Introduction – Secondary Immunodeficiency

00:01 Let’s look at secondary immunodeficiency.

00:03 This is immunodeficiency caused by an external agent.

00:07 In contrast to primary immunodeficiencies which are caused by gene defects.

00:13 So secondary immunodeficiency is defective immunity caused by an external factor.

00:20 Could be cytotoxic drugs, radiation, immunosuppressive drugs, malnutrition, metabolic and other diseases, tumors, immaturity, pregnancy, aging or infection.

00:43 All of these things can lead to secondary immunodeficiency.

00:48 Cytotoxic drugs for example, chemotherapy, targets rapidly dividing cells.

00:56 This restricts the ability of hematopoietic stem cells to produce progenitor cells.

01:03 This commonly results in neutropenia - low levels of neutrophils.

01:09 It also inhibits lymphocyte proliferation in response to antigen stimulation.

01:15 Radiation, for example environmental exposure, or radiotherapy given for the treatment of tumors and other conditions; just like cytotoxic drugs, radiation can restrict the ability of hematopoietic stem cells to produce progenitor cells. And also inhibits lymphocyte proliferation in response to antigen stimulation. Immunosuppressive drugs used to limit transplant rejection, autoimmune disease and allergy, can also lead to secondary immunodeficiency. For example, general immunosuppressive agents such as glucocorticoids. Monoclonal antibodies targeted to adhesion molecules, to cytokine receptors, to co-stimulatory molecules and so forth.

02:04 And inhibitors of signaling pathways such as the immunosuppressive drug cyclosporine.

02:10 Malnutrition, metabolic and other diseases are yet again a cause of secondary immunodeficiency.

02:20 Protein-calorie malnutrition and deficiency of micronutrients such as vitamin A, zinc, iron, magnesium, selenium, and so on can impair the immune response, particularly T-cell responses.

02:36 In diabetes mellitus, there is a impaired neutrophil chemotaxis and phagocytosis, a reduced delayed hypersensitivity skin test reaction and poor lymphocyte proliferation responses.

02:52 In the disease, intestinal lymphangiectasia, lymphocytes are passively lost into the intestine.

03:01 In contrast, in the disease nephrotic syndrome, proteins particularly antibodies are lost into the urine.

03:10 In tumors, cancer metastases can distrupt interactions in lymphoid tissues.

03:18 In leukemia and lymphoma, the tumor cells can “crowd out” the development of the normal immune responses.

03:27 And in myeloma, antibodies are dominated by the specificity of the malignant plasma cell at the expense of other antibody specificities against common pathogens.