Lymphatic System PDF

Lymphatic & Immune System LYMPHATIC SYSTEM RETURNS FLUIDS LEAKED FROM BLOOD VESSELS BACK TO BLOOD; CONSISTS OF THREE PARTS 1. NETWORK OF LYMPHATIC VESSELS (LYMPHATICS) 2. LYMPH: FLUID IN VESSELS 3. LYMPH NODES: CLEANSE LYMPH LYMPHOID ORGANS AND TISSUES PROVIDE STRUCTURAL BASIS OF IMMUNE SYSTEM...

Lymphatic & Immune System LYMPHATIC SYSTEM RETURNS FLUIDS LEAKED FROM BLOOD VESSELS BACK TO BLOOD; CONSISTS OF THREE PARTS 1. NETWORK OF LYMPHATIC VESSELS (LYMPHATICS) 2. LYMPH: FLUID IN VESSELS 3. LYMPH NODES: CLEANSE LYMPH LYMPHOID ORGANS AND TISSUES PROVIDE STRUCTURAL BASIS OF IMMUNE SYSTEM BY HOUSING PHAGOCYTIC CELLS AND LYMPHOCYTES STRUCTURES INCLUDE: SPLEEN THYMUS TONSILS LYMPH NODES OTHER LYMPHOID TISSUES LYMPHATIC SYSTEM RETURNS INTERSTITIAL FLUID AND LEAKED PLASMA PROTEINS BACK TO BLOOD LYMPHATIC VESSELS (LYMPHATICS): ELABORATE NETWORK OF DRAINAGE VESSELS CIRCULATES ~ 3L PER DAY ONCE INTERSTITIAL FLUID ENTERS LYMPHATICS, IT IS CALLED LYMPH LYMPHATIC VESSELS LYMPHATIC VESSELS OFFER A ONE-WAY SYSTEM, ENSURING LYMPH FLOWS ONLY TOWARD HEART LYMPH VESSELS (LYMPHATICS) INCLUDE LYMPHATIC CAPILLARIES AND LARGER LYMPHATIC VESSELS LYMPHATIC CAPILLARIES VESSELS THAT WEAVE BETWEEN TISSUE AND BLOOD CAPILLARIES MORE PERMEABLE THAN BLOOD CAPILLARIES CAN TAKE UP LARGER MOLECULES AND PARTICLES THAN BLOOD CAPILLARIES PROTEINS, CELL DEBRIS, PATHOGENS, AND CANCER CELLS ACTS AS ROUTE FOR PATHOGENS OR CANCER CELLS TO TRAVEL THROUGHOUT BODY LYMPHATIC CAPILLARIES ENDOTHELIAL CELLS OVERLAP LOOSELY TO FORM ONE-WAY MINIVALVES LACTEALS: SPECIALIZED LYMPH CAPILLARIES PRESENT IN INTESTINAL MUCOSA ABSORB DIGESTED FAT AND DELIVER FATTY LYMPH (CHYLE) TO THE BLOOD  Lymphatic & Immune System LARGER LYMPHATIC VESSELS LYMPH CAPILLARIES DRAIN INTO INCREASINGLY LARGER VESSELS CALLED COLLECTING LYMPHATIC VESSELS HAVE STRUCTURES AND TUNICS SIMILAR TO VEINS LYMPHATIC DUCTS RIGHT LYMPHATIC DUCT DRAINS RIGHT UPPER ARM AND RIGHT SIDE OF HEAD AND THORAX THORACIC DUCT DRAINS REST OF BODY IN ABOUT HALF OF INDIVIDUALS, STARTS OUT AS AN ENLARGED SAC, CISTERNA CHYLI EACH EMPTIES LYMPH INTO VENOUS CIRCULATION AT JUNCTION OF INTERNAL JUGULAR AND SUBCLAVIAN VEINS EACH DUCT EMPTIES ON ITS OWN SIDE OF THE BODY LYMPH TRANSPORT LYMPH SYSTEM IS A LOW-PRESSURE SYSTEM LIKE VENOUS SYSTEM LYMPH IS PROPELLED BY SAME MECHANISMS: MILKING ACTION OF SKELETAL MUSCLE PRESSURE CHANGES IN THORAX DURING BREATHING VALVES TO PREVENT BACKFLOW PULSATIONS OF NEARBY ARTERIES CONTRACTIONS OF SMOOTH MUSCLE PHYSICAL ACTIVITY INCREASES FLOW OF LYMPH LYMPHEDEMA: SEVERE LOCALIZED EDEMA CAUSED BY ANYTHING THAT PREVENTS NORMAL RETURN OF LYMPH LYMPHOID ORGANS CONTAIN STROMA: NETWORK-LIKE SUPPORT, SCAFFOLDING FOR IMMUNE CELLS PRODUCED BY RETICULAR CELLS  Lymphatic & Immune System LYMPH NODES 1. ACT AS LYMPH “FILTERS” MACROPHAGES REMOVE AND DESTROY MICROORGANISMS AND DEBRIS IN LYMPH PREVENT UNWANTED SUBSTANCES FROM BEING DELIVERED TO BLOOD 2. OFFER A PLACE FOR LYMPHOCYTES TO BECOME ACTIVATED AND MOUNT AN ATTACK AGAINST ANTIGENS 1 LYMPH NODES VARY IN SHAPE AND SIZE, MOST ARE BEAN SHAPED SMALL, LESS THAN 2.5 CM (~1 INCH) SURROUNDED BY EXTERNAL FIBROUS CAPSULE CAPSULE FIBERS EXTEND INWARD AS TRABECULAE THAT DIVIDE NODE INTO COMPARTMENTS TWO HISTOLOGICALLY DISTINCT REGIONS OF NODE: 1. CORTEX 2. MEDULLA CORTEX SUPERFICIAL AREA OF CORTEX CONTAINS FOLLICLES WITH GERMINAL CENTERS- HEAVY WITH DIVIDING B CELLS DEEP CORTEX HOUSES T CELLS IN TRANSIT CIRCULATE CONTINUOUSLY AMONG BLOOD, LYMPH NODES, AND LYMPH MEDULLA MEDULLARY CORDS EXTEND INWARD FROM CORTEX AND CONTAIN LYMPHOCYTES AND MACROPHAGES MEDULLARY SINUSES ARE FOUND THROUGHOUT NODE MACROPHAGES RESIDE ON FIBERS, CHECKING FOR AND PHAGOCYTIZING ANY FOREIGN MATTER LYMPH NODE CIRCULATION LYMPH ENTERS CONVEX SIDE OF NODE VIA AFFERENT LYMPHATIC VESSELS TRAVELS THROUGH LARGE SUBCAPSULAR SINUS AND THEN INTO SMALLER SINUSES FOUND THROUGHOUT CORTEX AND MEDULLA LYMPH THEN ENTERS MEDULLARY SINUSES FINALLY EXITS CONCAVE SIDE AT HILUM VIA EFFERENT LYMPHATIC VESSELS PRESENCE OF FEWER EFFERENT VESSELS CAUSES FLOW TO SOMEWHAT STAGNATE; ALLOWS LYMPHOCYTES AND MACROPHAGES TIME TO FUNCTION LYMPH TRAVELS THROUGH SEVERAL NODES  Lymphatic & Immune System DISORDERS- BUBOES INFLAMED, SWOLLEN, TENDER LYMPH NODES RESULT WHEN NODES ARE OVERWHELMED BY WHAT THEY ARE TRYING TO DESTROY OFTEN REFERRED TO AS SWOLLEN “GLANDS” SOMETIMES PUS-FILLED BUBONIC PLAGUE WAS NAMED AFTER THIS DISEASE DISORDERS- METASTATIC CANCER LYMPH NODES CAN BECOME SECONDARY CANCER SITES IF METASTASIZING CANCER CELLS BECOME TRAPPED IN NODE CANCER-INFILTRATED LYMPH NODES ARE SWOLLEN BUT USUALLY NOT PAINFUL DISTINGUISH CANCEROUS NODES FROM THOSE INFECTED BY MICROORGANISMS THE SPLEEN SPLEEN IS BLOOD-RICH ORGAN ABOUT SIZE OF FIST, LOCATED IN LEFT SIDE OF ABDOMINAL CAVITY, JUST BELOW STOMACH LARGEST LYMPHOID ORGAN SERVED BY SPLENIC ARTERY AND VEIN, WHICH ENTER AND EXIT AT THE HILUM