Maternal-fetal microchimerism is a fascinating phenomenon in which maternal cells migrate to the tissues of the offspring during both pregnancy and breastfeeding. These cells primarily consist of leukocytes and stem cells. Remarkably, these maternal cells possess functional potential in the offspring and play a significant role in shaping their immune system development. T lymphocytes, a cell population mainly found in various tissues of the offspring, have been identified as the major cell type derived from maternal microchimerism. These T lymphocytes not only exert effector functions but also influence the development of the offspring's T lymphocytes in the thymus and the maturation of B lymphocytes in the lymph nodes. Furthermore, the migration of maternal leukocytes also facilitates the transfer of immune memory across generations. Maternal microchimerism has also been observed to address immunodeficiencies in the offspring. This review article focuses on investigating the impact of maternal cells transported within maternal microchimerism on the immune system development of the offspring, as well as elucidating the effector functions of maternal cells that migrate through the placenta and breast milk to reach the offspring.
- MeSH
- chimérismus * MeSH
- imunologická paměť * MeSH
- lidé MeSH
- maternofetální výměna látek * imunologie MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: SARS-CoV-2, which causes COVID-19, has killed more than 7 million people worldwide. Understanding the development of postinfectious and postvaccination immune responses is necessary for effective treatment and the introduction of appropriate antipandemic measures. OBJECTIVES: We analysed humoral and cell-mediated anti-SARS-CoV-2 immune responses to spike (S), nucleocapsid (N), membrane (M), and open reading frame (O) proteins in individuals collected up to 1.5 years after COVID-19 onset and evaluated immune memory. METHODS: Peripheral blood mononuclear cells and serum were collected from patients after COVID-19. Sampling was performed in two rounds: 3-6 months after infection and after another year. Most of the patients were vaccinated between samplings. SARS-CoV-2-seronegative donors served as controls. ELISpot assays were used to detect SARS-CoV-2-specific T and B cells using peptide pools (S, NMO) or recombinant proteins (rS, rN), respectively. A CEF peptide pool consisting of selected viral epitopes was applied to assess the antiviral T-cell response. SARS-CoV-2-specific antibodies were detected via ELISA and a surrogate virus neutralisation assay. RESULTS: We confirmed that SARS-CoV-2 infection induces the establishment of long-term memory IgG+ B cells and memory T cells. We also found that vaccination enhanced the levels of anti-S memory B and T cells. Multivariate comparison also revealed the benefit of repeated vaccination. Interestingly, the T-cell response to CEF was lower in patients than in controls. CONCLUSION: This study supports the importance of repeated vaccination for enhancing immunity and suggests a possible long-term perturbation of the overall antiviral immune response caused by SARS-CoV-2 infection.
- MeSH
- B-lymfocyty imunologie MeSH
- buněčná imunita imunologie MeSH
- COVID-19 * imunologie MeSH
- dospělí MeSH
- ELISPOT MeSH
- glykoprotein S, koronavirus imunologie MeSH
- humorální imunita MeSH
- imunologická paměť MeSH
- leukocyty mononukleární imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- protilátky virové * krev imunologie MeSH
- SARS-CoV-2 * imunologie MeSH
- senioři MeSH
- T-lymfocyty imunologie MeSH
- vakcíny proti COVID-19 imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Natural killer (NK) cells play a pivotal role in the immune response against viral infections, including SARS-CoV-2. However, our understanding of memory NK cell responses in the context of SARS-CoV-2 remains limited. To address this, we investigated the memory-like response of NK cells to SARS-CoV-2 peptides, presented by autologous cells. Blood samples from 45 donors underwent analysis for SARS-CoV-2 IgG antibodies, categorizing them into four groups based on the antibody kind and level. NK cells from SARS-CoV-2-experienced donors demonstrated enhanced degranulation and activation levels, IFNγ production and proliferative potential in response to SARS-CoV-2 peptides. Investigation of highly proliferating NK cells demonstrated the formation of distinct clusters depending on the SARS-CoV-2 peptide supplementation and the donor group. RNA sequencing revealed differential gene expression patterns, highlighting metabolism, protein transport, and immune response genes. Notably, KIR2DS4 expression correlated with enhanced IFNγ production, degranulation and proliferation levels, suggesting a role in SARS-CoV-2 recognition. Collectively, these findings provide detailed insights into antigen-specific NK cell responses to SARS-CoV-2 peptides, indicating potential mechanisms underlying NK cell activation in antiviral immunity.
