1. Lymphatic and Immune Systems
Maintain fluid balance
Protect body from infection and disease

2. Functions of Lymphatic System
Immunity
fluids from all capillary beds are filtered
immune cells stand ready to respond to foreign cells or chemicals encountered
Lipid absorption
Lacteals in small intestine absorb dietary lipids
Fluid recovery
absorbs plasma proteins and fluid (2 to 4 L/day) from tissues and returns it to the bloodstream
interference with lymphatic drainage leads to severe edema

3. Lymphatic Capillary
Lymph is a clear, colorless fluid, similar to plasma but much less protein
Lymphatic capillaries are closed at one end and much ‘leakier’ than blood capillaries

4. Lymphatic Vessels Valves Larger lymphatics have 3 layers
tunica interna: endothelium and valves
tunica media: elastic fibers, smooth muscle
tunica externa: thin outer layer
Valves

5. Route of Lymph Flow Lymphatic capillaries
Collecting vessels: course through many lymph nodes
Lymphatic trunks: drain major portions of body
Collecting ducts :
right lymphatic duct – receives lymph from R arm, R side of head and thorax; empties into R subclavian vein
thoracic duct - larger and longer, begins as a prominent sac in abdomen called the cisterna chyli; receives lymph from below diaphragm, L arm, L side of head, neck and thorax; empties into L subclavian vein
course through many lymph nodes

7. Lymphatic Drainage of Mammary and Axillary Regions

8. Mechanisms of Lymph Flow
Lymph flows at low pressure and speed
Moved along by rhythmic contractions of lymphatic vessels
Flow aided by skeletal muscle pump (like veins)
Thoracic pump aids flow from abdominal to thoracic cavity (also like veins)
Valves prevent backward flow
The rapidly flowing blood in subclavian veins draws lymph into the vascular system
Exercise significantly increases lymphatic return

9. Cells that circulate in the lymph
Natural killer (NK) cells
can find and destroy tumor cells
T lymphocytes (mature in thymus)
B lymphocytes (mature in bone marrow)
activation makes cells that produce antibodies
Antigen Presenting Cells - APCs
macrophages (from monocytes)
dendritic cells (in epidermis, mucous membranes and lymphatic organs)

10. Lymphatic Tissue Diffuse lymphatic tissue Lymphatic nodules
lymphocytes in mucous membranes and connective tissues of many organs
Mucosa-Associated Lymphatic Tissue (MALT): prevalent in passages open to exterior
Lymphatic nodules
dense oval masses of lymphocytes, congregate in response to pathogens
Peyer patches: more permanent congregation, clusters found at junction of small to large intestine

11. Lymphatic Organs
At well defined sites; have connective tissue capsules
Primary lymphatic organs
site where T and B cells become immunocompetent
red bone marrow and thymus
Secondary lymphatic organs
immunocompetent cells populate these tissues
lymph nodes, tonsils, and spleen

12. Lymph Node Lymph nodes – are the only organs that filter lymph
Fewer efferent vessels, slows flow through node
Lymph nodes are divided into compartments containing stroma (reticular CT) and parenchyma (lymphocytes and APCs)
Lymph nodes are subdivided into cortex and medulla
reticular cells, macrophages phagocytize foreign matter
lymphocytes respond to antigens
lymphatic nodules-germinal centers for B cell activation

13. Fig a and b
Lymph Node

14. Lymphadenopathy Collective term for all lymph node diseases
Lymphadenitis
swollen, painful node responding to foreign antigen
Lymph nodes are common sites for metastatic cancer
swollen, firm and usually painless

15. Location of Tonsils Palatine tonsils Lingual tonsils
pair at posterior margin of oral cavity
most often infected
Lingual tonsils
pair at root of tongue
Pharyngeal tonsil (adenoid)
single tonsil on wall of pharynx

16. Thymus Very large in babies. Begins to involute at about 14 years
T lymphocytes mature here.
Secretes thymopoietin, thymulin and thymosins.

17. Spleen Parenchyma appears in fresh specimens as
red pulp: sinuses filled with erythrocytes
white pulp: lymphocytes, macrophages

18. Spleen Why is the ‘white pulp’ blue? Functions blood reservoir
RBC disposal
immune reactions: filters blood, quick to detect antigens

19. A Battle Metaphor
Your immune system’s structure and function is much like that of an earth army fighting alien invaders.
It is there in times of peace and in times of war.

20. The job of the immune system
To distinguish ‘self’ from ‘non-self’
to destroy ‘non-self’

21. The Immune System
The fortifications

22. The human body’s first line of defense is a set of physical barriers and chemical agents that prevent foreign invaders from getting inside.
An outer layer of intact skin
Hair in the nostrils
Mucous membranes
Cilia

23. Other external defenses
Tears
Sweat
Mucous
Oils
Acid in stomach
Urine

24. The Immune System
The soldiers and their weapons

25. White Blood Cells = Leukocytes
Non-specific (innate)
Neutrophils
Make antibodies
Macrophages
Natural Killer Cells
Specific (adaptive)
Lymphocytes
B cells make antibodies
T cells help them
Only vertebrates can do this!!

