Histocompatibility

Histocompatibilty is the condition in which the body allows the grafting of tissue or the transfusion of blood without rejection. Ultimately, this means that there is anabsence of interference from the body's immune system.

Histocompatibility is governed by Major Histocompatibility Complex (MHC) molecules. Crudely stated, their purpose is to distinguish "self" from "non-self". More specifically, their primary immunological function is to bind and present antigenic peptides on the surfaces of cells for recognition by antigen-specific T cell receptors.

Controlling and inducing histocompatibility is central to ensuring the success of organ transplants. This field is known as transplantation immunology.

Buoyancy question

Here's a question for people to ponder.

Say you have a boat floating in a swimming pool. Suppose that there's a rock sitting in the boat. Now suppose that someone takes the rock and drops it into the pool.

Does the water level rise or fall? Think about it.

Spot counting and "Zytokinen"

Durch automatische Auszählung mittels Software kann so bestimmt werden, welche spezielle Aktivität die Immunzellen besitzen, was für die Forschung und Diagnostik von Autoimmunerkrankungen, Transplantationsrisiken, Allergien und Infektionskrankheiten nützlich ist, ebenso wie für die Impfstoffforschung.

Cytokines

Cytokines are regulatory proteins that are released by cells of the immune system. These act as intercellular mediators in the generation of an immune response. They can have stimulating or suppressing effects on lymphocyte cells and immune responses.

Well-known examples include the interleukins, interferons and tumor necrosis factors. Cytokine production can be detected using certain laboratory techniques that have been discussed previously.

ELISA illustration

Today, I just wanted to post this link to an animated illustration of the ELISA process. They say that a picture paints a thousand words, and in this case, an animated (and interactive) picture says a whole lot more.

Scientific illiteracy

Scientific illiteracy is a tremendous problem in this country. I'd like to quote the following statements by George Dvorsky (as reproduced in this web essay).

Most of those who live in the West, particularly North Americans, are guilty of an anti-intellectual bias. Scientists are supposed to be nerds, right? And who wants to be a nerd? This sentiment, combined with a general suspicion of science and the predominance of aggressive theological and pseudoscientific memes, has resulted in much of the scientific illiteracy that now pervades our society.

It doesn't help that the educational system is in shambles and without focus, and that fatuous postmodernism and its insistence that nothing can truly be known now dominates many disciplines at most universities. Consequently, too many people wear their ignorance like a badge of honor, as if being clueless about science is something to be proud of.

Memory cells

Memory cells allow the body to remember previous infections and quickly mobilize defenses against them. This is the mechanism by which the human body remembers that someone contracted chicken pox, for example, and which prevents future infections of that type from occuring.

Time is short, so instead of discussing this at greater detail, I'll post a (slightly paraphrased, for brevity) excerpt from a technical paper on this subject.

Single-Cytokine-Producing CD4 Memory Cells Predominate in Type 1 and Type 2 Immunity

The patterns of Ag-induced cytokine coexpression in normal, in vivo-primed CD4 memory T cells has remained controversial because the low frequency at which these cells occur has effectively prevented direct ex vivo measurements. We have overcome this limitation by using two-color cytokine ELISPOT assays and computer-assisted image analysis. We found CD4 memory cells that simultaneously expressed IL-2, IL-3, IL-4, IL-5, and IFN--y to be rare (0-10%). This cytokine segregation was seen in adjuvant-induced type 1, type 2, and mixed immunity to OVA, in Leishmania infection regardless of the Ag dose used or how long after immunization the assay was performed. The data suggest that type 1 and type 2 immunity in vivo is not mediated by classic Thl or Th2 cells but by single-cytokine-producing memory cells.


Alexey Y. Karulin, Maike D. Hesse, Magdalena Tary-Lehmann, and Paul V. Lehmann, The Journal of Immunology, 2000, 164: 1862-1872.

Lymphocytes

Lymphocytes are a category of white blood cell, or leukocyte. The main categories of lymphocytes are B cells and T cells. B cells are responsible for manufacturing antibodies, whereas T cells have more complex roles. Depending on the category of the T cell, it may be responsible for destroying invading cells, for secreting cytokines in response to an antigen, or for activating macrophages and NK-cells. These processes shall be discussed at a later date.

Flow cytometry was previously mentioned, and one application of this technique is in counting specific lymphocyte population. The ELISPOT method was mentioned as well; this technique is used for counting the number of B cells that secrete a specific antibody, or the number of T cells that produce a given cytokine or granzyme.

Cytokines

Cytokines are regulatory proteins that are released by cells of the immune system. They are the means by which cells communicate in the generation of an immune response. Well-known cytokines include prostaglandin, the interleukins, the interferons and the lymphokines.

Cytokines trigger responses by binding to cell-specific receptors located in the cell membrane. This allows a distinct signal cascade to start in the cell, eventually generating biochemical and phenotypical changes in the target cell.

Production of a specific cytokine can be detected using the aforementioned ELISPOT assays, which can also determine the percentage of cells that produce the cytokine in question.

Robotic grasp theory

Robotic grasp theory is a magnificent marriage of science and engineering. The human hand is a magnificent piece of design -- flexible and adaptable beyond belief. It's no surprise that many robotic efforts have attempted to duplicate its capabilities.

