Journal of Allergy and Clinical Immunology
Chapter 16Secondary immunodeficiencies, including HIV infection
Section snippets
Newborn period
Neonates have an increased susceptibility to common and opportunistic infections and sepsis compared with older children.6 There is an inverse association of infection susceptibility and the age of prematurity. In early life there are fewer marginal-zone B cells in lymphoid tissue and a decreased expression of CD21 on B cells, thus limiting the ability of B cells to develop specific responses.7 Although they can develop humoral responses to some antigens after exposure in utero, impaired
Malnutrition
Worldwide, protein-calorie malnutrition is the most common cause of immunodeficiency.13 Malnutrition can result from limited access to food sources and chronic diseases that induce cachexia, such as neoplastic diseases. Diarrhea caused by infections and respiratory tract infections are common. T-cell production and function decrease in proportion to the severity of hypoproteinemia; however, specific antibody titers and immune responses to vaccines can be detected in a malnourished subject for a
Metabolic diseases: Diabetes mellitus and uremia
Many disease processes originating from dysfunctional metabolic pathways significantly affect the cells involved in the immune response. Diabetes mellitus and uremia resulting from kidney or liver disease are 2 common metabolic disorders with known deleterious effects on immunity. Optimal control of the metabolic abnormality usually leads to improved immune function. The defective immune functions reported in patients with diabetes mellitus include defective phagocytosis and macrophage
Inherited defects other than primary immunodeficiencies
Diseases caused by genetic defects might not primarily affect the immune system, but they can present with impaired immunity to infections resulting from metabolic and cellular dysfunction, such as poor expression of adhesion molecules or defects in the DNA repair machinery. The molecular mechanisms leading to immunologic defects remain not well defined. Genetic syndromes are relatively rare, and usually only a subset of patients present with an immune defect of clinical severity that increases
Anti-inflammatory, immunomodulatory, and immunosuppressive drug therapy
The use of drugs to ameliorate undesirable immune responses is common in clinical practice as a consequence of the increasing prevalence of inflammatory conditions. These diseases include the categories of autoimmune disorders, allergic disorders, transplant rejection, and graft-versus-host disease (GvHD). Broadly, we can study these drugs by dividing them into biologic, physical, and chemical categories. The chemical agents are the most available clinically and have in common their ability to
Surgery and trauma
Surgery and trauma cause disruption of epithelial barriers and cell destruction that triggers an inflammatory response to promote healing and local microbicidal activity.27, 28 Microorganisms contain surface pathogen–derived molecules that activate pattern-recognition receptors expressed on antigen-presenting cells and other immune cells to induce cytokine and chemokine release and recruitment of the adaptive immune system.29 Massive tissue injury further increases activation of proinflammatory
Environmental conditions: UV light, ionizing radiation, high altitude, chronic hypoxia, and space flights
There is increased awareness of potential adverse effects caused by chronic exposure to inhospitable environmental conditions, such as extreme cold or high altitude. It has been recommended to avoid exposure to sunlight because of increased risk of malignancies; however, beneficial effects of sunlight have also been observed, particularly in patients with skin inflammatory conditions, such as psoriasis.33 The biologic effect of sunlight in inflammation is mediated by UV light, which induces
Infectious diseases
Transient periods of immunosuppression have been associated with viral infections since the 1900s, when it was observed that tuberculin skin test results became negative in patients with measles during the acute phase of the infection. Some infectious agents or their toxins and metabolites might be present in excess amounts to activate the immune system, leading to a nonresponsive state, such as the T-cell anergy observed after toxic shock syndrome induced by staphylococcal superantigen. Tissue
Background
Without antiretroviral drug treatment, HIV infection almost always progresses to the advanced stage of the disease called AIDS that is characterized by profound lymphopenia and susceptibility to infections with opportunistic pathogens. HIV is transmitted sexually, for the most part, but it is also transmitted parenterally among intravenous drug users and vertically from mothers to their infants.39 Initially recognized during the early 1980s in a handful of cases, it is currently estimated that
Conclusion
There is an increased awareness of the variety of factors that can affect the immune response. When evaluating a patient with increased frequency or severity of infections suggesting immunodeficiency, physicians should consider that secondary immunodeficiencies are far more common than primary immune defects of genetic cause. A detailed clinical history might uncover the condition affecting the immune system, such as infection, malnutrition, age extremes, concomitant metabolic or neoplastic
References (64)
Primary immunodeficiencies
J Allergy Clin Immunol
(2010)- et al.
