1. 1

2. Foreign versus Self
Immune system protects organisms from foreign invaders
Protection from harmful organisms (pathogens) is based upon the ability to identify foreign molecules as “nonself”
Foreign may be bacteria, viruses, fungi, tumor, or transplanted cells
Molecules recognized by the immune system are called antigens and are usually protein fragments or carbohydrates 2

3. Foreign versus Self
Figure 17.1
Figure 1
Reading 17.1 3

4. Genetic Control of Immunity
Genes affect immunity by conferring susceptibility or resistance to infection
A few types of single genes encode antibodies and cytokines that directly attack foreign antigens
Genes also specify the cell surface antigens that mark the body’s cells as “self” 4

5. Genetic Control of Immunity
Understanding how genes control immunity makes it possible to enhance or redirect the system’s ability to fight disease
Mutations can impair immunity causing:
- Immune deficiencies
- Autoimmune disorders
- Allergies
- Cancer 5

6. The Human Immune System
A network of vessels called lymphatics and bean-shaped structures called lymph nodes
Lymph is the fluid filling the lymph ducts
- Carries macrophages and B- and T-lymphocytes
Organs involved in production or maturation of immune cells
- Spleen and Thymus
- Bone marrow 6

7. Figure 17.3

8. Immunity
The immune response attacks pathogens, cancer cells and transplanted cells with two lines of defense
- Innate immunity is immediate and generalized
- Adaptive immunity is specific and slower
These act after various physical barriers block pathogens 8

9. Levels of Protection
Figure 17.4
Figure 17.7

10. Physical Barriers The first line of defense Examples include:
- Unbroken skin
- Mucous membranes and secretions
- Waving cilia of the respiratory tract
- Flushing effect of tears, saliva, urination, and diarrhea
All of these are non-specific defenses 10

11. Innate Immune Response
General defenses found in the body
If pathogen breaches physical barriers produces a rapid broad response
Response time is in minutes
A central part is inflammation
- A process that creates a hostile environment for pathogens
- Sends in phagocytes that engulf and destroy pathogens via phagocytosis 11

12. Innate Immune Response
Figure 17.5 12

13. Innate Immune Response
Collectins
Cytokines
- Interferon = Anti-viral
- Interleukins = Fever-inducing
- Tumor necrosis factor a = Anti-cancer
Cytokines also play a role in adaptive immunity 13

14. Innate Immune Response
Complement
- Plasma proteins that assist or complement other defense responses
- Roles of complement proteins include:
- Puncture bacterial cells
- Dismantle viruses
- Trigger histamine release to dilate blood vessels
- Attract phagocytes 14

15. Adaptive Immunity Requires stimulation Response time is in days
Has three basic characteristics:
- Diversity: many different pathogens recognized
- Specificity: distinguishes particular molecules
- Memory: responds faster with subsequent exposure
- Primary immune response: reaction to first exposure
- Secondary immune response: reaction to exposure using “memory” of first response 15

16. Table 17.4

17. Abnormal Immunity
Immune system malfunction may be inherited or acquired
In addition, immunity may be too weak, too strong, or misdirected
Abnormal immune responses may be multifactorial or caused by a mutation in a single gene

18. Inherited Immune Deficiencies
At least 20 types
Affect innate and adaptive immunity
Examples
- Chronic granulomatous disease: Mutation of oxidase enzyme results in neutrophils that cannot kill bacteria
- Severe combined immune deficiency (SCID): Impacts both humoral and cellular immunity due to lack of mature B cells and/or T cells

19. Inherited Immune Deficiencies
David Vetter had an autosomal recessive form of SCID
- He was born without a thymus gland
- His T cells could not mature and activate B cells
Figure 17.11

20. Table 17.5

21. Human Immunodeficiency Virus (HIV)
An infectious virus enters the body with direct contact of bodily fluids
Infects macrophages, and later, helper T cells
Virus replicates and bursts out of the helper T cell, killing it
Loss of helper T-cells prevents B-cell activation
Infections occur because the immune system not functional
Replicates rapidly, mutates easily, and can hide

22. Acquired Immune Deficiency Syndrome (AIDS)
The disease resulting from HIV infection
The immune system impact of HIV infection has progressed to impairment of immune function
Due to genetically diverse population of HIV in a human host, treatment requires combination of medication with different actions
Drugs block/inhibit different points of infection
- Entry of virus into T cells
- Replication of viral genetic material
- Processing of viral proteins

