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Immunodeficiency Syndromes:           Part One:     Primer on Immunology            May 23, 2012        Roy C. Maynard, M....
Objectives• Understand basic concepts in immunology• Anatomy of the immune system: be able to  identify primary and second...
Immunology• Definition: Study of the immune system,  both in wellness and disease   -   Infectious disease   -   Autoimmun...
Anatomy of the Immune System• Primary   - Thymus   - Bone marrow• Secondary   - Spleen   - Lymph nodes   - Mucosa-associat...
Lymphoid Organs and Tissues                          5 of 45
Cells of the Immune System    http://www.hhmi.org/biointeractive/disease/immunology_primer/01.html                        ...
Innate Immune System• Relatively non-specific antimicrobial systems  that are innate in the sense they are not  intrinsica...
Innate Immune System• External   - Barrier functions   - Physical and chemical   - Skin: lactic acid, pH, fatty acids   - ...
Innate Immune System• Internal    - If microorganisms penetrate the external      barriers, then cells of the innate immun...
Phagocytic Cells  • Neutrophils  • Eosinophils  • Basophils  • Lymphocytes  • Macrophages  • Mast cells                   ...
Phagocytic Cells• Neutrophils    – Short-lived    – Pyogenic organisms    – Granules       •   Myeloperoxidase       •   C...
Phagocytic Cells• Macrophages  – Monocytes, microglia, kupffer cells, histiocytes,    osteoclasts, glomerular mesangial ce...
Phagocytic Cells                   13 of 45
Innate Immune System• NK Cells (natural killer cells)   – Granular leukocytes   – Recognize molecules surface virally infe...
Natural Killer Cellshttp://arapaho.nsuok.edu/~castillo/NotesImages/Topic17NotesImage2.jpg                           Access...
Innate Immune System• Eosinophils  – Parasites  – Allergies  – Autoimmune disease (Churg-Strauss syndrome)  – Cytokines (m...
Complement System• Complex series of 20 proteins in plasma• Enzyme activation of cascade• Complement facilitates phagocyto...
Complement System http://www.emc.maricopa.edu/faculty/farabee/biobk/biobookimmun.html                        Accessed on 5...
Ontogeny of Immune Cells• T cells processed in the thymus• B cells processed in fetal liver then  in bone marrow          ...
Adaptive Immune System• Antibody Production   – Antibody molecule evolved as a specific     adaptor to attach to microorga...
Antibodies or Immunoglobulins• Immune proteins• Manufactured by B cells and plasma cells• First function to recognize and ...
Immunoglobulin Classes• IgG   – 4 subclasses: IgG1, IgG2, IgG3 and IgG4   – Monoclonal disease – multiple myeloma   – Reco...
Immunoglobulin Classes• IgM  –     Pentameric  –     Interacts with complement  –     Early immune response  –     First l...
Immunoglobulin Classes• IgA   – Monomer in plasma, dimer in secretions   – Major defensive antibody in mucous secretions• ...
Anatomy of an Immunoglobulin      http://www.emc.maricopa.edu/faculty/farabee/biobk/ANTIBODY.gif                          ...
Anatomy of an Immunoglobulinhttp://upload.wikimedia.org/wikipedia/commons/thumb/3/31/Mono-und-Polymere.svg/170px-Mono-und-...
Serum Immunoglobulin Ontogeny                          27 of 45
Immunoglobulin Switching                           28 of 45
Antibody-Producing Cells                           29 of 45
Primary and Secondary Response                           30 of 45
Monoclonal Antibodies                        31 of 45
Ontogeny of Immune Cells• T cells processed in the thymus• B cells processed in fetal liver then in  bone marrow          ...
T Lymphocytes• CD4 – helper T cells, activate B  lymphocytes to make antibody or activate  cytotoxic T cells (CD8)• CD8 – ...
Antigen-Presenting Cell     http://en.wikipedia.org/wiki/Antigen-presenting_cell                     Accessed on 5/18/12  ...
Hypersensitivity (Type I)• Type 1• Anaphylactic hypersensitivity• IgE mediated cross-linking of receptors on mast  cells• ...
Hypersensitivity (Type I)                            36 of 45
Hypersensitivity (Type II)• Type II• Antibody-dependent cytotoxic hypersensitivity• Antibody binds to target cell and eith...
Hypersensitivity (Type II)                             38 of 45
Hypersensitivity (Type III)• Type III• Immune Complex-Mediated Hypersensitivity• Antigen and antibody combine and trigger ...
Hypersensitivity (Type III)                              40 of 45
Hypersensitivity (Type IV)• Type IV Cell Mediated Hypersensitivity• Exaggerated interaction between antigen and the  norma...
Hypersensitivity (Type IV)                             42 of 45
Hypersensitivity (Type V)• Type V Stimulatory Hypersensitivity• Antibody mediated stimulation of a hormone  receptor on ce...
Conclusions•   The immune system developed for your protection•   Involves complex interactions between antigens,    immun...
Q&AQuestions?Thank you for attending!                           45 of 45
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Immunodeficiency Syndromes: Part One: Primer on Immunology

