Immunology of HBV | Adam Gehring, PhD

Summary

The speaker discusses advancements in understanding the immune response to hepatitis B, particularly the T cell response in chronic infection. The presentation highlights the factors affecting T cell function, including age, genotype, and compartmentalization within the liver. Mechanisms of T cell exhaustion are explored, such as inhibitory receptor expression, metabolic defects, and active T cell elimination. The speaker also addresses the complexity of the B cell response, noting gaps in knowledge, and stresses the importance of enhancing innate immunity. Finally, upcoming events like the Global Hepatitis Summit and the HPV Cure Workshop are mentioned, emphasizing their significance in advancing the field.

Takeaways

• 😀 Chronic HBV infection leads to a diminished T cell response, with reduced frequency and function of HBV-specific T cells.
• 😀 Young patients tend to have stronger T cell responses compared to older individuals due to age-related differences in immune function.
• 😀 Genetic factors, including HBV genotypes and HLA profiles, significantly influence the T cell immune response in HBV infection.
• 😀 Liver T cells exhibit different functional profiles compared to circulating T cells, showing that compartmentalization plays a role in immune responses.
• 😀 T cell exhaustion in chronic HBV is driven by upregulated inhibitory receptors like PD-1, which reduces T cell function over time.
• 😀 The liver's immunosuppressive environment, combined with poor antigen presentation, impedes T cell activation in chronic HBV infection.
• 😀 Metabolic stress and mitochondrial dysfunction in T cells contribute to immune dysfunction and exhaustion in chronic HBV infection.
• 😀 B cells play a role in the immune-active phase of chronic HBV, though memory B cell detection remains challenging in these patients.
• 😀 NK cells in chronic HBV are less effective at producing interferon-gamma, which suppresses overall T cell immunity.
• 😀 Ongoing research into therapeutic vaccines and immunomodulatory treatments holds significant promise for restoring T cell function and treating chronic HBV.

Q & A

What is the focus of the speaker's presentation?

The speaker's presentation focuses on the immune responses in chronic Hepatitis B (HBV), particularly how T-cells and B-cells behave in the context of HBV infection and the mechanisms leading to immune exhaustion.

What is the significance of T-cell responses in chronic HBV patients?

In chronic HBV, T-cell responses are often reduced, particularly in those with inactive disease or when the infection becomes chronic. T-cell functionality, including the expression of inhibitory receptors like PD-1, is impaired, leading to immune exhaustion.

How do age and HBV genotype influence T-cell responses in chronic HBV?

T-cell responses in chronic HBV are more robust in younger patients, who show higher frequencies of HBV-specific T-cells. Additionally, the HBV genotype can affect the strength of T-cell responses, with some genotypes triggering stronger immune responses.

What role does the liver play in the immune response to HBV?

The liver serves as a tolerizing organ, which limits the strength of immune responses to HBV. It contains immune-suppressive cytokines and poor antigen-presenting cells, making it challenging for the immune system to mount an effective defense against the virus.

What is T-cell exhaustion, and how is it relevant to chronic HBV?

T-cell exhaustion refers to the reduced functionality of T-cells due to persistent antigen exposure and upregulation of inhibitory receptors. In chronic HBV, T-cells become exhausted over time, which impairs their ability to clear the virus.

How do B-cells function in chronic HBV infection?

B-cells in chronic HBV are less responsive, and although memory B-cells can be found in patients who have resolved the infection or been vaccinated, they are harder to detect in those with chronic HBV. Their precise role in the immune response to HBV remains unclear.

What is the role of NK cells in chronic HBV?

NK cells play an essential role in the innate immune response, but in chronic HBV, their functionality is reduced. They produce less interferon gamma, which can negatively regulate T-cell immunity and contribute to immune dysfunction.

How does chronic HBV affect the immune environment in the liver?

The liver in chronic HBV infection has a unique immune environment that is less responsive to viral infections. This includes the presence of immune-suppressive cytokines and a reduced ability of antigen-presenting cells to stimulate effective immune responses.

What are some of the challenges in developing therapeutic strategies for HBV?

Developing therapeutic strategies for HBV is challenging due to the immune exhaustion observed in chronic infection, as well as the complex immune environment of the liver. Additionally, there is limited understanding of the role of B-cells and other innate immune cells in HBV, which complicates the development of effective therapies.

What upcoming events related to HBV research does the speaker mention?

The speaker invites attendees to the Global Hepatitis Summit in Toronto, which will feature the latest research on HBV and liver disease. The speaker also promotes the fifth International HPV Cure Workshop, a focused event on early-stage drug development for HBV.