Borrelia burgdorferi

Evasion of the Immune System

This page was produced as an assingment for an undergraduate course at Davidson College.


Structural Features

Pathogen Life Cycle

Innate Immune Response

Humoral Immune Response

Cellular Immune Response

Evasion of the Immune System

Lyme Disease


Works Cited

While the exact mechanism by which B. burgdorferi evades the immune system is not known, several mechanisms have been hypothesized. One possibility is that the bacteria migrate to so-called immune-privileged sites including intracellular compartments and the extracellular matrix. A second possibility is that the bacterium frequently changes its surface antigens to evade immune detection.  Third, the B. burgdorferi bacteria may induce auto-immunity in the host following the initial infection, which could produce chronic infection. This hypothesis is supported by the discovery of the structural homology between OspA and human LFA-1.  A final hypothesis is that the pathogen immuno-modulates the host:  the pathogen is somehow able to control the host’s immune response so as to support the survival of the pathogen (Diterich and Hartung, 2001).  

In order to successfully disseminate from the site of initial infection to other sites in the host’s body, B. burgdorferi must utilize a mechanism to home to specific tissues.  The bacterium may bind to integrins, glycosaminoglycans, and extracellular matrix proteins, which differ based on tissue type.  Decorin, a glycosaminoglycan commonly found on collagen fibrils, is a specific integrin that has been studied in the pathophysiology of Lyme disease. B. burgdorferi have different subtypes of decorin-binding protein on their cell surface   While collagen fibers are found throughout the body, B. Burgdorferi seem to home to those of the heart, nervous system, and joints. A Lyme disease-infected mouse deficient for decorin was found to have less severe arthritis than normal, which supports the idea that B. burgdorferi uses decorin to aid in tissue destruction (Steere 2001).  

Upon entering the host, B. burgdorferi is faced with various stressful situations, some of which are part of the host’s immune system. The bacteria’s response to the stress helps it evade the host’s immune system. Primarily, when leaving the tick vector and entering the human, the bacteria’s external temperature increases.  The high temperature of the warm-blooded human is a non-specific defense that kills many pathogens before they have a chance to face the host’s specific immune system.  In addition, during the host’s inflammatory response, there is a marked increase in body temperature that manifests in either systemic fever or local inflammation.  This fever aids the host in destroying heat-sensitive pathogens. In response to elevated temperatures, B. burgdorferi have been shown to increase the production of several importance heat shock and stress proteins that may aid its survival during the host’s inflammatory response (Szczepanski and Benach, 1991).

While the importance of natural killer (NK) cells in combating Lyme disease is not understood with certainty, it has been determined that NK cell activity is inhibited in early and chronic Lyme disease, but not in patients who were in remission.  Szczepanski and Benach found that the bacteria itself inhibited NK cell, which could contribute to this organisms ability to evade the early, nonspecific immune response (Szczepanski and Benach, 1991).

Another possible mechanism by which B. burgdorferi may evade the immune system is through the down-regulation of particular surface antigens that would normally be targeted by bactericidal antibodies (Liang et. al., 2002).  Liang et. al. showed that the anti-OspC antibody can either down-regulate the expression of OspC or select for Osp-C negative phenotypes in the presence of OspC+ spirochetes.  OspC-negative spirochetes have been extracted from serum the serum of an infected tick (2002).  Decorin-binding protein A (DbpA) is another protein on the surface of B. burgdorferi that is thought to be up-regulated during mammalian infection.  Anti-DbpA does not protect the host against infection (Liang et. al., 2002).   


Development of Chronic Disease

The cause of chronic or Stage 3 Lyme disease (See Lyme disease) has yet to be determined, but there are several hypotheses regarding the possible development of chronic disease. One possibility, which involves molecular mimicry, is that the host produces self-determinants with structural similarity to B. burgdorferi antigens.  These self-determinants can thus induce the host immune system to respond, leading to chronic inflammatory response.  Chronic disease would then be the development of autoimmunity to self-particles that mimic the original B. burgdorferi antigens (Szczepanski and Benach, 1991).  

In synovial fluid of patients with Lyme arthritis, T-cells bind well to OspA, and OspA Th1 cells are prevalent in the synovial fluid of patients with Lyme arthritis. Gross et. al. hypothesize that in treatment-resistant Lyme arthritis, the disease may have developed autoimmunity due to a cross-reactive response between OspA and self-antigen. The Th1 cells that respond to OspA secrete IFN-γ, which induces antigen-presenting cells to increase production of ICAM-1 and MHCII expression.  ICAM-1 recruits cells expressing LFA-1 which includes activated Th1 cells. LFA-1 recruits more macrophage, beginning a cycle in which OspA-primed T-cells are continually activated by LFA-1, even after antibiotic treatment to eliminate spirochetes.  The constant stimulation of macrophages by LFA-1 leads to cytokine release and subsequent tissue damage that manifests in chronic Lyme arthritis.  (Gross et. al., 1998).


This page was created for an undergraduate Immunology course, Biology 307, at Davidson College in the Spring semester of 2007 under Dr. Sophia Sarafova (

Please direct all comments and questions to Meredith Prasse (


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