up:: [[List of Systems of the Human Body]] tags:: #on/physiology #on/anatomy #on/immunity # Immune System > The immune system provides layered defenses against pathogens, starting with physical barriers like the skin and progressing to innate and adaptive immune responses. The immune system functions as a network of biological systems protecting organisms from diseases by detecting and responding to various pathogens, cancer cells, and foreign objects while distinguishing them from healthy tissue. *It comprises two major subsystems*: the [[Innate Immune System]], which offers a generalized response to a wide range of threats, and the [[Adaptive Immune System]], which tailors its response to each stimulus by learning to recognize encountered molecules. > Dysfunction in the immune system can lead to autoimmune diseases, inflammatory diseases, and cancer. |[Innate immune system](https://en.wikipedia.org/wiki/Immune_system#Innate_immune_system)|[Adaptive immune system](https://en.wikipedia.org/wiki/Immune_system#Adaptive_immune_system)| |---|---| |Response is non-specific|Pathogen and [antigen](https://en.wikipedia.org/wiki/Antigen "Antigen") specific response| |Exposure leads to immediate maximal response|Lag time between exposure and maximal response| |[Cell-mediated](https://en.wikipedia.org/wiki/Cell-mediated_immunity "Cell-mediated immunity") and [humoral](https://en.wikipedia.org/wiki/Humoral_immune_response "Humoral immune response") components|[Cell-mediated](https://en.wikipedia.org/wiki/Cell-mediated_immunity "Cell-mediated immunity") and [humoral](https://en.wikipedia.org/wiki/Humoral_immune_response "Humoral immune response") components| |No immunological memory|Exposure leads to immunological memory| |Found in nearly all forms of life|Found only in [jawed vertebrates](https://en.wikipedia.org/wiki/Gnathostomata "Gnathostomata")| **Key points:** - The *innate immune system offers an immediate, nonspecific response* to pathogens and relies on pattern recognition receptors to identify them. It includes various cell types like phagocytes, dendritic cells, and natural killer cells. - Phagocytosis, performed by phagocytes, is a crucial aspect of innate immunity, allowing cells to engulf and eliminate pathogens. *Phagocytes generally patrol the body searching for pathogens, but can be called to specific locations by cytokines*. - Inflammation is an early response to infection characterized by symptoms like redness, swelling, and heat, mediated by cytokines and eicosanoids. - The [[Complement System]], a part of the innate immune response, attacks the surfaces of foreign cells and enhances the killing of pathogens. - The adaptive immune system, found in jawed vertebrates, provides a tailored response to specific pathogens and develops immunological memory for enhanced future responses. - [[Lymphocytes]], including B cells and T cells, are key players in the adaptive immune system, recognizing specific antigens and orchestrating immune responses. - Killer T cells, a subtype of T cells, target and eliminate cells infected with pathogens or are otherwise dysfunctional. [[Immunological Memory]] allows the immune system to remember specific pathogens encountered, mounting a stronger response upon subsequent exposure. Physiological regulation involves the immune system interacting with other systems in the body, such as the [[Endocrine System]] and [[Nervous System]], as well as playing a role in *tissue repair and regeneration*. Hormones like estrogen and testosterone can act as immunomodulators, altering the sensitivity of the immune system. Vitamin D has receptors in the immune system, but clinical evidence linking vitamin D deficiency to immune diseases is inconclusive. Sleep and rest play crucial roles in immune function, with sleep deprivation negatively affecting immune responses. Physical exercise has a positive effect on the immune system, though intense exercise can temporarily suppress immune function. Changes at the cellular level, such as an increase in circulating white blood cells during exercise, also impact immune function. ### Disorders of Human Immunity The immune system is involved in tissue repair and regeneration, with various immune cells playing roles in the process. Disorders of human immunity can manifest as [[#Immunodeficiencies]], [[#Autoimmunity]], or [[#Hypersensitivities]]. [[#Idiopathic Inflammation]] can occur without a known cause, while medical interventions can manipulate the immune response for therapeutic purposes, including immunosuppression to control autoimmune disorders or inflammation and stimulate protective responses against pathogens or cancer. #### Immunodeficiencies (see [Immunodeficiency - Wikipedia](https://en.wikipedia.org/wiki/Immunodeficiency)) In clinical contexts, *immunosuppressive drugs like steroids can induce intentional or unintentional immune suppression*, useful in scenarios like organ transplants to prevent rejection or in autoimmune diseases. Individuals with immunodeficiency are vulnerable to both opportunistic infections and regular infections, and they experience decreased cancer immunosurveillance, heightening susceptibility to infectious diseases and reducing vaccine protection. **Key Points** - Immunodeficiency encompasses various types categorized by affected components: humoral immune deficiency, T cell deficiency, granulocyte deficiency, asplenia, and complement deficiency. - Primary immunodeficiency disorders, often hereditary, manifest as a heightened susceptibility to infections from childhood. Treatments may include antibody infusions, long-term antibiotics, or stem cell transplantation. - Secondary immunodeficiencies, acquired from factors like medication, aging, certain diseases, or environmental toxins, can also lead to immunosuppression. HIV/AIDS is a prominent example. #### Autoimmunity Autoimmunity