scholarly journals What determines the FDC polarization and GC size in affinity maturation

2020 ◽  
Author(s):  
Zishuo Yan ◽  
Hai Qi ◽  
Yueheng Lan
Keyword(s):  
Deterministic Model ◽  
Cell Receptor ◽  
Affinity Maturation ◽  
Self Organization ◽  
Effective Competition ◽  
Humoral Immune ◽  
Humoral Immune System ◽  
Organization Process ◽  
Target Epitope ◽  
The Impact

AbstractGerminal center (GC) is a particular biological structure produced for affinity maturation in the lymphoid follicle during the T-dependent immune response and is an important component of the humoral immune system. However, the impact of morphological features of the GC on antibody production is not clear. According to the latest biological experiments, we establish a spatiotemporal stochastic model to simulate the whole self-organization process of the GC including the appearance of two specific zones: the dark zone(DZ) and the light zone (LZ). We find that the development of light and dark zones in GC serves to maintain an effective competition among different cells and promote affinity maturation. On the other hand, by varying the GC size, a phase transition is discovered, which determines a critical GC volume for best performance in both the stochastic and the deterministic model. This critical volume is determined by the distance between the activated B Cell Receptor(BCR) and the target epitope of the antigen. The conclusion is confirmed in both the 2D and the 3D simulations and explains partly the variability in the GC size.Author summaryGerminal center (GC) is an important component of the humoral immune system, which supports antibody affinity maturation and the generation of immunity memory. However, the impact of special morphological features of the GC on antibody production is not clear. According to the latest biological experiments, we establish a spatiotemporal stochastic model to simulate the whole self-organization process of the GC. We use the mixing index of different B cells to quantitatively describe the polarization in GC. With the increase of the mixing index, the affinity of plasma cells decreases gradually, even GC might collapse. Therefore, the development of light and dark zones in GC serves to maintain effective competition among different cells and promote affinity maturation. On the other hand, by varying the GC volume, a phase transition is discovered, which determines a critical GC volume for best performance in both the stochastic and the deterministic model. This critical volume is determined by the distance between the activated B Cell Receptor (BCR) and the target epitope of antigen. The conclusion is confirmed in both the 2D and the 3D simulations and explains partly the variability in the GC size.

MATHEMATICAL STUDY OF IN-HOST DYNAMICS OF HERPES SIMPLEX VIRUS TYPE 2 TO ASSESS THE IMPACT OF IMMUNE RESPONSE

2017 ◽  
Vol 25 (01) ◽  
pp. 47-70
Author(s):  
CHANDRA N. PODDER ◽  
SYEDA ELHAM SHAHED ◽  
OLUWASEUN SHAROMI ◽  
SAMIR K. BHOWMIK
Keyword(s):  
Immune Response ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Deterministic Model ◽  
Humoral Immune ◽  
Cell Mediated Immune Response ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2 ◽  
The Impact

A new deterministic model for Herpes Simplex Virus-2 (HSV-2) in vivo, which incorporates the cell-mediated and humoral immune responses, is designed and analyzed. The analyses of the model reveal that it has a globally-asymptotically stable (GAS) virus-free equilibrium (VFE) whenever the associated reproduction threshold is less than unity. Also, it has at least one virus-present equilibrium (VPE) when the reproduction threshold exceeds unity (and virus will persist in vivo under this condition). Furthermore, it is shown that a Herpes Simplex Virus-2 (HSV-2) vaccine will be effective in reducing HSV-2 burden in vivo if it reduces the ability of the virus without glycoprotein C (gC) to bind to the host cell or if it reduces the re-activation rate of latent HSV-2. Additionally, the vaccine will also be very effective if it results in an increase in the fraction of the re-activated latent viruses without gC. Numerical simulations of the model show that cell-mediated immune response is more effective (in controlling HSV-2 burden in vivo) than humoral immune response (the latter only offers marginal impact in reducing HSV-2 burden in vivo, except if its effectiveness level is very high). Thus, a future HSV-2 vaccine that boosts cell-mediated immune response is expected to be quite effective in controlling HSV-2 in vivo.

scholarly journals The Charcot Lecture | Beating MS: A story of B cells, with twists and turns

