Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 3 complete abstracts (581 words), 9 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
The body's defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Immune Systems; System, Immune; Systems, Immune.
Where it fits in the MeSH classification
- Broader topics
- Hemic and Immune Systems
- Narrower topics
- Antibody-Producing Cells; Antigen-Presenting Cells; Bone Marrow; Enterochromaffin Cells; Immunological Synapses; Leukocytes; Lymphatic System; Mast Cells; Mononuclear Phagocyte System; Phagocytes
Research landscape
PubMed indexes 1,376,007 records tagged with the MeSH heading “Immune System” (counts retrieved 2026-10-31). 223,091 of them (16.2%) were published from 2020 onward, and the busiest period so far is through 1999 with 570,627 records.
Reviews account for 140,503 records (10.2%) and meta-analyses for 2,898. Randomized controlled trials number 11,954 (0.9%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 570,627 |
| 2000-2009 | 263,350 |
| 2010-2019 | 318,939 |
| 2020 onward | 223,091 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 140,503 | 10.2% |
| Meta-analyses | 2,898 | 0.2% |
| Randomized controlled trials | 11,954 | 0.9% |
Method: PubMed query "Immune System"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in anatomy and physiology
Anatomy describes how body structures are built and physiology describes how they normally work, so most findings here are descriptive or mechanistic rather than evidence about treatment. Much of what is known comes from dissection, imaging, tissue studies and experiments in animals, and measurements in healthy volunteers can differ from those in people with disease or at different ages. Normal ranges vary between individuals and populations. Check whether a result was measured in people or in another species, the age and health of the participants, and the method used.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Artery tertiary lymphoid organs encode a pathogenic high-affinity autoantibody-autoantigen pair in atherosclerosis | 2026 | Research article Design not recorded in structured metadata | 1 | cc by PMID 42706439 · DOI · PMC13561875 |
| A macrophage-targeted TIMD4 Peptide-Nanoparticle attenuates colitis symptoms and monocyte recruitment in a mouse model | 2026 | Research article Design not recorded in structured metadata | 0 | cc by PMID 42905753 · DOI · PMC13686490 |
| Syntaxin11 deficiency inhibits CRAC channel priming to suppress cytotoxicity and gene expression in T lymphocytes independent of membrane trafficking | 2026 | Research article Design not recorded in structured metadata | 0 | cc by PMID 42895167 · DOI · PMC13679927 |
Artery tertiary lymphoid organs encode a pathogenic high-affinity autoantibody-autoantigen pair in atherosclerosis [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Artery tertiary lymphoid organs (ATLOs) emerge in atherosclerosis, which is a chronic inflammatory artery disease with an autoimmune component.
- Closing excerpt
- We suggest that ATLOs harbor a dysregulated immune tolerance environment permissive for autoreactive B cells that express pathogenic autoantibodies promoting atherosclerosis.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (163 words)
Artery tertiary lymphoid organs (ATLOs) emerge in atherosclerosis, which is a chronic inflammatory artery disease with an autoimmune component. However, whether disease-relevant autoimmune B cells emerge in ATLOs remains unknown. In this study, we isolate germinal center (GC) B cells from ATLOs and lymph nodes from healthy and atherosclerosis-burdened mice, expression clone 60 autoantibodies and screen them for arterial wall reactivity. ATLO GC B cell-derived autoantibodies skew to atherosclerosis-relevant autoantigens versus their counterparts in lymph nodes of both genotypes. One ATLO GC B cell-derived autoantibody (termed A6) binds to histone 2B (H2B) with high affinity. Both vaccination with H2B and adoptive transfer of A6 accelerate atherosclerosis, revealing a pathogenic autoantibody-autoantigen pair. Mechanistically, ATLOs specifically show both distorted B cell activation and immune tolerance checkpoint-regulating gene expression profiles. In a human cohort, circulating anti-H2B antibody titers positively correlate with aortic calcification in humans. We suggest that ATLOs harbor a dysregulated immune tolerance environment permissive for autoreactive B cells that express pathogenic autoantibodies promoting atherosclerosis.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42706439 · DOI · PMC13561875
A macrophage-targeted TIMD4 Peptide-Nanoparticle attenuates colitis symptoms and monocyte recruitment in a mouse model [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Macrophages play a pivotal role in the pathogenesis of inflammatory bowel disease (IBD).
