B cells

Immune system, Organ Transplants and Blood Chapter 13

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

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

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

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

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

Response to Infection

Animation: Immune responses

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

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

Animation: Understanding nonspecific defenses

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

HLA Complex on Chromosome 6

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

First Transplant from Twin Brother  Genetically identical

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

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

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

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

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

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 lifelong use

 Pig organs may carry viruses potentially dangerous to humans

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

Xenografts

Video: ABC News: Regenerative human organs

Video: ABC News: Second-chance heart

Summary of A, B, and O Blood Types

Inheritance of ABO  IOIO

Blood type 0

 IAIA  IAIO

Blood type A Blood type A (O recessive to A)

 IBIB  IB IO

Blood type B Blood type B (O recessive to B)

 IAIB

Blood type AB (A and B codominant)

Rh–

Plus antigens enter the maternal circulation.

Rh–

Antibodies against the plus antigen attack and destroy fetal blood cells. p. 212

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

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

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