2014 ◽  
Vol 21 (1) ◽  
pp. 8-21 ◽  
Author(s):  
Stephen L Hauser
Keyword(s):  
B Cells ◽  
Plasma Cells ◽  
Clinical Medicine ◽  
Affinity Maturation ◽  
Lessons Learned ◽  
Phase Ii Trials ◽  
Humoral Immune ◽  
Beneficial Effects ◽  
Inflammatory Phase ◽  
Humoral Immune System

Autoimmune B cells play a major role in mediating tissue damage in multiple sclerosis (MS). In MS, B cells are believed to cross the blood-brain barrier and undergo stimulation, antigen-driven affinity maturation and clonal expansion within the supportive CNS environment. These highly restricted populations of clonally expanded B cells and plasma cells can be detected in MS lesions, in cerebrospinal fluid, and also in peripheral blood. In phase II trials in relapsing MS, monoclonal antibodies that target circulating CD20-positive B lymphocytes dramatically reduced disease activity. These beneficial effects occurred within weeks of treatment, indicating that a direct effect on B cells—and likely not on putative autoantibodies—was responsible. The discovery that depletion of B cells has an impact on MS biology enabled a paradigm shift in understanding how the inflammatory phase of MS develops, and will hopefully lead to development of increasingly selective therapies against culprit B cells and related humoral immune system pathways. More broadly, these studies illustrate how lessons learned from the bedside have unique power to inform translational research. They highlight the essential role of clinician scientists, currently endangered, who navigate the rocky and often unpredictable terrain between the worlds of clinical medicine and biomedical research.

Burden of Congenital Rubella Syndrome (CRS) in Bangladesh: Systematic Review of Existing Literature and Transmission Modelling of Seroprevalence Studies

2020 ◽  
Vol 20 (3) ◽  
pp. 284-290
Author(s):  
Jocelyn Chan ◽  
Yue Wu ◽  
James Wood ◽  
Mohammad Muhit ◽  
Mohammed K. Mahmood ◽  
...  
Keyword(s):  
Systematic Review ◽  
Deterministic Model ◽  
Case Series ◽  
Controlled Vocabulary ◽  
Congenital Rubella Syndrome ◽  
Free Text ◽  
Childbearing Age ◽  
Vaccination Programs ◽  
Congenital Rubella ◽  
The Impact

Background and Objectives: Congenital Rubella Syndrome (CRS) is the leading cause of vaccine-preventable congenital anomalies. Comprehensive country-level data on the burden of CRS in low and middle-income countries, such as Bangladesh, are scarce. This information is essential for assessing the impact of rubella vaccination programs. We aim to systematically review the literature on the epidemiology of CRS and estimate the burden of CRS in Bangladesh. Methods: We conducted a systematic review of existing literature and transmission modelling of seroprevalence studies to estimate the pre-vaccine period burden of CRS in Bangladesh. OVID Medline (1948 – 23 November 2016) and OVID EMBASE (1974 – 23 November 2016) were searched using a combination of the database-specific controlled vocabulary and free text terms. We used an age-stratified deterministic model to estimate the pre-vaccination burden of CRS in Bangladesh. Findings: Ten articles were identified, published between 2000 and 2014, including seven crosssectional studies, two case series and one analytical case-control study. Rubella seropositivity ranged from 47.0% to 86.0% among all age population. Rubella sero–positivity increased with age. Rubella seropositivity among women of childbearing age was 81.0% overall. The estimated incidence of CRS was 0·99 per 1,000 live births, which corresponds to approximately 3,292 CRS cases annually in Bangladesh. Conclusion: The estimated burden of CRS in Bangladesh during the pre-vaccination period was high. This will provide important baseline information to assess the impact and cost-effectiveness of routine rubella immunisation, introduced in 2012 in Bangladesh.

