T Cell Maturation

T lymphocytes play an important role in cell–mediated immunity. The T cell receptor present on the cell differentiates them from other cells. Various subsets of T cells are present and each of them has a different function.

The T cells are produced in the hematopoietic stem cells of the bone marrow from where they migrate to thymus where maturation takes place. The naïve T cells divide in thymus and produce large number of immature thymocytes.

About 2 percent of total thymocytes survive the maturation and become mature immunocompetent T cells and possess CD4 or CD8 receptor.

Positive and Negative Selection

After maturation, two classes of MHC determine the fate of the thymocytes. The cells selected by MHC class I mature into CD4+ cells, whereas those selected by MHC class II mature into CD8+ cells. This method of selection is positive selection and it does not remove the cells that are likely to cause autoimmunity. This removal process is done by negative selection.

Negative selection removes the thymocytes which are capable of binding with “self” peptides presented by MHC. Thymocytes survived the positive selection migrate to the thymus medulla where they are exposed to self-antigen complex. Cells responding too strongly with the self-antigen are forced to go under apoptosis and the remaining cells mature as naive T cells and move out of the thymus. This is a very important process as it prevents the maturation of self-reactive T cells that can cause autoimmune diseases.

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A New Stem Cell Can Grow in Animals

Researches have been working with stem cells for quite some time, as they have a lot of potential in the field of artificial organ development and other tissue engineering aspects. Stem cells have a capability to divide indefinite number of times while maintaining their undifferentiated state and they also have the capability to differentiate into specialized cell type when required. But the main problem while experimenting with the stem cells is that the mortality rate of these cells is very high. About 99 percent of the cells isolated die, making it very difficult to alter the genetic code and divide them multiple times for the clinical use.

But in a recent breakthrough, the researchers from the Salt Institute for Biological Studies have altered growth medium of the cells and created a new type of stem cells which have a survival rate of 30 to 40 percent as compared to 1 percent of the already existing stem cells. In addition to this, it is easier to culture these cells and repair the genetic defects occurred in any of these cells.

Jun Wu, who is a researcher involved in this project said that these altered cells which are also termed as region-selective pluripotent stem cells, have a capability to differentiate inside a mouse. Wu stated that, “It offers the first proof of concept that it’s possible to incorporate human cells efficiently into another species.” It will also enable us to grow the organ inside of an animal and transplant it in to the patient once the full growth of the organ has been achieved. The research has been published in the May edition of Nature.

Amoebae possesses immunity like higher animals

The various birds and animal species have their own mechanism like migration, hibernation and aestivation to tackle the shortage of food due to the seasonal effects.  Like these mechanisms, the microorganisms have their own methods to tackle the shortage of food. A species of amoeba Dictyostelium discoideum, which is also known as social amoeba, get aggregated in a large number forming a spore which can be dispersed by the wind to the most suitable environment.  But in this quest all the amoeba do not survive. About 80% of the entire amoebae involved in formation of this specialized structure get transformed into Spores and approximately 20% sacrifice their life for the survival of the spore by forming the stalk.

But in a recent study published in Nature Communications, there is a third set of specialized cells found in the structure. These specialized cells are involved in performing the typical phagocytic functions of amoeba. These specialized cells are termed as sentinel cells. Thierry Soldati, the coauthor from the University of Geneva in Switzerland stated that, “They make up the primitive innate immune system of the slug and play the same role as immune cells in animals. Indeed, they also use phagocytosis and DNA nets to exterminate bacteria that would jeopardize the survival of the slug.”

In humans, any pathogen such as bacteria is attacked by the phagocytes in which the pathogen is enveloped by the cells and is digested by the lytic enzymes. Immune cells also form a toxic net by expelling their DNA in a process called as neutrophil extracellular trap (NET). In the similar way the amoeba also engulfs the bacteria and kills it by releasing the digestive enzymes. In the recent studies the researchers found that even the sentinel cells produce DNA-based extracellular traps (ETs) when they sense danger from bacteria or lipopolysaccharides.

