The Immune System:
Immunocytology, Immunophysiology
and Intro to Immunopathology
Companion tools:
Prepared and Presented b...
Nonspecific Immunity
• External:
– Skin:
• Protective barrier to resist infection.

– GI tract:
• Gastric juice acidity.

...
Phagocytosis
• Distinguish between the kinds of carbohydrates that
are produced by mammalian cells and those produced
by b...
Phagocytosis

(continued)

• Diapedesis:
– Neutrophils and
monocytes are
able to squeeze
through tiny
gaps between
adjacen...
Phagocytosis

(continued)

• Connective tissue has a resident population of all
leukocyte types.
– Neutrophils and monocyt...
Phagocytosis

(continued)

– Particle becomes
surrounded by
pseudopods.
– Forms vacuole.
• Vacuole fuses with
lysosomes wh...
Fever
• May be a component of nonspecific defense
system.
• Cell wall of gram – bacteria contains
endotoxin.
– Endotoxin s...
Nonspecific Immunity
• Body temperature is regulated by
hypothalamus (thermoregulatory center).
– Thermostat reset by endo...
Interferons (Cytokines)
• Act as short-acting messengers that protect other
cells in the vicinity from viral infection.
• ...
Antigens
• Molecules that stimulate the production of specific
antibodies.
– Combine specifically with antibodies produced...
Haptens
• Small organic molecules can become antigens
if they bind to proteins.
• Become antigenic determinant sites on th...
Immunoassays
• Tests that use the
antigen-antibody
complex reaction to
produce clumping
(agglutination).
• Agglutinated pa...
Lymphocytes and Lymphoid Organs
• Derived from stem cells in the bone marrow.
– Stem cells produce the specialized blood c...
Lymphocytes (T cells)
• Cell mediated immunity:
• Lymphocytes that seed the thymus become T cells.
– Have surface characte...
Thymus
• Grows during childhood, gradually regresses
after puberty.
• Lymphocytes from the fetal liver and spleen;
and bon...
Secondary Lymphoid Organs
• Lymph nodes, spleen, tonsils, and Peyer’s
patches.
– Located in areas where antigens could gai...
B Lymphocytes (B cells)
• Humoral immunity:
– Most of the lymphocytes that are not T cells are B
lymphocytes (B cells).
• ...
B Lymphocytes

(continued)

• Others are transformed
into plasma cells:
– Produce 2000 antibody
proteins/sec. when
exposed...
Local Inflammation
• Bacteria enter body (break in skin):
– Inflammatory reaction initiated by nonspecific mechanisms
of p...
Local Inflammation

(continued)

• Leukocytes interact with
adhesion molecules in
endothelial cell.
• Chemotaxis occurs, a...
Local Inflammation

(continued)

• Mast cells secrete
prostaglandins,
leukotrienes,
histamine, cytokines,
and TNF-a.
– Inc...
Local Inflammation

(continued)

• Characteristic effects of inflammation:
– Redness and warmth.
• Histamine stimulated va...
Antibodies
• Antibody proteins are also known as
immunoglobulins.
– Found in the gamma globulin class of plasma
proteins.
...
Antibodies

IVMS USMLE Step 1 Prep.

(continued)

25
Antibody Structure
• 100 million trillion
antibody molecules that
contain 4 polypeptide
chains.
• 2 long H chains are join...
The Complement System
• Nonspecific defense system.
– The combination of antibodies with antigens does not
cause destructi...
The Complement System
• The complement proteins are designated C-1 to C-9.
– These proteins are in an inactive state.
• Be...
The Complement System

(continued)

• Classic pathway:
• Antibodies of IgG and IgM attach to antigens on invading
cell mem...
Fixation of Complement Proteins

IVMS USMLE Step 1 Prep.

30
Complement Fixation
• C5b and C6 through C9 are inserted into bacterial cell
membrane, to form a membrane attach complex (...
Complement Fragments
• Chemotaxis:
– C5a acts as a cytokine to attract neutrophils and
monocytes to the site.
• Attract ph...
Killer (Cytotoxic) T Cells
• Cell mediated destruction.
– Can be identified by the CD8 coreceptor.

