There Is No Immune Response to Prions

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People die from infectious diseases when their immune systems have not made enough B or T cells to fight off the infection. In some cases, infectious agents carry antigens for which no amount of DNA rearrangement can yield the proper receptor. In other cases, one group of people may be able to rearrange their DNA to produce the right receptors while others do not. This partly explains why some people do not become ill when exposed to an infectious disease, while others die from the same exposure.

Memory cells will help the body respond more quickly if the pathogen is encountered again.

Virus antigen

■> Helper T cells secrete a substance that enhances humoral immunity (B cells) and cell-mediated immunity (T cells).

Memory cells will help the body respond more quickly if the pathogen is encountered again.

Clonal population

Cytotoxic T cells attack and kill body cells that have become infected with a pathogen.

Cytotoxic T cells attack and kill body cells that have become infected with a pathogen.

Virus antigen

■> Helper T cells secrete a substance that enhances humoral immunity (B cells) and cell-mediated immunity (T cells).

High Tea Hats

Substance amplifies immune response

Substance amplifies immune response

Figure 11.15 Cell-mediated immunity. T lymphocytes divide to produce different populations of cells: (1) Memory cells carry the specific antigen receptor; (2) cytotoxic T cells attack and kill cells; and (3) helper T cells boost the immune response.

Sometimes an infectious agent is effectively combated by the immune system, only to reemerge in a form that is newly pathogenic. Pathogens are under evolutionary pressure to change in order to evade the immune system (see Essay 9.2). Flu vaccines must be given every year because the flu virus rearranges its DNA sequences rapidly. This results in different proteins being encoded and placed on the surface of the virus, thereby preventing existing memory cells from recognizing a virus they have already met. Because the proteins on the surface of a flu virus change so quickly, a vaccine that was prepared to protect you from last year's flu virus will not necessarily work against this year's flu virus.

In the case of the spongiform encephalopathies, the immune system does not mount a response to misfolded prions at all, because they are just refolded versions of the normal prion protein. It seems that the refolded version of the protein is similar enough to the normal version that the immune system recognizes them both as self.

After misfolded bovine prions are ingested by humans, they move to the spleen and lymph nodes and refold all the prions there. From there, the refolded

Cjd Pathology

Figure 11.16 Prion infection. After being ingested (1), misfolded prions move through the small intestine into the blood (2) and gain access to the spleen and lymph nodes. Inside these lymph organs, normal prions are refolded until all of the host's prions are refolded. All of the misfolded prions then move to the brain to refold host prions there. When there are very few normal prions left, the cells of the brain can no longer function normally.

Figure 11.16 Prion infection. After being ingested (1), misfolded prions move through the small intestine into the blood (2) and gain access to the spleen and lymph nodes. Inside these lymph organs, normal prions are refolded until all of the host's prions are refolded. All of the misfolded prions then move to the brain to refold host prions there. When there are very few normal prions left, the cells of the brain can no longer function normally.

proteins move to the brain and spinal cord, where they refold even more normal proteins (Figure 11.16). The lack of normal proteins damages the brain and eventually causes the patient to die.

Prions are proteins, not bacteria or viruses, and conventional treatments for infectious diseases will not prevent or cure the spongiform encephalo-pathies. Bacterial infections are usually treated with antibiotics, which have no effect on prions. Many viral and bacterial infections can be prevented through the use of vaccines given in an attempt to bolster the immune system prior to actual exposure to a pathogen. Vaccines are made of components of the disease-causing organisms—such as proteins from the plasma membrane of a bacterial cell, parts of a virus, or a whole virus that has been inactivated. The immune system responds to the introduced vaccine's challenge by producing the clonal population of memory cells that will be prepared for a real infection by the virus, should it occur. Some vaccines require multiple doses before a sufficient response is generated; others require booster shots to maintain protection.

An anti-prion agent would have to be able to determine which prions were properly folded and which were not. This makes treating spongiform en-cephalopathies very difficult. Because heat and radiation—generally effective in destroying bacteria and viruses—do not work against prions either, scientists hope to discover how to stabilize the normal prion protein so it will maintain its normal shape in brain cells. Until this happens, epidemiologists and other scientists are focusing on preventing the spread of the disease.

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