Thus, the mechanism of immunity which was supposed to be present only in the higher organisms is also present in the unicellular organisms which were present around one billion years ago. The researcher Soldati and his colleagues wrote in their paper, “Our results demonstrate that D. discoideum is a powerful model organism to study the evolution and conservation of mechanisms of cell-intrinsic immunity, and suggest that the origin of DNA-based ETs as an innate immune defense predates the emergence of metazoans.”

 

 

3D structure of the biomolecules determined using an interdisciplinary technique

Biomolecules are among the key elements which are necessary to keep a cell alive. Biomolecules are involved in a lot of mechanisms going on inside the cell such as gaseous transport, damage and repair of the genetic material, replication of the genome, cell division, metabolic activities etc. The researchers from Karlsruhe Institute of Technology (KIT) have recently developed an efficient method to predict the three dimensional structure of the biomolecules. This method is used to predict the three dimensional structure of the biomolecule by analyzing the experimental data.

Biomolecules like DNA, RNA and proteins are the molecular machines which are involved in almost all the ongoing activities inside the cell. In order to know the working of various cellular mechanisms at the molecular level, it is very important to determine the three dimensional structure of these biomolecules. The knowledge of the spatial structure of the biomolecules is absolutely necessary in order to know its functioning. For example, in order to develop a drug to inhibit the expression of protein, it is very necessary to know the shape of its active site in order to design the substrate analog for the target site.

Although, various experimental methods are present which are capable of determining the spatial structure of the biomolecules, a lot of technical restrictions are present in these methods.

Alexander Schug and his colleagues from Steinbuch Centre of Computing at KIT have developed a different approach to determine the 3D structure of these biomolecules. This method is based on analysis of the statistical data of the biomolecules obtained from various organisms. They have developed an algorithm which analyze the data for mutation patterns and on the basis of this, the spatial structure can be determined.

This work from the researchers is a nice example of the interdisciplinary research in which the methods of theoretical physics and computer science were successfully applied in the field of molecular biology. The researcher Alexander Schug says, “We hope that our detailed structural predictions will not only be of relevance to fundamental research, but also be applied in pharmacological and medical research, as biomolecules are important to a number of diseases.”

Our Ancestors Explored ‘Out of Africa’ Despite Weak Nasal Faculties

A recent study published in PLOS Computational Biology explains how in humans inhaled air is conditioned poorly in the nasal cavity in comparison with primates.

The study was produced by Dr. Takeshi Nishimura from Kyoto University and his colleagues, and is the first investigation of nasal air conditioning in nonhuman hominoids based on computational fluid dynamics (CFD). Apparently, compared to the flat nasal features of chimpanzees and macaques, our protruding noses (a legacy of earlier Homo) condition the air poorly, but that didn’t stop our human ancestors to explore out of Africa and survive climate changes.

The team scanned six humans, four Japanese macaques, four chimps, and two Rhesus macaques using a CT and/or MRI scanner to create 3D models of the nasal passages. Then, they conducted CFD with heat and airflow to compare air conditioning in the different primates. They found that airflow direction in the nasal cavities of macaques and chimpanzees differs from ours in a few key ways: Inhaled air had a horizontal and straight flow in macaques and chimps but an upward and curved flow in humans – which impairs air conditioning.

Our ancestors, the genus Homo, diversified under the fluctuating climate of the Plio-Pleistocene, to be flat-faced with a short nasal cavity and a protruding external nose, as seen in modern humans. Anatomical change in nasal region is believed to be evolutionarily sensitive to the ambient climatic conditions of a given environment, but the nasal anatomy of early Homo was not sensitive to the ambient atmosphere conditions. The inhaled air can be fully conditioned in the pharyngeal cavity, which was lengthened in early Homo.

This study shows the importance of compensating human evolution, as well as adaptive evolution. The diversification of Pleistocene hominins is a significant evolutionary event in terms of understanding human evolution. These linked changes in the nasal and pharyngeal regions would in part have contributed to how flat-faced Homo members must have survived fluctuations in climate, before they moved out of Africa in the Early Pleistocene to explore the more severe climates and ecological environments of Eurasia.