1. The Lymphatic System and Immunity

2. Immunity Ability to ward off damage or disease through our defenses
2 types of immunity
Innate or nonspecific immunity – present at birth
--No specific recognition of invaders, no memory component
1st and 2nd line of defenses
Adaptive or specific immunity
--Specific recognition of invaders with a memory component

3. Structure and Function
Consists of lymph, lymphatic vessels, structures and organs containing lymphatic tissue, red bone marrow
Functions of the lymphatic system
Drain excess interstitial fluid
Transport dietary lipid
Carry our immune responses

4. The Lymphatic System

5. Lymph Vessels and Circulation
Vessels begin as lymphatic capillaries
-Closed at one end
Unite to form large lymphatic vessels
-Resemble veins in structure but thinner walls and more valves
Passes through lymph nodes
-Encapsulated organs with masses and B and T cells

6. Capillaries of the Lymph System
Slightly large diameter than blood capillaries
Unique one-way structure
Permits interstitial fluid to flow in but not out
Anchoring filaments pull openings wider when interstitial fluid accumulates
Small intestine has lacteal for dietary lipid uptake

7. Structure of the Lymph Capillary

8. The lymph fluid then drains into the lymph system

9. Trunks and Ducts of the Lymph System
Vessels unite to form lymph trunks
Principal trunks are the lumbar, intestinal, bronchomediastinal, subclavian and jugular
Passes from lymph trunks into 2 main channels (thoracic and right lymphatic ducts) before draining into venous blood

10. Major Trunks and Ducts of the Lymphatic System.
The thoracic duct drains a much larger portion of the body than does the right lymphatic duct.

11. Right Lymphatic Duct and Thoracic Duct
(left lymphatic)

12. Lymph Drainage

13. How lymph forms and how it flows
More fluid filters out of blood capillaries than returns to them by reabsorption
Excess filtered fluid – about 3L/day – drains into lymphatic vessels and become lymph
Important function of lymphatic vessels to return lost plasma proteins to blood stream
Contain valves
Same pumps aiding venous return also used
Skeletal muscle pump – milking action
Respiratory pump – pressure changes during breathing

14. How the lymph vessels and blood vessels work together

15. Tissues and Organs of the Lymphatic System
Two Groups
Primary lymphatic organs
Sites where stem cells divide and become immunocompetent
Red bone marrow and thymus
Secondary lymphatic organs
Sites where most immune response occurs
Lymph nodes, spleen, lymphatic nodules

16. Where do T cells mature? The Thymus
Cortex made up of large number of T cells
Immature T cells migrate here from red bone marrow where they multiply and begin to mature
Specialized epithelial cells help educate T cells through positive selection – only about 25% survive
Macrophages clear out dead and dying cells
Medulla
More mature T cells migrate here from cortex
More epithelial cells, dendritic cells and macrophages
Thymus is large and active in young children, shrinks to less than half its size in old age

17. Thymus in a full term fetus
FIG. 1178
The thymus of a full-time fetus, exposed in situ.
The thymus of a full-time fetus, exposed in situ.

18. Copyright 2009, John Wiley & Sons, Inc.

20. Lymph nodes Situated along lymphatic vessels Scattered throughout body
Stroma – supporting connective tissue
Capsule, trabeculae, reticular fibers and fibroblasts
Parenchyma – functional part
Cortex – aggregates of B cells called lymphatic nodules (follicles) – site of plasma cell and memory B cell formation
Inner cortex – mainly T cells and dendritic cells
Medulla – B cells, antibody producing plasma cells from cortex, and macrophages

21. Superficial structures that you should know from the lateral view of the neck. sternomastoid
trapezius
occipital lymph nodes (on)
retroauricular lymph nodes (ran)
superficial cervical lymph nodes (scn)
submental lymph nodes (smn)
buccal lymph nodes (bn)
parotid lymph nodes (pn)
submandibular lymph nodes (not labeled but uner angle of mandible

