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The Immune Response

The Immune Response. Outline. Introduction to Immune Response Innate Vs Acquired Immunity Cells and Organs of the Immune Response How Does it Work? Closing Comments. Introduction to the Immune Response. The central problem dealt with by the immune system is invasion by microbial

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The Immune Response

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  1. The Immune Response Outline Introduction to Immune Response Innate Vs Acquired Immunity Cells and Organs of the Immune Response How Does it Work? Closing Comments

  2. Introduction to the Immune Response The central problem dealt with by the immune system is invasion by microbial pathogens (the bad guys) The main task of the immune system is to distinguish self from non-self (good guys vs bad guys) It must not attack and destroy self, but must eliminate: 1. Whole organisms (bacteria and fungi, parasites, etc) 2. Intracellular pathogens (viruses)

  3. Innate VS Acquired Immunity Innate immunity Natural immunity, very old in evolution Anatomic barriers: skin- epidermis has keratin, low (acidic) pH, prevents bacterial growth mucous membranes- trap organisms Physiologic barriers: Temperature, pH, oxygen tension, soluble factors Soluble factors include: lysosyme- found in mucous, cleaves bacterial peptidoglycans interferons- antiviral effects, produced by infected cells complement- series of proteins, lead to bacterial lysis Innate immune cells eat and digest bad guys

  4. Acquired Immunity (Adaptive, Specific) Characterized by more rapid, stronger memory response (anamnestic) First appears in evolution in cartelagenous fishes (sharks, sting rays, etc) Can detect subtle changes in proteins, carbohydrates (sugars), and lipids This response is specific It must detect self versus non-self It must differentiate different forms of non-self (flu virus looks different than HIV) Antigen (Ag)- the molecule or structure against which the immune response is directed The immune response only sees bio-organic molecules (proteins, sugars, fats, etc) The antigenic universe is incredibly diverse This diversity must be overcome by the immune response

  5. Cells and Organs of the Immune Response

  6. The main Players in the acquired immune response Ag presenting cells (APC) Macrophages, dendritic cells *Digest Ag, display it for immune response *Activate T cells B cells. *Produce antibodies, soluble proteins that can attack Ag T cells: CD4 T cells ( Helper cells) *Help B cells and CD8 cells function CD8 T cells (cytotoxic cells) *kill virally infected cells and cancers

  7. Thymus = potential HIV infection

  8. Organs of the Immune System Most of the “action” in HIV disease Occurs in lymphoid tissues The gut is the first major site of T Cell destruction The bone marrow has blood-forming Stem cells, and makes B cells and Innate cells T cells are generated in the thymus Immune cells localize in these tissues and in lymph nodes

  9. Lymphatic System Fluid in blood leaks out of capillaries must be returned to circulation pressure in vessles too great to diffuse back Lymphoid system recovers fluid Picked up in capillary sinuses These coalesce into lymphatic vessels Form into larger ducts Fluid returned to subclavian vein Pumped by action of adjacent muscles Drains every part of body Lymph nodes screen for pathogens Nodes packed with leukocytes (lymphocytes, APCs, no granulocytes)

  10. How Does it Work?

  11. Generation of Diversity How can B and T cells make specific responses against so many different Ags? They express very diverse receptors for Ag on their surface 1. Multiple genes encoding different proteins with different specificities 2. Multiple gene segments which can differentially combine 3. Different junctional joining of gene segments, changing triplet codons (this would change the protein sequence) 4. Somatic mutation events (this also changes the protein sequence)

  12. B and T cells respond to Ag by proliferating and becoming active “effector” cells

  13. How do B and T cells work? (Disclaimer: It is not my fault, I did not design it this way!!) B cells see soluble (free) Ag Antibody (Ab) is released, binds Ag, removes it T cells need to see Ag on the surface of cells Pieces of Ag are “presented” in molecules called HLA molecules APC take up (eat/engulf) Ag Ag is digested (processed) Pieces of Ag get caught in HLA molecules, these go to the cell surface of the cell CD4 T cells see Ag in HLA-II molecules. They proliferate They secrete “helper factors” which help B cells and CD8 cells CD8 T cells see Ag in HLA-I molecules on infected cells They get help from CD4 T cells They proliferate They kill infected cells

  14. Closing Comments APCs, B cells, CD4 and CD8 T cells work together to fight infection HIV perturbs APC function, and kills CD4 T cells This allows secondary “opportunistic” infections to occur, leading to disease/death Vaccines have the potential to halt HIV infection, but thus far an efficacious vaccine strategy has proven elusive A vaccine approach that takes into account all aspects of the immune response will likely have the best chance of success

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