Sadly, these efforts often go too far in either extreme. Some attempt to duplicate the human hand too closely. The result? Anthropomorphic robot hands that require hopelessly complex control algorithms, and which lack the fine sensing capabilities of a human hand. These devices are cumbersome, and often impractical to use. Others use primitive parallel jaw grippers, which are decidedly more restricted in their capabilities. Since most parts require some custom tooling in order to be held securely, this greatly limits the range of workpieces that a parallel jaw gripper can hold.

(Other variants exist, such as three-fingered end-effectors. The end results is similar, though -- limited grasp capabilities.)

Velasco et al. offered a compromise in which rapid prototyping technology was used to develop gripper tooling based on CAD models of the parts to be grasped. The CAD capabilities allowed the tooling to be developed rapidly, and with due consideration to part clearances and manufacturing variability. This gave parallel jaw grippers a great deal more versatility than could be achieved using rudimentary tooling, without requiring the complex mechanisms or ocntrol algorithms required of anthropomorphic robot hands.

Vaccine development

The first vaccine was developed by Edward Jenner in an abhorrently crude fashion. Jenner noticed that milkmaids were not readily susceptible to smallpox infections, which had been ravaging the populace. He theorized that they had somehow gained immuniity through regularly exposure to cowpox lesions. In a bold move, Jenner inoculated an eight-year-old boy with scrapings from cowpox lesions, thus proving his theory.

Such an experiment would never be allowed nowadays, due to medical ethics. To Jenner's credit though, it worked, and this paved the way toward stamping out smallpox across the world.

Nowadays, more sophisticated techniques are available for vaccine development. In an earlier write-up, we discussed the ELISPOT technique in brief. Suffice to say that this methodology allows the monitoring of immunological responses to antigen invasion at the cellular level. This eliminates the need for crude experiments with human subjects under coarse conditions.

Asthma and immunology

I suffered a mild asthma attack while cycling to work today, thanks to the influx of cold air into my lungs. So, I decided to write a little about asthma.

Asthma is an immunological disorder in which the patient suffers respiratory difficulty. In this disease, the bronchioles in the lungs are narrowed by inflammation, thus requiring treatment with bronchodilators. The symptoms include wheezing and shortness of breath, which can prevent the afflicted person from engaging in prolonged exercise.

There are several theories which purport to explain the rising incidence of asthma. One places the blame on air pollution. Another purports that the hygenic conditions in the First World cause reduced bacterial exposure, causing inadequate stimulation of the immune system during early childhood. Yet another suggests that the problem is due to non-exposure to parasites such as tapeworms, since the cells which combat these parasites are the same ones which trigger the asthmatic reaction.

T cell clone avidity

Tonight I decided to cite the abstract of a published paper that I got my hands on. It's about memory cells, which are used to retain a record of previously encountered antigens. These cells allow the immune system to respond more rapidly to subsequent invasions.

The patterns of Ag-induced cytokine coexpression in normal, in vivo-primed CD4 memory T cells has remained controversial because the low frequency at which these cells occur has effectively prevented direct ex vivo measurements. We have overcome this limitation by using two-color cytokine enzyme-linked immunospot assays and computer-assisted image analysis. We found CD4 memory cells that simultaneously expressed IL-2, IL-3, IL-4, IL-5, and IFN--y to be rare (0-10%). This cytokine segregation was seen in adjuvant-induced type 1, type 2, and mixed immunity to OVA, in Leishmania infection regardless of the Ag dose used or how long after immunization the assay was performed. The data suggest that type 1 and type 2 immunity in vivo is not mediated by classic Thl or Th2 cells but by single-cytokine-producing memory cells.

(Maike D. Hesse, Alexey Y. Karulin, Bernhard O. Boehm, Paul V. Lehmann, and Magdalena Tary-Lehmann. The Journal of Immunology, 2001, 167: 1353-1361.)

Biotech

Biotechnology is the marriage of engineering and technology principles to the biological sciences. Common applications include the development of new microorganisms or biological substances for industrial applications. These can include hormone production, waste cleanup, bioconversion of organic wastes, genetic engineering of new organisms, drug manufacturing and so forth.

Biotechnology does not necessarily use living organisms. For example, it can focus on DNA chips in genetic research, or radioactive medical tracers. It can even use active cells from living organisms -- but not the organism itself -- such as when human lymphocytes are used in vaccine development.

Among the most exciting of biotech fields is the engineering of new microorganisms, with the goal of producing insulin or antibiotics cheaply and efficiently. Other applications include the development of transgenic plants and animals, in which foreign genes are introduced externally, so as to produce enhanced organisms (e.g. cows that produce extraordinary quantities of milk).

Viral plaques

Viral plaque assays are a simple yet ingenious way of enumerating the number of viruses within a sample. This technique requires introducing the viruses into a nutrient medium (typically agar) in which a culture of bacteria or other cells has been grown.

In this approach, the viruses spread through the cell culture, invading and destroying the cells in question. The viruses thus generate zones of cell destruction, which we call plaques. These plaques can be detected visually, but they may not necessarily be visible to the naked eye. Sometimes, they can only be seen through the assistance of other techniques such as staining, microscopy, hemadsorption or immunofluorescence.

Naturally, this technique is not foolproof, since plaques can overlap and even occlude one another. Statistical methods must then be used to estimate the actual number of viruses introduced into the sample.