- MeSH
- aktivace lymfocytů MeSH
- buňky NK * imunologie MeSH
- COVID-19 * imunologie MeSH
- degranulace buněk MeSH
- dospělí MeSH
- imunoglobulin G MeSH
- imunologická paměť MeSH
- interferon gama * imunologie metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- protilátky virové krev imunologie MeSH
- receptory KIR genetika metabolismus MeSH
- SARS-CoV-2 * imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Autologous tumor cell-based vaccines (ATVs) aim to prevent and treat tumor metastasis by activating patient-specific tumor antigens to induce immune memory. However, their clinical efficacy is limited. Mannan-BAM (MB), a pathogen-associated molecular pattern (PAMP), can coordinate an innate immune response that recognizes and eliminates mannan-BAM-labeled tumor cells. TLR agonists and anti-CD40 antibodies (TA) can enhance the immune response by activating antigen-presenting cells (APCs) to present tumor antigens to the adaptive immune system. In this study, we investigated the efficacy and mechanism of action of rWTC-MBTA, an autologous whole tumor cell vaccine consisting of irradiated tumor cells (rWTC) pulsed with mannan-BAM, TLR agonists, and anti-CD40 antibody (MBTA), in preventing tumor metastasis in multiple animal models. METHODS: The efficacy of the rWTC-MBTA vaccine was evaluated in mice using breast (4T1) and melanoma (B16-F10) tumor models via subcutaneous and intravenous injection of tumor cells to induce metastasis. The vaccine's effect was also assessed in a postoperative breast tumor model (4T1) and tested in autologous and allogeneic syngeneic breast tumor models (4T1 and EMT6). Mechanistic investigations included immunohistochemistry, immunophenotyping analysis, ELISA, tumor-specific cytotoxicity testing, and T-cell depletion experiments. Biochemistry testing and histopathology of major tissues in vaccinated mice were also evaluated for potential systemic toxicity of the vaccine. RESULTS: The rWTC-MBTA vaccine effectively prevented metastasis and inhibited tumor growth in breast tumor and melanoma metastatic animal models. It also prevented tumor metastasis and prolonged survival in the postoperative breast tumor animal model. Cross-vaccination experiments revealed that the rWTC-MBTA vaccine prevented autologous tumor growth, but not allogeneic tumor growth. Mechanistic data demonstrated that the vaccine increased the percentage of antigen-presenting cells, induced effector and central memory cells, and enhanced CD4+ and CD8+ T-cell responses. T-cells obtained from mice that were vaccinated displayed tumor-specific cytotoxicity, as shown by enhanced tumor cell killing in co-culture experiments, accompanied by increased levels of Granzyme B, TNF-α, IFN-γ, and CD107a in T-cells. T-cell depletion experiments showed that the vaccine's antitumor efficacy depended on T-cells, especially CD4+ T-cells. Biochemistry testing and histopathology of major tissues in vaccinated mice revealed negligible systemic toxicity of the vaccine. CONCLUSION: The rWTC-MBTA vaccine demonstrated efficacy in multiple animal models through T-cell mediated cytotoxicity and has potential as a therapeutic option for preventing and treating tumor metastasis with minimal systemic toxicity.
- MeSH
- antigeny CD40 MeSH
- antigeny nádorové MeSH
- imunologická paměť MeSH
- lidé MeSH
- mannany MeSH
- melanom * MeSH
- myši MeSH
- nádory prsu * terapie MeSH
- protinádorové vakcíny * terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Antigen-induced memory T cells undergo counterintuitive activation in an antigen-independent manner, which is called bystander response. Although it is well documented that memory CD8+ T cells produce IFNγ and upregulate the cytotoxic program upon the stimulation with inflammatory cytokines, there is only rare evidence that this provides an actual protection against pathogens in immunocompetent individuals. One of the reasons might be numerous antigen-inexperienced memory-like T cells that are also capable of the bystander response. Little is known about the bystander protection of memory and memory-like T cells and their redundancies with innate-like lymphocytes in humans because of the interspecies differences and the lack of controlled experiments. However, it has been proposed that IL-15/NKG2D-driven bystander activation of memory T cells drives protection or immunopathology in particular human diseases.
- MeSH
- aktivace lymfocytů * MeSH
- antigeny MeSH
- CD8-pozitivní T-lymfocyty * MeSH
- cytokiny MeSH
- imunologická paměť MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Recent studies emphasize the importance of low-density lipoprotein cholesterol (LDL-C) in altering the hematopoietic cell compartment of bone marrow and of high-density lipoprotein cholesterol (HDL-C) in inhibiting metabolic endotoxemia-induced inflammation. The data suggest that these lipoproteins may exert their inflammatory or anti-inflammatory roles by modulating innate immune memory. Targeting specific LDL-C and HDL-C subfractions could therefore potentially reduce the residual risk in hepatic and cardiometabolic disease.
