How Protein Energy Malnutrition Affects the Immune System

November 17, 2025 •

4 min read

Globally, malnutrition is the most prevalent cause of immunodeficiency, affecting hundreds of millions of people, especially children. This critical overview explains how protein energy malnutrition affects the immune system, leading to a vicious cycle of illness and worsening nutritional status.

Quick Summary

Protein energy malnutrition severely impairs both innate and adaptive immunity, causing lymphoid organ atrophy, reducing white blood cell function, and disrupting crucial cytokine production.

Key Points

Leading Cause of Immunodeficiency: Protein energy malnutrition (PEM) is the most common cause of secondary immunodeficiency worldwide, especially in vulnerable populations like children.
Compromised Innate Immunity: PEM weakens the first line of defense by damaging skin and mucosal barriers, impairing phagocytic cell function, and disrupting the complement system.
Impaired Adaptive Immunity: It causes severe atrophy of lymphoid organs (thymus, bone marrow), leading to reduced T-cell and B-cell production and function, and weakened antibody responses.
Vicious Cycle: Malnutrition increases infection risk, and infections further worsen malnutrition by depleting nutrient stores and increasing metabolic demands, creating a deadly loop.
Reversibility with Nutrition: Most immune deficits associated with PEM can be restored through appropriate nutritional rehabilitation, highlighting the critical role of a balanced diet for immune health.

The Vicious Cycle: Malnutrition and Infection

In many developing nations, the interaction between malnutrition and infection creates a detrimental cycle that severely impacts health and increases mortality rates. Protein-energy malnutrition (PEM) weakens the body's defenses, increasing susceptibility to infectious diseases like pneumonia, diarrhea, and tuberculosis. In turn, infections exacerbate malnutrition by depleting nutrient reserves, causing inflammation, and reducing appetite. This cycle is particularly dangerous for vulnerable populations such as infants, young children, and the elderly, who lack strong immune systems or sufficient nutritional reserves. The resulting immunodeficiency is sometimes referred to as Nutritionally Acquired Immune Deficiency Syndrome (NAIDS).

Impact on Innate Immunity

Innate immunity serves as the body's first line of defense, acting quickly and non-specifically to combat pathogens. PEM significantly compromises several components of this critical system:

Impaired Physical Barriers

The skin and mucosal membranes, which act as primary physical barriers against pathogens, are compromised by PEM. Deficiencies in nutrients like vitamin A can disrupt the integrity of epithelial tissues in the respiratory and gastrointestinal tracts, leaving the body more vulnerable to microbial invasion. PEM also reduces the production of essential antimicrobial peptides and the protective functions of mucus.

Phagocytic Cell Dysfunction

Phagocytes, such as neutrophils and macrophages, are crucial for engulfing and destroying pathogens. PEM impairs their function in several ways:

Reduced phagocytic activity and bactericidal capacity.
Impaired ability to engulf and kill invading microorganisms.
Decreased production of key cytokines and reactive oxygen species necessary for eliminating pathogens.

Compromised Complement System

The complement system is a network of serum proteins that helps clear pathogens. During PEM, the levels and activity of complement components, particularly C3, are significantly reduced. This reduces the body's ability to opsonize pathogens (tag them for destruction) and recruit inflammatory cells, thereby hindering an effective innate response.

Effects on Adaptive (Acquired) Immunity

The adaptive immune system provides a targeted, specific, and long-lasting defense against pathogens. PEM inflicts devastating damage on this system, particularly on cell-mediated immunity.

Lymphoid Organ Atrophy

Severe protein malnutrition, especially in newborns and infants, causes severe atrophy of the primary lymphoid organs, the thymus and bone marrow. This has catastrophic effects on the generation and maturation of B and T cell repertoires. Thymic atrophy leads to a significant reduction in T-cell numbers and impairs their maturation.

Reduced T-Cell and B-Cell Function

T-Cells: PEM consistently results in a reduction in circulating lymphocytes, particularly T-cells. This leads to impaired cell-mediated immunity, decreased proliferation in response to stimuli, and a reduced T-helper cell count. The ratio of CD4 to CD8 T-cells is also often altered.
B-Cells: While the impact on humoral immunity is less predictable than on cell-mediated immunity, PEM can impair the antibody response to vaccination and decrease antibody affinity. Severe undernutrition can also disrupt B-cell function and production.