• Destroy specific cel...
Killer (Cytotoxic) T Cells

(continued)

• Secrete granzymes:
– Enter the victim cell
activating caspases:
• Enzymes invol...
Helper T Cells
• Identified by CD4
coreceptor.
• Indirectly
participate by
regulating the
response of both
T killer and B ...
Interaction of Macrophages,
Helper T and Killer T cells

Insert fig. 15.18

IVMS USMLE Step 1 Prep.

36
Suppressor T Cells
• Indirectly participate in the specific immune
response.
• Inhibit T cell and B cell activities.
• Aff...
Lymphokines
• Interleukin-1:
– Secreted by macrophages and other cells.
• Activates T cells.

• Interleukin-2:
– Released ...
Subtypes of Helper T Cells
• TH1:

– Produces interleukin-2 and gamma interferon.
• Promotes cell mediated immunity and ac...
T Cell Receptor Proteins

• Only protein antigens are recognized by most T
cells.
– T cell receptors cannot bind to free a...
Major Histocompatability Complexes
(MHC)
• All cells except mature RBCs are genetically marked
with histocompatability ant...
Major Histocompatability Complexes
(continued)

• MHC class-1:
– Produced by all cells but RBCs.
– Picks up cytoplasmic pe...
Major Histocompatability Complexes
(continued)

• MHC class-2:
– Produced only by antigen-presenting cells and B cells.
• ...
Coreceptors on Helper and Killer T cells

IVMS USMLE Step 1 Prep.

44
T Cell Response to a Virus
• Foreign particle infects body.
– Macrophages engulf by phagocytosis.
– Partially digested vir...
T Cell Response to a Virus

(continued)

• Macrophages secrete interleukin-1 and TNF.
– Interleukin-1 stimulates cell divi...
T Cell Response to a Virus

(continued)

• Foreign antigens
attach to
immunoglobulins on
B cells.
• B cells can present
th...
Destruction of T Lymphocytes
• Activated T cells must be destroyed after the
infection has cleared.
• T cells produce a su...
Active Immunity
• Primary response:
– First exposure to pathogen, immune response insufficient
to combat disease.
– Latent...
Primary and Secondary Immune Responses

IVMS USMLE Step 1 Prep.

50
Clonal Selection Theory
• Mechanism by which secondary responses are produced.
– B lymphocytes inherit the ability to prod...
Clonal Selection Theory

(continued)

• Some of the cells become
plasma cells that secrete
primary response.
• Others beco...
Active Immunity
• Development of a secondary response
provides active immunity.
• Immunizations induce primary responses.
...
Immunological Tolerance
• Immunological competence occurs during the 1st
month postnatally.
– Ability to produce antibodie...
Passive Immunity
• Immune protection produced by the transfer of
antibodies to a recipient from a donor.
– The donor has b...
Monoclonal Antibodies
• Commercially prepared.
• Exhibit specificity for one antigenic determinant only.
• Results in more...
Tumor Immunology
• Tumors are interrelated with the functions of the
immune system.
– Division of tumor cells is not effec...
Tumor Immunology

(continued)

• Some of these antigens are proteins produced
in embryonic or fetal life.
– Are absent at ...
Natural Killer (NK) Cells

• Lymphocytes that are related to, but distinct from
T cells.
• Provide first line of cell-medi...
Immunotherapy for Cancer
• Interleukin-2 activates both killer T and B
lymphocytes.
– Patients treated with lymphocytes wi...
Effects of Aging and Stress
• Cancer risks increase with age.
– Aging lymphocytes accumulate genetic errors
that decrease ...
Diseases Caused by the Immune System
• Immune system can be deranged in its
ability to tolerate self-antigens while it
ide...
Autoimmunity
• Diseases produced by failure in the immune
system to recognize and tolerate self-antigens.
– Activates auto...
Autoimmunity

(continued)

– Antibodies may be produced that are directed against
other antibodies.
• Rheumatoid arthritis...
Immune Complex Diseases
• Damage produced by inflammatory response.
– Antigen-antibody combinations that are free rather
t...
Allergy
• Abnormal immune responses to allergens.
• Immediate hypersensitivity:
– Dendritic cells stimulate TH2 cells to s...
Immediate Hypersensitivity
• IgE antibodies attach
to mast cells and
basophils.
– When exposed again
to same allergen, the...
Delayed Hypersensitivity
• Symptoms take longer time to develop (hours
to days).
– Is a cell mediated T cell response.

