize and destroy foreign cells and tissues or virus-infected cells. If normal T cells re-encounter a specific antigen, they will rapidly differentiate into cytotoxic T cells, providing a speedy and effective defense.

Tumor Necrosis Factor (TNF): plays important roles in diverse cellular events such as cell survival, proliferation, differentiation, and death. TNF is secreted by inflammatory cells, which may be involved in inflammation-associated carcinogenesis.

Here are a few resources to learn more about this amazing discovery:

  1. The Nobel Prize in Physiology or Medicine 2011
  2. Innate Immunity
  3. Targeting Toll-like Receptors: Emerging Therapeutics?
  4. Development of Anti-TNF therapy for Rheumatoid Arthritis

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If you’re into learning about immunology, you’re in luck. This is only part one of my 2-part series on the innate immune system and new emerging immunotherapies!



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