Lymphatic System and Lymphocytes

Lymphatic System Function

• Composed of vessels, cells, and organs
• Carries excess fluids to bloodstream
• Filters pathogens from blood
• Drains body fluids
• Returns fluids to bloodstream
• Lymphatic capillaries collect excess fluid (lymph) from blood capillaries in tissues
• Blood pressure causes fluid leakage from capillaries, resulting in interstitial fluid accumulation
• Lymph is interstitial fluid that has entered lymphatic system
• Lymph passes through lymph nodes where it is filtered
• Immune cells in lymph nodes detect pathogens
• Lymph nodes are bean-shaped organs in the lymphatic system
• Clean lymph returns to circulatory system via subclavian veins
• This helps maintain fluid balance
• Lymphatic system operates in one direction, towards the heart

Cells of the Lymphatic System

• White blood cells are found in lymphoid tissue (lymphoid cells)
• Cells forming lymphoid tissue structures are mainly fibroblasts producing reticular fibers
• Lymphocytes (T cells, B cells, Natural Killer cells) are separated, like supporting cells (macrophages, dendritic cells, reticular cells)
• T cells (T lymphocytes) mature in thymus
• B cells (B lymphocytes) mature in bone marrow
• B and T cells address antigens, including bacteria, toxins, viruses, mismatched RBCs, and cancer cells

Immune Cell Functions

• Macrophages phagocytize foreign substances, engulf/destroy pathogens, and present antigens to lymphocytes
• Dendritic cells capture antigens, deliver them to lymph nodes and help activate T cells
• Natural Killer (NK) cells attack infected or cancerous cells without prior activation

Structure of Lymph Nodes

• Lymph nodes filter lymph, removing debris
• There are approximately 500-600 lymph nodes in the body
• Cortex: Superficial layer housing B and T cells
• Medulla: Middle layer, primarily reticular fibers forming a mesh network within which WBCs sit
  • Structure slows lymph flow, enabling lymphocytes to examine antigens for self/non-self
• Trabeculae extends to inner region
• Afferent lymphatic vessels (3-5) carry lymph into nodes
• Efferent lymphatic vessels (2-3) carry lymph away from nodes
• More lymph always enters than exits

Spleen Structure and Functions

• Spleen: largest lymphatic organ and a major secondary lymphoid organ
• Red pulp has sinusoids (blood-filled spaces), macrophages, and red blood cells (RBCs) Connective tissue surrounds the spleen
• Red pulp function:
  • Filters blood, removes old, damaged, or defective red blood cells
  • Macrophages recycle iron from broken-down RBCs and store iron from hemoglobin
  • Stores blood, releasing RBCs when needed
• White pulp consists of lymphatic tissues: lymphocytes (B and T cells) and macrophages organized around central arteries
• White pulp carries out the following:
  • Monitors blood for pathogens, foreign substances, and abnormal cells (immune function)
  • Lymphocytes initiate immune responses to antigens and produce antibodies (activation of immune response)
• Spleen enables immune defense, blood maintenance, and lymph examination

Tonsil Functions and Types

• Tonsils: Lymphoid cell clusters, located in pharynx, they play a key role in immune defense
• Capture bacteria, viruses, and other harmful particles from inhaled air/ingested food (trap and filter pathogens)
• Contain lymphocytes (T and B cells) that recognize and respond to pathogens, building immunity (initiate immune responses)
• Pharyngeal tonsils swell upon infection
• Palatine tonsils are located at the back of the throat and are commonly inflamed in tonsillitis
• Pharyngeal tonsil (adenoid) is found in the upper throat behind nasal cavity
• Lingual tonsils are located at the base of the tongue
• Tonsils are the first line of immune defense in upper respiratory/digestive tracts

Temporal Phases of Immune Response

• Innate immune defenses (immediate, 0-4 hours): body's first defense line
  • Utilizes physical barriers (skin, mucous membranes), chemical defenses (enzymes, pH), and cellular components (macrophages, neutrophils, dendritic cells, natural killer cells)
  • This is a nonspecific response that acts quickly
• Barrier defenses (early induced innate responses, 4-96 hours): body starts strategic maneuvers
  • Examples: fever and release of chemicals
  • Utilizes phagocytes like neutrophils and macrophages
• Adaptive (specific) immune responses (after 96 hours): antigen-specific response involving activation of B and T cells
  • B cells produce antibodies
  • T cells orchestrate immune response (helper T cells) or kill infected cells (cytotoxic T cells)
  • Generates immunological memory for future protection
• Humans are born with innate immunity (neutrophil, eosinophil, monocytes, basophil)
• Adaptive immunity must be learned or trained to deal with non-self antigens, lymphocytes

Innate Immune Response: Cells

• Phagocytic cells (macrophages, neutrophils, dendritic cells) ingest and engulf pathogens
• Macrophages move through tissues and capillary walls, cooperate with lymphocytes, and present antigens to adaptive immune cells
• Neutrophils act as first responders, migrate to infection sites rapidly, and contain vasoactive mediators (histamine)
• Dendritic cells bridge innate and adaptive immunity, and capture/present antigens to T cells
• Lymphocytes (T-cells & B cells) specifically coordinate adaptive immunity
• Cells with cytoplasmic granules (eosinophils, basophils, mast cells) mediate immune responses against parasites and intracellular pathogens (viruses)
• Eosinophils defend against parasites and contribute to allergic reactions
• Basophils release histamine and other inflammatory mediators, involved in allergic reactions

