1. The Immune System

2. Learning Objectives The need for an immune system- Distinguishing Self vs. Non-self Evolutionary trends in immune systems Non specific chemical defenses – Invertebrates – Vertebrates Mammals have specific immune responses – Pattern recognition by Toll like receptors – Cell mediated immune responses by T cytotoxic cells – Humoral response by B lymphocytes

3. The need for an immune system: Distinguishing Self vs. non-self The ability to distinguish self from other is seen in simple animals such as sponges and corals. This could have evolved from the prerequisite ability to attach specifically to “self” cells. Self Other

4. Evolutionary Trends in Immune Systems Taxonomic Group Innate nonspecific immunity Adaptive immunity Invasion induced protective enzymes PhagocytosisAntimicrobial proteins Pattern recognition receptors Graft Rejection T and B cells Antibodies Higher plants + - + - ++ --- Invertebrate animals Porifera (sponges) + - ?+??+ -- Annelids (earthworms) + - ?+??+ -- Arthropods (Insects, crustaceans) + - ++++? -- Vertebrate animals Cartilaginous fish +++++++++ Bony Fish +++++++++ Amphibians +++++++++ Reptiles ++++?++++ Birds ++++?++++ Mammals +++++++++

5. Non Specific Chemical Defenses Invasion induced protective enzymes – Some version of this defense is used by plants, arthropods, and vertebrates – Vertebrates produce the enzyme Lysozyme that digests bacterial cell walls.

6. Non Specific Chemical Defenses The Complement Proteins are antimicrobial proteins. – Present in the blood serum but inactive – Activated by microbial particles (e.g. bacterial cell wall molecules) – When activated bind to the microbe and enhance opsonization. – Form the membrane attack complex puncturing the microbe.

7. Mammals have Specific Immune Responses Mammalian B and T lymphocytes: – Respond to specific pathogens – Can remember and respond quickly if the same pathogen is encountered

8. Pattern Recognition Receptors Versions of this are seen in plants, arthropods and vertebrates Mammals have Toll Like receptors that recognize specific pathogen molecular patterns(PAMPs). Activation of toll like receptor increases expression of immune related genes. These are innate proteins: not adaptive and do not have “memory” like T cell receptors and B Cell antibodies

9. Toll Like receptors recognize pathogen specific molecules and allow phagocytes such as macrophages to detect and eliminate infection.

10. Cell Mediated: Phagocytes Humoral: Antibodies produced by B cells CELL MEDIATED HUMORAL

11. Cell mediated and humoral immune responses are specific and have memory Each B and T lymphocytes produces a receptor that has a conserved membrane region and a variable unique antigen binding domain Different variable regions are produced by gene rearrangement. Both B and T cell receptors are Tyrosine Kinases… so when they are activated by binding to antigen they initiate a signaling cascade that will change protein activity and change gene expression, and affect the cell cycle.

12. Clone Selection of B or T cells B and T cells are activated by specific antigens binding to their receptor. The selected “Clone” of B or T cells begins to divide and produce more of the same clone. After the infection is eliminated most of the clones die, however a few remain alive as memory cells. Memory cells respond to infection more rapidly.

13. Cell mediated Immune Responses T helper cells recognize exogenous pathogens T cytotoxic cells recognize endogenous pathogens

14. Mammals use the MHC proteins to distinguish self from other MHC Class I receptors are present on all cells and present endogenous antigen to T cytotoxic cells MHC class II receptors are present only on “Antigen presenting” immune cells (Macrophages and B Cells) and present exogenous antigen to T helper cells. Endogenous Antigen Exogenous Antigen

15. Humoral Response B cell receptors are membrane bound antibodies B cells are activated by exposure to antigen and signaling by T helper cells When B lymphocytes are activated they produce and secrete antibodies into the blood.

16. How Antibodies help clear infection Antibodies assist in agglutination and opsonization.

17. Immune System Memory: A small number of the clone of B and T cells that respond to the antigen on the first exposure remain alive and circulate throughout the body Memory cells are able to respond more quickly to the same antigen on the second exposure.