Science Current Events | Science News | Brightsurf.com
 
Email a Friend Send to a friend
Printer Friendly Print Caltech biologists spy on the secret inner life of a cell

Caltech biologists spy on the secret inner life of a cell

October 13, 2008

PASADENA, Calif.-- The transportation of antibodies from a mother to her newborn child is vital for the development of that child's nascent immune system. Those antibodies, donated by transfer across the placenta before birth or via breast milk after birth, help shape a baby's response to foreign pathogens and may influence the later occurrence of autoimmune diseases. Images from biologists at the California Institute of Technology (Caltech) have revealed for the first time the complicated process by which these antibodies are shuttled from mother's milk, through her baby's gut, and into the bloodstream, and offer new insight into the mammalian immune system.

Newborns pick up the antibodies with the aid of a protein called the neonatal Fc receptor (FcRn), located in the plasma membrane of intestinal cells. FcRn snatches a maternal antibody molecule as it passes through a newborn's gut; the receptor and antibody are enclosed within a sac, called a vesicle, which pinches off from the membrane. The vesicle is then transported to the other side of the cell, and its contents--the helpful antibody--are deposited into the baby's bloodstream.




Pamela Bjorkman, Max Delbrück Professor of Biology at Caltech and an investigator with the Howard Hughes Medical Institute, and her colleagues were able to watch this process in action using gold-labeled antibodies (which made FcRn visible when it picked up an antibody) and a technique called electron tomography. Electron tomography is an offshoot of electron microscopy, a now-common laboratory technique in which a beam of electrons is used to create images of microscopic objects. In electron tomography, multiple images are snapped while a sample is tilted at various angles relative to the electron beam. Those images can then be combined to produce a three-dimensional picture, just as cross-sectional X-ray images are collated in a computerized tomography (CT) scan.

"You can get an idea of movement in a series of static images by taking them at different time points," says Bjorkman, whose laboratory studies how the immune system recognizes its targets, work that is offering insight into the processes by which viruses like HIV and human cytomegalovirus invade cells and cause disease.

The electron tomography images revealed that the FcRn/antibody complexes were collected within cells inside large vesicles, called "multivesicular bodies," that contain other small vesicles. The vesicles previously were believed to be responsible only for the disposal of cellular refuse and were not thought to be involved in the transport of vital proteins.

The images offered more surprises. Many vesicles, including multivesicular bodies and other more tubular vesicles, looped around each other into an unexpected "tangled mess," often forming long tubes that then broke off into the small vesicles that carry antibodies through the cell. When those vesicles arrived at the blood-vessel side of the cell, they fused with the cell membrane and delivered the antibody cargo. The vesicles also appeared to include a coat made from a molecule called clathrin, which helps form the outer shell of the vesicles. Researchers previously believed that a vesicle's clathrin cage was completely shed before the vesicle fused with the cell membrane. The new results suggest that only a small section of that coating is sloughed off, which may allow the vesicle to more quickly drop its load and move on for another.

"We are now studying the same receptor in different types of cells in order to see if our findings can be generalized, and are complementing these studies with fluorescent imaging in live cells," Bjorkman says. "The process of receptor-mediated transport is fundamental to many biological processes, including detection of developmental decisions made in response to the binding of hormones and other proteins, uptake of drugs, signaling in the immune and nervous systems, and more. So understanding how molecules are taken up by and transported within cells is critical for many areas of basic and applied biomedical research," she adds.

California Institute of Technology



Related Antibodies Current Events and Antibodies News Articles Antibodies Current Events and Antibodies News RSS Antibodies Current Events and Antibodies News RSS
Evolution in action: Our antibodies take 'evolutionary leaps' to fight microbes
With cold and flu season in full swing, the fact that viruses and bacteria rapidly evolve is apparent with every sneeze, sniffle, and cough. A new report in the January 2009 issue of The FASEB Journal, explains for the first time how humans keep up with microbes by rearranging the genes that make antibodies to foreign invaders. This research fills a significant gap in our understanding of how the immune system helps us survive.

Cancer drug effectively treats transplant rejections
University of Cincinnati (UC) researchers have discovered a new therapy for transplant patients, targeting the antibody-producing plasma cells that can cause organ rejection.

Biomedical researchers create artificial human bone marrow in a test tube
Artificial bone marrow that can continuously make red and white blood cells has been created in a University of Michigan lab.

Scientists Reveal Structure of New Botulism Nerve Toxin Subtype
cientists at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory have determined the atomic-level structure of a third subtype of botulinum neurotoxin - a deadly toxin produced by certain bacteria that causes the disease botulism, and is also used in cosmetic and therapeutic applications such as reducing wrinkles and calming a hyperactive bladder.