26. Non-specific internal defenses
If something gets past the external barriers, the second line of defense are ‘innate’ immune defenses, primarily white blood cells.
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27. Defenses Against Pathogens
Nonspecific defenses - broadly effective, no prior exposure
first line of defense
external barriers
second line of defense – innate immune system
phagocytic cells, antimicrobial proteins, inflammation and fever
Specific defense - results from prior exposure, protects against only a particular pathogen
third line of defense – adaptive immune system

28. Neutrophils How do they distinguish self from non-self?
Phagocytize bacteria
These are most likely to dramatically increase in numbers during bacterial infection
Create a killing zone
degranulation
antimicrobial proteins are discharged into tissue fluid
respiratory burst
toxic chemicals are created (O2.-, H2O2)

29. Eosinophils Phagocytize antigen-antibody complexes
Antiparasitic effects
Promote action of basophils, mast cells
Enzymes block excess inflammation, limit action of histamine

30. Basophils The rarest WBCs in human blood
Aid mobility and action of WBC’s by release of
histamine (vasodilator)
 blood flow to infected tissue
heparin (anticoagulant)
prevents immobilization of phagocytes
The rarest WBCs in human blood

31. Monocytes Circulating precursors to macrophages
Specialized macrophage-like cells are found in specific localities
Dendritic cells
epidermis, oral mucosa, esophagus, vagina, and lymphatic organs
Microglia (CNS)
Alveolar macrophages (lungs)
Kupffer cells (liver)

32. Lymphocytes – adaptive immune system
There are 3 types but they look identical under a microscope!
Act to destroy cancer cells
Kill virus-infected cells
Make antibodies
The lymphocytes circulating in human blood are
80% T cells
15% B cells
5% NK cells
These are the cells that confer immunity through a vaccination!

33. That’s it for today

34. Antimicrobial Proteins
Interferons
Made by cells when they are invaded by a virus
Induce neighbor cells to activate anti-viral defenses
Can stimulate destruction of some cancer cells
Complement system
More than 20 different proteins
Are activated by the presence of pathogens
(like a booby trap)

35. Complement System Mechanisms of action enhanced inflammation
phagocytosis
promoted by opsonization
cytolysis
membrane attack complex forms on target cell
immune clearance
RBCs carry Ag-Ab complexes to macrophages in liver and spleen

36. Immune Surveillance NK cells (Natural Killer Cells)
destroy bacteria, cells infected by viruses, and cancer cells
also destroy transplanted cells

37. Inflammation Macrophages! Neutrophils Swelling Pain Redness & heat
hyperemia
Purulence
Macrophages!
Neutrophils
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38. Inflammation Three major processes mobilization of body defenses
containment and destruction of pathogens
tissue clean-up and repair

39. Mobilization of Defenses
Kinins, histamine, and leukotrienes are secreted by damaged cells
stimulates vasodilation that leads to hyperemia
causes redness and heat
 local metabolic rate, promotes cell multiplication and healing
dilutes toxins, provides O2, nutrients, waste removal
stimulates  permeability of blood capillaries
allows blood cells, plasma proteins (antibodies, complement proteins, fibrinogen) into tissue

40. Mobilization of Defenses
Leukocyte Deployment
margination
selectins cause leukocytes to adhere to blood vessel walls
diapedesis (emigration)
leukocytes squeeze between endothelial cells into tissue space

41. Containment and Destruction of Pathogens
Chemotaxis
leukocytes are attracted to chemotactic chemicals
Neutrophils are quickest to respond
phagocytosis
respiratory burst
secrete cytokines for recruitment of macrophages and neutrophils
macrophages and T cells secrete colony-stimulating factor to stimulate leukopoiesis

42. Shift in the blood profile
Total WBC: 4, ,000
Bands or stabs: %
Granulocytes
Neutrophils (or segs): % relative value ( absolute value)
Eosinophils: 1 - 3% relative value ( absolute value)
Basophils: 0.4% - 1% relative value ( absolute value)
Agranulocytes (or mononuclears)
Lymphocytes: % relative value ( absolute value)
Moncytes: 4 - 6% relative value ( absolute value)

43. Fever Defense mechanism: does more good than harm
promotes interferon activity
accelerating metabolic rate and tissue repair
inhibiting pathogen reproduction
A cytokine named interleukin 1
called a pyrogen
secreted by macrophages
stimulates anterior hypothalamus to secrete PGE2
Prosatglandin E2 resets the body’s thermostat higher
> 105F may cause delirium, 111F- 115F, coma-death

44. Course of a Fever
What if your patient is shivering with a normal or very slightly raised temp?
Stages of fever
onset (spiking a fever)
stadium
defervescence (breaking a fever)

45. Specific Immunity is accomplished by the adaptive immune system
Depends on lymphocytes
Specificity and memory
Cellular immunity: cell-mediated (T cells)
Humoral immunity: antibody mediated (B cells)
This is the half of the immune system that confers immunity through a vaccination!

