Every day, our bodies encounter millions of pathogens. In a single day, humans inhale about 12 million bacteria and viruses (1). In addition to mechanical (e.g. skin or tears) and chemical (e.g. low pH in stomach) barriers, our immune system protects us from potentially infectious pathogens.
The football tournament in our body
Human immune system has 2 main parts: adaptive and innate. The adaptive immunity is the “teachable” component and develops with us throughout our lives. Its response is slower but specifically targeted. Adaptive immunity is mainly highlighted due to the so-called immune memory. A process that allows the immune system to react faster if the same pathogen enters the body. The innate immunity is very fast, but not so specific (2). If we compare the functioning of immunity to football, the innate immune system recognises individual teams based on their jersey (i.e. it recognises whether a bacteria or virus is in the body) and the adaptive system recognises individual players (a particular virus or bacteria). Today, we will talk more about the mechanisms by which the innate immune system recognises the jerseys of the playing team.
Cells of the innate immune system
Cells of innate immunity include macrophages, granulocytes, and dendritic cells. Macrophages are the body’s cleaning ladies. They take part in the body’s repair processes and absorb “all the body’s junk”. Macrophages can also clean pathogenic microorganisms by ‘eating’ them in a process called phagocytosis. In addition, they produce molecules that promote inflammation, which bring other necessary cells to the site of infection. Granulocytes, as the name suggests, are cells that contain granules. The contents of the discharged granules are toxic substances that can alter the surface of the pathogen. These cells are especially important in the fight against parasites that are too large to be eaten by macrophages. Dendritic cells function as “tasters” in the body. They ingest material from their surroundings and monitor anything that is dangerous. But how do immune cells know if something is dangerous?
PRR and PAMPs/DAMPs
Just as we can tell a dog from a cat, innate immunity can tell a bacterium from a virus. You can also tell a cat immediately. It has a tail, pointy ears, and meows. Microorganisms have similar characteristics (probably without sound). Bacteria, for example, have a unique lipopolysaccharide that you can´t find in any human cell. Another example is viruses, with genetic information stored in a double-stranded RNA molecule that is not normally loose in the cell. These characteristics are called PAMPs (pathogen associated molecular patterns). Innate immunity can recognise them precisely because they are not normally found in our cells.
As you may have already read in the article about principles in immunology, in addition to PAMPs, immune cells recognise danger signals. These are the body’s own molecules that appear at the wrong time at the wrong place (e.g. a DNA molecule outside the cell). Such characteristic molecules are called DAMPs (damage associated molecular patterns). Cells of the immune system recognise PAMPs and DAMPs using receptors called PRRs (pattern recognition receptors) (2).
And what happens next?
Specialists for recognising almost all types of PAMPs and DAMPS are ‘tasters’ a.k.a. dendritic cells. When a cell recognises any PAMPs or DAMPs, it is activated. Such a cell starts to produce MHC glycoproteins on its surface in large quantities. These function almost identically to restaurant signs. On the surface of the MHC glycoproteins, the cell advertises what it has ingested or produced. The activated “tasters” travel to a lymph node where they show the signs to cells of the adaptive immune system called T-lymphocytes. If the T lymphocyte can read the sign, it will be activated. The number of T lymphocytes activated and targeted directly to the pathogen increases exponentially and after 4-5 days (3) their number is sufficient to fight the infection. The cells of adaptive and innate immunity then cooperate much more effectively and together eliminate the pathogen (summarised in (4,5).
What do you take from this?
The innate immune system is important for the initial recognition of the pathogen based on the ability of immunity to detect their common patterns, such as lipopolysaccharide in the membrane of bacteria. The innate immunity is necessary for activation of adaptive immune responses. Adaptive immunity recognises concrete pathogens and remembers them. If the same infection occurs, the adaptive immune system responds much more quickly.
Finally, I have a question for you to consider… (and a little hint for the next article of the month)
Has the innate immune system memory?
Feel free to share your insights in the comments section.
Have a great summer!
Lucka
Sources:
1. Prussin, A.J. et al. (2015). Environ Sci Technol Lett, 2, 84–88
2. Li, D. et al. (2021). Sig Transduct Target Ther, 6, 1–24
3. Lewis, D.A. et al. (2021). Frontiers in Cell and Developmental Biology, 9,
4. Charles A Janeway, J. et al. (2001). Immunobiology: The Immune System in Health and Disease. 5th edition,
5. Murphy, K. et al. Garland Science, New York London, 2016.
Figures created with Biorender.com. Schematic of antigen presentation by dendritic cells adapted from “How Dendritic Cells Become Competent to Stimulate T Cells” by Akiko Iwasaki (Biorender.com; 2023) available from: https://app.biorender.com/biorender-templates .
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