Lesson 20: Study Notes on the Lymphatic System and Immunity
20.1 Structure and Function of the Lymphatic System
Definition of the Lymphatic System: A group of organs and tissues that work in conjunction with the cardiovascular and immune systems to protect the body from pathogens, maintain fluid homeostasis, and absorb dietary fats. It forms a one-way drainage system.
Main Components:
Lymphatic Vessels: A vast network of blind-ended vessels that begin as lymphatic capillaries in the interstitial spaces. These vessels collect interstitial fluid (lymph) and transport it towards the heart.
Lymphatic Tissue and Organs: Specialized tissues and organs containing immune cells (leukocytes). These include:
Lymphoid follicles (e.g., tonsils in the pharynx for trapping pathogens, Peyer's patches in the small intestine).
Lymph nodes: Small, bean-shaped organs clustered along lymphatic vessels that filter lymph.
Spleen: The largest lymphoid organ, it filters blood, removes old erythrocytes, and houses lymphocytes.
Thymus: A gland located in the mediastinum where T lymphocytes mature.
Functions of the Lymphatic System
Regulation of Interstitial Fluid Volume:
At the arterial end of blood capillaries, a net filtration pressure of approximately 35 mmHg35 mmHg (hydrostatic pressure) forces about 20 liters20 liters of water and solutes out of the blood plasma daily into the interstitial spaces.
While most fluid returns to the blood capillaries via osmosis at the venule end (due to higher colloid osmotic pressure, ~28 mmHg28 mmHg), approximately 2–4 liters of water and dissolved solutes (like proteins) remain in the interstitial fluid.
Lymphatic vessels collect this excess interstitial fluid, which is then referred to as lymph once it enters the lymphatic capillaries, preventing accumulation and maintaining fluid balance.
Absorption of Dietary Fats:
In the small intestine, specialized lymphatic capillaries called lacteals absorb the breakdown products of dietary fats (chylomicrons) directly from the digestive tract.
These fat-containing lymph travel through the lymphatic vessels and eventually enter the bloodstream, bypassing the hepatic portal system initially.
Immune Functions:
Lymphoid organs and tissues serve as critical sites where immune cells mature, reside, and are activated.
They filter pathogens, cellular debris, and cancer cells from lymph (in lymph nodes) and blood (in the spleen), initiating immune responses.
Lymphatic Vessels and Lymph Circulation
Lymphatic Capillaries: Form networks where interstitial fluid enters. Extremely permeable due to unique flap-like minivalves formed by overlapping endothelial cells.
Lymph-Collecting Vessels: Lymphatic capillaries merge to form these vessels, which contain valves to prevent backflow and resemble venules.
Lymph Trunks: Lymph-collecting vessels merge to form larger lymph trunks. There are nine major trunks, most of which are paired:
Lumbar Trunks: Paired, drain lymph from the lower limbs, pelvis, and kidneys.
Intestinal Trunk: Single, drains fat-containing lymph (chyle) from the stomach, intestines, pancreas, and spleen.
Jugular Trunks: Paired, drain lymph from the head and neck.
Bronchomediastinal Trunks: Paired, drain lymph from the thoracic cavity, lungs, and heart.
Subclavian Trunks: Paired, drain lymph from the upper limbs, breasts, and superficial thoracic wall.
Cisterna Chyli: A large, swollen, sac-like vessel located anterior to the first two lumbar vertebrae. It receives lymph from the intestinal trunk and the lumbar trunks, serving as a significant reservoir for lymph before it ascends.
Thoracic Duct: The largest lymphatic vessel, beginning at the cisterna chyli and ascending through the thoracic cavity. It drains lymph from the entire lower body, left upper limb, left side of the head and neck, and left thoracic cavity.
It eventually drains into the junction of the left internal jugular vein and left subclavian vein.
Right Lymphatic Duct: A much shorter duct that drains lymph from the right upper limb, right side of the head and neck, and right thoracic cavity.
It drains into the junction of the right internal jugular vein and right subclavian vein.
Mechanics of Lymph Circulation
Low-pressure circuit: Unlike the cardiovascular system, the lymphatic system is a low-pressure circuit without a central pump to propel lymph.
Lymphatic Valves: Operate as one-way valves structurally similar to venous valves, preventing the backflow of lymph and ensuring its unidirectional movement towards the heart.