23. Autoimmunity
Immune system attacks the tissues of an individual’s own body
Autoantibodies recognize “self” proteins
About 5% of the population has an autoimmune disorder
The signs and symptoms reflect the cell types under attack

24. 24

25. Allergy
Immune response to a non-threatening foreign substance called an allergen
Size of allergens may determine type of allergic response
- Larger (e.g., grass pollen) produces hay fever
- Smaller (e.g., cat dander, dust mites) trigger asthma
Asthma is a chronic disease
- Contraction of the airways, inflammation and mucus production block air flow

26. Allergic Response
Severe allergic reaction throughout the body is called anaphylatic shock

27. Vaccination
A vaccine uses antigens from a pathogen to invoke immunity before an individual has been exposed to the pathogen
Antigens are chosen to be harmless alone
Ability to respond rapidly to subsequent exposure prevents infection to a degree that would cause disease
Vaccine technology dates back to 11th century China
Edward Jenner used cowpox as a vaccine for smallpox

28. Vaccination Smallpox has not naturally infected a human since 1977
- So vaccination are now unnecessary
Figure 17.15

29. Uses of Monoclonal Antibodies
Basic research and disease diagnosis
Home pregnancy test strips
- Contain anti-hCG monoclonal antibody
- If hCG is present in the urine it binds and changes the color of the test strip
Herceptin
- A monoclonal antibody-based drug
- Blocks receptors on breast cancer cells
- Prevents reception of cell-division signal

30. Transplantation Organs are moved from one individual to another
Hearts, kidneys, livers, lungs, corneas, pancreases, skin, and bone marrow are routinely transplanted
- Sometimes, several organs at a time
Today, thousands of transplants are performed annually and recipients gain years of life
Successful transplants lie in genetics

31. Transplantation
Types of transplantation are defined by the relationship between the donor and recipient:
- Autograft: from one person to self
- Isograft: from identical twin
- Allograft: members of same species
- Xenograft: from another species

32. Transplantation
Figure 17.21
Figure 17.17

33. Graft Rejection
The immune system reacts to grafted tissue recognized as foreign by trying to destroy it
Hyperacute rejection reaction
- A severe form of graft reaction in which the blood supply to the graft tissue is cut off
Graft versus host disease
- Occurs in bone marrow transplants
- Immune cells of the grafted bone marrow recognize host body as foreign and attack it

34. Genomic View of Immunity
Sequencing genomes of pathogens
- Can help us understand how they infect, and aid in development of treatments
Crowd diseases
- Spread rapidly through unexposed populations
- Examples: smallpox, measles, pertussis, typhus, influenza, and SARS
Bioweapons
- Bacteria and viruses have been used throughout history as weapons
- In their natural state or genetically-manipulated

35. Introduction Cancer has been part of human existence for eons
By 300 B.C., Hippocrates coined the term “cancer” to describe the crablike shape of a tumor invading normal tissue
Cancer has or will affect one in three of us
Diagnosis and treatment are becoming increasingly individualized 35

36. Introduction Cancer is genetic, but is not usually inherited
Carcinogens are substances that cause cancer
- Most are mutagens (damage DNA)
Cancer is a group of diseases caused by loss of cell cycle control
- If a cell escapes normal control over its division rate, it forms a growth called a tumor 36

37. Figure 18.1 37

38. Introduction
A tumor is benign if it does not spread or “invade” surrounding tissue
A tumor is cancerous or malignant if it infiltrates nearby tissues
Metastasis
- The tumor spreads to other parts of the body via the blood or lymph vessels 38

39. Cancer-Causing Genes Oncogenes - More than 100
- Cause cancer if inappropriately activated
Tumor suppressor genes
- More than 30
- Deletion or inactivation causes cancer
- Cell cycle control/checkpoints
In addition, changes in gene expression accompany cancer 39

40. Cell Cycle Control
Timing, rate, and number of cell divisions depend on:
- Protein growth factors
- Signaling molecules from outside the cell
- Transcription factors within
Checkpoints control the cell cycle
- Ensure that mitotic events occur in the correct sequence 40

41. Cell Cycle Control
Figure 18.2 41

42. Loss of Cell Cycle Control
Many types of cancer result from faulty check points
Cancer sends a cell down a pathway of unrestricted cell division
Cancer cells either lose specializations or never specialize 42

43. Figure 18.3 43

44. Telomeres and Telomerase
Loss of control of telomere length may also contribute to cancer
Telomerase is the enzyme (complex of RNA and protein) that adds telomere sequences to the ends of chromosomes
Normal, specialized cells have telomerase turned off, limits cell division
Cancer cells have to express telomerase to be able to divide indefinitely 44

