Structure and function of immunoglobulins Schroeder, Harry W., MD, PhD; Cavacini, Lisa, PhD
Journal of allergy and clinical immunology,
02/2010, Letnik:
125, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Immunoglobulins are heterodimeric proteins composed of 2 heavy and 2 light chains. They can be separated functionally into variable domains that bind antigens and constant domains that specify ...effector functions, such as activation of complement or binding to Fc receptors. The variable domains are created by means of a complex series of gene rearrangement events and can then be subjected to somatic hypermutation after exposure to antigen to allow affinity maturation. Each variable domain can be split into 3 regions of sequence variability termed the complementarity-determining regions (CDRs) and 4 regions of relatively constant sequence termed the framework regions. The 3 CDRs of the heavy chain are paired with the 3 CDRs of the light chain to form the antigen-binding site, as classically defined. The constant domains of the heavy chain can be switched to allow altered effector function while maintaining antigen specificity. There are 5 main classes of heavy chain constant domains. Each class defines the IgM, IgG, IgA, IgD, and IgE isotypes. IgG can be split into 4 subclasses, IgG1, IgG2, IgG3, and IgG4, each with its own biologic properties, and IgA can similarly be split into IgA1 and IgA2.
To demonstrate the importance of utilizing fiberoptic endoscopic evaluation of swallowing (FEES) when evaluating breastfeeding infants with suspected dysphagia. Failure to recognize and account for ...the fundamentally different physiology of the primarily breastfed infant can lead to false assumptions about the safety of breastfeeding in this understudied patient population.
Case-series. The medical records of patients referred to an urban, university-based, pediatric hospital for FEES from February 2017 to October 2020 were reviewed. Their presenting symptoms, dysphagia severity, comorbidity, dysphagia workup, and management were analyzed. The standardized Dysphagia Outcome and Severity Scale was used to appraise dysphagia severity.
204 FEES exams were reviewed. 35 were conducted on breastfed infants. 34 of the 35 infants calmed for the FEES exam while breastfeeding. Cohorts were defined by a particular presenting sign (cough, laryngeal congestion, choking, and respiratory illness) and anatomical characteristic (laryngomalacia, vocal cord paralysis, aspiration, penetration, etc.) and then compared to all other exams. The average dysphagia score for all the exams was 2.37. Patients presenting with laryngeal congestion had an average dysphagia score of 2.81. There was no difference in dysphagia score based on comorbidities or anatomy.
FEES is the instrumental exam of choice when evaluating a primarily breastfed infant who has suspected dysphagia. The exam is well tolerated and provides accurate, objective information while accounting for this population's unique swallowing physiology. Primarily breastfed infants presenting with laryngeal congestion are more likely to have clinically worse dysphagia than those presenting with other clinical symptoms.
Level 4 Laryngoscope, 2023.
Developing T cells face a series of cell fate choices in the thymus and in the periphery. The role of the individual T cell receptor (TCR) in determining decisions of cell fate remains unresolved. ...The stochastic/selection model postulates that the initial fate of the cell is independent of TCR specificity, with survival dependent on additional TCR/coreceptor "rescue" signals. The "instructive" model holds that cell fate is initiated by the interaction of the TCR with a cognate peptide-MHC complex. T cells are then segregated on the basis of TCR specificity with the aid of critical coreceptors and signal modulators Chan S, Correia-Neves M, Benoist C, Mathis (1998) Immunol Rev 165: 195-207. The former would predict a random representation of individual TCR across divergent T cell lineages whereas the latter would predict minimal overlap between divergent T cell subsets. To address this issue, we have used high-throughput sequencing to evaluate the TCR distribution among key T cell developmental and effector subsets from a single donor. We found numerous examples of individual subsets sharing identical TCR sequence, supporting a model of a stochastic process of cell fate determination coupled with dynamic patterns of clonal expansion of T cells bearing the same TCR sequence among both CD4⁺ and CD8+ populations.
While the aurora has attracted attention for millennia, important questions remain unanswered. Foremost is how auroral electrons are accelerated before colliding with the ionosphere and producing ...auroral light. Powerful Alfvén waves are often found traveling Earthward above auroras with sufficient energy to generate auroras, but there has been no direct measurement of the processes by which Alfvén waves transfer their energy to auroral electrons. Here, we show laboratory measurements of the resonant transfer of energy from Alfvén waves to electrons under conditions relevant to the auroral zone. Experiments are performed by launching Alfvén waves and simultaneously recording the electron velocity distribution. Numerical simulations and analytical theory support that the measured energy transfer process produces accelerated electrons capable of reaching auroral energies. The experiments, theory, and simulations demonstrate a clear causal relationship between Alfvén waves and accelerated electrons that directly cause auroras.