Skeletal Muscle Pump: Contraction of surrounding skeletal muscles compresses the lymphatic vessels, effectively pushing lymph along.
Respiratory Pump: Pressure changes in the thoracic and abdominal cavities during breathing help to propel lymph towards the heart.
Smooth muscle in lymph-collecting vessels: The walls of larger lymph-collecting vessels and trunks contain smooth muscle that undergoes rhythmic, pulsatile contractions (lymphatic pump), further aiding lymph movement.
Lymphedema
Definition: A debilitating and chronic swelling (severe edema) caused by a disruption or blockage of the normal lymphatic drainage, leading to an excessive accumulation of interstitial fluid.
Causes: Common causes include surgical removal of lymphatic vessels (e.g., during mastectomy for cancer treatment), damage to lymph nodes by radiation therapy, parasitic infections (e.g., filariasis by Wuchereria bancrofti), or congenital abnormalities of the lymphatic system.
Consequence: The persistent accumulation of fluid in the affected area leads to pronounced tissue enlargement, fibrosis, and increased susceptibility to infection.
20.2 Overview of the Immune System
Defense Mechanisms
Three Lines of Defense: The body employs a multi-tiered defense system:
First Line: External surface barriers that prevent pathogen entry. These include the cutaneous (skin) and mucous membranes (respiratory, gastrointestinal, genitourinary tracts), alongside various secretions (e.g., sweat, saliva, gastric acid, mucus, lysozyme).
Second Line: Innate (nonspecific) immunity responses, activated rapidly if pathogens breach the first line. These involve various cells (e.g., phagocytes like macrophages and neutrophils, natural killer cells) and proteins (e.g., complement, interferons), as well as general processes like inflammation and fever.
Third Line: Adaptive (specific) immunity responses, which provide a targeted and memory-driven defense against specific pathogens. This line primarily involves lymphocytes (B and T cells).
Categories of Immunity
Innate (Nonspecific) Immunity:
This type of immunity responds immediately and uniformly to any type of pathogen or foreign substance.
It provides a quick initial defense, typically lasting approximately 12 hours post-exposure.
Key characteristics include: no memory of past exposures, rapid response, and recognition of common pathogen-associated molecular patterns (PAMPs).
Adaptive (Specific) Immunity:
This immunity is highly specific to a particular antigen and improves with each subsequent exposure due to immunological memory.
It is initiated after exposure to specific antigens, with the primary response typically developing over 3-5 days.
It can be broadly categorized into:
Cell-mediated immunity: Involves T lymphocytes that directly attack infected cells or modulate immune responses.
Antibody-mediated (humoral) immunity: Involves B lymphocytes that differentiate into plasma cells to produce antibodies which target extracellular pathogens and toxins.
Immune System Cells and Proteins
Agranulocytes: Leukocytes characterized by the absence of visible granules in their cytoplasm. Key types involved in immunity are:
B lymphocytes (B cells): Primarily responsible for antibody-mediated immunity; differentiate into plasma cells that produce antibodies and memory B cells.
T lymphocytes (T cells): Crucial for cell-mediated immunity; include helper T cells, cytotoxic T cells, and regulatory T cells.
Monocytes: Phagocytic cells that circulate in the blood and differentiate into macrophages and dendritic cells in tissues.
Granulocytes: Leukocytes containing prominent cytoplasmic granules. Include:
Neutrophils: The most abundant white blood cells; highly phagocytic and effective against bacteria.
Eosinophils: Involved in allergic reactions and defense against parasites.
Basophils: Release histamine and other mediators of inflammation and allergic responses.
Natural Killer (NK) Cells: A type of lymphocyte that belongs to innate immunity. They recognize and destroy cancerous or virus-infected cells by inducing apoptosis, without requiring prior activation by specific antigens.
Antibodies (Immunoglobulins, Ig): Y-shaped proteins secreted by plasma cells that bind specifically to antigens, neutralizing them or marking them for destruction by other immune cells.
Cytokines: A diverse group of small signaling proteins (e.g., interleukins, interferons, tumor necrosis factors, chemokines) produced by various immune and non-immune cells. They act as chemical messengers to regulate and influence the immune response, cell growth, inflammation, and healing.
Interactions of Lymphatic and Immune Systems
The lymphatic system provides the infrastructure (lymphoid organs and vessels) that facilitates the immune system's function.
