Transcript T4 helper cell

Blood Types, Organ Transplants,
and HIV
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
 Problems with immune system can cause
serious disorders
.
Central Points (2)
 Allergies are related to the immune system
 Many people carry organ donor cards to make
their wishes known
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: Immunologic memory
Animation: Inflammation
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
13.3 Blood Types
 Also determined by antigens on cell’s surface
 Humans > 30 different blood types
 Defined by presence of specific antigens on
surface of blood cells
 Serve as markers that identify “self ” to immune
system
Examples of Blood Types
 ABO system, important in blood transfusions
 Rh factor: plays role in hemolytic disease of
newborns (HDN)
ABO Blood Types
 Determined by gene I that encodes for cell
surface proteins, or antigens
 Three alleles: I A, I B, and I O
 A, B, and O encode for A antigens, B antigens,
or no antigen
 Able to produce antibodies against antigens you
do not carry
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)
Blood Types
Blood Transfusions
 ABO antigens of donor and recipient must match
 If mismatch, recipient’s immune system will
make antibodies against antigens
• Causes the blood cells from donor to clump
 AB blood type: universal recipients
 O blood type individuals: universal donors
Transfusion Reaction
 Clumped blood cells block circulation
 Reduce oxygen delivery, often fatal results
 Clumped blood cells can break down, release
large amounts of hemoglobin into blood
 Hemoglobin forms deposits in kidneys, can
cause kidney failure
Transfusion Reaction
Rh Factor
 Rh blood group (discovered in rhesus monkey)
has complex organization
• Rh positive (Rh+) carries Rh antigen
• Rh negative (Rh-) does not carry antigen
 Rh+ allele dominant to Rh- allele
 Rh positive blood type: Rh+Rh+ or Rh+Rh Rh negative blood type: Rh-Rh-
Rh Factor and Problems in Newborns (1)
 During pregnancy or childbirth, small number of
fetal cells may cross placenta, enter mother’s
bloodstream
 If mother is Rh- and fetus is Rh+, fetal cells placenta
stimulate production of antibodies against Rh+
antigen
 If first pregnancy, usually not harm either the fetus
or mother
Rh Factor and Problems in Newborns (2)
 During second Rh+ pregnancy, mother’s antibodies
cross placenta and destroy the fetus’ red blood
cells
 Hemolytic disease of newborns
 To prevent HDN, Rh- women given RhoGAM (Rh+
antibodies) during pregnancy
 Must be given before mother produces antibodies
against Rh+ antigen
Animation: Rh and pregnancy
HDN
13.4 HIV, AIDS, and Immune System
 Acquired immunodeficiency syndrome (AIDS):
a clinical disease
 Develops after infected with human
immunodeficiency virus (HIV)
 HIV infects and kills T4 helper cells
 T4 important for the onset of immune reaction and
body’s ability to recognize foreign bacteria or viruses
T4 Helper Cell Attacked by HIV (1)
 T4 recognizes antigen and activates production of
antibodies by B cells
 HIV, once inside cell, copies its genetic information
and inserts it into a chromosome in infected cell
 Viral genetic information can remain inactive for
months or years
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
Photomicrograph
of HIV
RNA
Drawing of HIV, showing
its RNA genome and the
proteins it carries.
Protein
Nucleus
Viral DNA
After HIV injects its RNA into the T cell, the
RNA is copied into DNA which is
then integrated into the T cell’s DNA.
The viral DNA makes new
viral RNA and proteins,
creating new virus particles
that bud off the surface of
the infected cell.
New virus
particles
Stepped Art
p. 213
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
Frequency of CC-CKR5 in Populations
 Mutant allele present only in Europeans and those
of European ancestry
 Highest frequency in northern Europe, lowest
frequency in Greece and Sardinia
 In past, may have offered resistance to an
unknown but deadly infectious disease
 Carriers of mutant CC-CKR5 allele lived to pass on
gene to offspring
Drugs to Treat HIV
 Current drugs prevent the virus from replicating
once it is inside T4 helper cells
 Other drugs block HIV at other stages of its
infection and reproduction cycle
 Combinations of these drugs successful in
slowing or stopping progress of HIV
 Serious side effects, drug-resistant strains of
HIV developed
AZT
Drugs to Prevent HIV from Entering Cell
 Studying the way HIV enters cells leading to new
generation of drugs
 Prevent entry of virus into its target cells
 Enfuvirtide: approved by FDA for clinical trials
 Other drugs under development
Animation: Proteins - as described
through HIV
Animation: HIV replication
13.5 Allergies and Immune System
 Allergies: immune system overreacts to
antigens
 Allergens: carried by dust, pollen, and certain
foods and medicines
 Serious food sensitivity: allergy to peanuts
 Reactions to peanuts, bee stings, or others may
cause anaphylactic shock
Anaphylactic Shock
 Bronchial tubes constrict, restricting air flow in the
lungs, making breathing difficult
 Heart arrhythmias and cardiac shock can
develop, death 1-2 minutes
 Treat with injectable epinephrine, counters
molecular events in immune response
 80% of cases due to peanut allergies
Peanut Allergy
Peanut Allergies Increasing in U.S. (1)
 1988–1994, 2X as prevalent as 1980–1984
 Why? Unclear, but environmental factors appear
to play major role
 Extremely rare in China, but Chinese immigrant
children about same frequency of peanut allergies
as native-born American children
• Suggests involvement of environmental factors
Peanut Allergies Increasing in U.S. (2)
 Peanuts now a major part of the diet in U.S.
 Exposure of newborns and young children to
peanuts more common, possibly breast milk
 Immune system of newborns immature, exposure
to some antigens may cause food allergies
 More study needed, some recommend that
pregnant and young children avoid nuts
13.6 Legal and Ethical Issues Associated
with Organ Donation
 Siblings are best donors, but they cannot always
consent, most require 18 years of age to consent
 If declared incompetent, next of kin may give
consent, extended to comatose or unconscious
 Important to inform family of wish to donate
 Laws make organ donation easier, organ donor
stickers or cards, some considering assumed
consent