Immunological changes in SAM

Protein-Energy Malnutrition (PEM), particularly Severe Acute Malnutrition (SAM), is the most common cause of secondary immunodeficiency worldwide. This condition is often termed "Nutritionally Acquired Immunodeficiency Syndrome" due to the profound suppression of the immune system, which mimics acquired immunodeficiencies like AIDS,. The interaction between malnutrition and infection creates a vicious cycle where malnutrition increases susceptibility to infection, and infection further deteriorates nutritional status,.

1. Cell-Mediated Immunity (CMI)

Cell-mediated immunity is the most severely affected arm of the immune system in PEM.

• Thymic Atrophy: Severe malnutrition leads to significant atrophy of the thymus gland and other lymphoid tissues (tonsils, spleen, lymph nodes), a phenomenon termed "nutritional thymectomy",.
• T-Lymphocyte Reduction: There is a marked reduction in the number of circulating T-lymphocytes (lymphopenia),.
• Altered T-Cell Subsets: The ratio of T-helper (CD4) to T-suppressor (CD8) cells is often reduced.
• Anergy: Delayed Cutaneous Hypersensitivity (DCH) responses are impaired. Children often exhibit cutaneous anergy, meaning they fail to react to skin antigens like tuberculin (Mantoux test) and Candida, even if they have active infection. A negative Mantoux test does not rule out tuberculosis in a malnourished child,.
• Functional Deficits: T-lymphocytes show impaired proliferation in response to mitogens and reduced production of cytokines like Interleukin-2 (IL-2),.

2. Humoral Immunity

Humoral immunity is relatively better preserved than cell-mediated immunity, but specific functional deficits exist.

• Immunoglobulin Levels: Serum levels of immunoglobulins (IgG, IgM, IgA) are generally normal or often elevated due to the burden of repeated infections and antigenic stimulation,.
• Antibody Response: While total Ig levels are high, the specific antibody response to new antigens (e.g., response to diphtheria toxoid or yellow fever vaccine) may be impaired or blunted,.
• Secretory IgA (sIgA): There is a significant reduction in secretory IgA levels in mucosal secretions (tears, saliva, gut secretions). This loss of surface immunity predisposes the child to mucosal infections, particularly respiratory and gastrointestinal tract infections.

3. Non-Specific (Innate) Immunity

The body's first line of defense is severely compromised in SAM.

• Physical Barriers: Atrophy of the skin and mucous membranes of the gut and respiratory tract breaches the physical barrier against pathogen invasion,.
• Phagocytosis: Although the number of phagocytes may be normal, their function is impaired. There is a reduction in chemotaxis (movement toward bacteria) and intracellular bacterial killing power (bactericidal activity) due to a lack of glycolytic energy and enzymes,.
• Complement System: Serum complement components (especially C3 and Factor B) are reduced, impairing opsonic activity required for effective phagocytosis,,.
• Acute Phase Reactants: The acute phase response may be blunted due to hepatic compromise, though levels of proteins like alpha-1 antitrypsin may rise during infection.

4. Cytokine Response

Malnutrition disrupts the regulation of the inflammatory response.

• Cytokine Imbalance: There is often an imbalance between pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha) and anti-inflammatory cytokines (IL-10, IL-4). An uncontrolled inflammatory response or a failure to mount an adequate response can occur.
• Reduced Interleukin-2: Production of IL-2, which is critical for T-cell proliferation, is diminished,.

5. Clinical Implications of Immunodeficiency

• Silent Infections: Due to "reductive adaptation" and the suppressed inflammatory response (reduced endogenous pyrogens/cytokines), classic signs of infection like fever and inflammation are often absent. A child with severe pneumonia or sepsis may present only with lethargy, hypothermia, or hypoglycemia,,.
• Gram-Negative Sepsis: The combination of mucosal atrophy and immune paresis makes these children highly susceptible to gram-negative sepsis and bacteremia,.
• Progression of Tuberculosis: Latent TB can easily flare up into active, severe disease (miliary TB, meningitis) due to loss of T-cell control.