• ...
THE END
THANK YOU FOR YOUR ATTENTION

IVMS USMLE Step 1 Prep.

69
Resources for further study:
Vaccine Research Center Information regarding preventative
vaccine research studies
Immune Sy...
IVMS| The Immune System: Immunocytology, Immunophysiology and Intro to Immunopathology
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IVMS| The Immune System: Immunocytology, Immunophysiology and Intro to Immunopathology

  1. 1. The Immune System: Immunocytology, Immunophysiology and Intro to Immunopathology Companion tools: Prepared and Presented by Marc Imhotep Cray, M.D. BMS and CK Teacher Recommended Reading: Microbiology and Immunology On-Line Textbook - University of South Carolina SOM http://www.imhotepvirtualmedsch.com/ A scanning electron microscope image of a single neutrophil (yellow), engulfing anthrax bacteria (orange) From: http://upload.wikimedia.org/wikipedia/comm ons/f/f2/Neutrophil_with_anthrax_copy.jpg Clinical: e-Medicine Article Acute Respiratory Distress Syndrome
  2. 2. Defense Mechanisms • All structures and processes that provide a defense against pathogens. • Defenses: – Innate (nonspecific): • Inherited as part of the structure of each organism. – Adaptive (specific): • Prior exposure (B lymphocytes). N.B.-As much of immunology is also a hematology discussion, for horizontal integration also see — IVMS Hematology-Comprehensive Blood Physiology and Pathology Review IVMS USMLE Step 1 Prep. 2
  3. 3. Nonspecific Immunity • External: – Skin: • Protective barrier to resist infection. – GI tract: • Gastric juice acidity. – Respiratory tract: • Mucus and cilia. – Urinary tract: • Urine acidity. – Reproductive tract: • Vaginal acidity. IVMS USMLE Step 1 Prep. 3
  4. 4. Phagocytosis • Distinguish between the kinds of carbohydrates that are produced by mammalian cells and those produced by bacteria. – Bacterial carbohydrates “flag” the cell for phagocytic attack. • 3 major groups of phagocytic cells: – Neutrophils: • 1st to arrive at infection. – Mononuclear phagocyte system: • Macrophages and monocytes. – Organ-specific phagocytes: • Microglia and Kupffer cells. IVMS USMLE Step 1 Prep. 4
  5. 5. Phagocytosis (continued) • Diapedesis: – Neutrophils and monocytes are able to squeeze through tiny gaps between adjacent endothelial cells. IVMS USMLE Step 1 Prep. 5
  6. 6. Phagocytosis (continued) • Connective tissue has a resident population of all leukocyte types. – Neutrophils and monocytes are highly mobile. • Recruited to site of infections by chemotaxis: – Movement toward chemical (chemokines) attractants. – If infection has spread, new phagocytes from the blood are attracted to infection. • Phagocytes engulf particles similar to amoeba. IVMS USMLE Step 1 Prep. 6
  7. 7. Phagocytosis (continued) – Particle becomes surrounded by pseudopods. – Forms vacuole. • Vacuole fuses with lysosomes which digest the particle. – If lysosomes are released into the infected area before vacuole is completely fused: • Contribute to the inflammation. IVMS USMLE Step 1 Prep. 7
  8. 8. Fever • May be a component of nonspecific defense system. • Cell wall of gram – bacteria contains endotoxin. – Endotoxin stimulate release of cytokines: • Interleukin-1, interleukin-6, and tumor necrosis factor: – Produce fever, increase sleepiness, and decrease plasma iron. IVMS USMLE Step 1 Prep. 8
  9. 9. Nonspecific Immunity • Body temperature is regulated by hypothalamus (thermoregulatory center). – Thermostat reset by endogenous pyrogens. • Endogenous pyrogens: – Cell wall of gram – bacteria contains endotoxin. – Endotoxin stimulates monocytes and macrophages to release cytokines: • Interleukin-1, interleukin-2, TNF. – Increased activity of neutrophils. – Increased production of interferon. IVMS USMLE Step 1 Prep. 9
  10. 10. Interferons (Cytokines) • Act as short-acting messengers that protect other cells in the vicinity from viral infection. • a interferon: – Inhibits viral replication, increases NK cells, and induces MHC-I antigens. • b interferon: – Inhibits viral replication, increases NK cells, and induces MHC-I antigens. • g interferon: – Activates macrophages and induces MHC-II antigens. • Immunological defense against infection and cancer. IVMS USMLE Step 1 Prep. 10