Innate Immune Response: Inflammation

• Monocytes become macrophages or dendritic cells, rapidly drawn to infection by inflammation signals
• Inflammatory reaction brings phagocytic cells to clear debris and prepare for wound repair
• Inflammation alerts WBCs to infection/problem areas
• Mast cells detect injury, release histamine, and initiate inflammatory response
• Histamine increases blood flow to injury site, drawing phagocytes and other immune cells to neutralize pathogens

Soluble Mediators

• Cytokines (immune cell) are signaling molecules for short-distance communication between cells
• Immune cells are specialized to recognize and target specific pathogens
• Interferons (non-immune cells): secreted by virus-infected cells
  • Travel to adjacent cells and induce antiviral protein production
  • Alert other cells
• Non-immune cells participate in inflammation, tissue repair, and immune system support

Adaptive Immune Response

• Specific, systemic, and has memory
• The immune system's first exposure to a pathogen is called a primary adaptive response
• Re-exposure triggers a stronger and faster secondary adaptive response
• Humoral uses antibodies by B cells to attack infected cells
• The antigens will be floating in fluids of the body and if there is a viral infection B cells do not need to come near the infection
• Cellular: interaction of T cells with other cells, needing antigens presented by another cell
• B and T cells recognize antigens as self or non-self
• B cells recognize antigens independently and T cells need another cell to present the antigen to them: antigen-presenting cell
• Antigen-presenting cells (APCs): macrophages, dendritic cells, and B cells
• Antigens presented use a major histocompatibility complex (MHC) molecule
• MHC-I is on all nucleated cells
• MHC-II is only on antigen-presenting cells

T Cell Activation

• Helper T cells (CD4⁺) recognize antigens on MHC-II and release cytokines
• Cytotoxic T cells (CD8⁺) recognize antigens on MHC-I and directly kill infected cells
• Memory T cells: provide long-term immunity and respond quickly upon re-exposure

Lymphocyte Development

• Lymphocytes undergo development, maturation, and activation
• Development: T and B cells develop in bone marrow (primary lymphoid organ)
• Maturation: lymphocytes learn to recognize self vs foreign antigens: -B cells mature in bone marrow -T cells mature in thymus
• Activation: lymphocytes recognize foreign antigen in lymph nodes/blood and trigger adaptive immune response

T Cell Mediated Responses

• Helper T cells (CD4):
  • Activate B cells, macrophages, and cytotoxic T cells with cytokines
  • Recognize antigens presented by MHC-II on Antigen Presenting Cells
  • Target extracellular pathogens like bacteria, fungi, and parasites Cytotoxic cells (CD8): kill virus-infected, cancerous, or abnormal cells presented on MHC-I on all nucleated cells
• Target intracellular pathogens like viruses, tumors, and intracellular bacteria
• Regulatory T Cells (Treg) act to maintain immune homeostasis and are known as "The Peacekeepers"

B Cell Humoral Responses

• B cells induce humoral immune response, producing/releasing antibodies to attack, neutralize, or agglutinate antigens
• Classes of antibodies in humans: IgM, IgD, IgA, IgG, and IgE, each with specific function
• IgM: largest antibody, first produced during primary response, very effective against bacteria early in a primary response
• IgG: Major in both late primary and secondary responses; can cross placenta to attack fetal circulation or protect fetus, and exit blood to fight extracellular pathogens
• IgA is two antibodies connected, is the antibody that can go to body surfaces, important to newborns being present in breast milk
• IgE is associated with allergies and present in the lowest blood concentration
• IgD is the B cell receptor and is fixed and can't be secreted, remaining on the cell surface
• B cells get activated by their binding to the antigen in the lymph nodes
• Activated B cells develop into plasma cells
• Plasma cells produce specific antibodies against specific antigens
• Plasma cells survive a few days until the infection wanes, at which point, some activated B cells transform into memory cells

Primary vs. Secondary Responses

• The primary response is delayed several days (7-10 days) due to the time it takes the B cell into plasma cells
• Antibody levels reach a low level but is sufficient for immune protection
• In the secondary response, there is no time delay and the amount of antibody production is much higher
• The secondary antibody response overwhelms the pathogens quickly and in most situation no symptoms are felt

Active and Passive Immunity

• Active immunity involves pathogens so the body mounts an immune response
  • Subtypes are naturally acquired through exposure (flu virus or chicken pox) or artificially (vaccines)
• Passive immunity is no pathogen in the body, there are still antibiodies
  • Naturally acquired occurs through maternal transfer, such as IgA in breast milk
  • Artificially acquired involves injecting premade antibodies, such as cancer treatments

Immune Diseases

• AIDS and HIV
  • Acquired immune deficiency syndrome (AIDS) results from HIV, which targets T helper cells
  • HIV uses CD4 as a receptor to enter cells
• Autoimmune diseases
  • Immune cells lose tolerance and attack self cells, with unknown causes and severe consequences