45. Inherited vs. Sporadic Cancer
Somatic mutations
- Occur sporadically in nonsex cells
- Result from a single dominant mutation or two recessive mutations in the same gene
- Cancer susceptibility not passed on to offspring
Germline mutations
- Cancer susceptibility passed on to offspring
- Usually requires second somatic mutation
- Rarer but strike earlier than sporadic cancers 45

46. Inherited vs. Sporadic Cancer
Figure 18.4 46

47. Origin of Cancer Cancer begins at the genetic and cellular levels
If not halted, cancer spreads through tissues to take over organs and organ systems
The origin and spread of cancer are summarized next 47

48. Figure 18.5 48

49. 49

50. Origins of Cancer Cells
Cancer can begin at the cellular level in at least four ways:
- Activation of stem cells that produce cancer cells
- Dedifferentiation
- Increase in proportion of a tissue that consists of stem cells or progenitor cells
- Faulty tissue repair 50

51. Figure 18.8 51

52. Uncontrolled Tissue Repair May Cause Cancer
Figure 18.11 52

53. Oncogenes
Proto-oncogenes are normal versions of genes that promote cell division
Expression at the wrong time or in the wrong cell type leads to cell division and cancer
Proto-oncogenes are called oncogenes in their mutated form
One copy of an oncogenic mutation is sufficient to promote cell division 53

54. Oncogenes: Overexpression of a Normal Function
Viruses integrated next to a proto-oncogene can cause transcription when the virus is transcribed
Moving a proto-oncogene next to a highly transcribed gene can lead to overexpression of the proto-oncogene
Example: Burkitt lymphoma
- A translocation places a proto-oncogene next to an antibody gene 54

55. Oncogenes: Overexpression of a Normal Function
Chromosome 14
Chromosome 8
Figure 18.12 55

56. Breast Cancer Two main forms
- Familial form: A germline mutation is inherited and then a somatic mutation occurs in a breast cell
- Sporadic form: Two somatic mutations affect the same cell
Mutations in many genes can cause cancer 56

57. BRCA
The two major breast-cancer susceptibility genes are BRCA1 and BRCA2
- Encode proteins that join two others to form a complex that allows repair of double-stranded DNA breaks
Mutations in these genes have different incidences in different populations
Inheriting BRCA mutations increases the risk of other types of cancer 57

58. Other Genes
Genes whose protein products affect those of BRCA1, BRCA2, and p53 can cause breast cancer
Example: The ATM gene product adds a phosphate to the CHEK2 gene product, which then adds a phosphate to the BRCA1 protein
- Mutations in ATM and CHEK2 can cause breast cancer 58

59. Familial Adenomatous Polyposis (FAP)
5% of colon cancer cases are inherited
1 in 5000 in U.S. has FAP
Causes multiple polyps at an early age
Several mutations contribute
- APC genes mutate
- Activation of oncogenes (E.g. K-Ras)
- Mutations in TGF, p53, and other genes
- PRL-3 triggers metastasis
- Caretaker genes cause genomic instability 59

60. Familial Adenomatous Polyposis (FAP)
Figure 18.14 60

61. The Cancer Genome
Several large-scale projects are analyzing genomes of cancer cells
- These allow construction of descriptive “atlases” containing different types of information
Many mutations accompany cancer, but they interact in only a few pathways
- Once a pathway is implicated, scientists can look for or develop drugs to target it 61

62. Environmental Causes of Cancer
Environmental factors contribute to cancer by mutating or altering the expression of genes that control the cell cycle, apoptosis, and DNA repair
Inheriting a susceptibility gene places a person farther along the road to cancer
- However, cancer can happen in somatic cells in anyone

63. Environmental Causes of Cancer
Individuals can lower the chance of developing cancer by:
- Avoiding high-risk environmental factors, such as smoking and excess sun exposure
- Taking “chemopreventative” nutrients such as folic acid and vitamin D

64. Cruciferous Vegetables Can Lower Cancer Risk
Figure 18.15

65. Methods to Study Cancer-Environment Links
Population Study: Compares incidence of a type of cancer among different groups of people
Case Control: Identify differences between patients with a type of cancer and healthy individuals matched for multiple characteristics
Prospective Studies: Two or more groups of individuals follow a specific regimen ( e.g., diet or activity plan) and are checked regularly for cancer

66. Cancer Diagnosis and Treatment
Most often, discovery of cancer follows a screening test
Oldest treatment is surgery, which removes the tumor
Radiation and chemotherapy non-selectively destroy rapidly dividing cells
Other drugs help patients tolerate the side effects 66