Lymphoid organs serve as primary habitats for immune cells (e.g., B and T cell maturation in thymus/bone marrow, B cell activation in germinal centers of lymph nodes) and are strategically located to trap pathogens.
Dendritic cells, potent antigen-presenting cells (APCs), play a critical role in bridging innate and adaptive immunity by capturing antigens in tissues, migrating to lymphoid organs, and presenting these antigens to T cells.
20.3 Cells of Innate Immunity
Phagocytosis
Definition: The cellular process of ingesting and eliminating harmful particles, pathogens (bacteria, viruses), or cellular debris. Phagocytes engulf targets, enclosing them in a phagosome, which then fuses with lysosomes to form a phagolysosome for enzymatic destruction.
Primary Phagocytes:
Macrophages: Large, long-lived phagocytes derived from monocytes. They are professional antigen-presenting cells (APCs) found in various tissues (e.g., Kupffer cells in the liver, alveolar macrophages in the lungs). They secrete enzymes and cytokines to combat pathogens, clear dead cells, and initiate tissue repair.
Neutrophils: The most numerous phagocytes, serving as the first responders to infection. They are highly effective against bacteria and fungi, rapidly engulfing them and producing reactive oxygen species (e.g., superoxide, hydrogen peroxide) and hypochlorite ions (respiratory burst) to kill them. They can also release neutrophil extracellular traps (NETs).
Dendritic Cells: Although primarily known as antigen-presenting cells (APCs), they are also capable phagocytes. They are crucial for activating naive T cells and are considered the most effective APCs, acting as a crucial link between innate and adaptive immunity.
Natural Killer Cells
Mechanism: NK cells survey the body for abnormal cells, such as those infected with viruses or cancerous cells. They recognize these targets by detecting a reduction in MHC Class I molecules on the cell surface (a common tactic used by viruses and cancer cells to evade T cells) and the presence of stress-induced ligands.
Destruction: Upon recognition, NK cells release cytotoxic granules containing perforin and granzymes. Perforin forms pores in the target cell membrane, allowing granzymes to enter and induce apoptosis (programmed cell death) without requiring specific antigen recognition.
Cytokines and Antimicrobial Proteins
Complement System: A group of approximately 30 plasma proteins (C1-C9, factors B, D, P, etc.) that circulate in an inactive form. When activated (via classical, alternative, or lectin pathways), they enhance innate immunity by:
Opsonization: Coating pathogens to enhance phagocytosis.
Cell Lysis: Forming the membrane attack complex (MAC) to create pores in bacterial cell membranes.
Inflammation: Attracting phagocytes and promoting inflammatory responses.
Clearance of immune complexes.
Cytokines: Many cytokines, such as interferons (especially Type I interferons like IFN-αα and IFN-ββ), are crucial in innate immunity. Interferons are produced by virus-infected cells and act on surrounding cells to induce antiviral states, thus limiting viral spread. Other cytokines enhance immune response by promoting inflammation, fever (e.g., IL-1, TNF-αα), or chemotaxis.
Inflammatory Response
Definition: A localized, nonspecific tissue response to injury or infection, characterized by redness, heat, swelling, and pain. Its primary goals are to isolate the damaged or infected area, destroy pathogens, clear cellular debris, and initiate healing.
Stages:
Release of inflammatory mediators: Injured cells and immune cells (e.g., mast cells, macrophages) release chemical signals such as histamine, prostaglandins, leukotrienes, and kinins. These mediators induce vasodilation (causing redness and heat) and increase capillary permeability (leading to swelling and pain due to fluid leakage).
Vasodilation and increased permeability: Brings more blood flow, immune cells, and plasma proteins (e.g., complement components, clotting factors) to the site.
Arrival of phagocytes: Neutrophils are typically the first to arrive (within an hour), followed by macrophages. They migrate to the site via chemotaxis (chemical attraction), where they engulf pathogens and cellular debris through phagocytosis.
Clot formation: Aids in walling off the infected area and preparing for tissue repair.
20.4 Adaptive Immunity: Cell-Mediated Immunity
Cell-mediated immunity is carried out primarily by T lymphocytes (T cells), which directly recognize and destroy infected or abnormal cells, or orchestrate other immune responses.
Types of T Cells:
Helper T Cells (CD4+CD4+ T cells): These are the central orchestrators of the immune response. Upon activation, they secrete various cytokines that stimulate and activate other immune cells, including B cells (for antibody production), cytotoxic T cells, and macrophages. They do not directly kill infected cells but enhance the activity of other immune cells.