  11. 11. Antigens • Molecules that stimulate the production of specific antibodies. – Combine specifically with antibodies produced. • Foreign to blood and other body fluids. • Immune system can distinguish “self” molecules from nonself antigens. • Large, complex molecules can have different antigenic determinant sites. – Areas of the molecules that stimulate production of, and combine with different antibodies. IVMS USMLE Step 1 Prep. 11
  12. 12. Haptens • Small organic molecules can become antigens if they bind to proteins. • Become antigenic determinant sites on the proteins. – By binding haptens to proteins in the laboratory, new antigens are created for research or diagnostic purposes. IVMS USMLE Step 1 Prep. 12
  13. 13. Immunoassays • Tests that use the antigen-antibody complex reaction to produce clumping (agglutination). • Agglutinated particles can be used to assay a variety of antigens. • Generally use antibodies that exhibit specificity for just 1 antigenic determinant site. IVMS USMLE Step 1 Prep. 13
  14. 14. Lymphocytes and Lymphoid Organs • Derived from stem cells in the bone marrow. – Stem cells produce the specialized blood cells. • Replace themselves by cell division so the stem cell population is not depleted. – Lymphocytes produced by this process seed the thymus, spleen, and lymph nodes. • Produce self-replacing lymphoid colonies in these organs. • Primary lymphoid organs: – Since bone marrow and the thymus produce the T and B lymphocytes. • Both T and B cells function in specific immunity. IVMS USMLE Step 1 Prep. 14
  15. 15. Lymphocytes (T cells) • Cell mediated immunity: • Lymphocytes that seed the thymus become T cells. – Have surface characteristics and immunological function that differ from other lymphocytes. • Do not secrete antibodies. • Must come in close or direct contact to destroy them. – 65 – 85% of the lymphocytes in blood and most of the lymphocytes in the germinal centers of lymph nodes and spleen. • Attack host cells that have become infected with viruses, fungi, transplanted human cells, and cancerous cells. IVMS USMLE Step 1 Prep. 15
  16. 16. Thymus • Grows during childhood, gradually regresses after puberty. • Lymphocytes from the fetal liver and spleen; and bone marrow postnatally, seed the thymus: – Become transformed into T cells. • In adulthood, repopulation is accomplished by production in secondary lymphoid organs. IVMS USMLE Step 1 Prep. 16
  17. 17. Secondary Lymphoid Organs • Lymph nodes, spleen, tonsils, and Peyer’s patches. – Located in areas where antigens could gain entry to the blood or lymph. • Lymphocytes migrate from the primary lymphoid organs to the secondary lymphoid organs. – Spleen filters blood. – Secondary lymph nodes in tonsils and Peyer’s patches filter lymph. IVMS USMLE Step 1 Prep. 17
  18. 18. B Lymphocytes (B cells) • Humoral immunity: – Most of the lymphocytes that are not T cells are B lymphocytes (B cells). • Processed in the bone marrow. – Function in specific immunity. – B cells combat bacterial and some viral infections. • Secrete antibodies into the blood and lymph. – Provide humoral immunity as blood and lymph are body fluids (humors). – Stimulate production of memory cells: • Important in active immunity. IVMS USMLE Step 1 Prep. 18
  19. 19. B Lymphocytes (continued) • Others are transformed into plasma cells: – Produce 2000 antibody proteins/sec. when exposed to antigen. • These antigens may be isolated molecules or may be molecules at the surface of an invading foreign cell. – Serves to identify the enemy. • Secrete antibodies that bind to antigens. IVMS USMLE Step 1 Prep. 19
  20. 20. Local Inflammation • Bacteria enter body (break in skin): – Inflammatory reaction initiated by nonspecific mechanisms of phagocytosis and complement activation. • Complement activation attracts new phagocytes to the area. – After some time, B lymphocytes are stimulated to produce antibodies against specific antigens. – Attachment of antibodies to antigens amplifies nonspecific responses. • Activates complement. – Antibodies promote phagocytic activity of neutrophils, macrophages, and monocytes (opsinization). IVMS USMLE Step 1 Prep. 20
