Question

In Lubeck, Germany, in 1930 , a group of 251 infants was accidentally administered a tainted vaccine for tuberculosis that contained live Mycobacterium tuberculosis. This vaccine was administered orally, directly exposing the infants to the deadly bacterium. Many of these infants contracted tuberculosis, and some died. However, 44 of the infants never contracted tuberculosis. Based on your knowledge of the innate immune system, what innate defenses might have inhibited \(M\), tuberculosis enough to prevent these infants from contracting the disease?

Short answer

Physical barriers, phagocytic cells, inflammatory responses, and antimicrobial proteins are the probable innate defenses that helped prevent the infants from contracting tuberculosis.

Step-by-step solution

Identify the innate immune defenses

The first step is to identify the components of the innate immune system that could have played a role in protecting the infants from tuberculosis. Key innate defenses include physical barriers, phagocytic cells, inflammatory responses, and antimicrobial proteins.

Physical barriers

Consider how mucosal surfaces and epithelial linings serve as physical barriers to infection. The oral route of administration means that mucosal surfaces in the mouth and gastrointestinal tract were the first point of contact. Mucus and epithelial cells can trap and prevent bacteria from penetrating deeper tissues.

Phagocytic cells

Review the role of phagocytic cells, such as macrophages and neutrophils, in the innate immune response. These cells can ingest and destroy pathogens on contact. Specialized phagocytic cells located in mucosal tissues could have quickly responded to the presence of Mycobacterium tuberculosis.

Inflammatory response

Explain how the inflammatory response is an innate defense mechanism. Infection with Mycobacterium tuberculosis would trigger an inflammatory response characterized by the recruitment of immune cells, vasodilation, and increased permeability of blood vessels, which help contain and eliminate pathogens.

Antimicrobial proteins

Discuss the role of antimicrobial proteins such as lysozymes, defensins, and complement proteins. These proteins can directly kill bacteria or mark them for destruction by other immune cells. The presence of these proteins in saliva and mucosal secretions could have inhibited the bacteria.

Summary of defenses

Summarize how these various components of the innate immune system might have worked together to prevent infection. For instance, the mucus could have trapped the bacteria, phagocytes could have destroyed any breached cells, the inflammatory response could have contained the infection, and antimicrobial proteins could have directly killed the bacteria.

Key concepts

Physical Barriers in Innate Immunity

The innate immune system uses physical barriers as the first line of defense against pathogens like Mycobacterium tuberculosis. These barriers include the skin and mucosal surfaces lining the respiratory, gastrointestinal, and genitourinary tracts. In the case of the tainted tuberculosis vaccine, mucosal surfaces in the mouth and gastrointestinal tract were directly exposed.

Mucosal surfaces are lined with epithelial cells that are tightly joined together, preventing pathogens from penetrating deeper tissues. These cells also produce mucus, a sticky substance that can trap bacteria and other particles, stopping them from reaching body tissues.

This initial barrier helps keep the bacteria confined to the surfaces where they can be neutralized before causing harm. In the lucky infants who didn't contract the disease, a robust mucosal barrier likely played a critical role in trapping and expelling the bacteria out of the body.

Phagocytic Cells

Phagocytic cells are a vital component of the innate immune system, responsible for ingesting and destroying invading pathogens.

• Macrophages: These are large phagocytic cells found in tissue and can engulf numerous bacteria.
• Neutrophils: These are abundant white blood cells that quickly move to infection sites to ingest bacteria.

In the scenario with the tainted vaccine, these cells likely played a crucial role. Specialized phagocytic cells in the mucosal lining of the mouth and gut could have quickly recognized and ingested the Mycobacterium tuberculosis bacteria.

After ingesting the bacteria, phagocytes use lysosomes, which are small vesicles containing digestive enzymes and antimicrobial proteins, to break down and destroy the pathogen. By acting swiftly, these cells help prevent the bacteria from spreading to other parts of the body.

Inflammatory Response

The inflammatory response is another vital defense mechanism in innate immunity. When Mycobacterium tuberculosis bacteria enter the body, they trigger an inflammatory response aimed at containing and eliminating the infection.

This response includes:

• Recruitment of immune cells: Specialized cells release signaling molecules called cytokines that attract more immune cells to the infection site.
• Vasodilation: Blood vessels widen, increasing blood flow to the affected area. This delivers more immune cells and nutrients essential for fighting the infection.
• Increased permeability of blood vessels: This allows immune cells and proteins to move more easily from the bloodstream into the infected tissue.

By initiating inflammation, the body creates an environment that is hostile to pathogens. The inflammation works to localize and destroy the bacteria, preventing them from spreading further.

Antimicrobial Proteins

Antimicrobial proteins are essential weapons in the innate immune arsenal. These proteins can directly kill bacteria or make them easier targets for immune cells to destroy. Some key antimicrobial proteins include:

• Lysozymes: Found in saliva, tears, and other bodily fluids, these enzymes break down bacterial cell walls.
• Defensins: Small proteins that insert into bacterial membranes, creating pores that lead to the bacteria’s death.
• Complement proteins: A group of proteins in the blood that can mark bacteria for destruction and also lyse bacterial membranes directly.

In the case of the infants exposed to Mycobacterium tuberculosis, these antimicrobial proteins in saliva and mucosal secretions may have played a vital role. By acting quickly to neutralize the bacteria, these proteins helped support the other innate defenses in preventing infection.