WHAT IS LYME DISEASE?

Lyme Disease is a bacterial infection transmitted through ticks.  


WHAT IS VECTOR BORNE?

Lyme disease is also a vector-borne disease.  

The term “vector” refers to any arthropod (insect or arachnid) that transmits a disease through feeding activity.  Lyme is a "vector-borne disease" because it is transmitted to humans by a blood-sucking arthropod: Ixodes ticks.  


WHAT IS ZOONOTIC?

Lyme disease is Zoonotic, meaning that Lyme can be passed between animals and humans.


IS LYME DISEASE A VIRUS?

Lyme Disease is caused by a parasitic bacteria, not a virus. 

Bacteria are unicellular microorganisms that can be treated with antibiotics.  Viruses, on the other hand, are sub-microscopic particles to which vaccines can often aid in slowing the spread and antiviral medications can slow the reproduction of the virus, but cannot completely stop it. 


WHAT  BACTERIA CAUSES LYME?

The bacteria that causes Lyme is Borrelia Burgdorefi ("Bb"). 


WHAT ANIMALS CARRY Bb?

Bb can infect a wide range of animals, but ticks are the only natural agent through which humans can be infected. 

B. burgdorferi infects a wide range of vertebrate animals including small mammals, lizards, and birds. Ticks of the genus Ixodes transmit B. burgdorferi between hosts and are the only natural agents through which humans have been shown to become infected


WHAT IS THE TAXONOMIC RANK OF Bb?

B. Burgoderefi is a bacterial species of the Spirochete class and of the genus Borrelia.

  • Kingdom: Cellular Organism 
  • Phylum: Bacteria 
  • Class: Spriochaetes
  • Order: Spirochaetia, which is is divided into three families: BrachyspiraceaeLeptospiraceae, and Spirochaetaceae
  • Family: Spirochaetales
  • Genus: Borrelia
  • Species: Borrelia burgdorferi 

Thus, Bb is a highly specialized, spiral shaped, two-membrane bacteria.  


WHY IS Bb A SPIROCHETE?

Bacteria in the Spirochete class are defined by their spiral-shaped form and share other defining characteristics. 

The term "spirochete" comes from its genus name Spirochaete, which is a modern Latin term derived from the Greek word speira ("a coil" or "spiral") and the Greek word chat ("hair").  This etymology is fitting as spirochetes (and Bb) share a distinctive morphology that includes a spiral-shaped body and flagella (organs of motility) enclosed between the outer and inner membranes.  

Simply put, spirochetes look like a piece of uncoiled hair. 


WHAT MAKES SPIROCHETES UNIQUE?

Unlike most bacteria, Spirochetes are able to swim in even highly viscous, gel-like mediums, such as connective tissue. 

Due to the unique spiral structure of Spirochetes, their motility is different from that of other bacteria.  Motility is the ability to move spontaneously and actively. 

In particular, spirochetes have a special attribute that sets them apart from most other bacteria: spirochetes are able to swim in a highly viscous, gel-like mediums, such as connective tissue.  


WHAT IS THE IMMUNE SYSTEM'S REACTION WHEN INFECTED WITH Bb?  

The human immune system is meant to protect the body against disease, including bacterial infections.  It responds in a specific way to pathogens and displays a long term memory of earlier contacts with the disease agents.

The immune system consists of two functional components:

  • Non-specific defence (innate or non adaptive immune system)

  • Specific defence (adaptive immune system)

Non-specific defence: Prevents penetration and spread of many infectious agents by means of a variety of physical, biochemical and cellular barriers (skin, mucosa, lysozymes, complement and phagocytes). It does not improve with repeated exposure.

Specific defence: May be called upon to react against and clear the harmful agent. The adaptive immune system consists of a variety of cells and molecules, among which lymphocytes and immunoglobulins are the key elements.

Lymphocytes synthesize cell surface receptors or secrete proteins that specifically bind to foreign molecules. These secreted proteins are known as antibodies. Any molecule that can bind to an antibody is called an antigen (antibody generator). The term immunoglobulin is used interchangeably with antibody.


WHAT ARE ANTIBODIES?

Antibodies are large Y-shaped protein molecules created by the immune system to identify and neutralize foreign objects and pathogens, such as bacteria, viruses, fungi, parasites, and toxins. Also known as immunoglobulin, antibodies are manufactured by white blood cells called B-lymphocytes, or B-cells. 


WHAT ARE ANTIGENS?

An antigen is a foreign molecule which triggers the production of antibodies by the immune system (antibody generator).


WHAT ARE THE ANTIBODY CLASSES?

There are five classes, or isotypes, of antibodies — IgA, IgD, IgE, IgG, and IgM.

