Immune system, Organ Transplants and Blood

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: • Detection of the antigen activates T4 helper cell, which activate B cells • Activated B cells produce and secrete protein antibodies that bind to antigen • 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 forrapid 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 ofHLA 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 • IOIO Blood type 0 • IAIA Blood type A • IAIO Blood typeA (O recessive to A) • IBIB Blood type B • IBIO Blood type B (O recessive to B) • IAIB Blood type AB (A and B codominant)

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

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-CKR5gene, 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