Flame Ignites

Forest fires help our ecosystem by clearing out the aging dead vegetation and providing new nutrients back in the soil. Our bodies are the same, we are built to tolerate certain amounts of flames and fires here and there but when they get out of control or smolder for long periods of time, the result is not good for us. Inflammation is a very normal reaction to an event that happens to us and when well-regulated, helps us recover and get well.

To understand inflammation, you must have a basic understanding of our immune system as follows:

Immune System

Innate Immune System

• Rapid – usually within minutes

• Not Specific Receptors – general and broad

• Cells involved to name a few

  • Neutrophils

  • Basophils

  • Eosinophils

  • Dendritic cells

  • Macrophages

  • Natural Killer Cells

• Response Mediation – Damaged cells are recognized by cellular pattern recognition receptors (PRRs) such as toll-like receptors after signals alert them called pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs).

Adaptive Immune System

• Activates within days

• Specific antigen receptors

• Cells involved

  • Lymphocytes

    • B cells

    • T cells

      • CD4

      • CD8

• Response Mediation - antigen presenting cells (APC) will activate Lymphocytes.

Cytokines

It is hard to discuss inflammation without reviewing the term cytokines. Cytokines are small proteins that regulate the immune response. The term proinflammatory sounds negative to most people but that is not the case. When injured initially, we want to ignite the immune response to heal, and this is completed by turning on inflammation. Pro-inflammatory cytokines are often released by many immune cells including neutrophils, macrophages, T cells and B cells. Examples of cytokines are Tumor necrosis factor-alpha (TNFα), Interleukins (IL) such as IL1, IL6,IL8,IL10.

Examples of Immune System in Action

Common everyday events such as a minor cut on the skin

The damaged skin at the cut will signal damage (DAMPs) that is recognized by PRR’s to activate the innate immune response. The proinflammatory response includes many signaling pathways with the goal to heal the cut. The production of cytokines (small proteins that communicate with immune cells) that encourage neutrophils and macrophages to the wound site are recruited to help. This inflammation may result in hot, red, pus looking cells for a few days. Once neutrophils have done their job, they will undergo apoptosis (cell death), Macrophages will consume the neutrophils indicating that the inflammation has resolved. This is a healthy immune response.

What happens if the neutrophiles over-produce and do not undergo apoptosis? If that happens then there will be additional cytokines excreted, and the inflammatory process becomes prolonged, and the wound becomes a chronic problem. If this initial innate immune response fails to heal the wound, then the adaptive immune response kicks in when cytokines help release antigen presenting cells (APCs) who then activate lymphocytes. Activated APCs will travel to the lymph nodes where they introduce the antigen to a T cell. Activated T and B cells will begin to clone and expand allowing B cells to produce antibodies to help kill the pathogen and the activated CD8+ and CD4+ cells will release more proinflammatory cytokines. Once they have done their job clearing out the infection or pathogen, these lymphocytes will die with a few exceptions who remain alive with a memory to fight the same pathogen faster in the future.

Key Summary Points:

1. Inflammation is a natural defense that allows our bodies to heal.

2. Innate and Adaptive Immunity recruit a number of immune cells to fight damaged cells and when working properly allows our body to heal and return to baseline.

3. T-cells are so smart they remember the pathogen and help our system be efficient at putting out the flame if it ignites again in the future.

References:

Carty SA. Immunology 101: fundamental immunology for the practicing hematologist. Hematology Am Soc Hematol Educ Program. 2021 Dec 10;2021(1):281-286. doi: 10.1182/hematology.2021000260. PMID: 34889423; PMCID: PMC8791153.

Cioce A, Cavani A, Cattani C, Scopelliti F. Role of the Skin Immune System in Wound Healing. Cells. 2024 Apr 4;13(7):624. doi: 10.3390/cells13070624. PMID: 38607063; PMCID: PMC11011555.

Kany S, Vollrath JT, Relja B. Cytokines in Inflammatory Disease. Int J Mol Sci. 2019 Nov 28;20(23):6008. doi: 10.3390/ijms20236008. PMID: 31795299; PMCID: PMC6929211.

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