In a recent study published within the journal PNAS, a bunch of researchers in Israel quantitatively mapped the abundance, mass, and distribution of primary immune cells across human tissues using integrated biotechnological methods.
Immune System’s Cellular Network
The immune system’s intricate cellular network is significant for health, yet understanding its distribution stays difficult attributable to cellular diversity and past study limitations. Existing research, often narrow in focus and methodology, lacks comprehensive human-specific data, prompting debates on topics like essentially the most immunogenic organ. Further research is required to make clear immune cell distribution, reconcile study discrepancies, and deepen insights into immune functionality in humans.
Study: The overall mass, number, and distribution of immune cells within the human body. Image Credit: Created with the help of DALL·E 3
Mapping the Human Immune System
The current study thoroughly maps the human immune system, categorizing cells into lymphoid and myeloid groups, using a healthy young male as a reference for establishing baseline cell densities. The research is anchored in three methodologies: an in depth literature review, high-resolution multiplexed imaging, and novel methylation-based deconvolution. The review updates historical data to modern cell density estimates, considering unique tissue characteristics and using advanced methods like flow cytometry for relative abundance data. Tissues and organs are classified by anticipated immune cell presence, forming a scientific structure for evaluation.
Multiplexed imaging offers detailed tissue snapshots, identifying various immune cells with precision. This approach, analyzing quite a few molecular markers concurrently, presents an inclusive picture of immune populations. Meanwhile, methylation-based deconvolution deciphers the epigenetic footprints unique to every cell type, unraveling the proportions and absolute numbers of immune cells in tissues.
Findings on Immune Cell Density and Distribution
The current study uncovers detailed insights into the density and spread of immune cells in human tissues. The info, derived from a radical literature survey, denotes the density of varied cell types in tissues grouped by similar composition and roles. Lymphatic systems and bone marrow record the best densities, being primarily composed of immune cells, while epithelial organs maintain a significantly lower density.
The distribution of immune cells within the human body. Estimates of immune cell populations by cell type and tissue grouped by primary tissues and systems. The tissues are displayed via a chart of the human body. A waffle chart depicts the distribution of immune cells in each tissue, with each square representing a population of 109 cells. To facilitate the presentation, the populations were rounded to multiples of 109. The overall population of every tissue is shown with one significant digit. Throughout all of the figures, cell types are color-coded for ease of reference. GI = gastrointestinal tract. Other tissues and organs include the brain, heart, adipose tissue, skeletal muscles, kidneys, etc.
Distinct patterns emerge within the distribution of specific immune cells. Macrophages, T, and B cells vary greatly across tissues, while plasma cells and eosinophils are largely confined to the gastrointestinal tract. Intriguingly, adipose and skeletal muscle tissues, accounting for roughly 75% of the body’s cellular mass, house a mere 0.2% of the entire cell count, a fact ascribed to their larger cell size.
In a novel approach, the study melds tissue-specific immune cell densities with organ mass in a regular human model, approximating your complete count of immune cells in various tissues at around 1.8 × 1012. Most are situated within the bone marrow and lymphatic system, with diverse immune cell types dispersed in differing ratios across each organ system.
In-depth tissue evaluation reveals a heterogeneous immune cell makeup. The bone marrow is full of neutrophils, and the lymphatic system abounds with lymphocytes. Other tissues, equivalent to the gastrointestinal tract, skin, and lungs, host considerable mast cell and macrophage communities.
The lymphatic system is the first habitat for T cells, B cells, and dendritic cells, while the bone marrow harbors a wide range of other cells. Conversely, mast cells, NK cells, and macrophages are largely tissue-resident, not predominating in any specific system.
These estimates were validated using a methylation atlas-based deconvolution approach, confirming the literature-based findings, particularly for lymphocytes. Nonetheless, some discrepancies were noted, especially for granulocytes.
The study also ventured into uncharted territory by estimating the mass of those immune cells, a feat achieved by aggregating data on cell sizes and volumes. The overall immune cell mass within the body is estimated at 1.2 kg. The distribution by cell type reveals a major deviation from their distribution by number, primarily attributable to variations in cell sizes. As an example, macrophages account for a considerable portion of the entire immune cell mass attributable to their larger size.
Moreover, the research concludes these findings to other demographics, using a reference female and child. Interestingly, cell type and tissue distribution remain consistent across different sexes and ages, suggesting a standardized pattern in immune cell distribution throughout the human body.
Key Takeaways and Implications
To summarize, the study offered latest estimates on immune cell count, mass, and distribution in humans, difficult the idea that the majority reside within the gut; as a substitute, primary sites are bone marrow, lymph nodes, and spleen. It highlighted the gut’s role in antibody production and the liver’s immunological functions. Validation was achieved through multiple analyses, confirming the findings’ reliability. The research also considered variations attributable to sex, age, and health status, noting the immune system’s dynamic nature. Despite certain limitations and uncertainties, the study illuminates the complexity of immune cell distribution, underscoring the necessity for comprehensive data and advanced methodologies.