22. Sideways view showing lymph nodes.

23. Where are Lymph Nodes concentrated

24. The Lymph Node

25. Lymph Lymph flows through the node in 1 direction only
Enters through afferent lymphatic vessels
Directs lymph inward
Lymph enters sinuses (irregular channels)
Into medulla
Medullary sinuses drain into efferent lymphatic vessels
Conveys lymph, antibodies and activated T cells out of the node
Lymph nodes function as a filter
Foreign substances trapped
Destroyed by macrophages or immune response of lymphocytes

26. Copyright 2009, John Wiley & Sons, Inc.
Spleen
Largest single mass of lymphatic tissue in the body
Stroma – capsule, trabeculae, reticular fibers, and fibroblasts
Parenchyma
White pulp – lymphatic tissue (lymphocytes and macrophages)
B cells and T cells carry out immune function
Red pulp
Copyright 2009, John Wiley & Sons, Inc.

27. Red Pulp
Red pulp – blood-filled venous sinuses and splenic (Bilroth’s) cords – red blood cells, macrophages, lymphocytes, plasma cells, and granulocytes
Macrophages remove ruptured, worn out or defective blood cells
Storage of up to 1/3 of body’s platelet supply
Production of blood cells during fetal life

28. The spleen filters blood in much the way that the lymph nodes filter lymph. Lymphocytes in the spleen react to pathogens in the blood and attempt to destroy them. Macrophages then engulf the resulting debris, the damaged cells, and the other large particles.

29. Not surrounded by a capsule.
Lymphoid Nodules
Not surrounded by a capsule.
Scattered throughout lamina propria of mucous membranes lining GI, urinary, reproductive tract
Mucosa-associated lymphatic tissue (MALT) of respiratory tract
Most small and solitary
Some larger – tonsils, Peyer’s patches, appendix

31. Innate immunity Intact skin and mucous membranes.
Chemicals in saliva, sweat and stomach acid.
Normal (normal flora) microorganisms on the skin and in the body.
The inflammatory response.
Species selective immunity.

32. Innate Immunity Not Specific
Fluids
Lacrimal apparatus of eye
Washing action of tears
Lysozyme breaks down bacterial cell walls – also present in saliva, perspiration, nasal secretions, and tissue fluids
Saliva washes mouth
Urine cleanses urinary system
Vaginal secretions, defecation and vomiting
Chemicals
Sebaceous (oil) glands secrete sebum – protective film, acid
Perspiration, gastric juice, vaginal secretions – all acidic

33. Internal defenses Antimicrobial substances A. Interferons
Produced by lymphocytes, macrophages, and fibroblasts infected by viruses
Prevents replication in neighboring uninfected cells
B. Complement
Proteins in blood plasma and plasma membranes
“complement” or enhance certain immune reactions
Causes cytolysis of microbes, promotes phagocytosis, contributes to inflammation

34. More Internal Defenses
C. Iron-binding proteins
Inhibit growth of bacteria by reducing available iron
D. Antimicrobial proteins (AMPs)
Short peptides that have a broad spectrum of antimicrobial activity
Can attract dendritic cells and mast cells that participate in immune responses

35. More Internal Defenses
Natural Killer (NK) cells
Lymphocyte (not a B or T cells)
Ability to kill wide variety of infected body cells and certain tumor cells
Attack any body cell displaying abnormal or unusual plasma membrane proteins
Can release perforin (makes perforations) or granzymes (induce apoptosis)
Phagocytes
Neutrophils and macrophages (from monocytes)
Migrate to infected area
5 steps in phagocytosis

36. Phagocytosis of a microbe

39. Phagocytosis of a microbe

40. Inflammation Nonspecific, defensive response of body to tissue damage
4 cardinal signs and symptoms – redness, pain, heat and swelling
Attempt to dispose of microbes, prevent spread, and prepare site for tissue repair
3 basic stages
Vasodilation and increased blood vessel permeability
Emigration
Tissue repair

