1. Lymphatic System & Immunity Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Lymphatic capillaries Pulmonary capillary network Lymph node Lymphatic vessels Blood flow Lymph node Lymph flow Systemic capillary network Lymphatic capillaries Fluid Recovery, Fat Transport and DEFENSE

2. Lymphatic Capillaries: the beginning Tissue cells Arteriole Venule Lymphatic capillary Capillary bed Lymphatic vessel Similar to blood capillaries EXCEPT more permeable and lower pressure

3. Lymphatic Vessels The walls are similar but thinner than those of veins Lymphatic vessels are composed of three layers: An endothelial lining (inner) Smooth muscle (middle) Connective tissue (outer) Larger vessels lead to lymph nodes and then to larger lymphatic trunks © The McGraw-Hill Companies, Inc./Dennis Strete, photographer

4. Lymphatic Trunks The trunks drain lymph from the lymphatic vessels They are named for the regions they serve such as lumbar, intestinal, intercostal, bronchomediastinal, subclavian, and jugular Jugular trunk Right lymphatic duct Brachiocephalic vein Bronchomediastinal trunk Intercostal trunk Internal jugular vein Thoracic duct Subclavian trunk Thoracic duct Intestinal trunk Lumbar trunk Lymphatic vessels Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

5. Lymph nodes Thoracic duct Right lymphatic duct Right internal jugular vein (a) (b) Area drained by right lymphatic duct Right lymphatic duct Lymphatic trunks Lymphatic vessels Left internal jugular vein Left subclavian vein Cisterna chyli Right subclavian vein Axillary lymph nodes Lymphatics of mammary gland INTO 2 COLLECTING DUCTS

6. How are lymphatic vessels different from circulatory vessels? A)They are made of one tissue layer only B)They are under little or no pressure C)They begin as capillaries D)They return fluid to the intestines

7. What is the order from smallest to largest structures? A) ducts to trunks to vessels B) capillaries to ducts to vessels C) trunks to ducts to capillaries D) vessels to trunks to ducts

8. 16.3 Tissue Fluid Formation Capillary blood pressure filters water and small molecules from the plasma The resulting fluid has: Much the same consistency as plasma Contains water and dissolved substances EXCEPT: proteins which create plasma colloid osmotic pressure

9. Lymph Formation Filtration from the plasma normally exceeds reabsorption, leading to the net formation of tissue fluid This increases the tissue fluid hydrostatic pressure within interstitial spaces This pressure forces fluid into lymphatic capillaries forming lymph This process prevents accumulation of excess tissue fluid or edema

10. Lymph Function Lymphatic vessels play a role in: 1) Absorption & delivery of dietary fats fats 2)Collection & delivery of excess interstitial fluids 3) Delivering foreign particles to the lymph nodes Flow of lymph Epithelial cell Filaments anchored to connective tissue Movement of tissue fluid Overlap of cells creates a UNIQUE situation, acting like valves: when pressure is HIGH outside the cells remain open (are not collapsed)

11. Which of the following would increase the formation of lymph? A) An increase in osmotic pressure in blood vessels. B) An increase in the amount of fluid in the lymph capillaries. C) A blockage in the lymph capillaries D) An increase in the amount of fluids in the interstitial spaces (tissue fluid)

12. 16.4 Lymph Movement Hydrostatic pressure of tissue fluid drives the lymph into the lymphatic capillaries Muscle activity largely influences the movement of lymph through the lymphatic vessels via: 1) Action of skeletal muscles 2) Respiratory movements 3) Smooth muscle in the larger lymphatic vessels 4) Valves in the lymphatic vessels SOUND FAMILIAR?

13. 16.5 Lymph Nodes or glands Sinus Capsule (a) Nodule Hilum Artery Medulla (macrophages, T cells) Subcapsule (macrophages, B cells) Efferent lymphatic vessel Lymph flow Germinal center (B cells) Vein Lymph flow Afferent lymphatic vessel located along the lymphatic pathways They contain lymphocytes and macrophages to fight invading pathogens = FILTERS LYMPH Lymph nodules or follicles are functional unit MALT = Peyer’s patches,tonsils, appendix are collections of nodules

14. Which of these does NOT assist with the return of lymph? A) valves in the walls of vessels B) contraction of the skeletal muscle C) contraction of the heart D) normal inhaling and exhaling