Cytotoxic T Cells (CD8+CD8+ T cells): Also known as killer T cells, these cells directly identify and kill antigen-infected cells (e.g., virus-infected cells) and cancerous cells. They achieve this by releasing perforins and granzymes, similar to NK cells, to induce apoptosis in target cells.
Regulatory T Cells (Tregs): Suppress the activity of other T cells to prevent excessive immune responses and maintain self-tolerance.
Major Histocompatibility Complex (MHC): Cell surface proteins that display antigens to T cells.
MHC Class I: Found on the surface of nearly all nucleated cells in the body (not on red blood cells). They present endogenous antigens (peptides derived from proteins synthesized within the cell, such as viral proteins or abnormal self-proteins from cancer cells). MHC Class I molecules interact specifically with CD8+CD8+ cytotoxic T cells.
MHC Class II: Primarily found on antigen-presenting cells (APCs) like macrophages, dendritic cells, and B cells. They present exogenous antigens (peptides derived from proteins taken up by the cell from its external environment, such as phagocytosed bacteria or toxins). MHC Class II molecules interact specifically with CD4+CD4+ helper T cells.
Activation of T Cells
T cell activation is a complex process requiring two distinct signals for full activation, critical for preventing inappropriate immune responses (the concept of anergy). This ensures T cells only respond to legitimate threats.
First Signal (Antigen Recognition): A T cell receptor (TCR) on the T cell surface binds specifically to a unique antigen fragment presented by an MHC molecule on an APC. CD4+CD4+ T cells recognize antigens on MHC Class II, while CD8+CD8+ T cells recognize antigens on MHC Class I.
Second Signal (Costimulation): In addition to antigen recognition, T cells require a second costimulatory signal, usually involving the binding of specific molecules on the T cell (e.g., CD28) to corresponding ligands on the APC (e.g., B7 family molecules). This signal confirms that the antigen presentation warrants a full immune response, often indicating danger (e.g., infection).
Once fully activated, naive T cells proliferate and differentiate into effector T cells and memory T cells.
Effector T cells: Carry out immediate immune functions (e.g., helper T cells secrete cytokines, cytotoxic T cells kill infected cells).
Memory T cells: Long-lived cells that ensure faster, stronger, and more efficient responses (secondary response) upon subsequent exposure to the same antigen, forming the basis of immunological memory.
20.5 Adaptive Immunity: Antibody-Mediated Immunity
Antibody-mediated immunity, also known as humoral immunity, is mediated by B lymphocytes (B cells) and the antibodies they produce. It primarily targets extracellular pathogens and toxins.
B Cell Function:
Each B cell expresses a unique B cell receptor (BCR) on its surface, which is an antibody molecule specific for a particular antigen.
Upon encounter with its specific antigen, often with the help of activated CD4+CD4+ helper T cells, B cells become activated.
Activated B cells proliferate and differentiate into two main types of cells:
Plasma cells: Short-lived, antibody-producing factories that secrete large quantities of soluble antibodies (up to 2,000 antibodies per second) into the bloodstream and tissue fluids.
Memory B cells: Long-lived cells that circulate in the body. Upon re-exposure to the same antigen, they can quickly differentiate into plasma cells and effector B cells, leading to a rapid and robust secondary immune response.
Antibody Types: There are five major classes of antibodies (immunoglobulins), each with distinct structures and functions:
IgG (Immunoglobulin G): The most abundant antibody in plasma (about 75-80% of total antibodies). It is a monomer, readily crosses the placenta (providing passive immunity to the fetus), and is crucial in secondary immune responses. Functions include opsonization, neutralization, and complement activation.
IgA (Immunoglobulin A): Found primarily in secretions such as mucus, saliva, tears, breast milk, and gastrointestinal fluid. It typically exists as a dimer in secretions and functions to protect mucous membranes from pathogen entry (e.g., in respiratory and digestive tracts).
IgM (Immunoglobulin M): The first antibody produced and secreted during the primary immune response. It is a pentamer (five antibodies joined together) in its secreted form, making it particularly effective at agglutination and complement activation. It is also found as a monomer on the surface of naive B cells, acting as the B cell receptor.