41. Vasodilation and increased permeability of blood vessels
Increased diameter of arterioles allows more blood flow through area bringing supplies and removing debris
Increased permeability means substances normally retained in the blood are permitted to pass out – antibodies and clotting fctors
Histamine, kinins, prostaglandins (PGs), leukotrienes (LTs), complement

42. The inflammatory response

43. Emigration of phagocytes
Depends on chemotaxis
Neutrophils predominate in early stages but die off quickly
Monocytes transform into macrophages
More potent than neutrophils
Pus – pocket of dead phagocytes and damaged tissue

44. Adaptive immunity
Ability of the body to defend itself against specific invading agents
Antigens (Ags) – substances recognized as foreign and provoking an immune response
Distinguished from innate immunity by
Specificity
Memory

45. Maturation of T cells and B cells
Both develop from pluripotent stem cells originating in red bone marrow
B cells complete their development in red bone marrow
T cells develop from pre-T cells that migrate from red bone marrow to the thymus
Helper T cells (CD4 T cells) and cytotoxic T cells (CD8 T cells)
Immunocompetence – ability to carry out adaptive immune response
Have antigen receptors to identify specific antigen

46. Mounting the immune response (next three slides)

48. T Cell Response
                                                                                                                                                                                                                      

49. 2 types of adaptive immunity
Cell-mediated
Cytotoxic T cells directly attack invading antigens
Particularly effective against intracellular pathogens, some cancer cells and foreign tissue transplants
Antibody-mediated
B cells transform into plasma cells making antibodies (Abs) or immunoglobulins
Works against extracellular pathogens in fluids outside cells
Helper T cells aid in both types
2 types of immunity work together

50. Clonal selection
Process by which a lymphocyte proliferates and differentiates in response to a specific antigen
Clone – population of identical cells all recognizing the same antigen as original cell
Lymphocyte undergoes clonal selection to produce
Effector cell – active helper T cell, active cytotoxic T cell, plasma cell, die after immune response
Memory cell – do not participate in initial immune response, respond to 2nd invasion by proliferating and differentiating into more effector and memory cells, long life spans

51. Antigens Antigens have 2 characteristics
Antigens have 2 characteristics
Immunogenicity – ability to provoke immune response
Reactivity – ability of antigen to react specifically with antibodies it provoked
Entire microbes may act as antigen
Typically, just certain small parts of large antigen molecule triggers response (epitope or antigenic determinant)
The following slide shows an antibody attaching to the antigen

52. <img src="http://b. scorecardresearch. com/p. c1=2&c2=8556372&cv=2

53. Diversity of antigen receptors
Human immune system able to recognize and bind to at least a billion different epitopes
Result of genetic recombination – shuffling and rearranging of a few hundred versions of several small gene segments

54. Cont. Diversity of antigen receptors
Major Histocompatibility
Complex Antigens
MHC or human leukocyte antigens (HLA)
Normal function to help T cells recognize foreign or self
Class I MHC (MHC-I) – built into all body cells except RBCs
Class II MHC (MHC-II) – only on antigen presenting cells

55. Pathways of antigen processing
B cells can recognize and bind to antigens
T cells must be presented with processed antigens
Antigenic proteins are broken down into peptide fragments and associated with MHC molecules
Antigen presentation – antigen-MHC complex inserted into plasma membrane
Pathway depends on whether antigen is outside or inside body cells

56. Exogenous and Endogenous Antigens
Exogenous antigens – present in fluid outside body cells
Antigen-presenting cells (APCs) include dendritic cells, macrophages and B cells
Ingest antigen, process, place next to MHC-II molecule in plasma membrane, and present to T cells
Endogenous antigens – antigens inside body cells
Infected cell displays antigen next to MHC-I (next slide)

