Immunology

1. Immunology The Lymphatic System

2. Lymphatic System • Lymphatic System: Provides the body with a defense mechanism against foreign invaders. • Most interstitial fluid surrounding the capillary beds is reabsorbed into the capillaries - the lymphatic ducts picks up the remaining interstitial. • Pathogens are filtered out through the lymph nodes. • Lymph nodes contain concentrations of lymphocytes & macrophages to respond with to the pathogens.

3. Lymphatic System • Lymph: The clear fluid in the lymphatic vessels. • Subclavian Veins return the lymph into the heart.

4. The Lymphatic System • Major Functions of the Lymphatic System: • Draining excess fluid from tissues to be returned to the bloodstream. • Transporting lipids & vitamins reabsorbed in the gastrointestinal tract to the bloodstream. • Activating the body’s immune response to pathogens.

5. Lymphatic Anatomy • Lymph: Clear fluid within the lymphatic vessels that has been reabsorbed from the interstitial fluid. • Lymphatic Vessels: The vessel system that provides transportation for the lymph. • Lymphatic Capillaries: The start of the lymphatic system – endothelial cells that are closed at one end & have flaps that work as valves. • These allow fluid & large proteins & foreign bodies to enter. • Lacteals: Lymphatic capillaries in the small intestine that specialize in transporting lipids. • Lymphatic Vessels: Structured in the same 3 layers as the blood vessels, but with thinner walls & more valves. • Lymph Nodes: Bean-shaped structures positioned at regular intervals along the lymphatic vessel routes. • Approximately 600 total in the lymphatic system.

7. Lymphatic Path • Lymphatic capillaries  collecting lymphatic vessels  lymph nodes  more collecting vessels  six lymphatic trunks  two final collecting ducts  subclavian veins.

9. Lymphatic Trunks • Lymph Trunks: Larger lymphatic vessels that occur when vessels merge/unite. 5 major trunks! • Lumbar Trunk • Intestinal Trunk • Broncho-Mediastinal Trunk • Subclavian Trunk • Jugular Trunk

11. Lymphatic • Lymphatic Ducts: Trunks drain into one of two main ducts.. • Thoracic Duct aka Left Lymphatic Duct: Drains all parts of the body below the diaphragm and on the left side of the body (left arm, left side of head, etc) & empties into the left subclavian vein. • Cisterna Chyli: The prominent sac in the abdominal cavity that begins the thoracic duct. • Right Thoracic Duct: Drains the right upper extremity, the right part of the head & neck, and the right area of the thoracic region & empties into the right subclavian vein.

13. Lymphatic Nodes • Lymph Nodes: Bean-shaped structures positioned at regular intervals along the lymphatic vessel routes. Designed to filter the lymph fluid. • The most prolific & important organ in the lymphatic system. • Embedded in the connective tissue throughout the body. • Most concentrated in the cervical, axillary, abdominal, pelvic & thoracic regions.

15. Lymphatic Nodes • Capsule: Layers of connective tissue that cover the lymph node. • Trabeculae: Extensions that divide the node into compartments & provide support & a network for blood vessels to travel along.

16. Lymphatic Nodes • Cortex: Outer layer of the lymph node. • The outer area is responsible for collecting the B-lymphocytes or B-cells. • The inner area is responsible for collecting T-cells. • Medulla: The inner part of the lymph node that holds a concentration of macrophages, in addition to B cells & plasma cells.

17. Lymphatic Nodes • Afferent Lymphatic Vessels: Structure that lymph enters the node through and directs the lymph inward toward the sinuses. • Sinuses: The portion of the lymph node where most of the filtering takes place. • Efferent Lymphatic Vessels: Structures that leave the node at the hilum. • Hilum: A small depression where the efferent lymphatic vessels leave the lymph node.

19. Lymphatic Nodes • Lymphatic Nodules: Masses of lymphatic tissue that lack the capsule. • Found in mucous membranes of the gastrointestinal, urinary, & reproductive tracts. • Found in the respiratory airways. • Tonsils: The lymphatic nodules located at the entrance to the pharynx that are placed to deal with ingested & inhaled foreign particles & pathogens. Palatine, lingual, & pharyngeal tonsils located in that area.

