Lyme disease is a bacterial infection caused by Borrelia burgdorferi bacteria that are transmitted through the bite of infected ticks. Lyme disease can cause a variety of symptoms and lead to serious complications if left untreated. The immune system plays an important role in both fighting the initial infection and preventing recurrence of symptoms after treatment. Understanding how the immune system interacts with Lyme disease is key to finding better ways to diagnose, treat, and prevent this complex illness.
How is Lyme disease transmitted?
Lyme disease is transmitted to humans through the bite of infected ticks of the Ixodes genus, namely the deer tick (Ixodes scapularis) in North America. Ticks get infected with Lyme disease bacteria when they feed on infected hosts, such as mice, squirrels, and birds. The bacteria live in the tick’s gut and are transmitted to a human host during the tick feeding process. The risk of getting Lyme disease from an infected tick increases the longer the tick is attached, with transmission generally occurring 36-48 hours after attachment.
In most cases, prompt tick removal can prevent transmission of Lyme bacteria. However, small tick nymphs can easily go unnoticed on the human body, allowing enough time for transmission to occur. Nymphal stage ticks are responsible for the majority of Lyme disease cases. Adult stage ticks are larger and more likely to be discovered and removed before disease transmission. The prevalence of infected ticks varies by geographic region, with Lyme disease more common in areas like the northeastern and mid-Atlantic United States.
What are the stages of Lyme disease?
Lyme disease occurs in three main stages:
Early localized infection
This occurs 3 to 30 days after a tick bite and infection. A red circular “bull’s-eye” shaped rash called erythema migrans develops at the site of the bite in 70-80% of infected individuals. Flu-like symptoms like fever, chills, headache, and muscle aches may also occur. Without treatment, the infection can spread from the skin to other parts of the body.
Early disseminated infection
Weeks to months after the initial bite, the bacteria spread through the bloodstream and lymphatic system. Additional erythema migrans rashes may occur elsewhere on the body. Facial palsy, meningitis, and heart abnormalities like Lyme carditis are other potential symptoms during this stage.
Late Lyme disease
Months to years after infection, 60% of untreated patients may develop recurrent arthritis with severe joint pain and swelling, particularly in the knees. Neurological symptoms like numbness, cognitive impairments, and nerve pain may also emerge.
How does the immune system respond to Lyme disease?
The immune system reacts to Lyme disease bacteria in several key ways:
Innate immune response
The innate immune system acts as the body’s first line of defense against infection. Innate immune cells like neutrophils, macrophages, and dendritic cells recognize general molecular patterns on the surface of invading bacteria. These cells initiate an immediate inflammatory response and phagocytose (engulf and destroy) the bacteria. This innate response occurs within hours to days of infection.
Adaptive immune response
The adaptive immune system has more advanced pathogen-specific defenses. Lyme disease bacteria have outer surface proteins (Osps) that are detected by the immune system as foreign antigens. B cells start producing antibodies that specifically target the Osps. These Osp-specific antibodies bind to the bacteria, marking them for destruction. T cells also respond by attacking infected host cells and producing cytokines that further stimulate the immune response. The adaptive response peaks within 3 to 6 weeks.
Immunological memory
After an initial Lyme infection, the immune system retains a “memory” of the bacterial antigens. Memory B cells and T cells specific to Lyme bacteria remain in the body. If infected with Lyme again in the future, these memory cells launch a rapid, robust immune response that helps prevent repeat illness. However, some Lyme antigens may trigger an autoimmune reaction in certain individuals that contributes to persistent symptoms.
What role do antibodies play in immunity against Lyme?
Antibodies produced by B cells play a pivotal role in immunity and clearance of Lyme bacteria. During early infection, IgM antibodies targeting Lyme Osps are produced. As the immune response matures, IgG antibodies take over as the dominant antibody type. The antibody response throughout Lyme infection involves:
- Binding and neutralizing bacteria in the bloodstream
- Activating complement to promote bacterial destruction
- Opsonizing bacteria to enhance phagocytosis
- Signaling other immune cells to target infected host cells
People who generate high levels of anti-Osp antibodies early in infection are more likely to have mild Lyme disease symptoms that resolve faster. However, Borrelia burgdorferi reduce their Osp expression during later stages, which may allow them to evade portions of the antibody response and persist in some tissues.