57. Exogenous Antigens

58. Phagocytosis or
endocytosis of
antigen
Digestion of
antigen into
peptide fragments
Antigen peptide
fragments bind to
MHC-II molecules
Phagosome
or endosome
APCs present exogenous antigens in association with MHC-II molecules
Antigen-
presenting
cell (APC)
Vesicles containing antigen
peptide fragments and
MHC-II molecules fuse
Packaging of MHC-II
molecules into a vesicle
Synthesis of MHC-II molecules
MHC-II
self-antigen
Antigen
peptide
fragments
Key:
Endoplasmic
reticulum 1 5 6 4 3 2
Exogenous
Phagocytosis or
endocytosis of
antigen
Digestion of
antigen into
peptide fragments
Antigen peptide
fragments bind to
MHC-II molecules
Phagosome
or endosome
APCs present exogenous antigens in association with MHC-II molecules
Antigen-
presenting
cell (APC)
Vesicles containing antigen
peptide fragments and
MHC-II molecules fuse
Packaging of MHC-II
molecules into a vesicle
Synthesis of MHC-II molecules
MHC-II
self-antigen
Antigen
peptide
fragments
Key:
Endoplasmic
reticulum
Vesicle undergoes
exocytosis and
antigen–MHC-II
complexes are inserted
into plasma membrane 1 5 6 7 4 3 2
Exogenous
Phagocytosis or
endocytosis of
antigen
Digestion of
antigen into
peptide fragments
Phagosome
or endosome
APCs present exogenous antigens in association with MHC-II molecules
Antigen-
presenting
cell (APC)
Vesicles containing antigen
peptide fragments and
MHC-II molecules fuse
Packaging of MHC-II
molecules into a vesicle
Synthesis of MHC-II molecules
MHC-II
self-antigen
Antigen
peptide
fragments
Key:
Endoplasmic
reticulum 1 5 4 3 2
Exogenous
Phagocytosis or
endocytosis of
antigen
Digestion of
antigen into
peptide fragments
Phagosome
or endosome
APCs present exogenous antigens in association with MHC-II molecules
Antigen-
presenting
cell (APC)
Packaging of MHC-II
molecules into a vesicle
Synthesis of MHC-II molecules
MHC-II
self-antigen
Antigen
peptide
fragments
Key:
Endoplasmic
reticulum 1 4 3 2
Exogenous
Phagocytosis or
endocytosis of
antigen
Digestion of
antigen into
peptide fragments
Phagosome
or endosome
APCs present exogenous antigens in association with MHC-II molecules
Antigen-
presenting
cell (APC)
MHC-II
self-antigen
Antigen
peptide
fragments
Key: 1 2
Exogenous
Phagocytosis or
endocytosis of
antigen
Digestion of
antigen into
peptide fragments
Phagosome
or endosome
APCs present exogenous antigens in association with MHC-II molecules
Antigen-
presenting
cell (APC)
Synthesis of MHC-II molecules
MHC-II
self-antigen
Antigen
peptide
fragments
Key:
Endoplasmic
reticulum 1 3 2
Exogenous
Phagocytosis or
endocytosis of
antigen
APCs present exogenous antigens in association with MHC-II molecules
Antigen-
presenting
cell (APC)
MHC-II
self-antigen
Antigen
peptide
fragments
Key:
Exogenous 1

59. Cell-mediated immunity
Activation of T cells
First signal in activation
T-cell receptors (TCRs) recognize and bind to a specific foreign antigen fragments that are presented in antigen-MHC complexes
CD4 and CD8 proteins are coreceptors
Second signal required for activation
Costimulation – 20 known substances (cytokines, plasma membrane molecules)
May prevent immune response from occurring accidentally
Anergy – recognition without costimulation (in both B and T cells) leads to prolonged state of inactivity

60. Activation and clonal selection of helper T cells
Most that display CD4 develop into helper T cells (CD4 T cells)
Recognize exogenous antigen fragments associated with MHC-II molecules on the surface of an APC
After activation undergoes clonal selection
helper T cells and memory helper T cells Makes active T
Active helper T cells secrete variety of cytokines
Interleukin-2 (IL-2) needed for virtually all immune responses
Memory helper T cells are not active cells – can quickly proliferate and differentiate if the antigen appears again