Maternal and Child Undernutrition Study Group. Maternal and child undernutrition: global and regional exposures and health consequences
Lancet
(2008) - et al.
Immunomodulator therapy: Monoclonal antibodies, fusion proteins, cytokines, and immunoglobulins
J Allergy Clin Immunol
(2010) Development of the fetal and neonatal immune system
- et al.
Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates
Blood
(2009) - et al.
Innate immunity and aging
Exp Gerontol
(2008) - et al.
Host resistance and immune responses in advanced age
Clin Geriatr Med
(2007) - et al.
Micronutrient deficiencies are associated with impaired immune response and higher burden of respiratory infections in elderly Ecuadorians
J Nutr
(2009) - et al.
Mechanisms of nutrient modulation of the immune response
J Allergy Clin Immunol
(2005) - et al.
Uremia impairs monocyte and monocyte-derived dendritic cell function in hemodialysis patients
Kidney Int
(2007)
Intrinsic abnormalities of lymphocyte counts in children with Down syndrome
J Pediatr
Down syndrome: immunologic and epidemiologic association enigmas remain
J Pediatr
Systemic inflammation after trauma
Injury
Immunoparalysis after multiple trauma
Injury
Treatments for psoriasis and the risk of malignancy
J Am Acad Dermatol
Effects of radiation and latent virus on immune responses in a space flight model
J Allergy Clin Immunol
Suppression of human anti-inflammatory plasma cytokines IL-10 and IL-1RA with elevation of proinflammatory cytokine IFN-gamma during the isolation of the Antarctic winter
J Allergy Clin Immunol
Immune responses in adult female volunteers during the bed-rest model of spaceflight: antibodies and cytokines
J Allergy Clin Immunol
Viral reservoirs, residual viremia, and the potential of highly active antiretroviral therapy to eradicate HIV infection
J Allergy Clin Immunol
Predictors of immunologic long-term non progression in HIV-infected children: implications for initiating therapy
J Allergy Clin Immunol
Phase I/II trial of intermittent subcutaneous IL-2 administration in pediatric patients with moderate immune suppression: results of Pediatric AIDS Clinical Trials Study 402
J Allergy Clin Immunol
Increased incidence of asthma in HIV-infected children treated with highly active antiretroviral therapy in the National Institutes of Health Women and Infants Transmission Study
J Allergy Clin Immunol
Critical issues in mucosal immunity for HIV-1 vaccine development
J Allergy Clin Immunol
HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis
Lancet
Vaginal microbicides and the prevention of HIV transmission
Lancet Infect Dis
Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review
JAMA
Immunosuppressive preconditioning or induction regimens, evidence to date
Drugs
B cell responses to vaccination at the extremes of age
Nat Rev Immunol
The ageing immune system: is it ever too old to become young again?
Nat Rev Immunol
Biology of immune responses to vaccines in elderly persons
Clin Infect Dis
Acute lower respiratory infections in childhood: opportunities for reducing the global burden through nutritional interventions
Bull World Health Organ
Vitamin D in defense of the human immune response
Ann N Y Acad Sci
Cited by (169)
Coronavirus Disease-2019 in the Immunocompromised Host
2024, Infectious Disease Clinics of North AmericaRecommendations for Management of Secondary Antibody Deficiency in Multiple Myeloma
2023, Clinical Lymphoma, Myeloma and LeukemiaCoronavirus Disease-2019 in the Immunocompromised Host
2023, Clinics in Chest MedicineManagement of hypogammaglobulinemia
2023, Revue de Medecine Interne
Supported by National Institutes of Health grants AI27551, AI36211, AI6944I, HD41983, RR0188, HD79533, HL72705, and HD78522 and the David Fund, the Pediatrics AIDS Fund, and the Immunology Research Fund, Texas Children's Hospital.
Disclosure of potential conflict of interest: J. Chinen and W. T. Shearer have declared that they have no conflict of interest.