Acquired Immunodeficiency Syndrome Causes

Acquired Immunodeficiency

• Caused by other diseases or conditions, including aging, protein-calorie malnutrition, cancer treatment, immunosuppressive therapies, and HIV infection.
• HIV infection leads to severe secondary immunodeficiency, causing dysfunction and deficiency of B cells, T cells, and phagocytic cells, and decreased cell-mediated cytotoxicity by natural killer cells.

Immunomodulation

• HAART (Highly Active Antiretroviral Therapy) and IL-2 can reconstitute the immune system and slow apoptosis of HIV-infected cells.
• Chemokine receptor inhibitors can prevent HIV entry into host cells.
• Vaccines, including proteins, DNA, subunit, and recombinant virus (SIV-HIV chimeric virus), can stimulate immune response.

Problems with Immunomodulation

• HIV-1 infection allows the virus to shield itself from recognition by antibodies.
• Low immunogenicity and delayed response due to low CD4+ T cell counts.
• Destruction of CD4+ T cells by vaccine.
• Integration of virus in host genome.
• High rate of virus replication.
• Challenges with vaccine development, including route of exposure and lack of animal models.

Disorders of the Immune System

• Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease.
• Reactions of hypersensitivity, including allergic rhinitis and anaphylaxis.
• Autoimmune diseases, including rheumatoid arthritis and multiple sclerosis.
• Immunodeficiency syndromes, including primary and acquired immunodeficiency.

Inflammatory Bowel Disease (IBD)

• Caused by a dysregulated immune response.
• Two forms: ulcerative colitis (mucosal inflammation confined to the rectum and colon) and Crohn's disease (transmural inflammation of the GI tract).
• Etiologies include dysregulated immune response, host genetics, and environmental factors.

Etiologies of IBD

• Dysregulated immune response.
• Host genetics.
• Environmental factors, including commensals, pathogens, antibiotics, diet, stress, and barrier function.

Infectious Factors

• Certain bacterial strains produce toxins that cause mucosal damage.
• Bacteria produce peptides that cause an influx of inflammatory cells.
• Microbes may elaborate superantigens that stimulate global T lymphocyte stimulation.

Genetic Factors

• Positive family history is a significant risk factor.
• Increased concordance for the disease in monozygotic twins.
• Polygenic disease, with susceptibility loci on multiple chromosomes.
• Linkage mutations have been found on CARD15/NOD2, IBD5, and IBD3 loci.

The Role of NOD2 in the Immune System

• NOD2 recognizes bacterial molecules and stimulates an immune reaction.
• Encodes a protein with two caspase recruitment domains and eleven leucine-rich repeats.
• Expressed in peripheral blood leukocytes.
• Plays a critical role in immune response by recognizing bacterial molecules and activating NF-κB.

Immunological Mechanism of IBD

• The immune system plays a critical role in the pathogenesis of IBD.
• Infiltration of lymphocytes, plasma cells, mast cells, macrophages, and neutrophils in the bowel wall and mucosal layer.
• Inflammation is maintained by an influx of leukocytes from the vascular system into sites of active disease.
• The influx is promoted by expression of adhesion molecules on endothelial cells.

The Immune Theory of IBD

• IBD is caused by an inappropriate reaction of the immune system.
• Potential immunologic mechanisms include both autoimmune and non-autoimmune phenomena.
• Dysregulation of cytokines is a component of IBD.
• Th1 cytokine activity is excessive in CD, while Th2 cytokine activity is excessive in UC.
• Patients have an inappropriate T cell response to antigens from their own intestinal microflora.

This quiz covers the various causes of acquired immunodeficiency syndrome, including aging, malnutrition, cancer treatment, and HIV infection.