- Closing excerpt
- These findings support further preclinical evaluation of TIMD4-derived peptide delivery as a potential therapeutic approach for intestinal inflammation.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (227 words)
Macrophages play a pivotal role in the pathogenesis of inflammatory bowel disease (IBD). T-cell immunoglobulin and mucin domain-containing molecule 4 (TIMD4) is involved in the regulation of tissue-resident macrophages. TIMD4 expression is elevated in colonic tissues from patients with ulcerative colitis (UC) and mice with dextran sulfate sodium (DSS)-induced colitis, but its role in IBD pathogenesis remains unclear. In this study, we found that Timd4 deficiency aggravated DSS-induced colitis, accompanied by increased infiltration of monocytes into the colonic tissues. Treatment with a CCR2 antagonist attenuated colonic inflammation and reduced monocyte infiltration into colonic tissues in Timd4 KO mice. Mechanistically, in vitro studies revealed that TIMD4 stabilized the LKB1-STRAD-MO25 complex via its intracellular domain, thereby activating the AMPK pathway and suppressing NF-κB-dependent chemokine production in macrophages. Based on these findings, we designed a TIMD4-derived peptide and developed a macrophage-targeted nanoparticle system (T4(365-378)‑NPs). Treatment with T4(365-378)-NPs reduced P65 phosphorylation and attenuated DSS-induced colitis in mice. Treatment with either T4(365-378)-NPs or the CCR2 antagonist attenuated DSS-induced colitis, and no statistically significant differences in the assessed outcomes were detected between the two groups. Administration of T4(365-378)-NPs before DSS exposure also attenuated subsequent colitis. Furthermore, combining the T4(365-378)‑NPs with anti-α4β7 or anti-TNF-α antibodies produced greater improvements than either monotherapy in the DSS-induced colitis model. These findings support further preclinical evaluation of TIMD4-derived peptide delivery as a potential therapeutic approach for intestinal inflammation.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42905753 · DOI · PMC13686490
Syntaxin11 deficiency inhibits CRAC channel priming to suppress cytotoxicity and gene expression in T lymphocytes independent of membrane trafficking [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Mutations in Syntaxin11 (STX11), a Q-SNARE, result in a fatal immune disorder known as familial hemophagocytic lymphohistiocytosis 4 (FHLH4) in human patients.
- Closing excerpt
- Priming of ion channel pore subunits is, therefore, a primary function of specific SNAREs which may have preceded their role in membrane trafficking and vesicle fusion.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (191 words)
Mutations in Syntaxin11 (STX11), a Q-SNARE, result in a fatal immune disorder known as familial hemophagocytic lymphohistiocytosis 4 (FHLH4) in human patients. A key diagnostic feature of FHLH4 is defective T and natural killer cell cytotoxicity. Here, we show that STX11 directly binds and regulates Orai1, the pore-forming subunit of calcium release-activated calcium (CRAC) channels. CRAC channels enable store-operated calcium entry (SOCE) from the extracellular space and are crucial for granule exocytosis and nuclear factor of activated T cells (NFAT)-dependent gene expression in activated lymphocytes. STX11 depletion strongly inhibited SOCE, CRAC currents, NFAT activation, interleukin-2 gene expression, and degranulation in FHLH4 patient T lymphocytes and cell lines without affecting membrane trafficking. Remarkably, defects of cytolytic granule exocytosis, as well as interleukin-2 expression, could be reversed by ionomycin in patient T lymphocytes, and a constitutively active, H134S, mutant of Orai1 rescued calcium entry in STX11-depleted cells. Further analyses showed that STX11 'primes' Orai1 for optimal on-site multimeric assembly, which was Stim independent but required for gating. Priming of ion channel pore subunits is, therefore, a primary function of specific SNAREs which may have preceded their role in membrane trafficking and vesicle fusion.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42895167 · DOI · PMC13679927
