Immune system – the only cellular system, Day 2

When we think of the immune system, we picture a blood test: WBCs, lymphocyte percentages. Mechanistic immunology reminds us that 𝘪𝘮𝘮𝘶𝘯𝘪𝘵𝘺 𝘪𝘴 𝘯𝘰𝘵 𝘫𝘶𝘴𝘵 𝘣𝘭𝘰𝘰𝘥; it is a body-wide cellular network embedded in specialized organs and tissues. 

𝗣𝗿𝗶𝗺𝗮𝗿𝘆 𝗹𝘆𝗺𝗽𝗵𝗼𝗶𝗱 𝗼𝗿𝗴𝗮𝗻𝘀 (𝗯𝗼𝗻𝗲 𝗺𝗮𝗿𝗿𝗼𝘄, 𝘁𝗵𝘆𝗺𝘂𝘀) are where immune cells are generated. Bone marrow produces HSC. In the thymus, immature T cells undergo positive and negative selection – recognition of self-MHC but eliminating dangerous autoreactive clones [1]. Without it, adaptive immunity would collapse into autoimmunity.

𝗦𝗲𝗰𝗼𝗻𝗱𝗮𝗿𝘆 𝗹𝘆𝗺𝗽𝗵𝗼𝗶𝗱 𝗼𝗿𝗴𝗮𝗻𝘀 (𝗹𝘆𝗺𝗽𝗵 𝗻𝗼𝗱𝗲𝘀, 𝘀𝗽𝗹𝗲𝗲𝗻, 𝗣𝗲𝘆𝗲𝗿’𝘀 𝗽𝗮𝘁𝗰𝗵𝗲𝘀) are command centers where adaptive responses are orchestrated. Antigen-presenting cells bring signals from peripheral tissues, where naïve lymphocytes are activated, clonally expanded, and differentiated into effectors. The spleen, is indispensable for filtering blood-borne antigens and generating systemic antibody responses [2]. 

Immune system is different when compared to any other body organ-system. Cardiovascular system – the heart and blood vessels. The immune system, in contrast, is 𝘥𝘦𝘧𝘪𝘯𝘦𝘥 𝘣𝘺 𝘤𝘦𝘭𝘭𝘴 𝘪𝘯 𝘮𝘰𝘵𝘪𝘰𝘯 – T and B lymphocytes, macrophages, dendritic cells – circulating through blood, lymph, and tissues. 

This is why basic research goes beyond blood draws. In 𝘮𝘰𝘶𝘴𝘦 𝘪𝘮𝘮𝘶𝘯𝘰𝘭𝘰𝘨𝘺, 𝘸𝘦 𝘳𝘰𝘶𝘵𝘪𝘯𝘦𝘭𝘺 𝘪𝘴𝘰𝘭𝘢𝘵𝘦 𝘴𝘱𝘭𝘦𝘯𝘰𝘤𝘺𝘵𝘦𝘴 𝘢𝘯𝘥 𝘵𝘩𝘺𝘮𝘰𝘤𝘺𝘵𝘦𝘴 𝘵𝘰 𝘤𝘢𝘱𝘵𝘶𝘳𝘦 𝘵𝘩𝘦 𝘪𝘮𝘮𝘶𝘯𝘦 𝘳𝘦𝘴𝘱𝘰𝘯𝘴𝘦𝘴. Blood is the visible tip of a deeper network. 

Here’s 𝘁𝗵𝗲 𝘄𝗼𝗻𝗱𝗲𝗿: 

Some individuals 𝗹𝗶𝘃𝗲 𝘄𝗶𝘁𝗵 𝗰𝗵𝗿𝗼𝗻𝗶𝗰𝗮𝗹𝗹𝘆 𝗹𝗼𝘄 𝗹𝘆𝗺𝗽𝗵𝗼𝗰𝘆𝘁𝗲 𝗰𝗼𝘂𝗻𝘁𝘀, 𝘆𝗲𝘁 𝗱𝗼 𝗻𝗼𝘁 𝗲𝘅𝗽𝗲𝗿𝗶𝗲𝗻𝗰𝗲 𝗵𝗶𝗴𝗵 𝗶𝗻𝗳𝗲𝗰𝘁𝗶𝗼𝗻 𝗿𝗮𝘁𝗲𝘀, 𝗰𝗵𝗿𝗼𝗻𝗶𝗰 𝗶𝗻𝗳𝗹𝗮𝗺𝗺𝗮𝘁𝗶𝗼𝗻, 𝗼𝗿 𝗮𝘂𝘁𝗼𝗶𝗺𝗺𝘂𝗻𝗶𝘁𝘆. How can that be? 

This paradox highlights that blood counts are not the ideal representative of human health state for immune competence. This is why hardly any blood test is the wonder diagnostic product (e.g. infamous Theranos blood kit). 

I𝘮𝘮𝘶𝘯𝘪𝘵𝘺 𝘪𝘴 𝘯𝘰𝘵 𝘢 𝘯𝘶𝘮𝘣𝘦𝘳 𝘪𝘯 𝘢 𝘣𝘭𝘰𝘰𝘥 𝘵𝘦𝘴𝘵, 𝘣𝘶𝘵 𝘢 𝘸𝘩𝘰𝘭𝘦 𝘣𝘰𝘥𝘺 𝘤𝘦𝘭𝘭𝘶𝘭𝘢𝘳 𝘴𝘺𝘴𝘵𝘦𝘮 𝘴𝘶𝘴𝘵𝘢𝘪𝘯𝘦𝘥 𝘣𝘺 𝘴𝘱𝘦𝘤𝘪𝘢𝘭𝘪𝘻𝘦𝘥 𝘰𝘳𝘨𝘢𝘯𝘴 𝘢𝘯𝘥 𝘥𝘺𝘯𝘢𝘮𝘪𝘤 𝘤𝘪𝘳𝘤𝘶𝘭𝘢𝘵𝘪𝘰𝘯. [3,4] 

Stay tuned for 𝗗𝗮𝘆 𝟯: 𝗜𝗻𝗻𝗮𝘁𝗲 𝘃𝘀. 𝗮𝗱𝗮𝗽𝘁𝗶𝘃𝗲 𝗶𝗺𝗺𝘂𝗻𝗶𝘁𝘆 

 References 

1. https://pubmed.ncbi.nlm.nih.gov/12414722/ 

2. https://www.cell.com/action/showPdf?pii=S1074-7613%2813%2900470-6 

3. Janeway’s Immunobiology, 9th Ed. 

4. Abbas & Lichtman, Cellular and Molecular Immunology, 10th Ed. 

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