21. Thymus • Thymus: A two lobed lymph organ located between the lungs in front of the aorta. • Most often active in childhood & has both a lymphatic & endocrine function. • Secretes hormones critical for maturation of the T-cells. • Lobules: The divisions of the thymus, each made up of a cortex & medulla. • Cortex: The outer layer of the lobules that has a high T-cell concentration, some dendritic cells, & a few epithelial cells. • Meduulla: The inner layer that contains epithelial cells, T-cells, dendritic cells, and macrophages.

23. Spleen • Spleen: The largest mass of lymphatic tissue in the body, located in the hypochondriac region of the abdomen. • Composed of a capsule & extending trabiculae. • Two kinds of tissue in the spleen: • White Pulp: Composed mostly of lymphocytes & macrophages. • Red Pulp: Composed of blood-filled sinuses & Billroth’s cords or splenic cords (cords of splenic tissue).

25. Spleen • Primary functions of the Spleen: • Reservoir for blood • Place for destroying old red blood cells • Filter for the blood • Creation of blood cells during fetal development • Ruptured Spleen: A common physical injury that typically results in hemorrhage & can put the patient at risk for sepsis (blood infection).

27. Immune Response • Immune Responses: The defensive actions our body takes to respond to foreign invaders. • Nonspecific or Innate Defenses: Defenses that are innate & not geared toward specific pathogens. A generic response! • Immunity: The defense system where lymphocytes target & destroy specific pathogens. A learned response!

28. Immune Response • First Line of Defense: The first steps our body takes to defend against foreign invaders. • Epidermis: Keratinized cells form many layers that very few pathogens can infiltrate. • Mucous Membranes: Epithelial layers lining body cavities secrete mucus to trap microbes & contains protective chemicals.

29. Immune Response • Mucous membranes in the nose have hairs that filter microbes from the air. • Mucous membranes of the upper respiratory tract contain cilia to trap microbes & propel them back up the airway & out of the body. • Lacrimal apparatus of the eye contains lysozyme which clears the eyes of pollutants & microbes. • Saliva can wash microbes from the teeth & mouth.

30. Immune Response • Sebum created by the sebaceous glands of the skin prevent the growth of some bacteria. • Stomach acid, lysozomeenzymes in perspiration, and avid in the vagina deter pathogens. • Hyaluronic acid, found in connective tissue, inhibits the spred of pathogens in that tissue.

31. Immune Response • Second Line of Defense: The body’s internal defenses that take over if a pathogen gets through the first line of defense. • Leukocytes • Macrophages • Antimicrobial Proteins

32. Immune Response • Leukocytes: 5 major categories. • Neutrophils: Phagocytic cells that wander throughout the connective tissue destroying bacterias. • Eosinophils: Phagocytic cells that destroy allergens, antigen & anti-body complexes, & some inflammatory chemicals. • Surround larger parasites & attack them with enzymes to weaken or destroy them. • Defend against allergies & parasitic worm infections. • Basophils: Helper cells that secrete vasodilators & anticoagulants in order to speed other leukocytes to the infected zone.

33. Immune Response • Lymphocytes: A variety of cells active in the immune response. • Natural Killer Cells (NK Cells): Attack any cell with an unusual plasma membrane, such as cells that are infected by a virus or have become cancerous. • Cytolysis: Perforin protein is injected into the cell to cause it to “explode”. • Granzymes: Cause the cell to self-destruct. • Found in the spleen, red bone marrow, & lymph nodes. • Monocytes: Wandering cells that eventually turn into macrophages.

35. Immune Response • Phagocytosis: The process of an immune response cell “eating” a foreign invader. 5 steps: • Chemotaxis: Phagocytic cells are attracted to the site of damage via a chemical response. • Adherence: Occurs when the phagocytic cells attach to the microbe. • Ingestion: Extends the pseudopods to engulf the microbe. • Digestion: The microbe is dissolved through toxic chemicals (including hydrogen peroxide!) in an oxidative burst. • Killing: The microbe is destroyed & the phagocytic cell typically dies as well. • Apoptosis: The normal death of a cell.