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Single-cell meta-analyses reveal responses of tumor-reactive CXCL13+ T cells to immune-checkpoint blockade [4]
- Research article Prognostic value of inflammatory markers NLR, PLR, and LMR in gastric cancer patients treated with immune checkpoint inhibitors: a meta-analysis and systematic review [5]
- Research article Accuracy of spleen stiffness measurement for the diagnosis of clinically significant portal hypertension in patients with compensated advanced chronic liver disease: a systematic review and individual patient data meta-analysis [6]
- Research article A meta-analysis of immune-cell fractions at high resolution reveals novel associations with common phenotypes and health outcomes [7]
- Research article Neutrophil to lymphocyte ratio (NLR) prognostic effects on heart failure; a systematic review and meta-analysis [8]
- Research article The association between immune cells and breast cancer: insights from Mendelian randomization and meta-analysis [9]
References
- Zhang C, Zhang X, Ran Y, Wang Z, Li L, Wang S, et al.. Artery tertiary lymphoid organs encode a pathogenic high-affinity autoantibody-autoantigen pair in atherosclerosis. . 2026. PMID 42706439 · DOI · PMC13561875
- Liu H, Wang Y, Yu R, Liu K, Zheng D, Wang B, et al.. A macrophage-targeted TIMD4 Peptide-Nanoparticle attenuates colitis symptoms and monocyte recruitment in a mouse model. . 2026. PMID 42905753 · DOI · PMC13686490
- Datta S, Gupta A, Jagetiya KM, Bera R, Tiwari VR, Yamashita M, et al.. Syntaxin11 deficiency inhibits CRAC channel priming to suppress cytotoxicity and gene expression in T lymphocytes independent of membrane trafficking. . 2026. PMID 42895167 · DOI · PMC13679927
- Liu B, Zhang Y, Wang D, Hu X, Zhang Z. Single-cell meta-analyses reveal responses of tumor-reactive CXCL13+ T cells to immune-checkpoint blockade. Nat Cancer. 2022. PMID 36138134 · DOI
- Tan S, Zheng Q, Zhang W, Zhou M, Xia C, Feng W. Prognostic value of inflammatory markers NLR, PLR, and LMR in gastric cancer patients treated with immune checkpoint inhibitors: a meta-analysis and systematic review. Front Immunol. 2024. PMID 39050856 · DOI · PMC11266030
- Dajti E, Ravaioli F, Zykus R, Rautou PE, Elkrief L, Grgurevic I, et al.. Accuracy of spleen stiffness measurement for the diagnosis of clinically significant portal hypertension in patients with compensated advanced chronic liver disease: a systematic review and individual patient data meta-analysis. Lancet Gastroenterol Hepatol. 2023. PMID 37478880 · DOI
- Luo Q, Dwaraka VB, Chen Q, Tong H, Zhu T, Seale K, et al.. A meta-analysis of immune-cell fractions at high resolution reveals novel associations with common phenotypes and health outcomes. Genome Med. 2023. PMID 37525279 · DOI · PMC10388560
- Vakhshoori M, Nemati S, Sabouhi S, Yavari B, Shakarami M, Bondariyan N, et al.. Neutrophil to lymphocyte ratio (NLR) prognostic effects on heart failure; a systematic review and meta-analysis. BMC Cardiovasc Disord. 2023. PMID 37957565 · DOI · PMC10644447
- Xu W, Zhang T, Zhu Z, Yang Y. The association between immune cells and breast cancer: insights from Mendelian randomization and meta-analysis. Int J Surg. 2025. PMID 38935111 · DOI · PMC11745723
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.