Lecture #12 – Animal Immune Systems

1. Lecture #12 – Animal Immune Systems

2. Key Concepts: • Innate immunity provides broad-spectrum defense against many pathogens • Acquired immunity is very specific, develops over time, and relies on B and T cells • Antigen recognition properties of B and T cells • B and T cell binding sites develop randomly! • Integrated B and T cell function • When the immune system goes wrong…

3. Some definitions…. Generates Pathology • Pathogen = anything that causes disease • Microbes (bacteria, protozoans), viruses, fungal spores, pollen, dust mites, etc • Secretions (venoms, animal saliva) • Non-self tissue cells (transplant rejections) • Some cancer cells • Antigens = cell surface proteins and other molecules that the body recognizes as non-self Generates Antibodies Pathogens have Antigens

4. The immune system is spread diffusely throughout the body – a system of organs, nodes and lymph vessels Schematic of the human immune system

5. Remember, the white blood cells are the defenders Diagram of the blood cells

6. Some WBC’s circulate though the lymph, the blood and the interstitial fluidSome are permanently housed in lymph nodes, thymus gland, spleen, appendix and a few other glands

7. Defense is step-wise • 90% of pathogens are neutralized by innate immunity • Multiple strategies to destroy pathogens • Any remaining pathogens are normally attacked by the acquired immune system Table showing the stages of defense

8. Innate Immunity – you are born with it • Pathogens are ubiquitous • Innate immunity includes both external and internal systems to eliminate pathogens • Any and all pathogens are targeted • This system does not recognize specific pathogens – it goes after any non-self cell

9. Innate Immunity – external defenses • Skin – important barrier, acids • Mucous membranes – trap, cilia evacuate • Secretions – both skin and mucous secrete anti-microbial proteins; stomach secretes acids Sweeping cilia in trachea

10. Innate Immunity – internal defenses • Sometimes pathogens get past the barriers and into the tissues • Non-specific WBC’s attack • Neutrophils • Monocytes  macrophages • Dendritic cells • Eosinophils • Basophils

11. Innate Immunity – internal defenses • Phagocytic WBC’s cells ingest and destroy microbes in the tissues • Neutrophils – the most abundant, but short-lived • Macrophages develop from monocytes – large and long-lived • Dendritic cells – mostly function to stimulate the acquired immune system

12. Model of a macrophage ingesting a fungal spore

13. Micrograph of macrophage ingesting bacteria

14. Innate Immunity – internal defenses • Eosinophils destroy multi-cellular parasites by releasing toxic enzymes • Also contribute to allergic responses • Basophils contribute to inflammatory and allergic responses Schistosoma mansoni

15. Additional Internal Defenses • Antimicrobial proteins • Lysosymes work in macrophages; also found in saliva, tears and mucous • Complement proteins result in lysis; also help trigger inflammation and activate acquired immunity • Interferons limit intra-cellular spread of viruses • Defensins are secreted by macrophages, attack pathogens • Natural killer cells attack virus-infected cells and cancer cells • The inflammatory response

16. Complement Protein Function:these proteins complement other immune system processes Diagram showing complement protein function

17. Additional Internal Defenses • Antimicrobial proteins • Lysosymes work in macrophages; also found in saliva, tears and mucous • Complement proteins result in lysis; also help trigger inflammation and activate acquired immunity • Interferons limit intra-cellular spread of viruses • Defensins are secreted by macrophages, attack pathogens • Natural killer cells attack virus-infected cells and cancer cells • The inflammatory response

18. Interferons initiate production of proteins that inhibit viral reproduction Diagram of interferon activity

19. Additional Internal Defenses • Antimicrobial proteins • Lysosymes work in macrophages; also found in saliva, tears and mucous • Complement proteins result in lysis; also help trigger inflammation and activate acquired immunity • Interferons limit intra-cellular spread of viruses • Defensins are secreted by macrophages, attack pathogens • Natural killer cells attack virus-infected cells and cancer cells • The inflammatory response

20. Additional Internal Defenses • Antimicrobial proteins • Lysosymes work in macrophages; also found in saliva, tears and mucous • Complement proteins result in lysis; also help trigger inflammation and activate acquired immunity • Interferons limit intra-cellular spread of viruses • Defensins are secreted by macrophages, attack pathogens • Natural killer cells attack virus-infected cells and cancer cells • The inflammatory response

21. A natural killer cell (yellow) attacking a cancer cell (red).

22. Additional Internal Defenses • Antimicrobial proteins • Lysosymes work in macrophages; also found in saliva, tears and mucous • Complement proteins result in lysis; also help trigger inflammation and activate acquired immunity • Interferons limit intra-cellular spread of viruses • Defensins are secreted by macrophages, attack pathogens • Natural killer cells attack virus-infected cells and cancer cells • The inflammatory response

23. The Inflammatory Response • Usually localized, in response to tissue injury • Cascade of events • May also be systemic – increased WBC release from bone marrow; fever Diagram of the inflammatory response

24. Invertebrates Also Have InnateDefense Systems • Amoeboid cells ingest by phagocytosis in echinoderms • Insect exoskeleton acts as a barrier similar to skin • Hemocytes in insect hemolymph function similarly to vertebrate innate internal defenses • Research indicates little immune system memory • Little capacity for acquired immunity as seen in vertebrates