- MeSH
- HDL-cholesterol * MeSH
- imunologická paměť * MeSH
- LDL-cholesterol * MeSH
- lidé MeSH
- přirozená imunita * MeSH
- zánět MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Článek shrnuje historii poznávání vztahu výživy a imunity. Myšlenka podpory zdraví vhodnou stravou byla známa již starověkým lékařům, což dokumentuje Hippokratův (460–337 př. n. l.) citát „Když nevíš nic o stravě člověka, jak můžeš porozumět jeho nemoci.“ Často se ale na tuto mnohokrát ověřenou zkušenost na dlouhá desetiletí pozapomnělo, jak to už v dějinách lidského poznávání bývá, a zvláště pak v historii medicíny. Strava nemá jen význam výživový, ale má také přímý vliv na imunitu. V této souvislosti je si třeba uvědomit, že každá strava obsahuje antigeny, které přímo indukují imunologickou reakci v našem největším imunitním orgánu, lymfoidní tkání těsně nasedající na střevo (GALT). Každá imunitní reakce je vždy provázena vznikem imunologické paměti, a to jak imunity specifické (adaptivní), tak také, jak bylo nedávno prokázáno, i imunity nespecifické (přirozené), která je označována jako „vyškolená imunita.“ Přijímání potravy ve své podstatě znamená tedy neustále probíhající vakcinaci, stále se opakující indukci imunologických pamětí obou typů imunity, tzn. jak specifické (adaptivní), tak nespecifické (vyškolené).
The article summarizes the history of discovery of the relationship between nutrition and immunity. The idea of promoting good health through a right diet was already known to ancient physicians, as evidenced by Hippocrates' (460–337 BC) quote, "If you know nothing about a person's diet, how can you understand his illnesses." Diet not only has a nutritional meaning, but also has a direct effect on immunity. In this context, it is important to realize that every diet contains antigens that directly induce an immune response in our largest immune organ, the intestinal lymphoid tissue (GALT), which is always accompanied by the development of immunological memory, both immune specific (adaptive), as has recently been shown, non-specific immunity, which is referred to as "trained immunity". However, this time-tested experience has often been forgotten for many decades, as is the case in the history of human cognition, and especially in the history of medicine. Diet not only has a nutritional significance, but also it has a direct effect on immune status. In this context, it is important to realize that every diet contains antigens that directly induce an immune response in our largest immune organ, the intestinal lymphoid tissue (GALT), which is always accompanied by the development of immunological memory, both specific (adaptive) immunity, and as it has recently been shown, non-specific (natural) immunity, which is referred to as "trained immunity". In essence, food intake therefore means ongoing vaccination, a constantly recurring induction of immunological memories of both types, the specific (adaptive), and the non-specific (trained).
- MeSH
- fyziologie výživy * MeSH
- imunita * MeSH
- imunologická paměť MeSH
- lidé MeSH
- primární prevence MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Článek je připomínkou, že vedle klasických hygienických protiepidemických opatření existuje možnost prevence sdělných (nakažlivých, infekčních) nemocí, ale i nesdělných, chronických chorob, účelně zaměřenými výživovými programy. Již od starověku, kdy příčiny ani podstata nemocí nebyly známy (takže nemohly být k dispozici ani přesně směrované léky, natož antibiotika), byla jedinou možností, jak předcházet a léčit nemoci, úprava výživy. Nutriční podpora zdraví se sice mnohokrát osvědčila, ale jak je pro historii medicíny typické, občas se na to zapomínalo. Již Hippokrates (460-377 př. n. l.) si uvědomoval význam výživy pro zdraví, když připomínal: "Když nevíš nic o stravě člověka, jak můžeš porozumět jeho nemoci?". Autoři se zde pokusili poukázat na význam nutrice, která vždy obsahuje antigeny přímo indukující imunologickou paměť v našem největším orgánu imunity, lymfoidní tkáni těsně nasedající na střevo (GALT), a to jak imunity specifické (adaptivní), tak také, jak bylo nedávno prokázáno, i imunity nespecifické (přirozené). Ve své podstatě znamená tedy přijímání potravy vedle její výživové hodnoty také neustále probíhající vakcinaci.
The article is a reminder that in addition to classic anti-epidemic measures there is a possibility of prevention of communicable (infectious) diseases (but also of non-communicable chronic diseases) that are specifically targetted by nutrition programs. Since ancient times, when the causes and nature of diseases were unknown (so even precisely targetted drugs, let alone antibiotics, were unavailable), the only way to prevent and treat diseases was to change nutrition. Although nutritional health promotion has proven itself many times over it has, as typical in the history of medicine, sometimes been forgotten. Hippocrates (460-377 BC) was aware of the importance of nutrition for health when he wrote "If you know nothing about a person's diet, how can you understand his illness?" The authors have tried to highlight the importance of nutrition which always contains antigens that directly induce immunological memory in our largest organ of immunity, the intestinal lymphoid tissue (GALT), both specific (adaptive) immunity and, as has recently been shown, non-specific (natural) immunity. In essence, food intake is a process of ongoing vaccination along with its nutritional value.
- MeSH
- galaktosemie MeSH
- imunita genetika MeSH
- imunologická paměť MeSH
- infekční nemoci * dějiny dietoterapie MeSH
- lidé MeSH
- primární prevence MeSH
- strava, jídlo, výživa * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
