61 Age Related Dysfunctions of the Immune System

General Decrease in Immune Responses

The interactions of the immune system are very complex.  This makes it impossible to fully understand how the dysfunctions of individual components affect the system as a whole.  That being said, it is well known that there is a general decrease in immune response with age.  Simultaneously autoimmune responses increase with age.  This means that the body’s ability to fight invading pathogens is decreasing, while it becomes more likely that the immune system will attack the body’s own healthy tissue.

Age Associated T-Lymphocyte Defects

The reduced activity of T lymphocytes and the reduction in cell-mediated immunity that results in considered to be a factor in the reactivation of lymphoma, tuberculosis, and shingles that occurs most often in older people.

Acquired Immune Deficiency Syndrome

The Worldwide AIDS Epidemic

(a) As of 2008, more than 15 percent of adults were infected with HIV in certain African countries. This grim picture had changed little by 2012. (b) In this scanning electron micrograph, HIV virions (green particles) are budding off the surface of a macrophage (pink structure). (credit b: C. Goldsmith)

The top panel shows a color-coded world map. The bottom panel shows many viruses on a cell.

In June 1981, the Centers for Disease Control and Prevention (CDC), in Atlanta, Georgia, published a report of an unusual cluster of five patients in Los Angeles, California. All five were diagnosed with a rare pneumonia caused by a fungus called Pneumocystis jirovecii (formerly known as Pneumocystis carinii).

Why was this unusual? Although commonly found in the lungs of healthy individuals, this fungus is an opportunistic pathogen that causes disease in individuals with suppressed or underdeveloped immune systems. The very young, whose immune systems have yet to mature, and the elderly, whose immune systems have declined with age, are particularly susceptible. The five patients from LA, though, were between 29 and 36 years of age and should have been in the prime of their lives, immunologically speaking. What could be going on?

A few days later, a cluster of eight cases was reported in New York City, also involving young patients, this time exhibiting a rare form of skin cancer known as Kaposi’s sarcoma. This cancer of the cells that line the blood and lymphatic vessels was previously observed as a relatively innocuous disease of the elderly. The disease that doctors saw in 1981 was frighteningly more severe, with multiple, fast-growing lesions that spread to all parts of the body, including the trunk and face. Could the immune systems of these young patients have been compromised in some way? Indeed, when they were tested, they exhibited extremely low numbers of a specific type of white blood cell in their bloodstreams, indicating that they had somehow lost a major part of the immune system.

Acquired immune deficiency syndrome, or AIDS, turned out to be a new disease caused by the previously unknown human immunodeficiency virus (HIV). Although nearly 100 percent fatal in those with active HIV infections in the early years, the development of anti-HIV drugs has transformed HIV infection into a chronic, manageable disease and not the certain death sentence it once was. One positive outcome resulting from the emergence of HIV disease was that the public’s attention became focused as never before on the importance of having a functional and healthy immune system.

Although many viruses cause suppression of the immune system, only one wipes it out completely, and that is HIV. It is worth discussing the biology of this virus, which can lead to the well-known AIDS, so that its full effects on the immune system can be understood. The virus is transmitted through semen, vaginal fluids, and blood, and can be caught by risky sexual behaviors and the sharing of needles by intravenous drug users. There are sometimes, but not always, flu-like symptoms in the first 1 to 2 weeks after infection. This is later followed by seroconversion. The anti-HIV antibodies formed during seroconversion are the basis for most initial HIV screening done in the United States. Because seroconversion takes different lengths of time in different individuals, multiple AIDS tests are given months apart to confirm or eliminate the possibility of infection.

After seroconversion, the amount of virus circulating in the blood drops and stays at a low level for several years. During this time, the levels of CD4+ cells, especially helper T cells, decline steadily, until at some point, the immune response is so weak that opportunistic disease and eventually death result. CD4 is the receptor that HIV uses to get inside T cells and reproduce. Given that CD4+ helper T cells play an important role in other in T cell immune responses and antibody responses, it should be no surprise that both types of immune responses are eventually seriously compromised.

Treatment for the disease consists of drugs that target virally encoded proteins that are necessary for viral replication but are absent from normal human cells. By targeting the virus itself and sparing the cells, this approach has been successful in significantly prolonging the lives of HIV-positive individuals. On the other hand, an HIV vaccine has been 30 years in development and is still years away. Because the virus mutates rapidly to evade the immune system, scientists have been looking for parts of the virus that do not change and thus would be good targets for a vaccine candidate.

Lymphomas

Lymphomas are malignancies of the lymph nodes.  Typical symptoms include swollen lymph nodes, persistent fever, night sweat sweats, and weight loss.  Lymphomas are classifies as either Hodgkin’s disease or non-Hodgkin’s lymphoma bases on different patterns of spread, clinical behavior, and cells or origin.  Hodgkin’s disease shows a bimodal age distribution, with one peak occurring between 15 and 35 years of age and another peak between ages 50 and 80.  The incidence of non-Hodgkin’s lymphoma increases progressively with age.

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Biology of Aging by Lumen Learning is licensed under a Creative Commons Attribution 4.0 International License, except where otherwise noted.

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