Each isotype is uniquely suited to defend against different types of invaders. The constant region of the antibody determines both its class and function.

Immunoglobulin alpha (IgA) is found in mucosal areas of the body including the digestive, respiratory, and reproductive tracts. IgA is also present in saliva, tears, and breast milk, where its function is to coat the baby's intestinal mucosa to protect it from pathogens

Immunoglobulin delta (IgD) appears in very small amounts in the blood, but is mainly found as receptors on B-cells which have not yet encountered antigens, where its function is to activate the B-cell.

Immunoglobulin epsilon (IgE) is involved in defending the body against parasites and allergens. Consequently, it is often found attached to mast cells and basophils, although eosinophils, monocytes, macrophages, and blood platelets also have IgE receptors.

Immunoglobulin gamma (IgG) makes up about 75% of the antibodies found in the blood. IgG can bind with many types of pathogens, including bacteria, viruses and fungi. It is the only antibody that can pass through the placenta from mother to fetus, providing in utero protection.

Immunoglobulin mu (IgM) helps complement proteins to attack invaders by providing a bridge to which the proteins can attach themselves to an invader in order to begin their complement cascade.


HOW DO ANTIBODIES WORK? 

Antibodies function in three distinct ways.

ANTIGEN  BINDING

Antibodies can stimulate other parts of the immune system (e.g. complement proteins) to destroy the pathogens.

The antigen binding site of an antibody is located at the top of each of the two outstretched arms. Each site is defined by 6 loops called Complementary Determining Regions (CDR). Three are found on the heavy chain (H1, H2, and H3) and 3 on the light chain (L1, L2, and L3).

These protein loops mirror, or complement, the shape of specific antigens. As a result, they determine to which specific antigens the antibody can and will bind.

They bind directly to antigens, effectively coating the surface of the invader, in order to prevent pathogens from entering or damaging healthy body cells.

OPSONIZATION

 Antibodies can mark pathogens through a process called opsonization so that the pathogens can be identified and neutralized by other immune cells.

A principal way that pathogens are destroyed is through phagocytosis. In this process, white blood cells like macrophages, neutrophils, and dendritic cells destroy invading micro-organisms by surrounding them, drawing them inside their own membranes, and then neutralizing them with enzymes.

They are said to literally "eat" the invaders.

The problem is that the membranes of phagocytes and invading cells both carry a negative charge, so they naturally repel one another. The antibody bridges that gap by attaching ("binding") itself to the antigen with one of its antigen binding sites, and linking to the phagocyte with its "tail," or Fc region.

This serves to neutralize the charge and bring the antigen and phagocyte into proximity. The antibody can also activate the phagocyte, making it a much more hungry and effective eater.

STIMULATE  IMMUNE SYSTEM

Antibodies can also stimulate other parts of the immune system (e.g. complement proteins) to destroy the pathogens.


WHY DOESN'T MY IMMUNE SYSTEM KILL Bb?

Bb is able to survive the attack of the immune system and often, to resist any subsequent acquired immune response.

When B. burgdorferi enter a mouse, many components of the host innate immune response could potentially recognize the bacteria and help control their numbers. 

After the initial stage of B. burgdorferi infection, mice develop antibodies to numerous bacterial protein. When serum from infected mice was transferred to naïve mice, the recipient animals were protected from infection with the same strain of B. burgdorferi.

Similar transfer of T cells did not confer protection, suggesting that T cells play a lesser role than antibody in protection. Despite the presence of neutralizing antibodies, the host acquired immune response limits spirochete numbers but does not eradicate B. burgdorferi infection and most mice become persistently infected after needle inoculation or the bite of an infected tick.

Antibody does serve to limit disease and pathogenesis, since SCID mice, which lack both the cellular and antibody components of the acquired immune response, contain much higher spirochete loads in tissues and exhibit more severely arthitic joints than normal mice.

The ability of the bacteria to survive in the face of an antibody response suggests that either the bacteria “hide out” in sites protected from antibodies or that the bacteria evade antibody reactivity by varying antigens or otherwise masking reactive proteins. The low numbers of spirochetes typically found in infected mammalian blood limits direct detection of bacteria in human clinical samples, complicating diagnosis and analysis of the progress of an infection.

Sensitive molecular techniques now allow amplification of bacterial targets, but the bacterial numbers are at the lower limit detectable by such methods, so they are difficult to apply in the clinical laboratory.


While infected nymphal ticks feed, spirochetes in the midgut respond in several ways to the incoming blood and increased temperature. The population of spirochetes expands and their protein synthesis alters. Then, spirochetes migrate from the midgut to the salivary glands, allowing transmission into a new host.











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