Immunobiology

1. Immunobiology Dr. Ronald Smeltz rbsmeltz@vcu.edu

2. MICR 505 Course Director: Dr. Daniel Conrad dconrad@vcu.edu Required textbook: Immunobiology: The Immune System in Health & Disease 7th ed by Janeway et al.

3. MICR 505 course guidelines • Website for course is http://www.courses.vcu.edu/micr505/ • Syllabi as pdf files are on website as well as the lecture schedule. Powerpoint files for lectures are on the site and any outside reading unless told otherwise. Syllabi pdf and ppt files can be updated up to lecture time, so check (refresh) frequently. • Syllabi pdf, ppts and outside reading are under “lecture notes” heading. • Assigned Readings from textbook are listed on individual syllabi.

4. MICR 505 course guidelines

5. Course guidelines • Check website often for announcements & updates • Four non-cumulative exams. Exam schedule is on website. • Exams have a three-hour time limit. Exam style is essay – One question per lecture with (usually) 10 questions of which the two lowest scores will be dropped. • Last year's four exams are on website under “exams” – Use these as study guides.

6. The Mona Lisa of Immunology (III_7_1_T cell development movie)

7. Functions of Immune System • Elimination of anything that is non-self (ie. foreign) from the body • Pathogens, tissue/organ transplants • Concept of self/non-self discrimination (central tolerance) • Limiting harm caused by non-self which may not be eliminated from the body • Opportunistic pathogens • Surveillance and removal of “abnormal self” • Tumors • Wound healing • Bruises, cuts, bites & burns

8. General Concepts • Immunity is the ability to resist infection • Antigen is any substance capable of causing an immune response. • Immune system normally responds to non-self antigens, but maintains tolerance to self antigens. • All types of immunity participate in destroying or eliminating antigen from body. • Immune responses are not always beneficial and can cause tissue damage or death (breakdown in tolerance) • There are temporal, quantitative, and qualitative aspects to immunity

9. Temporal aspects of immunity

10. Quantitiative aspects of immunity

11. Qualitative aspects of immunity

12. Immunization leads to immunity • Immunization- deliberate induction of an adaptive immune response • Passive - Transfer of specific immunity from immunized person to non-immune person • Transfer of serum (ie. antibody) or cells • Immediate but short-term protection • Mainly used in life-threatening situations (anti-venom) • Natural form: Maternal antibodies in newborns • Active - Normal development of acquired immunity in the non-immune host- requires introduction of antigen • Delayed onset & long-term protection • Basis for vaccinations

13. The pathogenic challenges we face

14. How do pathogens get in?

15. Lymphoid tissues of the immune system Know your node!

16. Lymphoid tissues of the immune system

17. Cells of the immune system

18. Cooperation between cells results in an effective immune response • Cell-cell contact • Adhesion molecules • 2. Cytokines • Chemokines

19. Blood vessel Tissue Cells of the immune system must traffic and enter non-lymphoid tissues and organs

20. Cell migration into tissues

21. Overview: Bringing together pathogens and the immune system (IV_10_1_The Immune Response movie)

22. (adaptive) Not antigen-specific Antigen-specific

23. Innate or Natural Immunity • Defense mechanisms existing before antigen exposure • Rapid onset • Does not distinguish among antigens • Not antigen specific • No enhanced response on second antigen exposure • No memory! • Promotes initiation of acquired responses • Antigen presenting cells (APC) • Physical/mechanical/chemical barriers, inflammation, & natural killer (NK) cells

24. Inflammation

25. Acquired or Adaptive Immunity • Defense mechanisms stimulated or induced by antigen exposure • Delayed onset • Distinguishes among antigens • Antigen specific • Enhanced responses upon re-exposure to antigen • Memory! • May enhance innate immune responses • Lymphocytes & antibodies

26. Antigen transported to lymph node where acquired response starts

27. Types of acquired/adaptive immunity • Humoral- Major component in plasma or serum of blood • Proteins called antibodies are specific for antigen • Function to eliminate antigens • Important for extracellular pathogens • Cell-Mediated - Major component: lymphocytes specific for antigen • Kill infected cells & produce cytokines • Cannot be adoptively transferred with serum • Important for intracellular pathogens

28. Outcome Humoral CMI CMI Acquired/adaptive immunity driven by T cell subsets

29. Characteristics of acquired/adaptive immunity • ExquisiteSpecificity - Due to variable regions of antigen receptors expressed by B & T cells • HugeDiversity - Due to huge number of different antigen receptors of B & T cells • Regulation - Immune responses are self-limiting and stop • DistinguishesSelf vs. Non-Self - Tolerance to self antigens • Memory - Enhanced immune response on second exposure to antigen

30. Immune responses are not always beneficial

31. Vaccination • Concept: Immune response can be specifically manipulated, so the memory adaptive response will prevent a specific infectious disease. • Name comes from Vaccinia – the virus family that causes smallpox. • Countless lives have been saved as a result of vaccination.

32. Most important Medical Advance % of votes • Sanitation – clean water/sewage disposal • Antibiotics • Anesthesia • Vaccines 15.8 14.5 13.9 11.9

34. On May 14, 1796, Sarah Nelmes, a milkmaid, came to Jenner with cowpox. He devised a brave and dangerous experiment. He passed on the cowpox disease to James Phipps, his gardener's son, by scratching the boy's skin with infected metal (vaccination). When James recovered from cowpox, Jenner tried to give him smallpox. James failed to contract the smallpox disease.

38. Clonal selection: the foundation for adaptive immunity

39. Clonal selection: the foundation for adaptive immunity

40. Clonal selection: the foundation for adaptive immunity