What is immune dysfunction?

Immune dysfunction refers to abnormalities or dysregulation in the functioning of the immune system, which is responsible for protecting the body from harmful invaders such as viruses, bacteria, fungi, and other pathogens, as well as abnormal cells like cancer cells. The immune system is composed of various cells, tissues, and organs that work together to identify and eliminate foreign substances and maintain homeostasis in the body.


Immune dysfunction can manifest in different ways and may involve:


  • Immunodeficiency: Immunodeficiency disorders occur when the immune system is weakened or impaired, leading to increased susceptibility to infections and other diseases. Primary immunodeficiencies are genetic disorders that affect the development or functioning of the immune system from birth, while secondary immunodeficiencies can develop later in life due to factors such as infections, medications, or underlying medical conditions. Examples of immunodeficiency disorders include severe combined immunodeficiency (SCID), common variable immunodeficiency (CVID), and HIV/AIDS.


  • Autoimmunity: Autoimmune disorders occur when the immune system mistakenly attacks and damages healthy cells and tissues in the body, leading to chronic inflammation and tissue damage. Autoimmune diseases can affect multiple organs and systems, and the specific target tissues vary depending on the disorder. Examples of autoimmune diseases include rheumatoid arthritis, systemic lupus erythematosus (SLE), type 1 diabetes, multiple sclerosis, and inflammatory bowel disease (Crohn’s disease and ulcerative colitis).


  • Allergic and Hypersensitivity Reactions: Allergies and hypersensitivity reactions occur when the immune system overreacts to harmless substances in the environment, such as pollen, dust, food proteins, or medications. These exaggerated immune responses can lead to symptoms such as itching, swelling, hives, wheezing, and anaphylaxis. Allergic disorders include allergic rhinitis (hay fever), asthma, atopic dermatitis (eczema), and food allergies.


  • Immunosenescence: Immunosenescence refers to age-related changes in the immune system, characterized by gradual decline in immune function and increased susceptibility to infections, autoimmune diseases, and cancer. As people age, the immune system undergoes alterations in cell composition, function, and responsiveness, which can impair immune surveillance and defense mechanisms. Immunosenescence contributes to increased morbidity and mortality in older adults.


  • Inflammatory Disorders: Chronic inflammation is associated with many health conditions, including cardiovascular disease, metabolic syndrome, neurodegenerative diseases, and cancer. Dysregulated immune responses and persistent inflammation can contribute to tissue damage, organ dysfunction, and disease progression in these disorders.


What is the relationship between immune dysfunction and oxidative stress?

The relationship between immune dysfunction and oxidative stress is intricate and bidirectional, with each influencing the other in various ways. Here’s how immune dysfunction and oxidative stress are interrelated:


  • Immune Activation and Oxidative Stress: Immune activation, such as during infection, inflammation, or autoimmune responses, can lead to the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) by immune cells, such as macrophages, neutrophils, and T cells. These reactive molecules serve as essential mediators of host defense mechanisms, contributing to the elimination of pathogens and damaged cells. However, excessive or prolonged immune activation can result in the overproduction of ROS/RNS, leading to oxidative stress and cellular damage.


  • Oxidative Stress and Immune Dysfunction: Oxidative stress can modulate immune responses and contribute to immune dysfunction by affecting various aspects of immune cell function, including proliferation, activation, differentiation, and apoptosis. High levels of ROS/RNS can impair immune cell signaling pathways, disrupt redox-sensitive transcription factors (such as nuclear factor kappa B, NF-κB), and alter the expression of cytokines, chemokines, and immune receptors. These changes can lead to dysregulated immune responses, chronic inflammation, and susceptibility to infections or autoimmune diseases.


  • Antioxidant Defense Mechanisms: The immune system relies on antioxidant defense mechanisms to regulate oxidative stress and maintain redox homeostasis. Antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase, as well as non-enzymatic antioxidants like vitamin C, vitamin E, and glutathione, help neutralize ROS/RNS and protect immune cells from oxidative damage. Dysfunctional antioxidant defenses or depletion of antioxidant reserves can impair immune cell function and exacerbate oxidative stress-mediated immune dysfunction.


  • Chronic Inflammation and Oxidative Stress: Chronic inflammation, a hallmark of many immune-related disorders, is closely linked to oxidative stress. Persistent immune activation and inflammatory cytokine signaling can stimulate ROS/RNS production by immune and non-immune cells, contributing to oxidative stress and tissue damage. Conversely, oxidative stress can further perpetuate inflammation by activating pro-inflammatory pathways and amplifying immune responses, creating a vicious cycle of immune dysfunction and oxidative damage.


  • Age-Related Immune Senescence: Aging is associated with alterations in immune function and increased susceptibility to infections, autoimmune diseases, and cancer, partly due to immune senescence. Age-related changes in the immune system, such as thymic involution, decreased T cell diversity, and impaired immune cell function, can contribute to immune dysfunction and dysregulated inflammatory responses. Oxidative stress is implicated in the process of immune senescence, as ROS/RNS can induce cellular senescence, DNA damage, and mitochondrial dysfunction in immune cells, further exacerbating age-related immune dysfunction.


Overall, the relationship between immune dysfunction and oxidative stress is complex and multifaceted, with reciprocal interactions influencing immune responses, inflammation, and cellular homeostasis.