💀Anatomy and Physiology I Unit 21 – The Lymphatic and Immune System

Key Components and Functions

• Lymphatic system consists of lymphatic vessels, lymph nodes, and lymphoid organs (spleen, thymus, tonsils) that transport lymph fluid throughout the body
• Lymph fluid is a clear, colorless fluid derived from blood plasma that contains white blood cells (lymphocytes) and removes cellular debris, pathogens, and excess fluid from tissues
• Lymphatic capillaries are highly permeable, allowing for efficient uptake of fluids and particulate matter from the interstitial space
• Lymph nodes are small, bean-shaped structures that filter lymph fluid, trap pathogens and foreign substances, and house immune cells
  • Lymph nodes are strategically located throughout the body (cervical, axillary, inguinal) to monitor and respond to potential threats
• Lymphatic system plays a crucial role in maintaining fluid balance, facilitating immune responses, and absorbing dietary fats from the digestive tract
• Spleen acts as a blood filter, removing old or damaged red blood cells and storing platelets and white blood cells
  • Spleen also plays a role in the adaptive immune response by housing B and T lymphocytes
• Thymus gland is essential for the development and maturation of T lymphocytes, a key component of the adaptive immune system
• Tonsils and adenoids are lymphoid tissues located in the throat that serve as the first line of defense against pathogens entering through the nose and mouth

Lymphatic System Structure

• Lymphatic vessels are a network of thin-walled, valved structures that carry lymph fluid unidirectionally from tissues back to the bloodstream
  • Lymphatic capillaries are the smallest lymphatic vessels and are responsible for collecting interstitial fluid and forming lymph
  • Lymphatic vessels gradually increase in size, forming lymphatic trunks and ducts as they converge and transport lymph back to the venous system
• Lymph is propelled through the lymphatic vessels by the contraction of smooth muscles in the vessel walls, the action of skeletal muscles, and the pressure gradients created by the valves
• Right lymphatic duct drains lymph from the right upper quadrant of the body (right arm, right side of the head and neck, and right thorax) into the right subclavian vein
• Thoracic duct is the largest lymphatic vessel in the body, draining lymph from the rest of the body (left side, legs, and abdomen) into the left subclavian vein
  • Thoracic duct also receives chyle, a milky fluid containing absorbed dietary fats, from the intestinal lymphatic vessels (lacteals)
• Lymph nodes are encapsulated structures with an outer cortex containing B cell follicles and an inner medulla with T cells and macrophages
  • Afferent lymphatic vessels bring lymph into the lymph nodes, while efferent vessels carry filtered lymph out of the nodes
• Lymphoid organs (spleen, thymus, tonsils) are specialized structures that house immune cells and facilitate immune responses
  • Red pulp of the spleen filters blood, while white pulp houses lymphocytes and initiates adaptive immune responses
  • Thymus provides a microenvironment for T cell maturation and selection, ensuring self-tolerance and effective immune responses

Immune System Overview

• Immune system is a complex network of cells, tissues, and organs that work together to protect the body against pathogens (bacteria, viruses, fungi, parasites) and other harmful substances
• Innate immunity is the first line of defense, providing rapid, non-specific protection against pathogens
  • Innate immune components include physical barriers (skin, mucous membranes), chemical barriers (enzymes, pH), and cellular components (neutrophils, macrophages, natural killer cells)
• Adaptive immunity is a slower, more specific response that develops after exposure to a pathogen and provides long-lasting protection
  • Adaptive immune components include B lymphocytes (antibody-mediated immunity) and T lymphocytes (cell-mediated immunity)
• Lymphocytes originate from hematopoietic stem cells in the bone marrow and undergo maturation in primary lymphoid organs (bone marrow for B cells, thymus for T cells)
• Secondary lymphoid organs (lymph nodes, spleen, mucosa-associated lymphoid tissue) are sites where lymphocytes interact with antigens and mount immune responses
• Cytokines are signaling molecules secreted by immune cells that regulate the growth, differentiation, and activation of other immune cells
  • Examples of cytokines include interleukins, interferons, and tumor necrosis factors
• Complement system is a group of plasma proteins that enhance the immune response by promoting inflammation, opsonization (tagging pathogens for phagocytosis), and direct lysis of pathogens
• Immune system must maintain a delicate balance between protecting against pathogens and avoiding excessive or inappropriate responses that can lead to autoimmune disorders or allergies