15. Locations of Lymph Nodes Lymph nodes are found in groups or chains along the paths of the larger lymphatic vessels throughout the body, including the: Cervical region Axillary region Supratrochlear region Inguinal region Pelvic cavity Abdominal cavity Thoracic cavity Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Thoracic lymph node Axillary lymph node Cervical lymph node Supratrochlear lymph node Abdominal lymph node Pelvic lymph node Inguinal lymph node Know what areas “drain” through these

16. Functions of Lymph Nodes two primary functions: 1) Filter potentially harmful particles from the lymph 2)Act with immune surveillance provided by macrophages and lymphocytes Along with the red bone marrow, the lymph nodes are centers for lymphocyte production: attack viruses, bacteria and parasitic cells

17. What structures are drained by the cervical lymph nodes? A) the hand and forearm B) the pelvic region C) the thoracic viscera and mediastinum D) the face and nasal cavity

18. Larynx Thymus Lung Liver (a) (b) Diaphragm Thyroid gland Heart Stomach Spleen Lobule Trachea Connec- tive tissue b: © The McGraw-Hill Companies, Inc./Dennis Strete, photographer Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Divided into lobules: progenitor cells arrive from bone marrow and mature & divide here 16.6 Thymus Site of T lymphocyte (or T cell) maturation Controlled by: thymosins Larger in infancy and during puberty Replaced by fat and connective tissue in the elderly

19. And the Spleen The largest lymphatic organ Where do you find this? Has sinuses filled with blood Contains two tissue types: White pulp = lymphocytes Red pulp = red blood cells, lymphocytes and macrophages Spleen Artery of pulp White pulp Red pulp (a) (b) Capillary Capsule White pulp Red pulp Splenic artery Splenic vein Connective tissue Venous sinus b: © The McGraw-Hill Companies, Inc./Al Telser, photographer Note: spleen filters blood NOT lymph =specialized capillaries

20. How is the spleen similar to the lymph nodes? A)They both filter lymph. B)They both filter blood. C)They are both organized in nodules of lymphocytes & macrophages. D)They are many of these structures found scattered throughout the body.

22. 16.7 Bodily Defenses Against Infection YOU versus the encounter and colonization of a pathogen in the body Bacteria, viruses, complex microorganisms, and spores of multicellular organisms YOU have two types of RESPONSE 1) Innate or nonspecific defenses : 1 st & 2 nd line These are general defenses Readily available/fast They protect against many pathogens 2) Adaptive or specific defenses: 3 rd line Known as immunity More specific and precise targeting specific antigens Are carried out by lymphocytes ELEMENTS OF BOTH OCCUR IN ALL INFECTIONS

23. 16.8 Innate (Nonspecific) Defenses: the 1 st and 2 nd line

24. Species Resistance: Is it OK to Kiss Your Dog or Cat? Refers to a given type of organism, or species, that develops diseases unique to it. WHY??? Lack of receptors for pathogens, Wrong temperature Wrong pH or chemistry Examples, humans get measles, mumps, gonorrhea and syphillis….BUT not certain strains of malaria & TB

25. 1 st line: do not let them in, trap, or wash away! The skin and mucous membranes create mechanical barriers Mechanical barriers are considered the first line of defense (all other non-specific defenses are part of the second line of defense) Mucus, hair, dead epidermis, sweat, tears, saliva

26. If “they” do get in, there’s 2 nd line…. chemical barriers include: Interferons are hormone-like peptides released from infected lymphocytes…interfere with replication & stimulate phagocytosis Defensins are peptides produced by neutrophils and other granulocytes…They cripple microbes via holes in membrane. Collectins are proteins with broad protection against bacteria, yeast and some viruses…ID them as targets Complement is a group of proteins in plasma and other body fluids that stimulate inflammation, attract phagocytes and enhance phagocytosis (we will discuss with Ab later) Includes: gastric juice, lysozymes and salts in secretions

27. and then there’s this cell Natural Killer ( NK) cells a type of lymphocyte but not like T & B cells. defends against viruses and cancer by secreting cytolytic substances called perforins that destroy the infected cell NK may also enhance inflammation