61. Activation and clonal selection of cytotoxic T cells
Most that display CD8 develop into cytotoxic T cells (CD8 T cells)
Recognize antigens combined with MHC-I
Maximal activation also requires presentation of antigen with MHC-II to cause helper T cells to produce IL-2
Undergoes clonal selection
Active cytotoxic T cells attack body cells
Memory cytotoxic T cells do not attack but wait for a antigen to appear again

62. Activation and clonal selection of cytotoxic T cells

63. Activation and clonal selection of a cytoxic T cell

64. Elimination of invaders
Cytotoxic T cells migrate to seek out and destroy infected target cells
Kill like natural killer cells
Major difference is T cells have specific receptor for particular microbe while NK cells destroy a wide variety of microbe-infected cells
2 ways to kill cells
Granzymes cause apoptosis
Perforin and/ or granulysin causes cytolysis
Immunological surveillance
Tumor antigens displayed on cancerous cells targeted by cytotoxic T cells, macrophages and natural killer cells

65. Antibody-mediated immunity
Activation and clonal selection of B cells
During activation, antigen binds to B cell receptor (BCRs)
Can respond to unprocessed antigen
--Response much more intense when B cell processes antigen
Antigen taken into B cell, combined with MHC-II, moved to plasma membrane, helper T cell binds and delivers costimulation (interleukin-2 and other cytokines)
B cell undergoes clonal selection
Plasma cells secrete antibodies
Memory B cells do not secrete antibodies but wait for reappearance of antigen

66. Activation and clonal selection of B cells
                                                                                                    
Activation and clonal selection of B cells

67. Antibodies (Ab)
Can combine specifically with epitope of the antigen that triggered its production
Belong to group of glycoproteins called globulins
Ab are immunoglobulins (Igs)
4 polypeptide chains – 2 heavy (H) chains, 2 light (L) chains
Hinge region – antibody can be T shape or Y shape
Variable (V) region at tips of each H and L chain
2 antigen-binding sites - bivalent
Constant (C) region – remainder of H and L chain
Same in each 5 classes – determines type of reaction

68. Chemical structure of the immunoglobin (IgG) class of antibody

69. Antibody actions Neutralizing antigen Immobilizing bacteria
Agglutinating and precipitating antigen
Enhancing phagocytosis
Activating complement
Defensive system of over 30 proteins
Destroy microbes by causing phagocytosis, cytolysis, and inflammation
Acts in a cascade – one reaction triggers another
3 different pathways ass activate C3
C3 then begins cascade that brings about phagocytosis, cytolysis, and inflammation

70. Complement activation and results of activation

71. Immunological memory
Thousands of memory cells exist after initial encounter with an antigen
Next time antigen appears can proliferate and differentiate within hours
Antibody titer measure of immunological memory
Amount of Ab in serum
Primary response
Secondary response faster and stronger

72. Self-recognition and self-tolerance
Your T cells must have
Self-recognition – be able to recognize your own MHC
Self-tolerance – lack reactivity to peptide fragments from your own proteins
Pre-T cells in thymus develop self-recognition via positive selection – cells that can’t recognize your own MHC undergo apoptosis
Self-tolerance occurs through negative selection in which T and B cells that recognize self peptide fragments are eliminated
Deletion – undergo apoptosis
Anergy – remian alive but are unresponsive

73. Specific immunity includes active and passive humoral immunity
Specific immunity includes active and passive humoral immunity. Active immunity occurs when your body recognizes the antigen and produces antibodies against it. It can be acquired by exposure to the antigen naturally (you got the chickenpox as a child and are now immune) or you could acquire it by a vaccination and make antibodies from being exposed in that way. Both these are active. One naturally and one acquired. They are both long lived.

74. Passive immunity occurs when you use someone else's immunity
Passive immunity occurs when you use someone else's immunity. One way is when you inherent the immmunity at childbirth. Another way is by getting injections of immunoglobulin serum in the clinical setting. Both these are considered Passive. Your body is not making the antibodies. Getting immunity from your mother is natural passive. Getting it from injected serum is acquired passive. Both passive types are short lived.