FUNCTIONS SITE OF LYMPHOCYTE PROLIFERATION AND IMMUNE SURVEILLANCE AND RESPONSE CLEANSES BLOOD OF AGED BLOOD CELLS AND PLATELETS; MACROPHAGES REMOVE DEBRIS THE SPLEEN THREE ADDITIONAL FUNCTIONS OF SPLEEN: 1. STORES BREAKDOWN PRODUCTS OF RBCS (E.G., IRON) FOR LATER REUSE 2. STORES BLOOD PLATELETS AND MONOCYTES FOR RELEASE INTO BLOOD WHEN NEEDED 3. SITE OF FETAL ERYTHROCYTE PRODUCTION SPLEEN IS ENCASED BY FIBROUS CAPSULE  Lymphatic & Immune System THE SPLEEN CONSISTS OF TWO HISTOLOGICAL COMPONENTS: 1. WHITE PULP: SITE WHERE IMMUNE FUNCTION OCCURS CONTAINS ABUNDANCE OF LYMPHOCYTES APPEARS DARK PURPLE UNDER THE MICROSCOPE (DUE TO STAINING) 2. RED PULP: SITE WHERE OLD BLOOD CELLS AND BLOODBORNE PATHOGENS ARE DESTROYED RICH IN RBCS AND MACROPHAGES THAT ENGULF THEM APPEARS LIGHT UNDER MICROSCOPE SPLENECTOMY THE SPLEEN HAS A THIN CAPSULE, DIRECT BLOW OR SEVERE INFECTION MAY CAUSE IT TO RUPTURE- SPILLING BLOOD INTO PERITONEAL CAVITY SPLENECTOMY: SURGICAL REMOVAL OF RUPTURED SPLEEN ONCE STANDARD TREATMENT TO PREVENT HEMORRHAGE AND SHOCK, BUT HAS BEEN DISCOVERED SPLEEN CAN OFTEN REPAIR ITSELF IF SPLEEN MUST BE REMOVED, LIVER AND BONE MARROW TAKE OVER MOST OF ITS FUNCTIONS IN CHILDREN YOUNGER THAN 12, SPLEEN WILL REGENERATE IF A SMALL PART IS LEFT MALT MUCOSA-ASSOCIATED LYMPHOID TISSUE (MALT) LYMPHOID TISSUES IN MUCOUS MEMBRANES THROUGHOUT BODY PROTECTS FROM PATHOGENS TRYING TO ENTER BODY FOUND IN MUCOSA OF RESPIRATORY TRACT, GENITOURINARY ORGANS, AND DIGESTIVE TRACT; LARGEST COLLECTIONS FOUND IN: TONSILS PEYER’S PATCHES APPENDIX  Lymphatic & Immune System TONSILS FUNCTION: TO GATHER AND REMOVE PATHOGENS IN FOOD OR AIR PEYER’S PATCHES PEYER’S PATCHES: CLUSTERS OF LYMPHOID FOLLICLES IN WALL OF DISTAL PORTION OF SMALL INTESTINE LOCATION AIDS IN FUNCTIONS 1. DESTROY BACTERIA, PREVENTING THEM FROM BREACHING INTESTINAL WALL 2. GENERATE “MEMORY” LYMPHOCYTES THE APPENDIX APPENDIX: OFFSHOOT OF FIRST PART OF LARGE INTESTINE CONTAINS A LARGE NUMBER OF LYMPHOID FOLLICLES FUNCTIONS: 1. DESTROY BACTERIA, PREVENTING THEM FROM BREACHING INTESTINAL WALL 2. GENERATE “MEMORY” LYMPHOCYTES THYMUS THYMUS: IN INFERIOR NECK PARTIALLY OVERLIES HEART WHERE T CELLS MATURE MOST ACTIVE AND LARGEST IN SIZE DURING CHILDHOOD STOPS GROWING DURING ADOLESCENCE, THEN GRADUALLY ATROPHIES STILL PRODUCES IMMUNOCOMPETENT CELLS, THOUGH MORE SLOWLY THYMUS THYMUS IS BROKEN INTO OUTER CORTEX AND INNER MEDULLA CORTEX CONTAINS RAPIDLY DIVIDING LYMPHOCYTES AND SCATTERED macrophages MEDULLA CONTAINS FEWER LYMPHOCYTES AND HASSALL’S CORPUSCLES HASSALL’S CORPUSCLES ARE WHERE REGULATORY T CELLS DEVELOP HELPS PREVENT AUTOIMMUNITY  Lymphatic & Immune System THE IMMUNE SYSTEM - Part One! -Provides resistance to disease -Made up of two intrinsic systems Innate (nonspecific) defense system -Constitutes first and second lines of defense -First line of defense: external body membranes (skin and mucosae) -Second line of defense: antimicrobial proteins, phagocytes, and other cells (inhibit spread of invaders; inflammation most important mechanism) Adaptive (specific) defense system Third line of defense- attacks specific antigens(takes longer to react than innate) 1ST LINE OF DEFENSE- SURFACE BARRIERS Acid: acidic skin and mucosa inhibits growth (acid mantle) Enzymes: lysozyme of saliva, respiratory mucus, and lacrimal fluid; also enzymes in stomach. Kills many microorganisms Mucin: sticky mucus, lines digestive and respiratory tract, traps microorganisms Defensins: antimicrobial peptides that inhibit microbial growth Other chemicals: lipids in sebum and dermicidin in sweat are toxic to some bacteria 1ST LINE OF DEFENSE- RESPIRATORY SYSTEM - Mucus-coated hairs in nose trap inhaled particles - Cilia of upper respiratory tract sweep dust- and bacteria-laden mucus toward mouth SECOND LINE OF DEFENSE: CELLS AND CHEMICALS Protect when pathogens invade deeper tissues: -Phagocytes -Natural killer (NK) cells -Inflammatory response (macrophages, mast cells, WBCs, and inflammatory chemicals) -Antimicrobial proteins (interferons and complement proteins) -Fever  Lymphatic & Immune System PHAGOCYTES Phagocytes: white blood cells that ingest and digest foreign invaders Neutrophils: most abundant phagocytes, die fighting; become phagocytic upon exposure Macrophages: develop from monocytes, chief & most robust of the phagocytic cells Free macrophages: wander through tissue spaces Ex- alveolar macrophages Fixed macrophages: permanent residents of some organs stellate macrophages (liver) and microglia (brain) OPSONIZATION -Some microorganisms have external capsules that hide their surface carbohydrates, helping them evade phagocytosisOpsonization: immune system uses antibodies or complement proteins as opsonins that coat pathogens -Act as “handles” for phagocytes to grab on to, enhancing phagocytosis PHAGOCYTOSIS -Some pathogens are not killed with acidified lysosomal enzymes (tuberculosis bacteria) -Helper T cells trigger macrophage to produce respiratory burst, which kills By: -Releasing cell-killing free radicals -Producing oxidizing chemicals (e.g., H2O2) -Increasing pH and osmolarity of phagolysosome Defensins (in neutrophils) also help by piercing membrane of pathogen NATURAL KILLER CELLS (NK) -Nonphagocytic, large granular lymphocytes that police blood and lymph -Can kill cancer and virus-infected cells -Attack cells that lack “self” cell-surface receptors -Kill by inducing apoptosis in cancer cells and virus infected cells -Secrete potent chemicals that enhance inflammatory response  Lymphatic & Immune System INFLAMMATION -Triggered whenever body tissues are injured Injuries include: trauma, heat, irritating chemicals, or infections by microorganisms Benefits of inflammation: -Prevents spread of damaging agents -Disposes of cell debris and pathogens -Alerts adaptive immune system -Sets the stage for repair INFLAMMATION Four cardinal signs of acute inflammation: 1. Redness (rubor) 2. Heat (calor) 3. Swelling (tumor) 4. Pain (dolor) -Sometimes a fifth sign, impairment of function, is seen if movement or use of area is hampered INFLAMMATORY CHEMICAL RELEASE -Chemicals are released into ECF by injured tissues or immune cells -Example: histamine released by mast cells is key inflammatory chemical -Other inflammatory mediators: -Kinins, prostaglandins (PGs), cytokines & complement (if pathogens involved) -All cause vasodilation of local arterioles -All make capillaries leaky -Many attract phagocytes to area VASODILATION AND INCREASED VASCULAR PERMEABILITY Vasodilation causes hyperemia—congestion with blood -leads to redness and heat  Lymphatic & Immune System -Capillary permeability causes exudate—fluid containing clotting factors and antibodies— to leak into tissue -Results in local swelling (edema) pushes on nerve endings, resulting in pain BENEFITS OF EDEMA -Surge of fluid in tissue sweeps foreign material into lymphatic vessels for processing in lymph nodes -Delivers clotting proteins and complement to area -Forms fibrin mesh that acts as scaffold for repair & prevents spread of invaders PHAGOCYTE MOBILIZATION -Neutrophils flood area first; macrophages follow Leukocytosis: release of neutrophils from bone marrow Margination: capillary endothelial cells “grab” passing neutrophils Diapedesis: neutrophils flatten and squeeze between endothelial cells -Move to interstitial spaces Chemotaxis: inflammatory chemicals attract neutrophils to injured area Lastly, macrophages remain for cleanup prior to tissue repair PUS & ABSCESS Pus: creamy yellow mixture of dead neutrophils, tissue/cells, and living/dead pathogens -Abscess: collagen fibers are laid down, walling off sac of pus; may need to be surgically drained -Some bacteria, such as Tuberculosis bacilli, resist digestion by macrophages and remain alive inside -Can form tumor-like growths called granulomas—area of infected macrophages surrounded by uninfected macrophages and outer capsule -Bacteria may remain inactive forever, or if person’s immunity decreases, may break free, become activated, and cause disease ANTIMICROBIAL PROTEINS Antimicrobial proteins enhance innate defense by: Attacking microorganisms directly, or Hindering microorganisms’ ability to Reproduce INTERFERONS (INFS) -Family of immune modulating proteins -Cells infected with viruses can secrete IFNs that “warn” healthy  Lymphatic & Immune System neighboring cells -Stimulate production of proteins that block viral reproduction and degrade viral RNA -Also activate NK cells -Artificial IFNs are used to treat disorders such as hepatitis C, genital warts, and multiple sclerosis Complement system -consists of ~20 blood proteins that circulate in blood in inactive form -Provides major mechanism for destroying foreign substances -Activation enhances,inflammation and also directly destroys bacteria CLASSICAL COMPLEMENT PATHWAY 1. Classical pathway Antibodies first bind to invading organisms and then bind to complement components, activating them Activates complement cascade 2. Lectin pathway Proteins produced by innate system to recognize foreign invaders Bound lectin activates complement 3. Alternative pathway Complement cascade is activated spontaneously when bound to foreign invader COMPLEMENT CASCADE -Each pathway involves activation of proteins in an orderly sequence Cascade -Each pathway converges on C3 protein  Lymphatic & Immune System -Splitting C3: -Enhances inflammation -Promotes phagocytosis -Causes cell lysis MEMBRANE ATTACK COMPLEX (MAC) -C3b binds to target cell, inserts multiple complement proteins into cell membrane -Membrane attack complex (MAC) -MAC forms and stabilizes hole in membrane of microbe, causing influx of water and lysis of microbe FEVER -Abnormally high body temperature -Systemic response to invading microorganisms -Leukocytes and