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Blood Types, Organ Transplants, and HIV

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1 Blood Types, Organ Transplants, and HIV
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 Problems with immune system can cause serious disorders .

3 Central Points (2) Allergies are related to the immune system
Many people carry organ donor cards to make their wishes known

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 for rapid 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: Immunologic memory

12 Animation: Inflammation

13 Animation: Understanding nonspecific defenses

14 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

15 HLA Complex on Chromosome 6

16 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

17 First Transplant from Twin Brother
Genetically identical

18 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

19 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

20 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

21 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

22 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

23 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

24 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

25 Xenografts

26 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

27 Examples of Blood Types
ABO system, important in blood transfusions Rh factor: plays role in hemolytic disease of newborns (HDN)

28 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

29 Summary of A, B, and O Blood Types

30 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)

31 Blood Types

32 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

33 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

34 Transfusion Reaction

35 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-

36 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

37 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

38 Animation: Rh and pregnancy

39 HDN

40 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

41 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

42 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

43 then integrated into the T cell’s DNA.
Photomicrograph of HIV RNA Protein Drawing of HIV, showing its RNA genome and the proteins it carries. 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. Photomicrograph of HIV. New virus particles The viral DNA makes new viral RNA and proteins, creating new virus particles that bud off the surface of the infected cell. Stepped Art p. 213

44 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

45 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

46 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

47 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

48 AZT

49 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

50 Animation: Proteins - as described through HIV

51 Animation: HIV replication

52 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

53 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

54 Peanut Allergy

55 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

56 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

57 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

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