Dr. Maynard’s initial review of immunodeficiency syndromes and immunology (presented on 5/23/12).

1. Immunodeficiency Syndromes:
Part One:
Primer on Immunology
May 23, 2012
Roy C. Maynard, M.D.
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2. Objectives
• Understand basic concepts in immunology
• Anatomy of the immune system: be able to
identify primary and secondary lymphoid organs
• Role of the innate immune system in prevention
of disease
• Describe aspects of the adaptive immune
system as related to vaccines
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3. Immunology
• Definition: Study of the immune system,
both in wellness and disease
- Infectious disease
- Autoimmune disease
- Oncology
- Medical diagnostics
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4. Anatomy of the Immune System
• Primary
- Thymus
- Bone marrow
• Secondary
- Spleen
- Lymph nodes
- Mucosa-associated lymphoid tissue
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5. Lymphoid Organs and Tissues
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6. Cells of the Immune System
http://www.hhmi.org/biointeractive/disease/immunology_primer/01.html
Accessed on 5/1/12
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7. Innate Immune System
• Relatively non-specific antimicrobial systems
that are innate in the sense they are not
intrinsically affected by prior contact with the
infectious agent
• Active all the time
• External and internal
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8. Innate Immune System
• External
- Barrier functions
- Physical and chemical
- Skin: lactic acid, pH, fatty acids
- Mucous membranes: mucus contains
bactericidal components
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9. Innate Immune System
• Internal
- If microorganisms penetrate the external
barriers, then cells of the innate immune
system come into play
• 2 major defense strategies
- Phagocytic cells
- Soluble bactericidial chemical factors
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10. Phagocytic Cells
• Neutrophils
• Eosinophils
• Basophils
• Lymphocytes
• Macrophages
• Mast cells
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11. Phagocytic Cells
• Neutrophils
– Short-lived
– Pyogenic organisms
– Granules
• Myeloperoxidase
• Cathepsin G
• Lysozyme
• Lactoferrin
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12. Phagocytic Cells
• Macrophages
– Monocytes, microglia, kupffer cells, histiocytes,
osteoclasts, glomerular mesangial cells
– Longer half-life
– Intracellular pathogens
– Pattern recognition receptors (toll-like
receptors)
– Release cytokines
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13. Phagocytic Cells
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14. Innate Immune System
• NK Cells (natural killer cells)
– Granular leukocytes
– Recognize molecules surface virally infected
cells
– Become activated and release cytokines
(perforin, granzyme) to attack target cell
– Target cell death results by programmed cell
death and viral particle reproduction ends
– May be involved in cancer surveillance
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15. Natural Killer Cells
http://arapaho.nsuok.edu/~castillo/NotesImages/Topic17NotesImage2.jpg
Accessed 5/18/12
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16. Innate Immune System
• Eosinophils
– Parasites
– Allergies
– Autoimmune disease (Churg-Strauss syndrome)
– Cytokines (major basic protein, eosinophilic
cationic protein)
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17. Complement System
• Complex series of 20 proteins in plasma
• Enzyme activation of cascade
• Complement facilitates phagocytosis
• Complement (C3b) binds to bacteria and allows recognition by
phagocytes to engulf
• May stimulate (C3a and C5a) phagocytes make reactive oxygen
intermediates and enhance expression of cell surface receptors
• Trigger degranulation of mast cells and granulocytes
• MAC (membrane attack complex)
• Attract other inflammatory cells
• Part of anaphylaxsis
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18. Complement System
http://www.emc.maricopa.edu/faculty/farabee/biobk/biobookimmun.html
Accessed on 5/18/12
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19. Ontogeny of Immune Cells
• T cells processed in the thymus
• B cells processed in fetal liver then
in bone marrow
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20. Adaptive Immune System
• Antibody Production
– Antibody molecule evolved as a specific
adaptor to attach to microorganisms which
do not activate the complement pathway or
prevent activation of macrophages
– Supplementary route into the acute
inflammatory response enhanced by
antibodies which activate mast cells, form
immune complexes that stimulate cytokine
from macrophages
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21. Antibodies or Immunoglobulins
• Immune proteins
• Manufactured by B cells and plasma cells
• First function to recognize and bind to
