"Chronic Lyme" is a wrecked immune system
Scientifically, "chronic Lyme" is a condition of immunosuppression, increased susceptibility to infections of all kinds, and the hallmark of immunosuppression: reactivation of latent viruses. The viruses, primarily of the herpes family, are known to cause profound fatigue. The recent work of Kunal Garg and colleagues illustrates the serious nature of "chronic Lyme" as it resembles polymicrobial sepsis:
"However, the research by Garg et al. argues that prolonged exposure to tick transmitted microbes weakens the human immune system increasing the host’s vulnerability to other common microbes’ labelled "non-tick-borne opportunistic microbes," such as Chlamydia, Mycoplasma, Epstein-Barr virus and many more."
Anecdotally, many patients are being diagnosed with an immune deficiency condition such as Common Variable Immune Deficiency (CVID) or specific antibody deficiency. Such conditions render a person more susceptible to cancer. The mechanisms below explain how these outcomes occur.
Incompetent B cells
Spirochetes disseminate to the nearest lymph nodes within 24 hours, and to more distant lymph nodes, bone marrow, spleen and brain within a week of infection. Research by Nicole Baumgarth at University of California - Davis demonstrated premature germinal center collapse, meaning the lymph nodes appeared to be damaged so B cells could not properly mature to produce immunoglobulins.
A group led by Lisa K. Blum at Stanford University in 2018 confirmed again that those who have a stronger immune response are not as sick long-term as those with a weaker immune response. That's what Raymond Dattwyler said at the June 1994 FDA meeting where the Lyme disease case definition was discussed.
From the Blum report:
"The data show that patients who did not demonstrate strong B-cell immune responses were more likely to experience post-treatment symptoms...These data confirm previous findings in some animal models showing demonstrable immune system suppression after infection and wide variability in the immune response among different animals after infection.
"In addition to an association between plasmablasts and disease resolution, researchers also found that patients with persistent symptoms had a lower antibody response; more specifically, these patients exhibited reduced clonal expansion of B-cells."
According to the report, Role of TLR in B cell development: signaling through TLR4 promotes B cell maturation and is inhibited by TLR2, B cells don't mature when T cells fail to present antigen. That's exactly what happens when one is "tolerized" to a certain type of antigen.
Tolerance & cross tolerance
Also important are the concepts of "tolerance" and "cross tolerance". Tolerance is the lack of immune response, or hyporesponsiveness, to a type of threat that has been previously encountered, as if the immune system has been exhausted by exposure. Cross tolerance confers hyporesponsiveness by one type of antigen to a different type of antigen.
A German group studied tolerance from Lyme disease in 2002 and published Borrelia burgdorferi-Induced Tolerance as a Model of Persistence via Immunosuppression. Baumgarth noted in 2015, "Furthermore, influenza immunization administered at the time of Borrelia infection also failed to induce robust antibody responses, dramatically reducing the protective antiviral capacity of the humoral response." That's an example of cross-tolerance.
Immunosuppression reactivates viruses
It is a fact that viruses can become reactivated when a person is immune suppressed, such as occurs with shingles. Viral reactivation has been extensively studied in the context of certain professions (astronauts and medical students). And it's a phenomenon that has been observed in AIDS patients--the herpesviruses Epstein-Barr (EBV), and cytomegalovirus (CMV) drive much of the disease process.
From that perspective, what we know as "chronic Lyme" greatly resembles post-sepsis syndrome as described by Richard Hotchkiss at Washington University St. Louis in the report, Dormant viruses re-emerge in patients with lingering sepsis, signaling immune suppression.
"A provocative study links prolonged episodes of sepsis — a life-threatening infection and leading cause of death in hospitals — to the reactivation of otherwise dormant viruses in the body."
Due to tolerance and cross tolerance, EBV and CMV could be chronically reactivated but may not appear as "positive" on serologic tests.