Notes on Secondary Immunodeficiency

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What is Secondary Immunodeficiency?

• SE disorders are caused due to acquired defects in lymphocyte cell mediated immunity.

• Patients are susceptible to infections by viruses, protozoa, fungi, and bacteria.

• As the patient's condition worsens, infections by Infection with Herpes viruses, Toxoplasma gondii, and Mycobacterium tuberculosis result in chronic latent (not apparent) infection.

• Other infections include: Pneumocystis carinii, Cryptococcus neoformans (fungi) and Mycobacterium avium.

Protein-Calorie Malnutrition (PCM)

• Most common causes of SI due to cell-mediated immune system.

• Individuals are susceptible to infections like: Pneumocystis carinii, Mycobacterium, tuberculosis, Candida and common bacteria and viruses.

• High risk for gastrointestinal and parasitic infections.

• There is a reduction of CD4 and CD8 cells, and a lower CD4/CD8 ratio. Furthermore, there impaired delayed hypersensitivity reactions and thymic atrophy, and antigens are depressed.

• IgA and IgE are elevated, but IgA are reduced.

• There is impaired phagocyte function, defects in chemotaxis and bacterial/candidial killing.

• Opsonization is further affected.

• Malnutrition gives rise to frequent infections and leads to anorexia and muscle wasting caused by overproduction of INF-alpha, IL-1 an IL-6.

• Elderly are especially at risk for PCM.

Zink deficiency:

• Associated with damaged skin, gastrointestinal and respiratory tract epithelial barrier. Regular infections include diarrhea, bullous skin lesions and pneumonia. Furthermore, there is decreased activity of phagocytes and NK cells.

T-cell deficiency:

• Impaired DTH, atrophy of lymphoid organs, lower CD4/CD45RA T cells, decreased T helper cells and CD8 cells.

Iron deficiency:

• Impaired mitogenic lymphocyte proliferative responses, depressed DTH, reduced interferon production, and suppressed neutrophyl phagocytosis, and bacterial killing.

Nephrotic Syndrome

• Patients susceptible to pneumococcal diseases.

• Increased CD8 and CD16, and memory of CD4 and CD8 cells, and elevated Th1 cytokines.

Uremia and Dialysis-Related Immunodeficiency

• Diminished, chemotaxis, phagocytosis, intracellular, killing.

Diabetes Mellitus

• Reduction of CD4 cells and impaired lpr.

• Abnormalities in adherence, chemotaxis, phygocytosis, bactericidal and leukocyte antioxidant production.

• Autoantibody production.

Protein-Losing Enteropathy

• Intestinal protein loss caused by helicobacter pylori.

• Causes Hypogammaglobulinaemia, lymphopenia, and reduction in nymbers of CD4/45RA T cells.

Measles Virus

• Infection causes immunosuppression.

• Infects lymphoid tissues through CD46 molecule.

• Monocytes, T/B cells are affected.

Epstein-Barr Virus

• The body attacks EBV by increasing the numbers of CD8+ T cells - both cytotoxic and suppressor cells.

• IL10 and CD40 signals also enhance the production of B-cells.

Cytomegalovirus

• Monocytes and T-cells are infected.

• Rise in infections by tetanus toxoid and Candida albicans.

• There are low Ig serum levels.

Aging and The Immune System

• Decrease in the number of blood lymphocytes or serum Igs.

• IL4/6 increase with age.

• Th2 cytokines increase.

• Loss of naive T cells, with increase in memory T cells.

• Involution of thymus.

• Loss of DTH and T-cell proliferation responses.

• Dysregulation of Th1 and Th2.

• Impaired production of B cells.

• Oligoclonal and monoclonal Ig production.

Secondary Immunodeficiency induced by Surgery and Trauma

• This is due to altered functions of lymphocytes.

• Polymorphonuclear cells, and macrophages following injury.

Hormonal Mediators

• Cortisol.

• Glucagon.

• Catecholamines.

• Vasopressin.

• Aldosterone.

• Growth hormone.

Serum-borne Mediators of Inflammation

• Vasoactive amines.

• Cytokines.

• Interferon.

Splenectomy

• Increased risk of sepsis.

Symptoms and Signs of AIDS

• Peripheral CD4 count less than 200 cells/mm3.

• Candidiasis of oesophagus, trachea, bronchi.

• Invasive cervical cancer.

• Extra pulmonary coccidioidomycosis cryptococcosis, or histoplasmosis.

• Cryptosporidiosis or isosporiasis with diarrhoea > 1 month.

• Cytomegalovirus (organ other than liver, spleen, lymph nodes).

• Herpes simplex with chronic mucocutaneous ulcer, bronchitis/pneumonitis, esophagitis.

• HIV-associated dementia or wasting.

Progression of HIV infection

• Primary 3-6 weeks.

• Acute 1 week - 3 months.

• HIV specific immune response; Serum antibodies detectable 1-2 weeks.

• Clinical latency 10 years.

• AIDS defining illness 2 years.

• Death.

HIV screening done by ELISA; final confirmation done by Western blot. HIV infection reservoirs include lymphoid tissue, macrophages and dendrite cells.

Additional Readings:

Basic Immunology

1. Introduction to Immunology
2. Cells of Immunology
3. Selection of Lymphocytes
4. Primary Response to Antigen
5. Antigen Processing and Presentation
6. Humoral Effector Mechanism Generator
7. Cell-Mediated Effector Mechanism Generator
8. Vaccination and Immunotherapy
9. Immunodeficiency Diseases
10. Acquired Immunodeficiency Syndrome
11. Hypersensitivities and Autoimmunity Diseases
12. Immunology of Transplantation
13. Immunology of Cancer
14. Immunology Laboratory Technology
15. Acquired Immunity
16. Type II Hypersensitivity Reaction
17. Hypersensitivity Reactions
18. Primary Immunodeficiency
19. Secondary Immunodeficiency
20. Type III Hypersensitivity Reaction
21. Type IV Hypersensitivity Reaction
22. Type V Hypersensitivity Reaction
23. Tumor Immunology
24. Images of Antibodies
25. Th1 vs Th2 cells

Related Topics

1. Histology of Lymphoid Tissue

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