Impaired Humoral Response

The production and secretion of immunoglobulins, or antibodies, are critical for humoral immunity. In PEM, the secretory immunoglobulin A (IgA) response is impaired, weakening mucosal defenses. While serum IgG levels can sometimes remain normal or even increase in malnourished individuals due to chronic infection exposure, the ability to mount effective primary antibody responses to new infections is significantly compromised.

Comparison of PEM's Impact on Innate vs. Adaptive Immunity


Feature	Innate Immune System	Adaptive Immune System
Physical Barriers	Integrity of skin and mucosal membranes is compromised.	Not directly affected, but breaches facilitate entry for adaptive response to handle.
Phagocytic Function	Reduced activity, diminished ability to engulf and kill pathogens.	Dependent on signals from adaptive cells for enhanced function (e.g., macrophage activation by T-cells).
Complement System	Activation and activity of components like C3 are significantly decreased.	Less directly affected, but complement is a crucial link between innate and adaptive responses.
Lymphocyte Numbers	No direct impact, as these are adaptive cells.	Reduced number of T-cells and B-cells due to lymphoid organ atrophy.
T-Cell Function	Not applicable.	Impaired proliferation, differentiation, and overall activity.
Antibody Production	Not applicable.	Impaired production of certain immunoglobulins (e.g., secretory IgA), and compromised primary responses.
Speed of Effect	Rapidly affected by insufficient energy and protein, impairing immediate responses.	Slower onset, as lymphoid organs and cell populations are affected over time.

How Refeeding Restores Immune Function

Fortunately, much of the immune damage caused by PEM is reversible with nutritional rehabilitation. Studies show that refeeding, with an emphasis on protein and micronutrients like zinc and vitamin E, can lead to significant improvements in immune function. Refeeding has been shown to restore T-cell proliferation, enhance delayed-type hypersensitivity, boost antibody responses, and increase natural killer (NK) cell activity. This recovery underscores the critical role of adequate nutrition in maintaining a healthy and functional immune system.

Conclusion: The Public Health Imperative

Protein energy malnutrition is the most common cause of secondary immunodeficiency globally, creating a devastating cycle of weakened immunity and recurrent infections. By compromising both innate and adaptive immune systems, PEM leaves the body highly susceptible to a wide range of diseases. The atrophy of lymphoid organs, dysfunction of phagocytic cells, and impaired T-cell and antibody responses all contribute to a significantly increased risk of morbidity and mortality, particularly in children. The good news is that these negative effects are largely reversible with proper nutritional support. Addressing PEM is therefore not just a matter of improving nutritional status, but a fundamental public health strategy for strengthening immune resilience and breaking the deadly cycle of malnutrition and infection. For more information on the intricate relationship between nutritional deficiencies and immune suppression, one can consult reviews published by the National Institutes of Health.

Frequently Asked Questions

Protein energy malnutrition (PEM) is a deficiency of protein and calories, which are vital for body function and growth. It is a major cause of illness and death worldwide, especially in developing countries.

PEM impairs the body's general defenses by compromising physical barriers like skin and mucous membranes, which act as the first line of defense against pathogens. A deficiency in key nutrients like vitamin A, for example, can make these barriers more permeable.

Yes, PEM significantly impacts white blood cells. It reduces the number of circulating lymphocytes, especially T-cells, and impairs the function of phagocytic cells like neutrophils and macrophages, which are essential for fighting infection.

Severe PEM causes atrophy of the thymus gland, a primary lymphoid organ where T-cells mature. This atrophy leads to a significant reduction in T-cell numbers and impairs the development of the immune system, particularly in infants and young children.

PEM impairs the body's ability to produce effective antibodies, particularly the secretory IgA response which protects mucosal surfaces. It can also weaken the primary antibody response to new antigens, like those from vaccines.

No, the immune damage from PEM is largely reversible. With appropriate nutritional rehabilitation, including protein and micronutrient supplementation, many immune functions can be restored over time.

Malnutrition weakens the immune system, increasing susceptibility to infections. Infections, in turn, put a strain on the body, increasing metabolic demands and depleting nutrient reserves, thereby worsening malnutrition and weakening immunity further.