Secondary immunodeficiency due to underlying disease states, environmental exposures, and miscellaneous causes
- Francisco A Bonilla, MD, PhD
Francisco A Bonilla, MD, PhD
- Section Editor — Immunology and Immunodeficiency
- Associate Professor of Pediatrics
- Harvard Medical School
Immune system function is altered by many conditions, which primarily impair function of other organ systems (table 1). As with primary immunodeficiency, secondary immune dysfunction leads to an increased incidence of infection and malignancy and the occurrence of autoimmune disease.
The mechanisms and sequelae of the immune dysfunction, occurring as the result of biochemical abnormalities, environmental exposures, miscellaneous disorders, and infections other than human immunodeficiency virus (HIV), will be reviewed here. Secondary immunodeficiencies resulting from immunosuppressive agents and malignancy are discussed separately. (See "Secondary immunodeficiency induced by biologic therapies".)
HIV infection and the acquired immunodeficiency syndrome (AIDS) constitute an entire discipline by themselves and are discussed separately in the appropriate topic reviews.
DISORDERS OF BIOCHEMICAL HOMEOSTASIS
Disease processes that lead to chronic imbalances in hormones, nutrients, and toxic metabolic waste products in body fluids may have profound effects on the function of one or more components of the immune system. There are a great many diagnostic entities that may be grouped under this broad heading. It may be that many have unknown effects on immune function. A few disorders where clinically significant immune dysfunction is regularly encountered are presented in this section.
Diabetes mellitus — Neutrophil dysfunction underlies much of the predisposition to bacterial and fungal infections found in patients with diabetes [1-3]. In addition, poor peripheral circulation leads to skin ulceration and diminished delivery of neutrophils to sites of microbial entry. Some characteristic infectious complications of diabetes include disseminated candidiasis, rhinopulmonary zygomycosis (mucormycosis), malignant otitis due to Pseudomonas aeruginosa, and melioidosis (Burkholderia pseudomallei). Bacterial infections of surgical sites are also increased in patients with diabetes, possibly related to the deleterious effect of hyperglycemia on chemotaxis, phagocytosis, and adherence of granulocytes. Issues related to infection in patients with diabetes mellitus are reviewed in more detail separately. (See "Susceptibility to infections in persons with diabetes mellitus".)
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- Chanchamroen S, Kewcharoenwong C, Susaengrat W, et al. Human polymorphonuclear neutrophil responses to Burkholderia pseudomallei in healthy and diabetic subjects. Infect Immun 2009; 77:456.
- Hauser AB, Stinghen AE, Kato S, et al. Characteristics and causes of immune dysfunction related to uremia and dialysis. Perit Dial Int 2008; 28 Suppl 3:S183.
- Albillos A, Lario M, Álvarez-Mon M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol 2014; 61:1385.
- Bourke CD, Berkley JA, Prendergast AJ. Immune Dysfunction as a Cause and Consequence of Malnutrition. Trends Immunol 2016.
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- Kreitinger JM, Beamer CA, Shepherd DM. Environmental Immunology: Lessons Learned from Exposure to a Select Panel of Immunotoxicants. J Immunol 2016; 196:3217.
- Pedata P, Petrarca C, Garzillo EM, Di Gioacchino M. Immunotoxicological impact of occupational and environmental nanoparticles exposure: The influence of physical, chemical, and combined characteristics of the particles. Int J Immunopathol Pharmacol 2016; 29:343.
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- Hartung T, Corsini E. Immunotoxicology: challenges in the 21st century and in vitro opportunities. ALTEX 2013; 30:411.
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- Carson JL, Altman DG, Duff A, et al. Risk of bacterial infection associated with allogeneic blood transfusion among patients undergoing hip fracture repair. Transfusion 1999; 39:694.
- Silasi M, Cardenas I, Kwon JY, et al. Viral infections during pregnancy. Am J Reprod Immunol 2015; 73:199.
- Sappenfield E, Jamieson DJ, Kourtis AP. Pregnancy and susceptibility to infectious diseases. Infect Dis Obstet Gynecol 2013; 2013:752852.
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- Ruocco MG, Chaouat G, Florez L, et al. Regulatory T-cells in pregnancy: historical perspective, state of the art, and burning questions. Front Immunol 2014; 5:389.
- Kay AW, Bayless NL, Fukuyama J, et al. Pregnancy Does Not Attenuate the Antibody or Plasmablast Response to Inactivated Influenza Vaccine. J Infect Dis 2015; 212:861.
- Repasky EA, Eng J, Hylander BL. Stress, metabolism and cancer: integrated pathways contributing to immune suppression. Cancer J 2015; 21:97.
- Costa-Pinto FA, Palermo-Neto J. Neuroimmune interactions in stress. Neuroimmunomodulation 2010; 17:196.
- Namazi MR. The cellular immunodeficiency associated with post-traumatic stress disorder may be the result of sympathetic overactivity and be correctable by beta-2-blockers. Neuro Endocrinol Lett 2003; 24:468.
- Griffin DE. Measles virus-induced suppression of immune responses. Immunol Rev 2010; 236:176.
- Coughlin MM, Bellini WJ, Rota PA. Contribution of dendritic cells to measles virus induced immunosuppression. Rev Med Virol 2013; 23:126.
- Boeckh M, Nichols WG. Immunosuppressive effects of beta-herpesviruses. Herpes 2003; 10:12.
- Koch S, Larbi A, Ozcelik D, et al. Cytomegalovirus infection: a driving force in human T cell immunosenescence. Ann N Y Acad Sci 2007; 1114:23.
- Langley R, Patel D, Jackson N, et al. Staphylococcal superantigen super-domains in immune evasion. Crit Rev Immunol 2010; 30:149.
- Guenin-Macé L, Siméone R, Demangel C. Lipids of pathogenic Mycobacteria: contributions to virulence and host immune suppression. Transbound Emerg Dis 2009; 56:255.
- Maizels RM, McSorley HJ. Regulation of the host immune system by helminth parasites. J Allergy Clin Immunol 2016; 138:666.
- Motran CC, Ambrosio LF, Volpini X, et al. Dendritic cells and parasites: from recognition and activation to immune response instruction. Semin Immunopathol 2017; 39:199.
- Moormann AM, Bailey JA. Malaria - how this parasitic infection aids and abets EBV-associated Burkitt lymphomagenesis. Curr Opin Virol 2016; 20:78.
- DISORDERS OF BIOCHEMICAL HOMEOSTASIS
- Diabetes mellitus
- Dialysis and uremia
- DISORDERS OF PROTEIN LOSS
- Nephrotic syndrome
- Peritoneal dialysis
- Protein-losing enteropathies
- - Intestinal lymphangiectasia
- Other disorders
- ENVIRONMENTAL EXPOSURES
- Ionizing radiation
- Ultraviolet radiation
- Toxic chemicals
- ALLOGENEIC BLOOD TRANSFUSION
- SPLENECTOMY OR HYPOSPLENISM
- NORMAL LIFE STAGES AND EVENTS
- INFECTIONS (OTHER THAN HIV)
- Viral infections
- - Measles
- - Herpesviruses
- Bacterial infections
- Mycobacterial infections
- Parasite infestation
- - Malaria
- SUMMARY AND RECOMMENDATIONS