  21. 21. Local Inflammation (continued) • Leukocytes interact with adhesion molecules in endothelial cell. • Chemotaxis occurs, attracting leukocytes. – Diapedesis occurs. – First to arrive are neutrophils, then monocytes, and T lymphocytes. • Adherence of monocytes to extracellular matrix proteins promotes conversion into macrophages. IVMS USMLE Step 1 Prep. 21
  22. 22. Local Inflammation (continued) • Mast cells secrete prostaglandins, leukotrienes, histamine, cytokines, and TNF-a. – Increases membrane permeability. – Vasodilation of blood vessels. – Recruit neutrophils. IVMS USMLE Step 1 Prep. 22
  23. 23. Local Inflammation (continued) • Characteristic effects of inflammation: – Redness and warmth. • Histamine stimulated vasodilation. – Swelling (edema). – Pus. • Accumulation of dead leukocytes. – Pain. – If infection continues, endogenous pyrogens released. IVMS USMLE Step 1 Prep. 23
  24. 24. Antibodies • Antibody proteins are also known as immunoglobulins. – Found in the gamma globulin class of plasma proteins. • Different antibodies have different structure, as the antibodies have specific actions. IVMS USMLE Step 1 Prep. 24
  25. 25. Antibodies IVMS USMLE Step 1 Prep. (continued) 25
  26. 26. Antibody Structure • 100 million trillion antibody molecules that contain 4 polypeptide chains. • 2 long H chains are joined to 2 shorter L chains. – Fab regions are variable. • Provide specificity for a bonding to an antigen. – Fc region of different antibodies are constant. • B cells have antibodies that serve as receptors for antigens. IVMS USMLE Step 1 Prep. 26
  27. 27. The Complement System • Nonspecific defense system. – The combination of antibodies with antigens does not cause destruction of the antigens or pathogen. • Antibodies serve to identify the targets for immunological attack. – Stimulate opsinization. • Antibody-induced activation of the complement. IVMS USMLE Step 1 Prep. 27
  28. 28. The Complement System • The complement proteins are designated C-1 to C-9. – These proteins are in an inactive state. • Become activated by the attachment of antibodies to antigens. • Complement proteins can be subdivided into 3 components: – C1: recognization. – C4, C2, C3: activation. – C5-C9: attack (complement fixation). IVMS USMLE Step 1 Prep. 28
  29. 29. The Complement System (continued) • Classic pathway: • Antibodies of IgG and IgM attach to antigens on invading cell membranes. – Binding to C1 activates the process. • Activated C1 hydrolyzes C4 into C4a and C4b. • C4b binds to the cell membrane and becomes an active enzyme. • C4b splits C2 into C2a and C2b. • C2a attaches to C4b and cleaves C3 into C3a and C3b. – Alternate pathway converges with classic pathway. • Fragment C3b becomes attached to the complex in the cell membrane. • C3b converts C5 to C5a and C5b. IVMS USMLE Step 1 Prep. 29
  30. 30. Fixation of Complement Proteins IVMS USMLE Step 1 Prep. 30
  31. 31. Complement Fixation • C5b and C6 through C9 are inserted into bacterial cell membrane, to form a membrane attach complex (MAC). – Create large pores in membrane, causing osmotic influx of H20. • Complement proteins kill the cell. IVMS USMLE Step 1 Prep. 31
  32. 32. Complement Fragments • Chemotaxis: – C5a acts as a cytokine to attract neutrophils and monocytes to the site. • Attract phagocytes. • Opsinization: – Phagocytes have receptors for C3b. • Form bridges between phagocyte and victim cell. • C3a and C5a stimulate mast cells to secrete histamine: – Increase blood flow and capillary permeability. • Bring in more phagocytes. IVMS USMLE Step 1 Prep. 32
  33. 33. Killer (Cytotoxic) T Cells • Cell mediated destruction. – Can be identified by the CD8 coreceptor. • Destroy specific cells with antigens on their surface. – Must be in actual contact with their victim cells. • Secrete perforins: – Perforins polymerize in the cell membrane and form cylindrical channels through the membrane. • Osmotic destruction of the cell. IVMS USMLE Step 1 Prep. 33
  34. 34. Killer (Cytotoxic) T Cells (continued) • Secrete granzymes: – Enter the victim cell activating caspases: • Enzymes involved in apoptosis. • Destruction of victims cell’s DNA. IVMS USMLE Step 1 Prep. 34
