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Transplantation and immunosuppression

Organ transplantation between individuals, such as kidney transplants, expose the recipient to the foreign antigens of the donor. Upon identifying the foreign antigens, the recipient's immune response mounts a defence via production of specific B- and T-cells, attacking and damaging the new organ.

Kidney transplantation involves using a dead or live donor's kidney to rescue kidney function of a patient on dialysis, or preemptively before they require dialysis. It is a 3-hour operation that attaches the new kidney to the patient's blood supply, without removing the old kidneys (their removal has been shown to increase surgery outcome problems). Kidney transplants successfully increase lifespan, with better results seen the sooner it is performed relative to time on dialysis.

Donors are relatives, friends, altruistic strangers or sellers on the kidney market which is legal and supported in some parts of the world, such as Iran. Different locations have different approaches to kidney donation, with some prohibiting payment, and others openly encouraging donation through financial incentives. Successful donation chains have been established in some countries. They work by passing on incompatible kidneys from donors aimed at their relatives, onto strangers who are compatible with their kidney. In exchange, they get a compatible kidney from another stranger, and so on and so forth, creating a donation chain that addresses compatibility issues while encouraging kidney donation and extending the available organ pool.

Patients reach healthy kidney function following the transplant within a few days to weeks, and must adhere to a strict immunosuppressant drugs course indefinitely to maximise the success of their transplant.

Immunosuppressant drugs act by preventing the production of specific B- and T-cells. They work by inhibiting DNA replication. Alternatively, disabling their production can be accomplished via X-ray irradiation. The patient will no longer mount an immune response via specific B- and T-cells when presented with the antigens of the new organ, but as a side effect, will be more prone to infections.

Blood groups

The basis for blood compatibility is down to antigens found on the surface of red blood cells. There are multiple configurations possible between different people: antigen A, antigen B, both antigens A and B, or neither (0). Additionally, rhesus antigen (D) may be absent or present.

Multiple alleles involve three or more variations (alleles) of a gene. A common example is blood type: A, B, AB or 0 given by three alelles, i, IA and IB.

Relative to type 0 (i-i), both A (i-IA or IA-IA) and B (i-IB or IB-IB) are dominant, while A and B are codominant enabling option AB (IA-IB).

Those with antigen A, B or both cannot have antibodies against them in their blood (since it is part of themselves and recognised as such). Blood type 0 is the universal donor, as it presents no antigens. Type AB is the universal acceptor, as it recognises both antigens A and B as self. Types A and B can donate to AB and A, or AB and B respectively. They can accept from 0 and A, or 0 and B respectively.

If an incompatible blood transfusion were to take place, antibodies against the new antigen on the donated red blood cells would be made. This would result in antibody-antigen complexes being formed on the cell surface. Agglutination of red blood cells would occur, i.e. clumping together; this would pose a dangerous threat to the recipient in the form of blockages in blood vessels. Pars of the body may be starved of oxygen, resulting in their breakdown or death.

Rhesus antigen (antigen D) can lead to Rhesus disease in a newborn who is Rhesus positive, whose parent during pregnancy is Rhesus negative. No one has antibodies for the Rhesus antigen, so a previous exposure to a Rhesus positive foetus in an earlier pregnancy would give enough time to develop these antibodies. In a further pregnancy, these antibodies readily identify the baby's Rhesus positive red blood cells and attack them.

Extreme untreated cases of the diseases can lead to stillbirth. Current treatment for this includes screening early in pregnancy for Rhesus positive foetuses, and if this is the case, inject anti-D immunoglobulins that can remove the foetus cells before they are encountered by the parent's immune system. This prevents the host production of antibodies against the Rh positive foetus cells. However, if these antibodies are already present from a previous pregnancy, the treatment won't be effective. Closer monitoring of the baby is carried out before and after birth.

Microbial resistance

The use of antibiotics is a common example of how evolutionary arms races are critical in the development and deployment of medicines that target organisms. As long as some individuals in a targeted population are able to survive the antibiotic, or in time can develop resistance, under the selection pressure of antibiotic use an ever increasing resistant population will emerge.

This process can happen many times, as organisms are extremely versatile. Bacteria have already been subjected to many natural antibiotic attacks from other organisms (the original penicillin is produced by the fungus Penicillium) so they already have certain resistance genes or pathways they can develop when required.

The key is to understand the adaptation cycle of different organisms and use antibiotics effectively.

1. Not use antibiotics inappropriately, such as to treat colds (caused by viruses not bacteria)

2. Complete prescribed antibiotics treatments so bacteria are effectively killed and there is little to no chance of remaining bacteria coming back stronger

3. Avoid overuse of the same antibiotic in the same setting such as in hospitals where patients are susceptible to infection and spread can be rapid

4. Keep many different antibiotics archived, especially the strongest ones, so that they can be used against multi-resistant strains if they develop, to avoid a situation where no antibiotics are available that bacteria are susceptible to

In the field of disease, pathogens are organisms found at the crossroads between species and their way of surviving and reproducing. At these specific crossroads, the actions of one organism hurt the other. The pathogenic organism is the one inflicting disease upon the victim.

The mechanism of transmission for pathogens can include carriers and disease reservoirsCarriers are infected with the pathogen but do not suffer from disease as a result of infection. Sometimes, this state can make them better at spreading the pathogen to others who might be more susceptible. Disease transmission can be effective when many carriers act as disease reservoirs in a population. They carry a pathogen that does not affect them negatively, is perhaps dormant, but could still be spread to others. People with weak immune systems, the very young and the very old may suffer from disease. An example of a disease with large reservoirs in certain clusters around the world is tuberculosis.

In the case of malaria for example, the parasite-caused disease is transmitted to humans via mosquitoes. They are vectors of the malarial parasite. This means they carry around and move the pathogen and enable infection of humans, without which this wouldn't happen.

Where disease is present constantly over time, it is said to be endemic, for example as tuberculosis is endemic to parts of India. When an otherwise absent or infrequent disease surges in cases in a population, it creates an epidemic. If an epidemic spreads internationally, then it becomes a pandemic.

Antibiotic resistance poses a major worldwide health concern, which highlights how critical the discovery of new classes of antibiotics and other antimicrobials is. When the health of so many people suffers, it not only impacts them negatively, but has far-reaching ramifications that can be felt across society and in the economy.

Monoclonal antibodies

These are antibodies which can be cloned from a single cell to make a high amount of them. They can bind to pretty much any substance, and are used in pregnancy tests as well as cancer treatment.The process involves taking a cell which produces antibodies such as a lymphocyte, and crossing it with a tumour cell. Tumour cells divide uncontrollably, so the end hybrid cell will produce many antibodies via its many clones.

The antibodies are also used to customise drugs to make them target specific cell types, as well as in medical diagnosis. This is often done via a basic detection technique called ELISA (enzyme-linked immunosorbent assay). It takes advantage of the antigen-antibody specificity to produce a signal by attaching an enzyme to the antibody and adding its substrate. If the antibody binds to the antigen in the sample, the enzyme attached to it reacts with the substrate to produce the signal, often a colour change. This indicates the presence of the antigen that the specific antibody has an affinity for. Sometimes both primary and secondary antibodies are used in sequence.

The extent of colour change can be quantified using a spectrophotometer. This reads the absorbance of light passed through the sample of coloured liquid. This varies finely according to the colour and can be obtained at specific wavelengths (green light, red light, etc.).

Ok byeeeeee

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