28. 28 Which leads to Inflammation 4 cardinal signs: local redness, swelling, heat and pain Table 16.2 summarizes the process which is triggered by INVADED or INJURED CELLS Recall chemotaxis. neutrophils are first then macrophages. The fibroblasts contain the invasion or injury

29. Phagocytosis Phagocytosis removes foreign particles from the lymph Found in blood vessels and the spleen, liver or bone marrow, some are free some are fixed. The most active phagocytic cells are neutrophils (20) and monocytes which become macrophages (100)

30. And even Fever is part of our nonspecific defense begins when a viral or bacterial infection stimulates lymphocytes to proliferate, producing cells that secrete a substance called interleukin-1 (IL-1) = pyrogen What does this target? Effects of higher temperature = activation of phagocytes AND sequestering of iron by liver & spleen

31. Which of the following is a mechanical defense? A) saliva & urine B) gastric juice C) fever D) complement production

32. How does interferon defend you? A) it produces pyrogens (IL-1) B) it punches holes in the cell’s plasma membrane. C) it interferes with viral replication D) it phagocytoses the pathogen

33. 16.9 Adaptive (Specific) Defenses This is 3 rd line of defense and known as immunity It is resistance to particular pathogens, their toxins or their metabolic by-products It is based on the ability to distinguish molecules that are part of the body = “self” from “non-self” Antigens…how we tell the “bad guys” from our cells. Recall we used this term in blood typing

34. Antigens (Ag) may be: Proteins Polysaccharides Glycoproteins Glycolipids The most effective antigens are large and complex Haptens are small molecules that are not antigenic by themselves, but when they combine with a large molecule can stimulate an immune response, e.g., penecillin, animal dander, dust, household chemicals http://www.biology.ualberta.ca/facilities/multimedia /uploads/testing/hapten.html

35. Lymphocyte Origins: Different paths B cell Thymus T cell 1 2 3 4 B cell Stem cells in red bone marrow give rise to lymphocyte precursors. Red bone marrow Some lymphocyte precursors are processed within the bone marrow to become B cells. Both T cells and B cells are transported through the blood to lymphatic organs, such as the lymph nodes, lymphatic ducts, and spleen. Some lymphocyte precursors are processed in the thymus to become T cells. Blood transport Blood transport Lymphocyte precursors Blood transport Lymph node T cells are 70 - 80% of circulating lymphocytes There are millions of varieties of B & T cells differ in their Ag receptors

36. T Cells = Cellular Immune Response A lymphocyte must be activated before it can respond to an Ag activation requires antigen-presenting cell (accessory cell) e.g., macrophages, B cells and several other types of cells which process Ag Requires major histocompatibility complex (MHC) [human leukocyte antigens (HLA)] to recognize “non-self” Response: T cells can synthesize and secrete cytokines (polypeptides), toxins, growth inhibitors, and interferons

37. IL-1 = activation of T cells IL-2 = T cell proliferation

39. Types of T cells Helper T cells, Cytotoxic T cells & Memory T cells Helper: Have CD4 markers and Ag receptors combine with foreign Ag. Stimulates B cells to produce antibodies (Ab) SPECIFIC to the Ag. Cytotoxic: have CD8 markers activated by helper cells, combines with foreign Ag, proliferates, and releases perforin to KILL cell Memory: produced from activated CD8 cells remains

40. Which of these factors activates cytotoxic T cells? A) perforin B) interleukin 1 C) colony stimulating factor D) interleukin 2

41. What would an antigen presenting cell do? A) release interleukin 2 to activate T cells B) display pieces of antigens and MHC C) release perforin to kill cells with antigens D) differentiate into memory cells

42. B Cells = Humoral Immune Response Most of the time B cell activation requires helper T cells ….B cells can be activated when an antigen fits the shape of its receptor helper T cells release cytokines that stimulate B cells and attract macrophages & leukocytes WHY? Some B cells may become memory B cells while others differentiate into plasma cells and produce and secrete large globular proteins called antibodies (Ab) or immunoglobulins (Ig) which have SAME receptors as B cell

43. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Activated B cell Proliferation B cells Antigen Cytokines Activation 1 2 3 Antigen receptor Stimulation by activated helper T cell Clone of B cells

44. Antigen Proliferation Antigen receptor Receptor-antigen combination Activated B cell Cytokines from helper T cell Clone of B cells Proliferation and Differentiation Proliferation and Differentiation Endoplasmic reticulum Released antibodies Plasma cell (antibody-secreting cell) Memory cell (dormant cell) Plasma cell (antibody-secreting cell) Memory cell (dormant cell) Clone of B cells Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Plasma cells are factories: 2000 Ab/sec. Carried in fluids & INDIRECTLY kill

45. While B cells & T cells have clear differences which of these is something they share? A) They both require antigen presenting cells. B) They are both able to kill the cell they bind to. C) They are both stimulated by helper T cells. D) They are found in the same places in the body.

