Adaptive immunity, chronic inflammation and the clock

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Adaptive immunity, chronic inflammation and the clock

Abstract

The adaptive arm of the immune system facilitates recognition of specific foreign pathogens and, via the action of T and B lymphocytes, induces a fine-tuned response to target the pathogen and develop immunological memory. The functionality of the adaptive immune system exhibits daily 24-h variation both in homeostatic processes (such as lymphocyte trafficking and development of T lymphocyte subsets) and in responses to challenge. Here, we discuss how the circadian clock exerts influence over the function of the adaptive immune system, considering the roles of cell intrinsic clockwork machinery and cell extrinsic rhythmic signals. Inappropriate or misguided actions of the adaptive immune system can lead to development of autoimmune diseases such as rheumatoid arthritis, ulcerative colitis and multiple sclerosis. Growing evidence indicates that disturbance of the circadian clock has negative impact on development and progression of these chronic inflammatory diseases and we examine current understanding of clock-immune interactions in the setting of these inflammatory conditions. A greater appreciation of circadian control of adaptive immunity will facilitate further understanding of mechanisms driving daily variation in disease states and drive improvements in the diagnosis and treatment of chronic inflammatory diseases.

https://link.springer.com/article/10.10 ... 22-00919-7

What cells are responsible for immune memory?
B lymphocytes are the cells of the immune system that make antibodies to invading pathogens like viruses. They form memory cells that remember the same pathogen for faster antibody production in future infections.

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Adaptive immune resistance: How cancer protects from immune attack

Adaptive immune resistance is a process where the cancer changes its phenotype in response to a cytotoxic or pro-inflammatory immune response, thereby evading it. This adaptive process is triggered by the specific recognition of cancer cells by T cells, which leads to the production of immune-activating cytokines. Cancers then hijack mechanisms developed to limit inflammatory and immune responses and protect themselves from the T cell attack. Inhibiting adaptive immune resistance is the mechanistic basis of responses to PD-1 or PD-L1 blocking antibodies, and may be of relevance for the development of other cancer immunotherapy strategies.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4560619/

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Introduction

The circadian clock is an internal timing mechanism which imprints daily rhythms on animal physiology. These oscillations in physiological processes such as sleep, feeding, metabolism and immunity allow animals to thrive in the 24-h environment generated by Earth rotating on its axis. Here, we review what is known about the rhythmic physiology of adaptive immune cells and discuss evidence for functional intrinsic clocks and rhythmic extrinsic signals directing this behaviour. We address bi-directional links between the clockwork machinery and the function of adaptive immune cells, both in health and disease. Recognising the daily rhythmicity of a number of chronic inflammatory diseases, we consider how circadian clocks contribute to these daily oscillations and ask how understanding circadian input into the adaptive immune system may benefit the diagnosis and treatment of inflammatory conditions.

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Adaptive immunity and the key cellular players

The immune system incorporates two functionally distinct, yet intertwining, arms of defence against pathogenic invasion or insult. The initial arm involves innate defence and includes maintaining barrier sites and non-specific killing of pathogens. Cells of the innate immune system recognise foreign bodies via their pathogen-associated molecular patterns (PAMPs), allowing an element of discrimination between self and non-self. Although crucial and effective, the first line of defence is not without limitations. The adaptive defence is far more fine-tuned, allowing specific recognition of foreign particles and the selective expansion of cells prepared to target specific pathogens and develop immunological memory. T and B lymphocytes are key component cells for adaptive immune responses with dendritic cells (DCs), which survey for foreign antigens, linking the innate and adaptive responses. Exogenous antigen is processed within DCs and displayed on their surface (via major histocompatibility complexes (MHC)). DCs then travel to lymph nodes where they interact with naïve T cells. Once in close proximity, the presented antigen joins with a corresponding T cell receptor (TCR) on the T cell surface; in the presence of a co-stimulatory signal, this triggers T cell activation and proliferation. If a B cell has encountered the same antigen, T cell-dependent B cell activation may occur (via CD40-CD40 ligand interaction) driving transformation of B cells to plasma cells, which secrete immunoglobulins.

What are the 3 types of antigens?
There are three types of antigens, classified based on where they are produced. Self-antigens, or autoantigens, are produced in the body's own cells; endogenous antigens are produced in intracellular bacteria or viruses; exogenous antigens are produced outside the body and are foreign to the immune system.