25. Defense is step-wise • 90% of pathogens are neutralized by innate immunity – both external and internal • Any remaining pathogens are normally attacked by the acquired immune system

26. Acquired Immunity • Develops over time, in response to exposure to pathogens • Highly specific – lymphocytes develop that match each incoming pathogen • B cells and T cells • Circulate in tissues; some are also permanently located in lymph nodes, the spleen and other lymph system structures • Pathogen contact with lymphocytes, phagocytes, and other triggers initiates rapid immune responses

27. Remember – the lymph system is closely tied to the circulatory system • Lymph vessels absorb excess fluids in capillary beds • Pathogens in the blood are rapidly exposed to the phagocytes and lymphocytes in the lymph system • Every heart beat pushes blood, and any pathogens it carries, past the immune system structures

28. The next 3 slides show the relationship between the capillary beds and the lymph vessels

31. Remember – the lymph system is closely tied to the circulatory system • Lymph vessels absorb excess fluids in capillary beds • Pathogens in the blood are rapidly exposed to the phagocytes and lymphocytes in the lymph system • Every heart beat pushes blood, and any pathogens it carries, past the immune system structures

32. Antigen Recognition • Remember, antigens are the non-self molecules that initiate the immune response • Mostly cell surface proteins, other cell surface molecules, or toxins dissolved in fluid (venoms and other secretions) • Most pathogens have several different kinds of antigens • Because of this, there are usually several different lymphocytes that recognize and respond to the pathogen • Antigens have specific binding sites = epitopes

33. Membranes are complex, with many surface molecules Diagram showing structure of the cell membrane

34. Antigen Recognition • Remember, antigens are the non-self molecules that initiate the immune response • Mostly cell surface proteins, other cell surface molecules, or toxins dissolved in fluid (venoms and other secretions) • Most pathogens have several different kinds of antigens • Because of this, there are usually several different lymphocytes that recognize and respond to the pathogen • Antigens have specific binding sites = epitopes

35. Epitopes are the specific binding sites found on all antigens Diagram showing epitope structure

36. Lymphocytes – B and T Cells • Remember, lymphocytes are one of the categories of white blood cells • Each B or T cell has ~100,000 antigen receptors – all of the exact same type • Each B or T cell recognizes a single epitope • The receptor molecules and recognition process are different for B cells vs. T cells • Both types of receptors are protein-based • Both have both constant and variable regions

38. Lymphocytes – B and T Cells • Remember, lymphocytes are one of the categories of white blood cells • Each B or T cell has ~100,000 antigen receptors – all of the exact same type • Each B or T cell recognizes a single epitope • The receptor molecules and recognition process are different for B cells vs. T cells • Both types of receptors are protein-based • Both have both constant and variable regions

39. Constant regions have stable amino acid sequences from cell to cell;Variable regions have different amino acid sequences from cell to cell Diagram showing the receptor molecules in B cells and T cells. This diagram is used several times in the next sequence of slides.

40. Antigen Recognition – B Cells • B cell receptors are Y-shaped • Each branch of the “Y” has 2 parts, called chains • Inner, heavy chain makes the full “Y” • Outer, light chain is located on the branches of the “Y” • Both chains are proteins • Chains are linked by chemical bonds • The bottom of the “Y” is anchored in the B cell membrane

41. B Cell Receptor Structure

42. The protein structure of a B cell receptor

43. Antigen Recognition – B Cells • The bottom regions of both chains have constant amino acid sequences • The outer branches of both chains, have variable amino acid sequences • These variable ends are the antigen binding sites • They bind directly to the epitopes • B cells recognize unaltered antigens!

44. B Cell Receptor Structure

45. Antigen Recognition – T Cells • T cell receptors are unbranched • α chain and β chain are chemically linked • Both are anchored in the membrane • Both have basal constant regions and terminal variable regions • A single antigen binding site is at the terminus

47. T Cells DO NOT recognize intact antigens on intact pathogens • T cells recognize antigen fragments that have been bound to a self-cell protein called an MHC molecule • MHC  major histocompatibility complex of genes codes for these molecules • MHC molecules bind to antigen fragments inside a self-cell, and present the fragments at the surface of the cell • T cells detect the presented antigen+MHC complex

48. MHC – self-cell proteins Diagram showing the production of MHC molecules, how they become attached to antigen fragments, and how the complex is presented at the cell surface. This diagram is used repeatedly in the next sequence of slides.

49. T Cells DO NOT recognize intact antigens on intact pathogens • T cells recognize antigen fragments that have been bound to a self-cell protein called an MHC molecule • MHC  major histocompatibility complex of genes codes for these molecules • MHC molecules bind to antigen fragments inside a self-cell, and present the fragments at the surface of the cell • T cells detect the presented antigen+MHC complex

50. Development of MHC Variation • MHC alleles are numerous • Many more than just the 2 alleles common for most genes (ie: not just dominant vs. recessive) • As a result, MHC molecules are the most polymorphic proteins known • Almost all antigens are recognized • Also, because of the high degree of variation, it is very rare for any two individuals to have the exact same set of MHC molecules • MHC molecules are unique to the “self” • Help to distinguish “self” from “non-self” cells