47. Different classes vary in their constant heavy chains Every antibodies variable region is different and is the receptor for a specific Ag Just to let you know….

48. Actions of Antibodies NOT killing but activating, stimulating and containing Antibodies bind via receptors on variable region. This exposes reactive sites on the constant region free to act as a “flag” to ID the now bound pathogen as a threat

49. Immune Responses Plasma antibody concentration 1002030 Primary response Secondary response 40 Days after exposure to antigen Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

50. Immune Response Primary: first encounter, plasma cells release IgM then IgG into lymph and find pathogen with specific Ag. Lasts for several weeks. Memory B cells are made. Detectable levels 5 – 10 days after exposure Secondary: same Ag encountered at later date, clones of memory cells proliferate, produce IgG, detectable levels after 1 day

51. Which of these is NOT a method that antibodies use to defend you? A) releasing cytokines which destroy the cell B) attracting macrophages to the correct cellular target C) activating complement to lyse the cell D) neutralizing toxins released by the cell

52. Which of these correctly describes the secondary and primary immune response A) both of these produce about the same number of antibodies but the 2 nd is faster B) the 2 nd is slower but produces more antibody C) the primary response means you may get sick while the secondary you probably won’t D) there is no difference, it is just the order of encounter of the antigens

53. Practical Classification of Immunity Our very existence is dependent on knowing self from non- self….SO this classification is on 1) HOW we get introduced and 2) HOW we respond Recall what type RhoGAM is

54. Which type of immunity are you most likely to become ill? A) naturally acquired active immunity B) artificially acquired active immunity C) naturally acquired passive immunity D) artificially acquired passive immunity

55. Allergic Reactions: response to non- threatening Ag = hypersensitivity Type I Immediate-reaction allergy…minutes after contact with allergen thank your parents! inherited ability to overproduce IgE Symptoms include hives, hay fever, asthma, eczema, gastric disturbances, and anaphylactic shock Mediated by B cells IgE attaches to Mast cells & basophils Type II Antibody-dependent cytotoxic reaction Takes 1-3 hours to develop Transfusion reaction Type III Immune-complex reaction Takes 1-3 hours to develop Antibody complexes cannot be cleared from the body = Damage of body Type IV: mediated by T cells Delayed-reaction allergy Results from repeated exposure to allergen Eruptions and inflammation of the skin Takes about 48 hours to occur

56. B cell Plasma cell Mast cell IgE receptor Granule (a) 1 2 3 5 4 Allergen Allergic reaction Histamine and other chemicals Mast cell releases allergy mediators Subsequent contact with allergen Antibodies attach to mast cell Released IgE antibodies Initial B cell contact with allergen Plasma cell secretes antibodies Immediate reaction allergy

57. Which type of allergic response is mediated by T cells? A) type I immediate reaction B) type II C) type III D) type IV delayed reaction

58. Transplantation and Tissue Rejection Successfully transplanted tissues and organs: Cornea, Kidney, Liver, Pancreas, Heart, Bone marrow & Skin When the donor’s tissues are recognized as foreign there is a tissue rejection reaction Resembles the cellular immune response against antigens Must reduce rejection by: matching MHC antigens administering immunosuppressive drugs BEFORE transplant BUT these have side effects, e.g., infection, kidney damage & cancer

59. Just to Let You Know

60. Autoimmunity The immune system fails to distinguish “self” from “non- self” and the body produces antibodies called autoantibodies, and cytotoxic T cells to attack the body’s tissues and organs

61. causes Virus incorporates a protein from host’s cell surface and expresses it on their surface T cell programming fails Nonself Ag resembles a self Ag, e.g., rheumatic fever caused by streptococcus A Sometimes fetal cells persist in mom and are detected by Ab at a later date, e.g., scleroderma