Potential autoimmunity-inducing cells found in healthy adults
It's not just patients with autoimmune diseases like lupus and rheumatoid arthritis (RA) that have self-attacking immune cells-healthy people have them too, according to a new report in the Journal of Experimental Medicine.

Mathematical models of adaptive immunity
More than five million people die every year from infectious diseases, despite the availability of numerous antibiotics and vaccines.

USC researchers identify key mechanism that occurs at the inception point of many human lymphomas
Researchers at the Keck School of Medicine of the University of Southern California (USC) have explained how certain key mutations occur in human lymphomas-a process that has, until now, remained a mystery.

Vaccine and drug research aimed at ticks and mosquitoes to prevent disease transmission
Most successful vaccines and drugs rely on protecting humans or animals by blocking certain bacteria from growing in their systems. But, a new theory actually hopes to take stopping infectious diseases such as West Nile virus and Malaria to the next level by disabling insects from transmitting these viruses.

Pediatric obesity may alter thyroid function and structure
In addition to its strong associations with hypertension, cardiovascular disease, and diabetes, pediatric obesity may induce alterations in thyroid function and structure, according to a new study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM).

Stanford blood scanner detects even faint indicators of cancer
A team led by Stanford researchers has developed a prototype blood scanner that can find cancer markers in the bloodstream in early stages of the disease, potentially allowing for earlier treatment and dramatically improved chances of survival.
More Antibodies Current Events and Antibodies News Articles


Antibodies: A Laboratory Manual
by Ed Harlow, David Lane

Introduction to immunochemistry for molecular biologists and other nonspecialists....



Making and Using Antibodies: A Practical Handbook

Antibodies are an indispensable tool in the study of biology and medicine. Making and Using Antibodies: A Practical Handbook presents techniques in a single, comprehensive source for the production and use of antibodies. It enables researchers to immediately access lab-tested, proven protocols. Written and edited by an elite team of scientists, who have developed and refined many of the...



Antibody Technology (Introduction to Biotechniques Series)
by Eryl Liddell

A comprehensive overview of antibody...



Basic Methods in Antibody Production and Characterization

Written for researchers and professionals in the fields of biomedical research, immunology, biochemistry, molecular biology, pathology, and biotechnology, Basic Methods in Antibody Production and Characterization uses a cookbook approach to presenting the methods for the production, characterization, and use of antibodies. Antibodies described include polyclonal and monoclonal and those made by...



Antibody Engineering: Methods and Protocols (Methods in Molecular Biology)

Univ. of Cambridge, UK. Presents cutting-edge techniques for the generation and optimization of recombinant antibodies for offers protocols for affinity maturation and reducing immunogenicity of antibodies. Discusses the novel applications of antigen-binding affinity and specificity. DNLM: Antibodies--therapeutic use--Laboratory...



Manual of Diagnostic Antibodies for Immunohistology
by Anthony S-Y. Leong, Kumarasen Cooper, F. Joel W-M. Leong

The rapid acceptance of immunohistochemistry as an important and even indispensable adjunct to morphological examination and diagnosis requires the modern anatomical pathology laboratory to be conversant with, and proficient in, immunostaining procedures, as well as methods of tissue processing and antigen retrieval and the underlying characteristics of the increasing number of antibodies and...



Antibodies in Diagnosis and Therapy: Technologies Mechanisms and Clinical Data (Studies in Medicinal Chemistry Series)
by Matzku

Monoclonal antibodies have had their impact on biomedical research for more than a decade. Besides their exuberant use as reagents, quite a number of diagnostic and therapeutic approaches have been followed, and an impressive number of technological improvements, e.g., humanization, recombinant miniantibodies, have been elaborated to strengthen the principle. With respect to clinical...



Handbook of Therapeutic Antibodies 3-Volume Set

In this most comprehensive reference source for the development, production and therapeutic application of antibodies, Volume I contains general chapters presenting established technologies and clinical applications. Volume II provides a look at emerging technologies, new therapeutic concepts, and clinical studies. The third volume features detailed and specific information about each currently...



Therapeutic Antibodies: Methods and Protocols (Methods in Molecular Biology)

With revenues from the top five therapeutic antibodies accounting for a majority of the recent pharmaceutical sales, the research and development in the field has exploded over the past several years and is expected to grow with new emerging monoclonal antibodies like Numax, Lucentis, Actemra, and others. In Therapeutic Antibodies: Methods and Protocols, leading experts from academic laboratories...



Monoclonal Antibodies: Methods and Protocols (Methods in Molecular Biology)

Monoclonal Antibodies: Methods and Protocols examines a collection of state-of-the-art methods that employ monoclonal antibodies in a clinical setting with opening chapters focusing on the gold standard method for generating mouse monoclonal antibodies through hybridoma technology, future methods for engineering recombinant and humanized antibodies, methods for engineering soluble Fc fusion...

© 2009 BrightSurf.com