macrophages secrete pyrogens -Molecules that act on hypothalamus (temperature center) & raise body temperature -Benefits of moderate fever -Causes liver and spleen to sequester(isolate) iron and zinc (needed by microorganisms) -Increases metabolic rate, which increases rate of repair IMMUNE SYSTEM PART 2 - ADAPTIVE DEFENSES Adaptive immune system -Specific defensive system that eliminates almost any  Lymphatic & Immune System pathogen or abnormal cell in body -Must be primed by initial exposure to specific foreign Substance -Takes time Adaptive Immunity Specific: recognizes and targets specific antigens Systemic: not restricted to initial site Has memory: mounts an even stronger attack to “known” antigens (second and subsequent exposures) Two Branches of Adaptive Immunity 1. Humoral immunity (antibody mediated) -Antibodies, produced by lymphocytes, circulate freely in body fluids -Bind to target cell -Temporarily inactivate -Mark for destruction by phagocytes or complement 2.Cell-Mediated Immunity -Lymphocytes act against target cell Directly—by killing infected cells Indirectly—by releasing chemicals that enhance inflammatory response; or activating other lymphocytes or macrophages Antigens -Substances that can mobilize adaptive defenses and provoke an immune response -Large, complex molecules not normally found in body (non-self) Complete Antigens Immunogenicity: ability to stimulate proliferation of specific lymphocytes Reactivity: ability to react with activated lymphocytes and antibodies released by immunogenic reactions Examples: foreign proteins, polysaccharides, lipids, and nucleic acids; seen on many foreign invaders such as pollen and microorganisms Incomplete Antigens (Haptens) NOT immunogenic by themselves Too small to be seen  Lymphatic & Immune System Examples: small peptides, nucleotides, some hormones -May become immunogenic if hapten attaches to body’s own proteins -Protein and hapten is seen as foreign Antigenic determinants: parts of antigen that antibodies or lymphocyte receptors binds Self-antigens: cover the cell surface and are not antigenic to self -but may be antigenic to others in transfusions or grafts MHC proteins- Set of important self- glycoproteins -Major histocompatibility complex (MHC) -Are unique to each individual Cells of the Adaptive Immune System Lymphocytes B lymphocytes (B cells)—humoral immunity T lymphocytes (T cells)—cellular immunity Antigen-presenting cells (APCs) -Do not respond to specific antigens -Play essential auxiliary roles in immunity Lymphocyte Development 1.Originate in red bone marrow 2.Mature in primary lymphoid organs (maturation) T cells- thymus B cells- bone marrow Immunocompetence: lymphocytes must be able to recognize only 1 specific antigen Self-tolerance: lymphocytes must be unresponsive to own antigens 3. Immunocompetent B and T cells not yet exposed to antigen are called naive -Exported from primary lymphoid organs to secondary lymphoid organs (lymph nodes, spleen, etc.) -Increases chance of encounter with antigen 4. Antigen encounter and activation -Naive lymphocyte’s first encounter with antigen triggers lymphocyte to develop further -Binding to its specific antigen activates lymphocyte (clonal selection) 5.Proliferation and differentiation Once selected and activated, lymphocyte proliferates (CLONES) Most clones become effector cells that fight infections  Lymphatic & Immune System -A few remain as memory cells -Able to respond to same antigen more quickly second time it is encountered -B and T memory cells and effector T cells circulate continuously in blood Antigen receptor diversity -Genes, not antigens, determine which foreign substances the immune system will recognize -∼25,000 different genes codes for up to a billion different types of lymphocyte antigen receptors -Huge variety of receptors: gene segments are shuffled around, resulting in many combinations Lymphocyte Selection Tests Positive selection- T cells that can recognize self-MHC proteins are selected -Those that cannot are destroyed by apoptosis Negative selection- T cells that bind too tightly to self-MHC antigens are destroyed by Apoptosis -Ensures self-tolerance Antigen-Presenting Cells (APCs) -Cells that engulf antigens and present fragments of antigens to T cells for recognition Dendritic Cells- found in connective tissue and epidermis Most effective antigen presenting cell Macrophages- found in connective tissue & lymphoid organs Activates T cells, other macrophages & promotes inflammation Antigen-Presenting Cells (APCs) B lymphocytes Do not activate naive T cells When an antigen is encountered, humoral response is provoked Specific antibodies are produced Plasma Cells -Most become plasma cells, antibody-secreting effector cells -Secrete specific antibodies at rate of 2000  Lymphatic & Immune System molecules per second for 4 to 5 days, then die -Antibodies