Rolle von Lymphotoxin Beta und Zelladhäsionsmolekül (CEACAM1) in Angeborene und adaptive Immunaktivierung
Bibliographic record
Abstract
The induction of the adaptive and innate immune system is essential for controlling viral infections. Balance between the innate immune system and adaptive immune responses results in better antiviral immune activation. Not enough or too much activation can lead to impairment of immune responses. In this thesis, we have investigated the role of enforced viral replication and different mechanisms by which adequate innate and adaptive immune responses are generated. Recently, it was shown that Usp18 dependent viral replication in splenic CD169+ macrophages are important to induce a sufficient type I interferon response resulting in the subsequent activation of adaptive immune responses. Here, in one study, we have shown that the intracellular replication of viral particles is sufficient to generate virus specific CD8 T cell responses. On the other hand, extracellular distribution of viral particles along the splenic conduits was necessary for inducing systemic levels of type I interferon (IFN-I). We have shown that Usp18 is important for viral replication, but that B cell-derived lymphotoxin beta is necessary for the extracellular distribution of virus along the marginal zone in spleen. In a further study, we have demonstrated a role of CEACAM1 in B cell survival, proliferation and innate immune activation. B cells are important part of immune system because they are in close proximity of blood-borne antigen in splenic circulation, they secrete antibodies and maintain the lymphoid architecture. We have shown that cell intrinsic signalling of CEACAM1 is essential for survival of proliferating B cells. CEACAM1 is involved in B-cell receptor and signals through the Btk/Syk/NF-κB axis. Absence of CEACAM1 signalling leads to reduced number of B-cells in lymphoid organs especially marginal zone B cells and CD169+ macrophages. Absence of CEACAM1 leads to poor anti-viral antibody secretion after systemic infection with cytopathic virus resulting in early death of Ceacam1–/– mice. In another set of experiment, we investigated the role of virus specific antibodies on adaptive immune activation. With the use of chronic virus strain LCMV-Docile, we determined whether enforced viral replication could occur in presence of virus-specific antibodies or virus-specific CD8 T cells. We found that after systemic recall infection, virus-specific antibodies allow viral replication in splenic marginal zone but controlled in peripheral organs resulting in strong CD8 T cell priming whereas, virus-specific CD8 T cells blunted viral replication in spleen but failed to control the persistent chronic viral infection. In conclusion, using several mouse models of noncytopathic and cytopathic viral infection, we have elucidated the functional role of lymphotoxin beta, CEACAM1 and virus-specific antibodies in immune function particularly during enforced viral replication in the spleen.
Stored with the screening record, where it is evidence for the labels above.
How this classification was reachedexpand
The three-model screen
all 5,600 screened works →All three models called this out of scope.
Immunology thesis on lymphotoxin beta and CEACAM1 in immune activation.
This thesis investigates immune mechanisms in viral infection using biological models, not research itself.
Immunology work on lymphotoxin beta and CEACAM1 in immune activation; domain biomedicine.
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".