Lecture notes on Systemic Immunometabolism: Immunology of Human Disease (6BBBI308)
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Course
Immunology of Human Disease (6BBBI308)
Institution
Kings College London (KCL)
These detailed notes on systemic immunometabolism explore the intricate interactions between the immune system and metabolic processes. The document delves into key concepts, mechanisms, and the impact of metabolic states on immune function. Additionally, it includes recommended further reading to ...
Green info: Wang et al paper that is useful for understanding
Orange: Wang et al additional information not included in Dr Peruscha’s lecture
L1 Systemic Immunometabolism
• Immune system controls whole body energetics
• Glucose is the key molecule to fuel glycolysis (needed for immune cells)
• Low grade chronic inflammation is the underlying cause of diseases (not including surgery). E.g.
cancer, type 2 diabetes, obesity, metabolic syndrome
• Examples of metabolic tissues are liver, muscle and adipose tissue
Homeostatic SIM (normal situation between immune system and metabolism-
how they normally interact)
Favourable caloric environments: Homeostatic SIM
- Healthy person: there is food available which means we have a favourable caloric environment
and generally the control of the systemic metabolism is controlled by the brain (controls
homeostasis)
- What we do to food eaten (because we have an excess of carbon and ATP): Anabolism-
transform the carbons/nutrients into building blocks
- The energy is used for growth or reproduction
- This is called life history traits
Unfavourable caloric environment: Homeostatic SIM
• Two main ways maintenance programs are induced when there are unfavourable environments:
1. Catabolism (Dormancy program)
2. Anabolism (Defence program)
We also need basic energy so there will be an aspect of catabolism:
- Catabolism becomes apparent when there is no food
- There is an unfavourable caloric environment (low nutrient availability or other environmental
factors); two main ways environment can become unfavourable: absence of sufficient resources
(typically nutrients) or presence of factors with negative impact on fitness (e.g. predators,
pathogens and toxins)
- Catabolism is the breaking down of blocks to obtain energy which leads to dormancy
- Scarcity of resources induces a state of dormancy where non-essential functions, including
growth and reproduction, are temporarily suppressed
- Dormancy programs promote energy conservation, reply on catabolic metabolism and generally
associated with high resistance to environmental stressors (e.g. hibernating mammals)
- Happens in tissues such as adipose, muscle and liver – cuts of the building blocks from these are
using to get fatty acids and ATP circulating
- Unfavourable environments: lack of food, drop in temperature (e.g. animals that hibernate)
, - Anabolism and defence program: Occur at the expense of growth and reproduction (like
dormancy it inhibits the organism’s ability to grow and reproduce) but in contrast to dormancy,
they require energy and involve anabolic metabolism to support protective responses against
pathogens and adverse environmental conditions, all at the cost of growth and reproduction.
Adipose tissue example but can be applied to metabolic tissues in general
Lean adipose tissue --> food available --> (obese) white adipose tissue
- When adipose tissues grow in size (become obese), they secret leptin; leptins are cytokines
released by adipose tissue which signal to the brain to tell it that the body does not need to eat
any more as the adipocytes are already big
- Leptin: Secreted upon lipid accumulation, Increases insulin resistance, Inhibits lipogenesis,
Signals satiety
(Obese) white adipose tissue --> environmental stress (e.g. starvation, predation, injury, infection) -->
lean white adipose tissue
- Adiponectin secreted; signals for insulin resistance and an anti-inflammatory status
- Adiponectin: Secreted under low nutrient conditions Reduces insulin resistance Dormancy (anti-
inflammatory)
- Balance between leptin and adiponectin is important
Metabolic tissues (adipose, muscle and liver) are full of immune cells
- Immune cells have leptin receptors
Lean white adipose tissue: ANTI-INFLAMMATORY
• Has an immune composition of many different types of cells such as eosinophils, B cells (IgD+,
IgM+), Bregs, Tregs, Th2 and M2 (the cells infiltrate the adipose tissue)
• This is anti-inflammatory type of immunity
• These cells (above) such as Th2 secrete cytokines such as IL-10, IL-4 and IL-33 and the adipocyte
is able to understand these signals
• At the same time, the adipocyte will secrete adiponectin 9when we are in homeostasis) and this
signal will promote the macrophages to stay in M2
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