46. Passive and Active Immunity
Active immunity produces memory cells
Natural – you catch the measles
Artificial – you’re vaccinated for the measles
Passive immunity is not long lasting
Natural - fetus acquires antibodies from mother
Natural – nursing child gets antibodies from colostrum
Artificial - treatment for snakebite or tetanus

47. Antigens Trigger an immune response Complex molecules
> 10,000 amu, unique structures
proteins, polysaccharides, glycoproteins, glycolipids

48. Life Cycle of T cells
Stem cells in red bone marrow
Mature in thymus

49. In the thymus
Immature T cells must be able to recognize signals from other parts of the immune system
If they don’t – they are destroyed
Immature T cells must not recognize proteins on your tissue cells as ‘foreign’
If they do – they are destroyed
Only 2% of immature T cells survive these steps that are called ‘selection’

50. Life Cycle of T cells Stem cells in red bone marrow Mature in thymus
Circulate through blood and lymph
Naïve T cells colonize lymph nodes, Peyer’s patches, tonsils, spleen

51. B Lymphocytes (B cells)
Sites of development
bone marrow
B cells also undergo selection (just not in the thymus)
Self-tolerant B cells form B cell clones
each cell in a clone has the same antigen receptors

52. Antigen-Presenting Cells (APCs)
DCs and macrophages (some B cells) display antigens to T cells

53. Cellular Immunity
T cells attack foreign cells and diseased host cells; memory of Ag
Three classes of T cells:
Cytotoxic T cells (Tc cells) carry out attack
Helper T cells: help promote Tc cell and B cell action
Memory T cells: provide immunity from future exposure to antigen

54. T cell Activation
T Cells must be activated by APCs before they go to work.

55. Attack Phase: Cytotoxic T Cells
Cytotoxic T cells directly attack enemy cells
Lethal hit mechanism
docks on cell with antigen-MHC-I protein complex
releases perforin, granzymes - kills target cell
interferons - decrease viral replication and activates macrophages
tumor necrosis factor: kills cancer cells

56. Cytotoxic T Cell Function
Cytotoxic T cell binding to cancer cell

57. Memory Memory T cells T cell recall response
following clonal selection some T cells become memory cells
long-lived; in higher numbers than naïve cells
T cell recall response
upon reexposure to same pathogen, memory cells launch a quick attack

58. Humoral Immunity = antibodies
Helper T cells (TH cells) have been informed of the invader by APCs
Helper T cells (TH cells) stimulate the B cells that have the right ‘weapon’ for this disease
The B cells turn into Plasma cells
Plasma cells make antibodies that circulate in the blood and can incapacitate the pathogen
Memory
some B cells differentiate into memory cells

59. B cells and Plasma cells

60. Antibodies are the most important component of humoral immunity!
Antibody Structure
ALL antibodies are proteins!
IgG is Y-shaped.
80% of your circulating antibody is IgG.
There are other classes of Ig
Antibodies are the most important component of humoral immunity!
Antibody and immunoglobulin are synonyms

61. Antibody Diversity
Immune system capable of as many as 1 trillion different antibodies
Somatic recombination
DNA segments shuffled and form new combinations of base sequences to produce antibody genes
Somatic hypermutation
B cells in lymph nodules rapidly mutate creating new sequences

62. Humoral Immunity - Attack
Neutralization
antibodies mask pathogenic region of antigen
Complement fixation
antigen binds to IgM or IgG, antibody changes shape, initiates complement binding; primary defense against foreign cells, bacteria
Agglutination
antibody has 2-10 binding sites; binds to multiple enemy cells immobilizing them
Precipitation
antibody binds antigen molecules (not cells); creates antigen-antibody complex that precipitates, phagocytized by eosinophil

63. Agglutination and Precipitation

64. The Joy of Memory!

65. Hypersensitivity (Allergy)
Excessive immune reaction against antigens that most people tolerate - allergens
Type I Antibody mediated (IgE), acute reaction
Asthma, Hay fever, Anaphylaxis
Type II Antibody mediated (IgG, IgM), subacute
Type III Antibody mediated (IgG, IgM), subacute
glomerulonephritis, systemic lupus
Type IV Cell mediated, delayed (12 to 72 hrs)
TB test
Poison ivy

66. Autoimmune Diseases Failure of self tolerance
cross-reactivity
abnormal exposure of self-antigens
changes in structure of self-antigens
Production of autoantibodies

67. Immunodeficiency Diseases
Severe Combined Immunodeficiency Disease (SCID)
hereditary lack of T and B cells
vulnerability to opportunistic infection
currently treatable with gene therapy

68. This Thursday is the next lecture exam Bring a number 2 pencil.