  35. 35. Helper T Cells • Identified by CD4 coreceptor. • Indirectly participate by regulating the response of both T killer and B cells. • B cells must be activated by helper T cells before they produce antibodies. IVMS USMLE Step 1 Prep. 35
  36. 36. Interaction of Macrophages, Helper T and Killer T cells Insert fig. 15.18 IVMS USMLE Step 1 Prep. 36
  37. 37. Suppressor T Cells • Indirectly participate in the specific immune response. • Inhibit T cell and B cell activities. • Affect the amount of antibodies secreted. • Moderate immune response. IVMS USMLE Step 1 Prep. 37
  38. 38. Lymphokines • Interleukin-1: – Secreted by macrophages and other cells. • Activates T cells. • Interleukin-2: – Released by helper T cells. • Activates killer T cells. • Interleukin-3: – Serves as a growth factor. • Activates killer T cells. • Interleukin-4: – Secreted by T cells. • Required for proliferation and clone development of B cells. • G-CSF and GM-CSF: – Promote leukocyte development. IVMS USMLE Step 1 Prep. 38
  39. 39. Subtypes of Helper T Cells • TH1: – Produces interleukin-2 and gamma interferon. • Promotes cell mediated immunity and activates killer T cells. • Stimulates NO production. – Interleukin-12: • Changes “uncommitted” helper T cells into TH1 cells. • TH2: – Secretes interleukin-4, interleukin-5, and interleukin-10. • Promotes humoral immunity and stimulates B lymphocytes. – Activates mast cells. IVMS USMLE Step 1 Prep. 39
  40. 40. T Cell Receptor Proteins • Only protein antigens are recognized by most T cells. – T cell receptors cannot bind to free antigens. – In order for T cells to respond to foreign antigens: • Antigen must be presented to T cells on the membrane of antigen presenting cells. – Chief antigen presenting cells are macrophages and dendritic cells. – To interact with correct T cells, dendritic cells migrate to secondary lymphoid organs. • Secrete chemokines. IVMS USMLE Step 1 Prep. 40
  41. 41. Major Histocompatability Complexes (MHC) • All cells except mature RBCs are genetically marked with histocompatability antigens on the membrane surface. – Also called human leukocyte antigens (HLAs). • The histocompatability antigens are coded for a group of genes called MHC located on chromosome 6. • MHC genes produce 2 classes of MHC molecules: – Class-1. – Class-2. IVMS USMLE Step 1 Prep. 41
  42. 42. Major Histocompatability Complexes (continued) • MHC class-1: – Produced by all cells but RBCs. – Picks up cytoplasmic peptides and transports to membrane. • Killer T cells (cytotoxic) interact with antigens. – Coreceptor CD8 permits each type of T cell to interact only with a class-1 MHC molecules. IVMS USMLE Step 1 Prep. 42
  43. 43. Major Histocompatability Complexes (continued) • MHC class-2: – Produced only by antigen-presenting cells and B cells. • Present class-2 MHC together with antigens to helper T cells. • Activates T cells. – Helper T cells react with antigens. • Promotes B cell response. – Appear only on cell membrane when cell is processing antigens. – Coreceptor CD4 interacts with only a specific class of MHC molecule. IVMS USMLE Step 1 Prep. 43
  44. 44. Coreceptors on Helper and Killer T cells IVMS USMLE Step 1 Prep. 44
  45. 45. T Cell Response to a Virus • Foreign particle infects body. – Macrophages engulf by phagocytosis. – Partially digested virus particles (foreign antigens) are moved to surface of cell membrane. – Foreign antigens forms a complex with class-2 MHC molecules. – Presented to helper T cells. IVMS USMLE Step 1 Prep. 45
  46. 46. T Cell Response to a Virus (continued) • Macrophages secrete interleukin-1 and TNF. – Interleukin-1 stimulates cell division and proliferation of T cells. • Activated T cells secrete M-CSF and g- interferon. – Promote the activity of the macrophages. • Killer T cells destroy infected cell if class-1 MHC present. – Helper T cells activate B cells. IVMS USMLE Step 1 Prep. 46
  47. 47. T Cell Response to a Virus (continued) • Foreign antigens attach to immunoglobulins on B cells. • B cells can present the antigen with class-2 MHC molecules to helper T cells. – Stimulate B cell production, conversion to plasma cells, and antibody production. IVMS USMLE Step 1 Prep. 47