refers to the immune system's response against the body's own healthy cells, tissues, and constituents, leading to autoimmune diseases such as [[Celiac Disease]], [[Type 1 Diabetes]], [[Rheumatoid Arthritis]], and [[Multiple Sclerosis]], among others. This phenomenon involves the presence of antibodies or T cells that react with self-proteins, potentially causing tissue damage. Throughout history, the understanding of autoimmunity evolved from early beliefs that the immune system couldn't target the body's own tissues to recognition in the 20th century that autoimmune responses could occur. Recent research suggests that low levels of autoimmunity might serve beneficial functions in the body, such as contributing to rapid immune responses during infections. Immunological tolerance, the ability of the immune system to differentiate between self and non-self, is crucial in preventing autoimmune diseases. Various theories, including clonal deletion, clonal anergy, and idiotype network theory, have been proposed to explain the mechanisms behind immunological tolerance. *Dysfunction in tolerance mechanisms can lead to autoimmune responses*, particularly by B lymphocytes producing autoantibodies. Environmental factors, including *infectious diseases, parasites, and chemical agents like certain drugs or cigarette smoking, can influence the development of autoimmune conditions*. Pathogenesis of autoimmunity involves complex mechanisms such as T-cell bypass, T-cell–B-cell discordance, and aberrant B cell receptor-mediated feedback. **Key Points:** - Autoimmunity involves the immune system's response against the body's own healthy cells, leading to autoimmune diseases. - Immunodeficiency syndromes often exhibit characteristics of autoimmunity. - Genetic susceptibility, sex, and environmental factors play significant roles in autoimmunity. - Pathogenesis of autoimmunity involves complex mechanisms including T-cell bypass and aberrant B cell receptor-mediated feedback. ##### Mechanisms for Autoimmune Diseases - **Molecular Mimicry**: Exogenous antigens resemble host antigens, amplifying the immune response. - **Idiotype Cross-Reaction**: Interaction between antiviral antibody idiotype and host cell receptors. - **Cytokine Dysregulation**: Imbalance in Helper T-cell cytokines influences inflammatory responses. - **Dendritic Cell Apoptosis**: Leads to systemic lymphocyte activation and loss of self-tolerance. - **Epitope Spreading**: Immune response targets primary and subsequent epitopes. - **Epitope Modification**: Exposure of cryptic epitopes induces autoimmune responses. - **Specialized Immunoregulatory Cell Involvement**: Regulatory cells play roles in the development or suppression of autoimmune diseases. Autoimmune diseases are classified as *systemic or organ-specific*. Systemic autoimmune diseases include [[Lupus]], [[Rheumatoid Arthritis]], and [[Scleroderma]], while organ-specific disorders affect specific tissues or organs such as the endocrine system, gastrointestinal tract, skin, blood, and nervous system. A newer classification suggests an immunological disease continuum ranging from classical autoimmune diseases to those primarily driven by the innate immune system, impacting disease mechanisms and therapy development. **Key Points:** - Diagnosis relies on patient history, physical examination, and laboratory tests. - Treatment involves *immunosuppressive, anti-inflammatory, or palliative approaches*, with emerging therapies such as helminthic therapy and T-cell vaccination. - Nutrition, particularly vitamin D, omega-3 fatty acids, probiotics, and antioxidants, plays a role in managing autoimmune diseases. #### Hypersensitivity Hypersensitivity reactions encompass abnormal immune responses to antigens, leading to immune diseases like allergies and autoimmunity. Classified by Gell and Coombs, there are four types, Type I reactions are immediate, while Types II, III, and IV have delayed onset. - **Type I Hypersensitivity**: IgE-mediated, immediate reactions to allergens such as nuts, pollen, insect venom. - **Type II Hypersensitivity**: Antibody-mediated cellular destruction targeting cell surface antigens, leading to dysfunction. - **Type III Hypersensitivity**: Immune complex formation causing tissue deposition and inflammation, seen in lupus, rheumatoid arthritis. - **Type IV Hypersensitivity**: T cell-mediated, delayed inflammatory response against antigens, involved in contact dermatitis, autoimmune diseases. Treatment for hypersensitivity reactions varies depending on the type and severity. Immediate reactions, like [[Anaphylaxis]], require prompt management with adrenaline, antihistamines, and supportive care. Allergic [[Asthma]] may necessitate bronchodilators, corticosteroids, or monoclonal antibodies targeting IgE. Autoimmune disorders like [[Lupus]] might require anti-inflammatory drugs or immunosuppressants. Delayed hypersensitivity reactions, such as contact [[Dermatitis]], can be managed by avoiding triggers or using medications like corticosteroids or immunomodulators. #### Idiopathic Inflammation Inflammation is one of the first responses of the immune system to infection, but it can appear without known cause. Inflammation is produced by [[Eicosanoids]] and [[Cytokines]], which are released by injured or infected cells. Eicosanoids include *prostaglandins that produce fever and the dilation of blood vessels* associated with inflammation, and *leukotrienes that attract certain white blood cells* (leukocytes). Common cytokines include [[Interleukins]] that are responsible for communication between white blood cells; chemokines that promote chemotaxis; and interferons that have anti-viral effects, such as shutting down protein synthesis in the host cell. --- #### Resources * [[2021 - Immune]] * [Immune system - Wikipedia](https://en.wikipedia.org/wiki/Immune_system)