foreign material (antigen)
• Second function to trigger elimination of
foreign material
• Five classes of immunoglobulins
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22. Immunoglobulin Classes
• IgG
– 4 subclasses: IgG1, IgG2, IgG3 and IgG4
– Monoclonal disease – multiple myeloma
– Recombinant antibody technology
– Major antibody in plasma and tissue
– Major “memory” antibody
– Fc and complement interaction
– Primary component of gammaglobulin
infusions
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23. Immunoglobulin Classes
• IgM
– Pentameric
– Interacts with complement
– Early immune response
– First line defense against bacteremia
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24. Immunoglobulin Classes
• IgA
– Monomer in plasma, dimer in secretions
– Major defensive antibody in mucous secretions
• IgE
– Binds to mast cells
– “Allergic” antibody
– Parasitic infections
• IgD
– Surface of naïve B cells
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25. Anatomy of an Immunoglobulin
http://www.emc.maricopa.edu/faculty/farabee/biobk/ANTIBODY.gif
Accessed on 5/1/12
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26. Anatomy of an Immunoglobulin
http://upload.wikimedia.org/wikipedia/commons/thumb/3/31/Mono-und-Polymere.svg/170px-Mono-und-Polymere.svg.png
Accessed on 5/1/12
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27. Serum Immunoglobulin Ontogeny
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28. Immunoglobulin Switching
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29. Antibody-Producing Cells
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30. Primary and Secondary Response
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31. Monoclonal Antibodies
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32. Ontogeny of Immune Cells
• T cells processed in the thymus
• B cells processed in fetal liver then in
bone marrow
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33. T Lymphocytes
• CD4 – helper T cells, activate B
lymphocytes to make antibody or activate
cytotoxic T cells (CD8)
• CD8 – cytotoxic T cells, involved in killing
viral infected cells and cancer surveillance
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34. Antigen-Presenting Cell
http://en.wikipedia.org/wiki/Antigen-presenting_cell
Accessed on 5/18/12
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35. Hypersensitivity (Type I)
• Type 1
• Anaphylactic hypersensitivity
• IgE mediated cross-linking of receptors on mast
cells
• Triggers explosive release of histamine
• Hypotension (vasodilitation), bronchoconstriction
(smooth muscle)
• death
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36. Hypersensitivity (Type I)
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37. Hypersensitivity (Type II)
• Type II
• Antibody-dependent cytotoxic hypersensitivity
• Antibody binds to target cell and either
activates complement system or effector cell
to kill target cell
• Transfusion reactions, drug reactions, RhD
disease of newborns, ITP
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38. Hypersensitivity (Type II)
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39. Hypersensitivity (Type III)
• Type III
• Immune Complex-Mediated Hypersensitivity
• Antigen and antibody combine and trigger
activation of inflammatory disease
• Hypersensitivty pneumonitis, immune complex
kidney disease, Autoimmune disease (rheumatoid
arthritis, SLE)
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40. Hypersensitivity (Type III)
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41. Hypersensitivity (Type IV)
• Type IV Cell Mediated Hypersensitivity
• Exaggerated interaction between antigen and the
normal cell-mediated immune mechanisms
• Memory T cells stimulated to release cytokines that
activate other cell types
• Tissue damage
• Basis for PPD (mantoux) reaction
• Contact dermatitis, sarcoidosis
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42. Hypersensitivity (Type IV)
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43. Hypersensitivity (Type V)
• Type V Stimulatory Hypersensitivity
• Antibody mediated stimulation of a hormone
receptor on cell surface
• Grave’s disease – autoimmune antibody
triggers thyroid cells to produce excess thyroid
hormone
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44. Conclusions
• The immune system developed for your protection
• Involves complex interactions between antigens,
immune cells and cytokines
• Responsible for killing bacteria, viruses, fungi and
parasites
• Deficits within the immune system may be congenital
or acquired and lead to immunodeficiency
• Relative to transplantation and tumor immunology
• Imbalances in the regulatory mechanisms of the
immune system may lead to organ-specific or
nonorgan-specific autoimmune diseases
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45. Q&A
Questions?
Thank you for attending!
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