Blood Types, Organ Transplants, and HIV Chapter 13.

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

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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 life-long 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

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)

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

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Stepped Art

Photomicrographof HIV

RNA

Protein

Drawing of HIV, showingits RNA genome and theproteins it carries.

Nucleus

Viral DNA

After HIV injects its RNA into the T cell, the RNA is copied into DNA which isthen integrated into the T cell’s DNA.

New virus particles

The viral DNA makes newviral RNA and proteins,creating new virus particlesthat bud off the surface ofthe infected cell.

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