  48. 48. Destruction of T Lymphocytes • Activated T cells must be destroyed after the infection has cleared. • T cells produce a surface receptor called FAS. – Production of FAS increases during the infection. • After a few days, activated T cells begin to produce FAS ligand. – FAS binds to FAS ligand and triggers apoptosis (cell suicide). • Help maintain immunologically privileged sites. IVMS USMLE Step 1 Prep. 48
  49. 49. Active Immunity • Primary response: – First exposure to pathogen, immune response insufficient to combat disease. – Latent period of 5-10 days before measurable amounts of specific antibodies appear in blood. • Secondary response: – Subsequent exposure to same antigen. – Antibody production is much more rapid. • Maximum antibody concentration reached in < 2 hrs. – Maintained longer period of time. IVMS USMLE Step 1 Prep. 49
  50. 50. Primary and Secondary Immune Responses IVMS USMLE Step 1 Prep. 50
  51. 51. Clonal Selection Theory • Mechanism by which secondary responses are produced. – B lymphocytes inherit the ability to produce a particular antibody. – T lymphocytes inherit the ability to respond to particular antigens. • A given B cell can produce only 1 type of antibody with specificity for 1 antigen. – Inherited specificity reflected in antigen receptor proteins. • Exposure stimulates specific lymphocytes to divide many times until a large population of genetically identical cells (clone) is produced. IVMS USMLE Step 1 Prep. 51
  52. 52. Clonal Selection Theory (continued) • Some of the cells become plasma cells that secrete primary response. • Others become memory cells that secrete antibodies during the secondary response. • Antigens select lymphocytes that are already able to make antibodies. IVMS USMLE Step 1 Prep. 52
  53. 53. Active Immunity • Development of a secondary response provides active immunity. • Immunizations induce primary responses. – Inoculating people with pathogens whose viruses have been attenuated or destroyed. IVMS USMLE Step 1 Prep. 53
  54. 54. Immunological Tolerance • Immunological competence occurs during the 1st month postnatally. – Ability to produce antibodies against non-self antigens while tolerating self-antigens. • Requires continuous exposure to those antigens. • Autoantibodies: – Exposure to self-antigens results in antibody production. • Autoreactive T cells: – Killer T cells attack self-antigens. IVMS USMLE Step 1 Prep. 54
  55. 55. Passive Immunity • Immune protection produced by the transfer of antibodies to a recipient from a donor. – The donor has been actively immunized. • Person who receives these ready-made antibodies is passively immunized. – Occurs naturally in mother to fetus during pregnancy and mother to infant during nursing. • Immunological competence: – Ability to mount a specific immune response. – Does not develop until 1 month after birth. – Passive immunity disappears when infant is 1 month old. • Infant did not itself produce lymphocytes. IVMS USMLE Step 1 Prep. 55
  56. 56. Monoclonal Antibodies • Commercially prepared. • Exhibit specificity for one antigenic determinant only. • Results in more sophisticated clinical laboratory tests. – May aid in the diagnosis of cancer. • May result in production of drugs combined with monoclonal antibodies against specific tumor antigens. IVMS USMLE Step 1 Prep. 56
  57. 57. Tumor Immunology • Tumors are interrelated with the functions of the immune system. – Division of tumor cells is not effectively controlled by normal inhibitory mechanisms. • Tumor cells also dedifferentiate (become similar to less specialized cells of an embryo). – As tumor cells dedifferentiate, they reveal surface antigens that can stimulate the immune destruction of the tumor. IVMS USMLE Step 1 Prep. 57
  58. 58. Tumor Immunology (continued) • Some of these antigens are proteins produced in embryonic or fetal life. – Are absent at the time immunological competence is established. – Body treats these antigens as foreign. • Release of these antigens provides the basis of laboratory diagnosis of some cancers. IVMS USMLE Step 1 Prep. 58