IgE (Immunoglobulin E): Present in very low concentrations in plasma. It is involved in allergic reactions and the response to parasitic infections. IgE binds to mast cells and basophils, triggering the release of histamine and other inflammatory mediators upon antigen exposure.
IgD (Immunoglobulin D): Primarily functions as a B cell receptor on the surface of naive B cells, playing a role in B cell activation. Its precise role is still being researched, but it is typically not secreted in large amounts.
Phases of Antibody-Mediated Response
Phase 1: B cell Activation and Differentiation: A naive B cell encounters its specific antigen. Antigen binding (and often CD4+CD4+ Helper T cell costimulation) leads to B cell activation, clonal proliferation, and differentiation into plasma cells and memory B cells.
Phase 2: Antibody Production and Action: Plasma cells secrete antibodies specific to the encountered antigen. These antibodies then mediate various defensive mechanisms:
Neutralization: Antibodies bind to pathogen-binding sites, preventing the pathogen from infecting target cells or tissues.
Agglutination: Antibodies clump pathogens together, making them easier for phagocytes to engulf.
Precipitation: Antibodies bind to soluble antigens, forming insoluble immune complexes that precipitate out of solution, which are then cleared by phagocytes.
Opsonization: Antibodies (especially IgG) coat pathogens, enhancing phagocytosis (act as "handles" for phagocytes).
Complement Activation: Antibodies (IgM and IgG) activate the classical pathway of the complement system, leading to cell lysis, enhanced inflammation, and opsonization.
Phase 3: Memory Cell Formation and Rapid Response on Subsequent Exposure: Memory B cells (and memory T cells) persist in the body for long periods. Upon re-exposure to the same antigen, these memory cells enable a rapid, potent, and long-lasting secondary immune response, often preventing the development of symptoms.
20.6 Putting It All Together: The Big Picture of the Immune Response
The immune system integrates innate and adaptive components to provide comprehensive protection. The response varies depending on the type and location of the pathogen.
Scenarios of Immune Response
Common Cold (Viral Infection):
Innate Immunity: Viral infection triggers the release of interferons by infected cells, which limit viral replication and signal to surrounding cells. Natural Killer (NK) cells recognize and destroy virus-infected cells. Phagocytes (macrophages) also attempt to engulf viral particles and infected cells. Inflammation may occur, contributing to symptoms like congestion.
Adaptive Immunity: Dendritic cells present viral antigens on MHC Class II (to CD4+CD4+ Helper T cells) and MHC Class I (to CD8+CD8+ Cytotoxic T cells). CD4+CD4+ Helper T cells activate B cells, leading to antibody production (IgM, then IgG) that neutralizes free virus particles. CD8+CD8+ Cytotoxic T cells directly kill virus-infected cells. Memory cells are formed for future protection.
Bacterial Infection:
Innate Immunity: Neutrophils are typically the first responders, rapidly phagocytosing bacteria. Macrophages follow, also performing phagocytosis and acting as APCs. The complement system is activated (e.g., via the alternative pathway), leading to opsonization, inflammation, and direct lysis of some bacteria. The inflammatory response helps to contain and eliminate the infection.
Adaptive Immunity: Macrophages and dendritic cells present bacterial antigens to CD4+CD4+ Helper T cells (on MHC Class II). These Helper T cells activate B cells specific to bacterial antigens, leading to the production of antibodies (primarily IgG and IgM) that opsonize, neutralize toxins, and activate complement, aiding in bacterial clearance. CD8+CD8+ T cells may also be involved if bacteria infect host cells intracellularly.
Cancer Recognition: Cancer cells often develop mutations that lead to the expression of abnormal proteins (tumor antigens) or an altered display of MHC molecules.
Innate Immunity: Natural Killer (NK) cells are continuously scanning for cells with reduced MHC Class I expression or stress-induced ligands, characteristic of many tumor cells. They can directly kill cancerous cells without prior sensitization.
Adaptive Immunity: Dendritic cells internalize tumor antigens and present them to T cells. CD8+CD8+ Cytotoxic T cells are crucial for recognizing and directly killing tumor cells that present tumor antigens via MHC Class I. CD4+CD4+ Helper T cells are important for providing cytokine support to activate and sustain the cytotoxic T cell response. The immune system attempts to eliminate these aberrant cells through immune surveillance.
20.7 Disorders of the Immune System
Dysfunctions of the immune system can lead to a range of disorders where the body either overreacts, under-reacts, or reacts inappropriately to self-components.