circulate in blood or lymph, binding to free antigens, marking them for destruction by innate or other adaptive mechanisms Memory Cells -Clone cells that do not become plasma cells become memory cells Provide immunological memory -Mount an immediate response to future exposures to same antigen Immunological Memory -First time exposure to antigen has a response lag time of 3 to 6 days -Re-exposure leads to more prolonged & effective Response: -Responds in hours -Higher & quicker peak antibody levels -Antibodies bind with greater affinity Active humoral immunity: when B cells encounter antigens and produce specific antibodies agains them Two types 1. Naturally acquired: formed in response to actual bacterial or viral infection 2. Artificially acquired: formed in response to vaccine of dead or attenuated pathogens Passive humoral immunity: when antibodies are introduced into body -No immunological memory -Protection ends when antibodies degrade Two types of passive humoral immunity 1. Naturally acquired: antibodies delivered via placenta or through milk 2. Artificially acquired: injection of serum, such as gamma globulin Protection immediate but ends when antibodies naturally degrade in body Antibodies Y shaped protein consisting of four chains: -Two identical heavy (H) chains  Lymphatic & Immune System -Two identical light (L) chains -Constant region Determines class Where it can bind Variable (V) regions at one end of each arm Antibody Classes Five major classes of antibodies: IgM- activates complement IgA- Found in mucus helps prevent entry of pathogens IgD- Functions as B cell receptor IgG- Most abundant in plasma, can cross placenta IgE- Active in allergies and parasitic infections Summary of antibody actions Antigen-antibody complexes do not destroy antigens; they prepare them for destruction by innate defenses Antibodies go after extracellular pathogens Monoclonal antibodies: commercially prepared pure antibodies that are specific for a single antigenic Determinant -Many used as medications Types of T cells CD4 cells usually become helper T cells (TH) Activate B cells, other T cells, and macrophages Some become regulatory T cells Decrease immune response Can also become memory T cells Types of T cells CD8 cells become cytotoxic T cells (TC) Capable of destroying cells harboring foreign antigens Also become memory T cells CD4 or CD8 are naïve T cells Helper, cytotoxic, and regulatory T cells are activated Hypersensitivity Reactions Hypersensitivities: immune responses to perceived (otherwise harmless) threat that cause tissue damage Also called acute (type I) hypersensitivities (allergies)  Lymphatic & Immune System -begin in seconds after contact with allergen -Histamines causes vasodilation and leakiness of the vessels, leading to symptoms of runny nose, itchy hives, or watery eyes Hypersensitivities Allergic reactions can be local or systemic Local reaction involves mast cells of skin, respiratory or gastrointestinal mucosa Systemic response is anaphylactic shock -Bronchioles constrict, making breathing difficult -Vasodilation results in low blood volume, which could cause circulatory collapse -Treatment: epinephrine Subacute hypersensitivities Slow onset (1–3 hours) and long duration (10–15 hours) Cytotoxic (type II) reactions Antibodies bind to antigens on specific body cells, stimulate phagocytosis and complement-mediated lysis of cellular antigens Example: mismatched blood transfusion reaction Immune complex (type III) hypersensitivity -Insoluble antigen-antibody complexes form Intense inflammation Delayed hypersensitivities (type IV) Slow onset (1–3 days) Helper T cells involved Allergic contact dermatitis (poison ivy), TB test Hypersensitive Reactions ABCD A- Allergies, Anaphylaxis B- Antibody C- Complex D- Delayed Hypersensitivity Reactions ACID A- Anaphylaxis C- Cytotoxic mediated I- Immune Complex mediated D- Delayed hypersensitivity TOPICS TO KNOW 1. Lines of Immune Defense  Lymphatic & Immune System First Line of Defense (Physical Barriers and Secretions): ○ Skin: The outermost layer of keratinized epithelial cells acts as a physical barrier to pathogens. The skin also secretes sebum, which has antimicrobial properties. ○ Mucous Membranes: Found in the respiratory, digestive, and urogenital tracts, mucous membranes trap pathogens, preventing their entry into deeper tissues. Cilia in the respiratory tract sweep mucus and trapped particles upward. ○ Secretions: Tears and Saliva: Contain lysozyme, an enzyme that breaks down bacterial cell walls. Stomach Acid: Kills most ingested pathogens by lowering pH. Urine: Flushing action helps eliminate pathogens from the urinary tract. Second Line of Defense (Innate Immunity): ○ Phagocytosis: Immune cells like macrophages and neutrophils recognize and engulf pathogens via pattern recognition receptors (PRRs) that bind to pathogen-associated