1. Immune system, Organ Transplants and Blood Chapter 13

2. Central Points (1)  Genetics plays a part in the development of the immune system  Immune system compatibility is an important consideration in organ transplantation  Human blood types are inherited

3. Case A: Sister Wants to Donate Kidney  17-year-old Maria is healthy but has many family members with kidney disease  Her 15-year-old brother on list for transplant  Maria was tested, is a close match, and wants to donate a kidney  Father refuses to give permission

4. 13.1 What Does the Immune System Do?  Protects body from infection caused by bacteria, viruses, and other foreign invaders  Composed of chemicals and cells that attack and inactivate things that enter the body  First line of defense is the skin, blocks invaders  T cells and B cells: white blood cells, more specific forms of protection

5. Antigens (1)  Molecules are detected by immune system Trigger response usually involves several stages: 1.Detection of the antigen activates T4 helper cell, which activate B cells 2.Activated B cells produce and secrete protein antibodies that bind to antigen 3.White blood cells attack bacteria marked by antibodies

6. Antigens (2)  May enter body via blood transfusion, cut, or transplanted organ  May be attached to disease-causing agent such as a virus, bacteria, or fungus  Activated B cells produce specific antibodies Bind to an antigen Mark it for destruction by other cells Produce memory cells for rapid response on second exposure

7. Response to Infection

8. Animation: Immune responses

9. Vaccine  Memory cells basis of vaccination against infectious diseases  Contains an inactivated or weakened antigen from disease-causing agent  Does not cause an infection, stimulates immune system to produce antibodies and memory cells  Provides protection from disease

10. Several Gene Sets Control Immunity  Code for antibodies that attack antigens and antigens themselves Mutations can cause:  Diseases of immune system  Autoimmune disorders  Allergies

11. Animation: Understanding nonspecific defenses

12. 13.2 Transplantation of Organs or Tissues  Transplanted organ has different antigens, molecular identification tags  Coded by gene cluster, HLA complex  Haplotype: set of HLA alleles on each chromosome 6  Many alleles, combinations nearly endless, difficult to find two people with same HLA haplotypes

13. HLA Complex on Chromosome 6

14. Successful Transplants  Successful organ transplants, skin grafts, and blood transfusions depend on matches between the HLA  Many allele combinations, rarely have a perfect HLA match, often takes long time to find  HLA markers of donor and recipient analyzed, if least a 75% match, usually successful

15. First Transplant from Twin Brother  Genetically identical

16. Organ Rejection (1)  Can occur because mismatch of cell surface antigens  Can test HLA haplotypes of potential donor and match with recipient  After surgery, recipient takes immunosuppressive drugs, reduces possibility of rejection

17. Organ Rejection (2)  Cells of recipient’s immune system attack and rapidly destroy the transplanted organ  Patient will need another organ or will die  Closely matching HLA haplotypes absolutely necessary to ensure successful transplants  25% chance that sibling will match

18. Organ Waiting List  74,000 need kidney transplant  Only ~17,000 kidney transplants performed/year  Hundreds on waiting list die each year before receiving transplant  Estimated several thousand lives saved/year if enough donor organs were available

19. Animal Transplants  Animal donors would increase supply of organs for transplants  Xenotransplants, attempted many times, with little success  Problems related to rejection currently prevent use of animal organs

20. Pig-Human Transplants (1)  Surface proteins (antigens) of pig cells trigger hyperacute rejection, an immediate and massive immune response  Destroys transplanted organ within hours  Research to create transgenic pigs with human antigens on their cells  Transplants from genetically engineered pigs to monkey successful

21. Pig-Human Transplants (2)  Even if hyperacute rejection can be suppressed, transplanted pig organs may cause other problems  Requires high levels of immunosuppressive drugs, with many side effects and may be toxic over life- long use  Pig organs may carry viruses potentially dangerous to humans

22. Chimeric Immune System  Transplant bone marrow from a donor pig to human, make pig blood cells part of the human recipient’s immune system  Chimeric immune system: pig-human immune system  Recognize organ as “self” and still retain normal immunity to fight infectious diseases  Used in human-to-human heart transplants

23. Xenografts

24. Video: ABC News: Regenerative human organs

25. Video: ABC News: Second-chance heart

26. Summary of A, B, and O Blood Types

27. Inheritance of ABO  I O I O Blood type 0  I A I A Blood type A  I A I O Blood type A (O recessive to A)  I B I B Blood type B  I B I O Blood type B (O recessive to B)  I A I B Blood type AB (A and B codominant)

28. p. 212 Rh – Plus antigens enter the maternal circulation. Antibodies against the plus antigen attack and destroy fetal blood cells.

29. T4 Helper Cell Attacked by HIV (2)  When infected, T4 cell called upon to participate in an immune response Viral genes become active New viral particles formed in the cell Bud off the surface, rupturing, and killing it  Over the course of an HIV infection: Number of T4 helper cells gradually decreases Body loses its ability to fight infection

30. AIDS  Body loses its ability to fight infection  HIV infection disables immune system, AIDS causes death from infectious diseases  HIV transmitted through body fluids, including blood, semen, vaginal secretions, and breast milk  Not transmitted by food, water, or casual contact

31. Natural Resistance to HIV  Some individuals with high-risk behaviors, did not become infected with HIV  Homozygous for mutant allele of CC-CKR5 gene, encodes a protein that signals infection present  HIV uses CC-CKR5 to infect T4 helper cells  Mutation has small deletion (32 base pairs), protein shorter, HIV cannot use this protein to infect