37. Immune Response • Macrophages: Two categories of cells that “eat: foreign invaders or damaged cells. • Fixed Macrophages: Non-motile cells that are found in a particular tissue where they permanently stand guard. • Wandering Macrophages: Motile cells that roam through the body looking for foreign invaders. • Include histiocytes in connective tissue, reticular cells in the liver, microglia in the nervous system, and the alveolar microphages in the lungs.

38. Immune Response • Antimicrobial Proteins: Found in the blood and intestinal fluid to prevent infection. 3 types • Interferons (IFNs): Polypeptides secreted by cells that have been invaded by a virus. • Travel to adjacent cells & stimulate the production of anti-viral proteins. • Activate natural killer cells & macrophages & aid in the destruction of cancerous cells. • Transferrins: Can bind to & reduce the amount of iron available in bacteria, which can inhibit the spread of certain bacteria. • Complement System: Group of twenty plus beta gobulins (proteins in the blood plasma) that enhance the immune, allergic, & inflammatory reactions. • Optimization: Where the complement system chemically coats the surface of bacteria which in tern makes them easier to phagocytize.

39. Inflammation • Inflammation: One of the body’s most common responses to tissue damage. Occurs in roughly the same way in any tissue. • Four Cardinal signs of Inflammation: • Redness • Swelling • Heat • Pain

41. Inflammation • 3 Stages of Inflammation: • Vasodilation of Blood Vessels: Increases blood flow & increases the permeability of capillaries. • Prompted by histamines & kinins. • Capillary dilation is the cause of redness. • Emigration (Movement) of Phagocytes: Phagocytes move to effected areas to remove dead cells & toxins. • Basophils secrete leukotrienes to increase this reaction. • Leukocytosis: The sudden increase of white blood cells migrating to the area. • Repair of Damaged Tissues: The tissues repaire itself. • Platelet Derived Growth Factor (PDGF): Prompts fibroblasts to multiply faster & speed up tissue repair.

43. Fever • Fever: An increase in body temperature often due to the interaction of bacteria & macrophages. • Interleukin-1: Released by macrophages, which triggers prostaglandin E to be secreted by the hypothalamus, which increases the body’s internal thermostat. • Positive Effects: Promotes interferon activity, speeds up metabolism & other processes that aid in repair, slows down the growth of some bacteria & viruses. • Negative Effects: Cellular dysfunction & brain damage possible if the fever gets too high.

44. Immune System • Immune System: A combination of cells designed to recognize specific foreign substances & neutralize or destroy them. • Specific Immune Defenses: The cells are specifically geared toward fighting certain invaders, and remembers previous foreign invaders so that they can be rapidly eliminated in the future.

45. Immune System • Two Divisions of the Immune System: • Humoral Immunity aka Antibody-Mediated Immunity: Involves antibodies which bind to foreign substances like toxins & bacteria to “tag” or mark them for destruction. Driven by T cells & B cells. • Cellular Immunity: Cell-mediated immunity which includes the actions of lymphocytes that attack foreign cells or cells infected with cancer, viruses, or parasites. Driven by T cells.

46. Antigens • Antigen (Ag): Any substance recognized as foreign to the body & triggering an immune response. • Typically large molecules, often proteins. • Two defining characteristics: • Immunogenicity: Stimulate the immune system to produce specific antibodies. • Reactivity: An antigen will react with the appropriate antibody once it is produced.

48. Antigens • Epitope: The part of a molecule that initiates an immune response. • The antigen could be an entire microbe. • Typically it is just a portion of the microbe or a specific chemical or toxin component. • Antigens can include blood cells of a different type, pollen, egg whites, etc.

49. Antigens • Haptens: Smaller substances that can cause reactivity, but not full immunogenicity. • Stimulate an immune response only if attached to a larger carrier molecule. • Example: Toxin in poison ivy, which only triggers a response when bound to particular proteins in the body.