molecular patterns (PAMPs). ○ Inflammation: Caused by the release of chemicals such as histamine and cytokines, inflammation promotes vasodilation, bringing more immune cells (neutrophils, macrophages) to the site of infection, resulting in redness, heat, and swelling. ○ NK Cells (Natural Killer Cells): Destroy infected or transformed (cancerous) cells by recognizing a lack of self-MHC I molecules and inducing apoptosis via perforin and granzymes. ○ Complement System: A cascade of proteins that enhances phagocytosis (opsonization), induces inflammation, and forms the membrane attack complex (MAC) to lyse pathogen cells. Third Line of Defense (Adaptive Immunity): ○ Antibody-Mediated Immunity (Humoral): B cells produce antibodies, which bind to specific antigens, neutralizing them or marking them for destruction. ○ Cell-Mediated Immunity: T cells (CD4 and CD8) recognize antigens on infected cells and either assist in activating other immune cells (helper T cells) or directly kill infected cells (cytotoxic T cells). ○ Memory Cells: Both B and T cells develop into memory cells after an initial infection, ensuring a faster and more efficient response to subsequent exposures to the same pathogen. 2. Functions of the Lymphatic System  Lymphatic & Immune System Fluid Recovery: The lymphatic system drains excess interstitial fluid from tissues, preventing swelling (edema), and returns it to the bloodstream. Lipid Absorption: Lymphatic capillaries called lacteals in the small intestine absorb dietary fats and transport them as chylomicrons to the bloodstream. Immune Surveillance: Lymphatic organs filter lymph for pathogens, foreign particles, and dead cells. It facilitates immune cell interactions to detect and respond to infections. 3. What is Lymph and Where Does it Come From? Formation: Lymph is formed from interstitial fluid that leaves blood capillaries due to hydrostatic pressure, entering the lymphatic capillaries, where it is transported through the lymphatic vessels. Composition: Lymph consists of water, electrolytes, white blood cells (mainly lymphocytes), waste products, and pathogens or debris collected from tissues. 4. Lymphatic Organs and Their Functions Primary Lymphoid Organs: ○ Bone Marrow: Origin of all blood cells, including lymphocytes. Involved in the maturation of B cells. ○ Thymus: Site where T cells mature. It ensures T cells can recognize self-MHC and eliminates those that react with self-antigens (negative selection). Secondary Lymphoid Organs: ○ Lymph Nodes: Filter lymph and provide a site for immune cell activation. They contain B cell-rich follicles and T cell-rich paracortex. ○ Spleen: Filters blood, removes aged RBCs, and houses immune cells. White pulp is involved in immune response, while red pulp filters the blood. ○ Tonsils: Protect mucosal surfaces, especially in the throat, from airborne or ingested pathogens. ○ Peyer’s Patches: Located in the intestines, these detect pathogens and activate immune responses. 5. Pathway of Lymph Flow  Lymphatic & Immune System 1. Lymphatic Capillaries → Afferent Lymphatic Vessels → Lymph Nodes → Efferent Lymphatic Vessels → Lymphatic Trunks → Thoracic Duct (left side) or Right Lymphatic Duct (right side) → Subclavian Veins (into bloodstream). 6. Cells of the Innate Immune System Macrophages: Recognize and engulf pathogens, presenting antigens to T cells via MHC II. They also release cytokines to recruit other immune cells. Neutrophils: The first responders to infection, they engulf pathogens and release enzymes to break down pathogens. Mast Cells: Found in connective tissue, they release histamine, triggering inflammation and recruiting other immune cells to the site of infection. NK Cells: Detect and destroy virus-infected cells or cancer cells by releasing cytotoxic proteins. 7. Lymph Nodes and Their Functions Structure: Composed of the cortex (B cells), paracortex (T cells), and medulla (plasma cells and macrophages). Functions: Lymph nodes filter lymph, trapping pathogens and foreign particles, and provide a site for lymphocyte activation and proliferation. 8. Cells of the Adaptive Immune System B Cells: Differentiate into plasma cells that produce antibodies. They are activated by helper T cells and encounter antigens in lymph nodes or spleen. T Cells: ○ CD4 (Helper T Cells): Activate B cells, macrophages, and cytotoxic T cells. ○ CD8 (Cytotoxic T Cells): Directly kill infected or cancerous cells by inducing apoptosis. 9. MALT (Mucosa-Associated Lymphoid Tissue)  Lymphatic & Immune System Function: MALT provides immune protection to mucosal surfaces by detecting and responding to pathogens. ○ Examples: Tonsils, Peyer’s patches in the intestines, and lymphoid tissue in the respiratory tract. 