Types of Immunity

• Innate immunity is the first line of defense against pathogens, providing immediate, non-specific protection
  • Physical barriers include skin, mucous membranes, and secretions (tears, saliva, mucus) that prevent pathogen entry
  • Chemical barriers include enzymes (lysozyme), antimicrobial peptides (defensins), and acidic pH that inhibit pathogen growth
  • Cellular components of innate immunity include phagocytes (neutrophils, macrophages), natural killer cells, and dendritic cells
    • Phagocytes engulf and destroy pathogens, while natural killer cells target virus-infected and tumor cells
    • Dendritic cells are antigen-presenting cells that link innate and adaptive immunity by processing and presenting antigens to T cells
• Adaptive immunity is a slower, more specific response that develops after exposure to a pathogen and provides long-lasting protection
  • Humoral immunity is mediated by B lymphocytes and the antibodies they produce
    • Antibodies are Y-shaped proteins that bind specifically to antigens, neutralizing or marking them for destruction
    • Different classes of antibodies (IgM, IgG, IgA, IgE, IgD) have specific functions and locations in the body
  • Cell-mediated immunity is mediated by T lymphocytes, which directly attack infected or abnormal cells
    • Helper T cells (CD4+) coordinate the immune response by secreting cytokines and activating other immune cells
    • Cytotoxic T cells (CD8+) directly kill virus-infected and tumor cells
    • Regulatory T cells (Tregs) help maintain self-tolerance and prevent autoimmunity
• Passive immunity is the transfer of preformed antibodies from one individual to another, providing temporary protection
  • Examples include maternal antibodies passed to the fetus through the placenta and antibodies in breast milk
  • Artificial passive immunity involves the administration of antibodies (immunoglobulins) for immediate, short-term protection (rabies, tetanus)
• Active immunity is the development of an immune response following exposure to a pathogen or vaccine, providing long-lasting protection
  • Natural active immunity occurs after infection with a pathogen, stimulating the production of memory B and T cells
  • Artificial active immunity is induced by vaccination, which exposes the immune system to weakened, killed, or component parts of pathogens to elicit a protective response without causing disease

Immune Response Process

• Innate immune response is initiated when pattern recognition receptors (PRRs) on immune cells detect pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs)
  • Binding of PAMPs or DAMPs to PRRs triggers the release of inflammatory mediators (cytokines, chemokines) and the activation of innate immune cells
  • Activated macrophages and neutrophils phagocytose pathogens, while natural killer cells release cytotoxic granules to kill infected or abnormal cells
• Adaptive immune response begins with the activation of naive T and B lymphocytes by antigen-presenting cells (APCs) in secondary lymphoid organs
  • Dendritic cells, the most potent APCs, process and present antigens on major histocompatibility complex (MHC) molecules to T cells
  • Helper T cells (CD4+) recognize antigens presented on MHC class II molecules and secrete cytokines to activate other immune cells
    • Th1 cells promote cell-mediated immunity by activating cytotoxic T cells and macrophages
    • Th2 cells promote humoral immunity by activating B cells to produce antibodies
  • Cytotoxic T cells (CD8+) recognize antigens presented on MHC class I molecules and directly kill infected or abnormal cells
• B cell activation occurs when B cell receptors (BCRs) bind to specific antigens and receive co-stimulatory signals from helper T cells
  • Activated B cells proliferate and differentiate into plasma cells, which secrete large amounts of antibodies
  • Some activated B cells become memory B cells, providing long-lasting protection against future encounters with the same pathogen
• Antibodies contribute to the immune response by neutralizing pathogens, opsonizing them for phagocytosis, and activating the complement system
  • Neutralization involves antibodies binding to viral or bacterial surface proteins, preventing their attachment and entry into host cells
  • Opsonization is the coating of pathogens with antibodies, making them more easily recognized and engulfed by phagocytes
  • Antibody-antigen complexes can activate the classical pathway of the complement system, leading to inflammation and direct lysis of pathogens
• Memory T and B cells are generated during the adaptive immune response, providing rapid and enhanced protection upon subsequent encounters with the same pathogen
  • Memory cells have a lower activation threshold and can quickly proliferate and differentiate into effector cells, mounting a faster and stronger immune response