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

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Transcript of "Immunodeficiency Syndromes: Part One: Primer on Immunology"

  1. 1. Immunodeficiency Syndromes: Part One: Primer on Immunology May 23, 2012 Roy C. Maynard, M.D. 1 of 45
  2. 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 2 of 45
  3. 3. Immunology• Definition: Study of the immune system, both in wellness and disease - Infectious disease - Autoimmune disease - Oncology - Medical diagnostics 3 of 45
  4. 4. Anatomy of the Immune System• Primary - Thymus - Bone marrow• Secondary - Spleen - Lymph nodes - Mucosa-associated lymphoid tissue 4 of 45
  5. 5. Lymphoid Organs and Tissues 5 of 45
  6. 6. Cells of the Immune System http://www.hhmi.org/biointeractive/disease/immunology_primer/01.html Accessed on 5/1/12 6 of 45
  7. 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 7 of 45
  8. 8. Innate Immune System• External - Barrier functions - Physical and chemical - Skin: lactic acid, pH, fatty acids - Mucous membranes: mucus contains bactericidal components 8 of 45
  9. 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 9 of 45
  10. 10. Phagocytic Cells • Neutrophils • Eosinophils • Basophils • Lymphocytes • Macrophages • Mast cells 10 of 45
  11. 11. Phagocytic Cells• Neutrophils – Short-lived – Pyogenic organisms – Granules • Myeloperoxidase • Cathepsin G • Lysozyme • Lactoferrin 11 of 45
  12. 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 12 of 45
  13. 13. Phagocytic Cells 13 of 45
  14. 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 14 of 45
  15. 15. Natural Killer Cellshttp://arapaho.nsuok.edu/~castillo/NotesImages/Topic17NotesImage2.jpg Accessed 5/18/12 15 of 45
  16. 16. Innate Immune System• Eosinophils – Parasites – Allergies – Autoimmune disease (Churg-Strauss syndrome) – Cytokines (major basic protein, eosinophilic cationic protein) 16 of 45
  17. 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 17 of 45
  18. 18. Complement System http://www.emc.maricopa.edu/faculty/farabee/biobk/biobookimmun.html Accessed on 5/18/12 18 of 45
  19. 19. Ontogeny of Immune Cells• T cells processed in the thymus• B cells processed in fetal liver then in bone marrow 19 of 45
  20. 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 20 of 45
  21. 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 21 of 45
  22. 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 22 of 45
  23. 23. Immunoglobulin Classes• IgM – Pentameric – Interacts with complement – Early immune response – First line defense against bacteremia 23 of 45
  24. 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 24 of 45
  25. 25. Anatomy of an Immunoglobulin http://www.emc.maricopa.edu/faculty/farabee/biobk/ANTIBODY.gif Accessed on 5/1/12 25 of 45
  26. 26. Anatomy of an Immunoglobulinhttp://upload.wikimedia.org/wikipedia/commons/thumb/3/31/Mono-und-Polymere.svg/170px-Mono-und-Polymere.svg.png Accessed on 5/1/12 26 of 45
  27. 27. Serum Immunoglobulin Ontogeny 27 of 45
  28. 28. Immunoglobulin Switching 28 of 45
  29. 29. Antibody-Producing Cells 29 of 45
  30. 30. Primary and Secondary Response 30 of 45
  31. 31. Monoclonal Antibodies 31 of 45
  32. 32. Ontogeny of Immune Cells• T cells processed in the thymus• B cells processed in fetal liver then in bone marrow 32 of 45
  33. 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 33 of 45
  34. 34. Antigen-Presenting Cell http://en.wikipedia.org/wiki/Antigen-presenting_cell Accessed on 5/18/12 34 of 45
  35. 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 35 of 45
  36. 36. Hypersensitivity (Type I) 36 of 45
  37. 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 37 of 45
  38. 38. Hypersensitivity (Type II) 38 of 45
  39. 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) 39 of 45
  40. 40. Hypersensitivity (Type III) 40 of 45
  41. 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 41 of 45
  42. 42. Hypersensitivity (Type IV) 42 of 45
  43. 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 43 of 45
  44. 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 44 of 45
  45. 45. Q&AQuestions?Thank you for attending! 45 of 45
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