10. Classes of Antibodies and Their Functions IgG: The most abundant antibody in blood and tissues; provides long-term immunity and neutralizes toxins and pathogens. Can cross the placenta to provide passive immunity to the fetus. IgA: Found in mucosal areas (respiratory and gastrointestinal tracts), saliva, and tears; prevents pathogen entry at mucosal surfaces. IgM: The first antibody produced in response to infection; activates the complement system. IgE: Involved in allergic reactions and responses to parasitic infections. It binds to mast cells and basophils. IgD: Found on B cells, it helps with the activation of B cells during immune responses. 11. T and B Cell Maturation B Cells: Mature in the bone marrow where they undergo receptor rearrangement and selection to avoid self-reactivity. T Cells: Mature in the thymus, where they undergo positive and negative selection to ensure functional TCRs and tolerance to self. 12. CD4 vs. CD8 T Cells CD4 (Helper T Cells): Recognize antigens presented by MHC II molecules and help activate other immune cells (B cells, macrophages, CD8 T cells). CD8 (Cytotoxic T Cells): Recognize antigens presented by MHC I molecules and directly kill infected or cancerous cells. 13. Vaccines and Illness Prevention  Lymphatic & Immune System Vaccines contain inactivated or weakened pathogens or their components (antigens). The immune system reacts to these antigens by producing antibodies and memory cells. Upon later exposure to the actual pathogen, memory cells mount a faster and stronger immune response, preventing illness. 14. Complement System The complement system is a group of plasma proteins that, when activated, help destroy pathogens. ○ Pathways: Classical (antibody-driven), Alternative (spontaneous activation), and Lectin (triggered by carbohydrate binding). ○ Actions: Opsonization (enhances phagocytosis), recruitment of immune cells (chemotaxis), and formation of MAC, which directly lyses pathogen membranes. 15. Afferent vs. Efferent Vessels Afferent Vessels: Carry lymph into lymph nodes. Efferent Vessels: Carry filtered lymph out of the lymph node. 16. Inflammation Process: Initiated by tissue damage or infection, resulting in the release of inflammatory mediators (e.g., histamine, prostaglandins). These cause vasodilation and increased vascular permeability, allowing immune cells and proteins to enter the affected tissue. Signs: Redness, heat, swelling, pain, and loss of function. Purpose: Helps contain infection, repair tissue, and activate immune responses. 17. Flow of Lymph Lymph Flow: Starts in lymphatic capillaries and moves through afferent vessels into lymph nodes, where immune cells filter pathogens. From the nodes, lymph travels via efferent vessels to lymphatic trunks and finally into the thoracic duct or right lymphatic duct, returning to the bloodstream. 18. What is a Hapten?  Lymphatic & Immune System Definition: A hapten is a small molecule that, by itself, cannot induce an immune response. However, when it binds to a larger carrier protein (such as a serum protein), it can trigger an immune response. This process is called haptenization. Example: Penicillin, which is small and does not typically provoke an immune response, may become immunogenic when it binds to proteins in the body, potentially leading to allergic reactions. 19. Primary vs. Secondary Lymphoid Organs Primary Lymphoid Organs: These are where lymphocytes are generated and mature. ○ Bone Marrow: Site of origin and maturation for B cells. ○ Thymus: Site of maturation for T cells. Secondary Lymphoid Organs: These are where immune responses are initiated, and lymphocytes interact with pathogens. ○ Lymph Nodes: Filter lymph, where T and B cells are activated. ○ Spleen: Filters blood, removes old RBCs, and houses immune cells to react to blood-borne pathogens. ○ MALT (Mucosa-Associated Lymphoid Tissue): Includes structures like tonsils, Peyer’s patches, and lymphoid tissues in mucosal linings, where immune responses to pathogens entering via mucosal surfaces are initiated. 20. Passive vs. Active Immunity (Both Natural and Artificial) Passive Immunity: Immunity transferred from another individual or organism. ○ Natural Passive Immunity: Antibodies passed from mother to fetus through the placenta or via breast milk. ○ Artificial Passive Immunity: Transfer of antibodies via serum from an immune individual, such as in antivenom or immunoglobulin therapies. Active Immunity: The body produces its own antibodies or T cells in response to an antigen. ○ Natural Active Immunity: Immunity gained after recovering from an infection. ○ Artificial Active Immunity: Immunity developed after receiving a vaccine, which stimulates the production of antibodies without causing disease. 21. What Are Interferons and How Do They Help the Body Fight Infection?  