Humoral Immunity in Heart Failure

2019 ◽  
Vol 19 (1) ◽  
pp. 14-18 ◽  
Author(s):  
Amrita Sarkar ◽  
Khadija Rafiq
Keyword(s):  
Heart Failure ◽  
Humoral Immunity ◽  
Treatment Strategies ◽  
Pathophysiological Mechanism ◽  
Peripheral Vascular ◽  
Cardiac Inflammation ◽  
Humoral Immune ◽  
Humoral Immune System ◽  
New Treatment ◽  
Immunity Function

Cardiovascular Disease (CVD) is a class of diseases that involve disorders of heart and blood vessels, including hypertension, coronary heart disease, cerebrovascular disease, peripheral vascular disease, which finally lead to Heart Failure (HF). There are several treatments available all over the world, but still, CVD and heart failure became the number one problem causing death every year worldwide. Both experimental and clinical studies have shown a role for inflammation in the pathogenesis of heart failure. This seems related to an imbalance between pro-inflammatory and anti-inflammatory cytokines. Cardiac inflammation is a major pathophysiological mechanism operating in the failing heart, regardless of HF aetiology. Disturbances of the cellular and humoral immune system are frequently observed in heart failure. This review describes how B-cells play a specific role in the heart failure states. There is an urgent need to identify novel therapeutic targets and develop advanced therapeutic strategies to combat the syndrome of HF. Understanding and describing the elements of the humoral immunity function are essential and may suggest potential new treatment strategies.

Pure red cell aplasia due to parvovirus B19 in a patient treated with rituximab

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 1184-1186 ◽  
Author(s):  
Vivek R. Sharma ◽  
Donald R. Fleming ◽  
Stephen P. Slone
Keyword(s):  
Monoclonal Antibody ◽  
B Lymphocytes ◽  
Parvovirus B19 ◽  
Pure Red Cell Aplasia ◽  
Red Cell ◽  
Humoral Immune ◽  
Red Cell Aplasia ◽  
Point Of Interest ◽  
Humoral Immune System ◽  
Parvovirus B19 Infection

Abstract Rituximab is a chimeric monoclonal antibody directed against CD20 and used in the treatment of B-cell non-Hodgkin's lymphoma. Due to its ability to deplete B lymphocytes, rituximab can interfere with humoral immunity, causing it to be suppressed for several months after treatment. The reported case depicts a serious consequence of this effect of rituximab therapy: pure red cell aplasia resulting from chronic parvovirus B19 infection. The point of interest in this case is not only the association between rituximab therapy and pure red cell aplasia, but the diagnostic and therapeutic utility of the knowledge of parvovirus B19 as the likely etiologic link between the two. Given the known efficacy of intravenous immunoglobulin (IVIg) in the treatment of chronic parvovirus B19 infection, this therapy can cure some of these patients and successfully render most others transfusion-independent until recovery of their own humoral immune system.

PREDICTION AND ANALYSIS OF VACCINATION POSSIBILITIES IN AUTOIMMUNE DISEASES: AN APPLICATION OF ARTIFICIAL IMMUNE SYSTEM

2002 ◽  
Vol 10 (02) ◽  
pp. 107-126
Author(s):  
RAJANI R. JOSHI ◽  
BHUVANESWARAN NATARAJAN
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Artificial Immune System ◽  
Real Data ◽  
Affinity Maturation ◽  
Artificial Immune ◽  
Humoral Immune ◽  
Machine Learning Model ◽  
Experimental Findings

We present an adaptive machine learning model of the humoral immune response. Antigens (epitopes/ids) and antibodies (paratopes/anti-ids) are represented here as sequences of single letter amino acid codes. The model effectively simulates dynamic affinity maturation, memory and associativity. Specific age-function is derived here based on recent experimental findings and is used to incorporate self and non-self antigens. Computational experiments using real data on Type-1 Diabetes and Systemic Lupus Erythematosus offer quantitative elucidation of autoimmunity. The results also provide applications towards vaccine design and possible solution to the therapeutic difficulties in the autoimmune diseases and disorders of the above kind.

