Causes: Aging & Infections – Secondary Immunodeficiency Diseases

00:01 As we get older, things begin to go wrong, and the immune system is no exception to this.

00:05 Immunosenescence particularly affects T-cells.

00:10 The thymus shrinks by about 3% each year following puberty.

00:17 And therefore, there is a reduced production of naïve T-cells.

00:22 In infancy, the thymus produces T-cells with a mixture of different specificities.

00:28 The T-cell numbers in the peripheral pool are maintained by replication of circulating cells.

00:35 In early adult life, the thymus produces fewer T-cells.

00:42 Proliferation in the periphery maintains the size of the T-cell pool.

00:48 Replicative senescence related to the shortening of telomeres limits the number of times a cell can divide.

00:55 Cytomegalovirus-specific T-cells become dominant at the expense of other specificities during aging.

01:02 And the response to vaccines and to infection declines.

01:08 So in the elderly, nearly no new T-cells are produced by the thymus.

01:14 And this replicative senescence makes it harder for proliferation in the periphery to maintain T-cell numbers.

01:23 In addition, the T-cell pool has become very oligoclonal.

01:28 That means there are very few different clones of T-cells.

01:31 Their specificity becomes more limited as we age.

01:35 In fact as we age, neutrophils have a lower ability to produce reactive oxygen species, they have a lower ability to be chemotactically attracted to the site of the infection, and they have a reduced ability to phagocytose microorganisms. Dendritic cells have a reduced ability to co-stimulate for T-cell activation.

02:00 Macrophages again like neutrophils, have a reduced ability to produce reactive oxygen species, also to produce reactive nitrogen intermediates, the amount of IL-6 they can produce goes down, and the amount of prostaglandin E2, a pro-inflammatory substance goes up.

02:21 Natural killer cells have reduced cytokine production and a decreased ability to kill infected cells, in other words reduced cytotoxicity.

02:31 Antibody levels overall do not decline, but there is a reduced affinity of the antibodies produced, and also there are greater numbers of autoantibodies against self antigens that are produced.

02:44 Infection can be an important cause of secondary immunodeficiency.

02:54 So to just give you a few examples; Example of a parasite- malaria, a protozoan parasite.

03:01 In malaria, hemozoin which is produced from host hemoglobin upon infection with the Plasmodium species that causes malaria, this substance inhibits dendritic cell function.

03:17 An example of a virus - the measles virus.

03:20 Infection of dendritic cells leads to reduced T-cell responsiveness.

03:27 Example amongst the bacteria - Staphylococcus.

03:31 The toxic shock syndrome that you see in Staphylococcal infections is caused by a superantigen that leads to T-cell exhaustion.

03:41 A superantigen is a molecule that stimulates lots and lots and lots of different T-cell clones, not just the ones specific for the antigen, but many others as well.

03:52 And then finally of course, the Human Immunodeficiency Virus that leads to the Acquired Immune Deficiency Syndrome (AIDS).