Can Lyme disease bacteria evade the immune system?
Borrelia burgdorferi have evolved several methods that allow them to partially avoid and modulate the immune response:
- Binding host complement regulators to inhibit complement activation
- Altering surface protein expression to avoid antibodies
- Forming biofilms to resist phagocytosis and antibodies
- Suppressing adaptive immune cell function
- Cyst formation that makes them less visible to the immune system
These survival tactics contribute to the establishment of early infection and the microorganisms’ ability to disseminate from the skin to other tissues. They also allow the bacteria to persist at low levels in some individuals despite treatment.
What are the tests for immunity against Lyme?
Doctors can test the level of Lyme immunity in a few different ways:
Antibody tests
These tests, either ELISA or Western blot, detect IgM and IgG antibodies against Lyme bacteria. However, antibody levels vary person-to-person and at different disease stages. There is no defined antibody concentration that clearly indicates protective immunity.
Bactericidal antibody test
Measures the ability of a patient’s antibodies in serum to kill live Lyme bacteria in the lab. A high bactericidal capacity suggests immune defenses can neutralize infection. But some individuals can harbor infection despite having bactericidal antibodies.
T cell assays
Quantify the responsiveness of Lyme antigen-specific T cells. Robust T cell activation indicates adaptive immunity against Lyme is primed and ready to respond. This doesn’t necessarily mean infection has been cleared or the patient is protected from reinfection though.
There is still considerable debate over what level of immune response confers true Lyme immunity. The complex interactions between Borrelia burgdorferi and the immune system make assessment of protective immunity complicated.
Can Lyme disease recur after antibiotic treatment?
| Lyme Disease Recurrence Rate | Details |
|---|---|
| 5-20% recurrence rate | Based on placebo groups in antibiotic clinical trials |
| Up to 25% recurrence rate | In highly endemic areas after standard antibiotic regimen |
| 0-14% recurrence rate | After aggressive IV antibiotic treatment for chronic Lyme |
Symptoms of Lyme disease may recur in some patients even after standard 2-4 week antibiotic treatment. Recurrence most often occurs within 3 to 6 months post-treatment. The reasons for recurrence may include:
- Residual bacteria not completely cleared by short antibiotic course
- Reinfection from another tick bite
- Autoimmunity triggered by initial infection
- Co-infections from other tick-borne pathogens
Patients with certain symptoms like Lyme arthritis are at higher risk for recurrence. More aggressive and prolonged IV antibiotic therapy is sometimes used for recurrent Lyme, though efficacy is uncertain. The immune system’s ability to prevent recurrence likely depends on the robustness and durability of the initial anti-Lyme antibody and T cell response.
What are potential immune-based treatments for Lyme?
Researchers are exploring using the immune system itself to treat or prevent Lyme disease:
Lyme vaccines
A Lyme vaccine called LYMErix was licensed in 1998 based on the immune-stimulating Lyme OspA surface protein. However, concerns over vaccine side effects led to its withdrawal from market several years later. New Lyme vaccines in development target multiple surface proteins to try to enhance immunity and avoid adverse reactions.
Lyme immunoglobulin
Administering pooled antibodies from other Lyme patients could provide short-term protection against infection for at-risk individuals like hikers. Though challenging to produce on a large scale.
Monoclonal antibodies
Lab-engineered antibodies targeting key Lyme antigens may have therapeutic potential to clear infection. They could also guide development of improved Lyme diagnostics.
Anti-tick vaccines and immunity
Vaccines that block tick feeding or transmission of Lyme bacteria could offer another avenue for indirectly boosting immunity against Lyme infection.
More research is still needed to determine whether these immune-focused approaches can provide clinically meaningful benefits for Lyme disease prevention and treatment.
Conclusion
The immune system plays an intricate role in both defending against acute Lyme infection and shaping long-term outcomes of the disease. Robust antibody and T cell responses are crucial for controlling infection. However, Borrelia burgdorferi have evolved methods to evade and suppress the immune response, contributing to persistent symptoms in some individuals. Developing a deeper understanding of Lyme immunity may ultimately pave the way for improved diagnostics, vaccines, and immunotherapies to conquer this complex infectious disease.