Lymphatic and Immune Disorders

• Lymphedema is the swelling of tissues caused by the accumulation of lymph fluid due to damaged or blocked lymphatic vessels
  • Primary lymphedema is caused by genetic or developmental abnormalities of the lymphatic system
  • Secondary lymphedema can result from surgery, radiation therapy, infection, or trauma that damages lymphatic vessels or nodes
• Lymphadenopathy refers to the enlargement of lymph nodes, often in response to infection, inflammation, or malignancy
  • Localized lymphadenopathy affects a single region of lymph nodes and may indicate a nearby infection or tumor
  • Generalized lymphadenopathy involves multiple regions of lymph nodes and may suggest systemic diseases (mononucleosis, HIV, lymphoma)
• Lymphomas are cancers of the lymphatic system that originate from lymphocytes
  • Hodgkin lymphoma is characterized by the presence of Reed-Sternberg cells and typically affects lymph nodes in the neck and chest
  • Non-Hodgkin lymphomas are a diverse group of cancers that can arise from B or T cells and may involve lymph nodes, spleen, or other organs
• Autoimmune disorders occur when the immune system mistakenly attacks the body's own tissues, leading to inflammation and damage
  • Examples include rheumatoid arthritis (joints), systemic lupus erythematosus (multiple organs), and multiple sclerosis (central nervous system)
  • Autoimmune disorders may result from a combination of genetic, environmental, and immunological factors that disrupt self-tolerance mechanisms
• Immunodeficiencies are conditions in which the immune system is compromised, leading to increased susceptibility to infections
  • Primary immunodeficiencies are genetic disorders that affect the development or function of immune cells (severe combined immunodeficiency, X-linked agammaglobulinemia)
  • Secondary immunodeficiencies are acquired and may result from malnutrition, certain medications (chemotherapy, corticosteroids), or infections (HIV)
• Hypersensitivity reactions are exaggerated or inappropriate immune responses to specific antigens, leading to tissue damage and inflammation
  • Type I hypersensitivity (immediate) involves IgE antibodies and the release of histamine and other mediators from mast cells (allergies, anaphylaxis)
  • Type II hypersensitivity (antibody-mediated) occurs when antibodies bind to cell surface antigens, triggering complement activation or cell-mediated cytotoxicity (autoimmune hemolytic anemia, Graves' disease)
  • Type III hypersensitivity (immune complex-mediated) involves the deposition of antigen-antibody complexes in tissues, leading to inflammation and damage (serum sickness, systemic lupus erythematosus)
  • Type IV hypersensitivity (delayed, cell-mediated) is mediated by T cells and can cause tissue damage through the release of cytokines or direct cytotoxicity (contact dermatitis, graft-versus-host disease)

Clinical Applications

• Lymph node biopsy is a diagnostic procedure that involves removing a lymph node or a portion of it for microscopic examination
  • Lymph node biopsies can help diagnose infections, autoimmune disorders, and cancers (lymphoma, metastatic tumors)
  • Fine-needle aspiration biopsy uses a thin needle to remove a small sample of cells from a lymph node for cytological analysis
  • Excisional biopsy involves removing an entire lymph node for histological examination and is often used to diagnose lymphomas
• Immunotherapy is a type of cancer treatment that harnesses the power of the immune system to fight tumors
  • Checkpoint inhibitors are antibodies that block inhibitory signals on T cells (PD-1, CTLA-4), enhancing their ability to recognize and kill tumor cells
  • Chimeric antigen receptor (CAR) T cell therapy involves genetically modifying a patient's T cells to express receptors that target specific tumor antigens
  • Cancer vaccines are designed to stimulate the immune system to recognize and attack tumor cells expressing specific antigens
• Vaccination is the administration of weakened, killed, or component parts of pathogens to elicit a protective immune response without causing disease
  • Vaccines can be live attenuated (weakened viruses or bacteria), inactivated (killed pathogens), subunit (purified antigens), or toxoid (inactivated bacterial toxins)
  • Herd immunity refers to the indirect protection of unvaccinated individuals when a large proportion of the population is vaccinated, reducing the spread of the pathogen
• Monoclonal antibodies are laboratory-produced antibodies that target specific antigens and have various therapeutic and diagnostic applications
  • Monoclonal antibodies can be used to treat cancer (rituximab for lymphoma), autoimmune disorders (adalimumab for rheumatoid arthritis), and infections (palivizumab for respiratory syncytial virus)
  • Diagnostic applications include immunohistochemistry, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) to detect specific antigens or antibodies
• Stem cell transplantation is a treatment that involves infusing hematopoietic stem cells to restore the immune system in patients with certain cancers or immunodeficiencies
  • Autologous stem cell transplantation uses the patient's own stem cells, which are collected before high-dose chemotherapy or radiation therapy
  • Allogeneic stem cell transplantation uses stem cells from a donor (sibling or unrelated) and can provide a graft-versus-tumor effect in cancer patients
• Immunosuppressive therapy is used to suppress the immune system in patients with autoimmune disorders or those undergoing organ transplantation
  • Corticosteroids (prednisone) are widely used immunosuppressive drugs that inhibit inflammation and the production of cytokines
  • Calcineurin inhibitors (cyclosporine, tacrolimus) and antimetabolites (azathioprine, mycophenolate mofetil) are used to prevent graft rejection in transplant recipients
  • Biological agents, such as monoclonal antibodies (basiliximab) and fusion proteins (abatacept), target specific components of the immune system to achieve immunosuppression

Key Takeaways and Review

• Lymphatic system consists of a network of vessels, nodes, and organs that transport lymph fluid, filter pathogens, and facilitate immune responses
• Lymph fluid is derived from blood plasma and contains lymphocytes, macrophages, and cellular debris
• Lymph nodes are strategically located throughout the body to monitor and respond to potential threats by filtering lymph and housing immune cells
• Spleen, thymus, and tonsils are lymphoid organs that play crucial roles in the development and function of the immune system
• Immune system is divided into inn