Download Chimeric Immune System

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