  59. 59. Natural Killer (NK) Cells • Lymphocytes that are related to, but distinct from T cells. • Provide first line of cell-mediated defense. – NK cells destroy tumors in a nonspecific fashion. • NK cells attach to cells that lack class-1 MHC antigens. – Release perforins and granzymes. • Do not require prior exposure for sensitization to the tumor antigens. • Stimulated by interferon. IVMS USMLE Step 1 Prep. 59
  60. 60. Immunotherapy for Cancer • Interleukin-2 activates both killer T and B lymphocytes. – Patients treated with lymphocytes with IL-2 produce lymphokine-activated killer T cells. • Gamma interferon is used to treat particular forms cancer. – Lymphomas, renal carcinomas, melanoma, Kaposi’s sarcoma. • Tumor infiltrating lymphocyte is promising. IVMS USMLE Step 1 Prep. 60
  61. 61. Effects of Aging and Stress • Cancer risks increase with age. – Aging lymphocytes accumulate genetic errors that decrease effectiveness. – Thymus functions decline. • Stress: – Tumors grow faster. • Increased production of corticosteroids. IVMS USMLE Step 1 Prep. 61
  62. 62. Diseases Caused by the Immune System • Immune system can be deranged in its ability to tolerate self-antigens while it identifies and attacks foreign antigens. • Diseases caused by the immune system can be grouped into 3 categories: – Autoimmune disease. – Immune complex diseases. – Allergy or hypersensitivity. IVMS USMLE Step 1 Prep. 62
  63. 63. Autoimmunity • Diseases produced by failure in the immune system to recognize and tolerate self-antigens. – Activates autoreactive T cells and stimulates production of autoantibodies by B cells. • Failure due to: – An antigen that does not normally circulate in the blood may be exposed to the immune system. • Thyroglobulin. – A self-antigen that is otherwise tolerated may be altered by combining with a foreign hapten. • Thrombocytopenia. IVMS USMLE Step 1 Prep. 63
  64. 64. Autoimmunity (continued) – Antibodies may be produced that are directed against other antibodies. • Rheumatoid arthritis. – Antibodies produced against foreign antigens may cross-react with self-antigens. • Rheumatic fever. – Self-antigens may be presented to the helper T cells together with class-2 MHC molecules. • Type I diabetes. IVMS USMLE Step 1 Prep. 64
  65. 65. Immune Complex Diseases • Damage produced by inflammatory response. – Antigen-antibody combinations that are free rather than attached to bacterial or other cells: • Activate complement proteins and promotes inflammation. – When large # of immune complexes are continuously formed, inflammation may be prolonged. • Hepatitis B. – Formation of complexes between self-antigens and autoantibodies: • Rheumatoid arthritis. IVMS USMLE Step 1 Prep. 65
  66. 66. Allergy • Abnormal immune responses to allergens. • Immediate hypersensitivity: – Dendritic cells stimulate TH2 cells to secrete interleukin-4 and interleukin-13: • Stimulate B cells and plasma cells to secrete IgE antibodies. – Do not circulate in the blood. IVMS USMLE Step 1 Prep. 66
  67. 67. Immediate Hypersensitivity • IgE antibodies attach to mast cells and basophils. – When exposed again to same allergen, the allergen binds to antibodies attached to mast cells and basophils. • Stimulate secretion of histamine, leukotrienes, and prostaglandin D. –IVMS USMLE Step 1 Prep. Produce symptoms. 67
  68. 68. Delayed Hypersensitivity • Symptoms take longer time to develop (hours to days). – Is a cell mediated T cell response. • Symptoms caused by secretion of lymphokines, not histamine. – Antihistamines provide little benefit. IVMS USMLE Step 1 Prep. 68
  69. 69. THE END THANK YOU FOR YOUR ATTENTION IVMS USMLE Step 1 Prep. 69
  70. 70. Resources for further study: Vaccine Research Center Information regarding preventative vaccine research studies Immune System - from the University of Hartford Immunobiology; Fifth Edition – Online version of the textbook by Immunology - BioMed Central (free content) scientific journal The Microbial World - Animal defenses against microbes - Chapter in on-line microbiology textbook Microbiology and Immunology On-Line Textbook - from the University of South Carolina School of Medicine IVMS USMLE Step 1 Prep. 70

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