Lymphatic & Immune System Interferons (IFNs): Proteins released by virus-infected cells to signal neighboring cells to initiate antiviral defenses. ○ Types: Type I IFNs (IFN-α, IFN-β): Trigger antiviral states in cells, inhibit viral replication, and enhance the immune response. Type II IFN (IFN-γ): Activates macrophages and enhances antigen presentation to T cells. ○ Mechanism: Interferons bind to receptors on adjacent cells, stimulating them to produce antiviral proteins that block viral replication. 22. What Is Fever and How Does It Protect the Body? Fever: An elevated body temperature often caused by an infection. It is regulated by the hypothalamus in response to pyrogens, which are substances released by pathogens or immune cells. Mechanism of Action: ○ Fever enhances the immune system by speeding up enzymatic reactions and increasing the production of immune cells. ○ It may also inhibit pathogen growth, as many bacteria and viruses are sensitive to changes in temperature. Benefits: Promotes the activity of immune cells like macrophages and neutrophils, accelerates tissue repair, and inhibits pathogen replication. 23. What Is Chemotaxis? Definition: Chemotaxis is the movement of immune cells toward the site of infection in response to chemical signals, known as chemokines, released by pathogens or injured tissues. Process: ○ Immune cells like neutrophils and macrophages follow the concentration gradient of chemokines, migrating toward areas of infection or inflammation. ○ This helps recruit and concentrate immune cells to the site where they are most needed to fight infection. 24. Anatomy of Lymph Capillaries  Lymphatic & Immune System Structure: Lymphatic capillaries are tiny, thin-walled vessels that are more permeable than blood capillaries. They have one-way valves that prevent lymph from flowing backward. Function: They collect excess tissue fluid (interstitial fluid) from around tissues and transport it as lymph to larger lymphatic vessels. These capillaries are especially important in absorbing dietary fats from the intestines (via lacteals). 25. What Is a Monoclonal Antibody and What Can They Be Used For? Monoclonal Antibodies (mAbs): Laboratory-made molecules that mimic the immune system’s ability to fight off harmful pathogens such as viruses. They are created by cloning a single B cell that produces a specific antibody. Uses: ○ Cancer Therapy: Monoclonal antibodies can be used to target specific cancer cells for destruction. ○ Infectious Disease: mAbs are used as treatments for diseases like COVID-19 and Ebola. ○ Autoimmune Diseases: Monoclonal antibodies can block the action of cytokines involved in autoimmune diseases like rheumatoid arthritis. 26. Types of Hypersensitivity Reactions Type I (Immediate Hypersensitivity): IgE-mediated allergic reactions, such as hay fever, asthma, or anaphylaxis. Mast cells and basophils release histamine. Type II (Cytotoxic Hypersensitivity): IgG or IgM antibodies bind to cells, marking them for destruction by phagocytes or complement. Example: Hemolytic anemia. Type III (Immune Complex-Mediated): Formation of antigen-antibody complexes that deposit in tissues, causing inflammation. Example: Systemic lupus erythematosus (SLE). Type IV (Delayed-Type Hypersensitivity): T cell-mediated response causing tissue damage, often seen in conditions like contact dermatitis or graft rejection. 27. Be Able to Label Important Parts of a Lymph Node Parts to Label:  Lymphatic & Immune System ○ Capsule: The outer connective tissue layer. ○ Cortex: Contains B cell follicles, which are the sites of B cell activation. ○ Paracortex: Area between the cortex and medulla, where T cells are located. ○ Medulla: Contains plasma cells, macrophages, and lymphatic sinuses. ○ Afferent Lymphatic Vessel: Brings lymph into the node. ○ Efferent Lymphatic Vessel: Carries filtered lymph out of the node. 28. Be Able to Label Major Lymph Nodes and Vessels of the Body Major Lymph Nodes: ○ Cervical: Located in the neck, filter lymph from the head and neck. ○ Axillary: Located in the armpits, filter lymph from the arms and upper chest. ○ Inguinal: Located in the groin, filter lymph from the lower limbs. ○ Popliteal: Located behind the knee, filter lymph from the lower legs. ○ Mesenteric: Located in the abdomen, filter lymph from the intestines. Major Lymphatic Vessels: ○ Thoracic Duct: Drains lymph from the left side of the body and lower body. ○ Right Lymphatic Duct: Drains lymph from the right side of the head, right arm, and right chest. 29. Be Able to Label an Antibody Including Light and Heavy Chains, Variable and Constant Regions Structure of an Antibody: ○ Heavy Chains: Two larger polypeptide chains that form the bulk of the antibody structure. ○ Light Chains: Two smaller polypeptide chains that bind to the heavy chains at the variable regions. ○ Variable Region: The tip of the antibody that binds to the specific antigen. ○ Constant Region: The part of the antibody that determines the class of the antibody (IgA, IgG, IgM, IgE, IgD) and can interact with immune cells.