The Immune System <ul><li>What does it mean to be “immune” to something? </li></ul>
The Immune System <ul><li>How does the immune system get rid of a pathogen? </li></ul><ul><ul><li>Humoral immunity: B lymp...
The Immune System <ul><li>The immune response must: </li></ul><ul><ul><li>Respond to a  specific  pathogen (specific Ag) <...
Cell-Cell Interactions Y Y Y Y Y Y Y specific  activated B cell makes Ab specific  activated T C  cell kills infected cell...
Two Immune System Questions <ul><li>How does an immune-system cell specifically interact with and activate another cell? <...
The “Immunological Synapse” <ul><li>e.g., APC interacts with T H </li></ul><ul><ul><li>APC digests Ag, presents peptides b...
The “Immunological Synapse” <ul><li>Multiple receptor-MHC complexes cluster </li></ul><ul><li>Signalling molecules recruit...
The “Immunological Synapse” <ul><li>Inner ring of signalling molecules (c-SMAC) </li></ul><ul><li>Outer ring of adhesion m...
The “Immunological Synapse” <ul><li>Initial data is primarily descriptive </li></ul><ul><li>What is the function of the sy...
Pathogen recognition <ul><li>Innate immunity: </li></ul><ul><ul><li>Phagocytosis of pathogens by macrophages and neutrophi...
Pathogen recognition <ul><li>PAMPs: pathogen-associated molecular patterns </li></ul><ul><ul><li>LPS in outer membrane of ...
Pathogen recognition <ul><li>PAMPs recognized by Toll-like receptors (TLRs) </li></ul>
Pathogen recognition <ul><li>PAMPs recognized by Toll-like receptors (TLRs) </li></ul><ul><ul><li>APCs: macrophages and de...
Pathogen recognition <ul><li>Specific roles of TLRs in response to specific microbes have yet to be thoroughly studied </l...
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  1. 1. The Immune System <ul><li>What does it mean to be “immune” to something? </li></ul>
  2. 2. The Immune System <ul><li>How does the immune system get rid of a pathogen? </li></ul><ul><ul><li>Humoral immunity: B lymphocytes produce antibody (Ab) </li></ul></ul><ul><ul><li>Cell-mediated immunity (CMI): cytotoxic T lymphocytes (T C ) kill infected cells </li></ul></ul>Y Y Y Y Y Y neutralization of a virus Y Y Y opsonization of a bacterial cell
  3. 3. The Immune System <ul><li>The immune response must: </li></ul><ul><ul><li>Respond to a specific pathogen (specific Ag) </li></ul></ul><ul><ul><li>Distinguish “self” from “foreign” Ag </li></ul></ul><ul><ul><li>Choose appropriate response (Ab, CMI or both) </li></ul></ul><ul><ul><li>Have memory: respond more quickly 2 nd time </li></ul></ul>opsonization of a bacterial cell
  4. 4. Cell-Cell Interactions Y Y Y Y Y Y Y specific activated B cell makes Ab specific activated T C cell kills infected cells TARGET specific activated T H cell activates effector cells macrophage or dendtritic cell = antigen-presenting cell (APC) activates specific T H cell pathogen (foreign Ag)
  5. 5. Two Immune System Questions <ul><li>How does an immune-system cell specifically interact with and activate another cell? </li></ul><ul><li>How does the APC recognize the foreign Ag? </li></ul>
  6. 6. The “Immunological Synapse” <ul><li>e.g., APC interacts with T H </li></ul><ul><ul><li>APC digests Ag, presents peptides bound to MHC II </li></ul></ul><ul><ul><li>T H with specific T-cell receptor recognizes Ag + MHC </li></ul></ul><ul><ul><li>CD4 on T H binds MHC II </li></ul></ul>
  7. 7. The “Immunological Synapse” <ul><li>Multiple receptor-MHC complexes cluster </li></ul><ul><li>Signalling molecules recruited </li></ul><ul><li>Adhesion molecules strengthen interaction, e.g. ICAM-LFA1 </li></ul><ul><li>Additional interactions, e.g. CD28 – B7 </li></ul>
  8. 8. The “Immunological Synapse” <ul><li>Inner ring of signalling molecules (c-SMAC) </li></ul><ul><li>Outer ring of adhesion molecules (p-SMAC) </li></ul><ul><li>Specific, directional release of activating cytokines </li></ul>
  9. 9. The “Immunological Synapse” <ul><li>Initial data is primarily descriptive </li></ul><ul><li>What is the function of the synapse? Assumed to be necessary for specific cell-cell communication to occur </li></ul>
  10. 10. Pathogen recognition <ul><li>Innate immunity: </li></ul><ul><ul><li>Phagocytosis of pathogens by macrophages and neutrophils </li></ul></ul><ul><ul><li>Inflammation </li></ul></ul><ul><ul><li>Activation of defensive molecules (e.g., complement) </li></ul></ul><ul><ul><li>Protection against many different pathogens </li></ul></ul><ul><ul><li>Involved in activation of specific defenses </li></ul></ul><ul><ul><li>Originally thought to be “non-specific” </li></ul></ul><ul><ul><li>…BUT, how would a pathogen be recognized? </li></ul></ul><ul><ul><li>must be some kind of specific receptors! </li></ul></ul>
  11. 11. Pathogen recognition <ul><li>PAMPs: pathogen-associated molecular patterns </li></ul><ul><ul><li>LPS in outer membrane of Gram-negative cell </li></ul></ul><ul><ul><li>Peptidoglycan in bacterial cell wall </li></ul></ul><ul><ul><li>Lipoteichoic acid in Gram-postive cell wall </li></ul></ul><ul><ul><li>Flagellin protein of motile bacteria </li></ul></ul><ul><ul><li>Zymosan from fungal cell wall </li></ul></ul><ul><ul><li>dsRNA </li></ul></ul><ul><ul><li>unmethylated CpG nucleotides </li></ul></ul>
  12. 12. Pathogen recognition <ul><li>PAMPs recognized by Toll-like receptors (TLRs) </li></ul>
  13. 13. Pathogen recognition <ul><li>PAMPs recognized by Toll-like receptors (TLRs) </li></ul><ul><ul><li>APCs: macrophages and dendritic cells </li></ul></ul><ul><ul><li>Signal transduction  expression of adhesion and costimulator molecules </li></ul></ul><ul><ul><li>Interaction with T H cell triggers immune-system activation </li></ul></ul>
  14. 14. Pathogen recognition <ul><li>Specific roles of TLRs in response to specific microbes have yet to be thoroughly studied </li></ul><ul><li>Understanding TLRs could lead to better vaccines… </li></ul>
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