MODELING THE IMPACT OF VOLUNTARY TESTING AND TREATMENT ON TUBERCULOSIS TRANSMISSION DYNAMICS

2012 ◽  
Vol 05 (04) ◽  
pp. 1250029 ◽  
Author(s):  
S. MUSHAYABASA ◽  
C. P. BHUNU
Keyword(s):  
Deterministic Model ◽  
Reproduction Number ◽  
Positive Impact ◽  
Transmission Dynamics ◽  
Effective Control ◽  
Reproductive Number ◽  
Voluntary Testing ◽  
Manifold Theory ◽  
The Impact ◽  
Disease Free

A deterministic model for evaluating the impact of voluntary testing and treatment on the transmission dynamics of tuberculosis is formulated and analyzed. The epidemiological threshold, known as the reproduction number is derived and qualitatively used to investigate the existence and stability of the associated equilibrium of the model system. The disease-free equilibrium is shown to be locally-asymptotically stable when the reproductive number is less than unity, and unstable if this threshold parameter exceeds unity. It is shown, using the Centre Manifold theory, that the model undergoes the phenomenon of backward bifurcation where the stable disease-free equilibrium co-exists with a stable endemic equilibrium when the associated reproduction number is less than unity. The analysis of the reproduction number suggests that voluntary tuberculosis testing and treatment may lead to effective control of tuberculosis. Furthermore, numerical simulations support the fact that an increase voluntary tuberculosis testing and treatment have a positive impact in controlling the spread of tuberculosis in the community.

Periodically forced self-organization in the long-term evolution of planktic foraminifera

2001 ◽  
Vol 38 (2) ◽  
pp. 293-308 ◽  
Author(s):  
Andreas Prokoph ◽  
Anthony D Fowler ◽  
R Timothy Patterson
Keyword(s):  
Sea Level ◽  
Logistic Map ◽  
Late Eocene ◽  
Self Organization ◽  
Extinction Data ◽  
Sea Level Fluctuations ◽  
Global Sea Level ◽  
Extinction Events ◽  
The Impact

Wavelet transform and other signal analysis techniques suggest that the planktic foraminiferal (PF) long-term evolutionary record of the last 127 Ma can be attributed to complex periodic and nonlinear patterns. Correlation of the PF extinction pattern with other geological series favors an origin of the ~30 Ma periodicity and self-organization by quasi-periodic mantle-plume cycles that in turn drive episodic volcanism, CO2-degassing, oceanic anoxic conditions, and sea-level fluctuations. Stationary ~30 Ma periodicity and a weak secular trend of ~100 Ma period are evident in the PF record, even without consideration of the mass extinction at the K–T boundary. The 27–32 Ma periodicity in the impact crater record and lows in the global sea-level curve, respectively, are ~6.5 Ma and ~2.3 Ma out of phase with PF-extinction data, although major PF-extinction events correspond to the bolide impacts at the K–T boundary and in late Eocene. Another six extinction events correspond to abrupt global sea-level falls between the late Albian and early Oligocene. Self-organization in the PF record is characterized by increased radiation rates after major extinction events and a steady number of baseline species. Our computer model of long-term PF evolution replicates this SO pattern. The model consists of output from the logistic map, which is forced at 30 Ma and 100 Ma frequencies. The model has significant correlations with the relative PF-extinction data. In particular, it replicates singularities, such as the K–T event, nonstationary 2.5–10 Ma periodicities, and phase shifts in the ~30 Ma periodicity of the PF record.

Serum immunoglobulins in patients with chronic tonsillitis

1984 ◽  
Vol 98 (12) ◽  
pp. 1213-1216 ◽  
Author(s):  
Harbans Lal ◽  
O. P. Sachdeva ◽  
H. R. Mehta
Keyword(s):  
Immune System ◽  
Mean Value ◽  
The Body ◽  
Antigenic Stimulation ◽  
Chronic Tonsillitis ◽  
Serum Immunoglobulin ◽  
Control Group ◽  
Humoral Immune ◽  
Humoral Immune System ◽  
The Mean

AbstractSerum immunoglobulin (IgG, IgA and IgM) levels were determined in patients with chronic tonsillitis before and one month after tonsillectomy. The preoperative levels of serum IgG, IgA and IgM were significantly higher when compared with the controls. The increase may be due to repeated antigenic stimulation. The post-operative levels for the three immunoglobulins were decreased; however, a significant reduction was observed for IgG only where the mean value was comparable with the control group. The data confirm that tonsillectomy does not disturb the humoral immune system of the body.

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