We have developed a very simple method, termed absorbance summation (AS), for comparing protein concentrations between samples in ELISA assays without a standard. This method sums the observed ...absorbance values from all dilutions to obtain one data point for each sample to be used for comparison. AS is less computationally intensive than fitting sigmoidal curves, and it avoids the difficulty of parameter estimation for samples with absorbance values lying primarily at the lower tail of the curve. Our simulation studies showed that it performs much better than the sigmoidal curve fitting method and the conventional endpoint titer method. The power of this simple method is as high as the formal curve fitting followed by the estimation of area under the curve (AUC).
Achieving a low mean transverse energy or temperature of electrons emitted from the photocathode-based electron sources is critical to the development of next-generation and compact x-ray free ...electron lasers and ultrafast electron diffraction, spectroscopy, and microscopy experiments. In this Letter, we demonstrate a record low mean transverse energy of 5 meV from the cryo-cooled (100) surface of copper using near-threshold photoemission. Further, we also show that the electron energy spread obtained from such a surface is less than 11.5 meV, making it the smallest energy spread electron source known to date: more than an order of magnitude smaller than any existing photoemission, field emission, or thermionic emission based electron source. Our measurements also shed light on the physics of electron emission and show how the energy spread at few meV scale energies is limited by both the temperature and the vacuum density of states.
Objectives/Hypothesis
The conventional treatment for deep neck abscesses in adults is antibiotic therapy with surgical drainage, whereas in children there is debate about the role of surgical ...drainage versus conservative therapy. It is presently unclear if delayed surgical drainage negatively affects outcomes.
Study Design
We performed a multicenter, prospective, risk‐adjusted cohort study of adult and pediatric patients with deep neck abscess who received incision and drainage within 7 days of admission in the American College of Surgeons National Surgical Quality Improvement Program from 2005 to 2013 (adults) and from 2012 to 2013 (pediatrics).
Methods
Patients were compared based on age (≤ 18 years, > 18 years), timing of surgical drainage (day 0, day 1–2, or day 3–7), and complication rates (specifically, abscess‐specific morbidity and mortality M&M). Multivariate regression was performed to control for preoperative differences.
Results
A total of 1,012 cases of deep neck abscess were identified (347 adult, 665 pediatric). In adults, delay in surgical drainage was associated with increased abscess‐specific M&M, from 11.5% (day 0) to 17.3% (day 1–2) to 25.0% (day 3–7) (P = 0.02). On multivariate regression, delay in drainage of ≥ 3 days in adults was associated with a 2.38‐fold increase in M&M (95% confidence interval 1.01–5.59, P = 0.019). In pediatrics, there was no association between surgical delay and increased abscess‐specific M&M, with rates of 5.0% (day 0), 4.0% (day 1–2), and 4.8% (day 3–7) (P = 0.68).
Conclusion
In adults, delay in surgical drainage of deep neck abscess is associated with increased M&M. There is no association between timing of drainage and M&M in children.
Level of Evidence
2c. Laryngoscope, 126:1753–1760, 2016
The microtubule motors kinesin and dynein function collectively to drive vesicular transport. High-resolution tracking of vesicle motility in the cell indicates that transport is often bidirectional, ...characterized by frequent directional changes. However, the mechanisms coordinating the collective activities of oppositely oriented motors bound to the same cargo are not well understood. To examine motor coordination, we purified neuronal transport vesicles and analyzed their motility via automated particle tracking with nanometer resolution. The motility of purified vesicles reconstituted in vitro closely models the movement of LysoTracker-positive vesicles in primary neurons, where processive bidirectional motility is interrupted with frequent directional switches, diffusional movement, and pauses. Quantitative analysis indicates that vesicles copurify with a low number of stably bound motors: one to five dynein and one to four kinesin motors. These observations compare well to predictions from a stochastic tug-of-war model, where transport is driven by the force-dependent kinetics of teams of opposing motors in the absence of external regulation. Together, these observations indicate that vesicles move robustly with a small complement of tightly bound motors and suggest an efficient regulatory scheme for bidirectional motility where small changes in the number of engaged motors manifest in large changes in the motility of cargo.
► Axonal transport vesicles purify with a low number of stably bound motors ► Vesicles move bidirectionally in vitro and in live cells ► Directional switching during processive motility is frequent and stochastic ► Model: “tug of war” between opposing motors in the absence of external regulation
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