Types of Disorders
Hypersensitivity Disorders (Allergies): Characterized by an overactive or exaggerated immune response to a harmless antigen (allergen), leading to tissue damage and uncomfortable symptoms. Often involve IgE and histamine release.
Immunodeficiency Disorders: Occur when the immune system's ability to fight off infectious diseases and cancer is compromised or absent. This leads to increased susceptibility to infections and certain malignancies.
Autoimmune Disorders: Result from the immune system incorrectly identifying self-antigens as foreign and launching an attack against the body's own tissues or organs. This leads to chronic inflammation and tissue damage.
Hypersensitivity Types
Type I (Immediate Hypersensitivity):
Mechanism: Involves IgE antibodies binding to mast cells and basophils. Upon re-exposure to the allergen, these cells rapidly degranulate, releasing histamine and other inflammatory mediators. This is a rapid response, occurring within minutes.
Examples: Seasonal allergies (hay fever), allergic asthma, food allergies, and anaphylaxis (a severe, systemic reaction).
Type II (Antibody-Mediated Cytotoxic Hypersensitivity):
Mechanism: Involves IgG or IgM antibodies binding to antigens on the surface of specific body cells. This leads to cell destruction through complement activation, antibody-dependent cell-mediated cytotoxicity (ADCC), or opsonization.
Examples: Transfusion reactions (e.g., ABO incompatibility), Rh incompatibility (hemolytic disease of the newborn), autoimmune hemolytic anemia, and some drug reactions.
Type III (Immune Complex-Mediated Hypersensitivity):
Mechanism: Involves the formation of antigen-antibody (immune) complexes in the bloodstream. These complexes deposit in tissues (e.g., blood vessel walls, glomeruli in kidneys, joints), where they activate complement and trigger inflammation, leading to tissue damage.
Examples: Systemic lupus erythematosus (SLE), rheumatoid arthritis, post-streptococcal glomerulonephritis, and serum sickness.
Type IV (Delayed-Type Hypersensitivity - DTH):
Mechanism: Involves T cells, not antibodies. Antigen-specific T cells (especially CD4+CD4+ Helper T cells and sometimes CD8+CD8+ Cytotoxic T cells) are activated and release cytokines that recruit and activate macrophages and other immune cells to the site. The reaction typically develops 24-72 hours after antigen exposure.
Examples: Tuberculin skin test (for TB exposure), contact dermatitis (e.g., poison ivy, nickel allergy), and graft rejection.
Immunodeficiency Overview
Immunodeficiency disorders can be categorized as:
Primary (Congenital) Immunodeficiencies: Genetically determined defects in one or more components of the immune system. Examples include Severe Combined Immunodeficiency (SCID) and X-linked agammaglobulinemia.
Secondary (Acquired) Immunodeficiencies: Result from external factors, such as infections, malnutrition, immunosuppressive drugs (e.g., chemotherapy, corticosteroids), or certain diseases (e.g., cancer, diabetes).
AIDS Pathophysiology: Acquired Immunodeficiency Syndrome (AIDS) is caused by the Human Immunodeficiency Virus (HIV). HIV primarily infects and destroys CD4+CD4+ Helper T cells. The progressive loss of these critical cells leads to a severe compromise of both cell-mediated and antibody-mediated immunity, making individuals highly vulnerable to opportunistic infections and certain cancers.
Autoimmune Mechanisms
Autoimmune disorders result from a breakdown in self-tolerance, meaning the immune system fails to distinguish between self-antigens and foreign antigens. This can be due to various factors:
Molecular Mimicry: Pathogen antigens resemble self-antigens, causing an immune response against the pathogen that cross-reacts with self-tissues (e.g., rheumatic fever following streptococcal infection).
Bystander Activation: Tissue damage (e.g., due to infection or trauma) releases self-antigens, and local inflammation activates APCs, which then present these self-antigens to T cells in a context that triggers an autoimmune response.
Genetic Predisposition: Certain genes (e.g., specific MHC alleles like HLA-B27) increase susceptibility to autoimmune diseases.
Environmental Triggers: Infections, toxins, or drugs can sometimes initiate or exacerbate autoimmune conditions in genetically susceptible individuals.
The aberrant immune response can involve autoantibodies (B cells) attacking self-components or autoreactive T cells directly damaging self-tissues.