67. Cancer Diagnosis and Treatment
New types of cancer drugs:
- Stimulate cells to regain specialized characteristics
- Inhibit telomerase
- Induce apoptosis
- Inhibit angiogenesis
Genomics information is increasingly used
- Enables physicians to better match patient to treatment 67

68. Genes and Behavior
Behavior is a complex continuum of emotions, moods, intelligence, and personality
Behavior occurs in response to environmental factors, but how we respond has genetic underpinnings
Behavioral genetics considers nervous system function and variation
- Including mood and mind 68

69. The Human Brain The human brain weighs about 3 pounds
- Consists of 100 billion neurons and at least a trillion other supportive and nurturing cells called neuroglia
Neurons communicate across synapses using neurotransmitters
Genes control the production and distribution of these chemical signals 69

70. Neurotransmission
Figure 8.1 70

71. Behavioral Genetics
Uses empirical risk, twin studies, and adoption studies
Association studies with SNPs and analysis of specific mutations that are present in individuals with the behavior
Genetic studies of behavioral disorders are challenging traditional psychiatric classification
- These disorders may lie on a continuum with many genes having input 71

72. 72

73. Eating Disorders In the US, 5-10 million people have eating disorders
- About 10% are male
Twin studies reveal a heritability ranging from
Genes whose products control appetite or regulate certain neurotransmitters may predispose to eating disorders 73

74. Eating Disorders
Anorexia nervosa – Psychological perception of obesity and intentional starvation
Bulimia – Psychological perception of obesity and intentional vomiting
Muscle dysmorphia – Psychological perception of being too small 74

75. Sleep Without sleep animals die The function remains unclear
Twin studies indicate 4 of the 5 stages of sleep have a hereditary component
- The fifth stage, REM sleep, is associated with dreaming and so reflects input of experience more than genes 75

76. Narcolepsy with Cataplexy
Daytime sleepiness with tendency to rapidly fall asleep (narcolepsy) and periods of muscle weakness (cataplexy)
The genetic basis was first identified in dogs, then humans
Figure 8.3 76

77. Familial Advanced Sleep Phase Syndrome
A disorder characterized by a very unusual sleep-wake cycle
Affected members of a large family enabled researchers to identify the first “clock” gene in humans
- The period gene enables a person to respond to day and night environmental cues 77

78. Familial Advanced Sleep Phase Syndrome
A pedigree of the autosomal dominant form of the disease
Figure 8.4
Figure 8.4

79. Intelligence
A complex and variable trait subject to multiple genes, environmental influences, and intense subjectivity
Refers to the ability to reason, learn, remember, synthesize, deduce, and create
The IQ (intelligence quotient) test was first developed in France in 1904
- To predict academic success of developmentally disabled children 79

80. The IQ Test
Was later modified at Stanford University to assess white, middle-class Americans
IQ is normally distributed around a mean of 100
▪ Below 50 = Severe mental retardation
▪ = Mild mental retardation
▪ = Average intelligence
▪ Above 115 = Above average intelligence 80

81. IQ has been a fairly accurate predictor of success in school and work
Figure 8.5 81

82. The environment has less of an influence on IQ as a person ages
IQ tests verbal fluency, mathematical reasoning, memory, and spatial visualization ability
The “g” value measures a general intelligence factor that represents the inherited portion of IQ
The environment has less of an influence on IQ as a person ages 82

83. Drug Addiction
Compulsively seeking and taking a drug despite knowing its adverse effects
Characteristics:
- Tolerance = The need to take more of a drug to achieve the same effect
- Dependence = The onset of withdrawal symptoms with cessation of drug 83

84. Drug Addiction Heritability is 0.4-0.6
- Twin and adoption studies support role of genes in drug addiction
Drug addiction produces long-lasting changes in the brain
Brain changes that contribute to addiction are in the limbic system 84

85. The Events of Addiction
Figure 8.6 85

86. Drugs of Abuse Abused drugs are often derived from plants
- Cocaine, opium, and tetrahydrocannabinol (THC), the main ingredient in marijuana
- These chemicals bind receptors in human neurons
Endorphins and enkephalins are the human equivalents of opiates
- Are pain relievers 86

87. Mood Disorders
Mood disorders represent the extremes of normal behavior
The two most prevalent are:
- Major depressive disorder = Marked by unexplained lethargy, sadness, and chronic depression
- Bipolar affective disorder = Marked by depression interspersed with mania 87

88. Major Depressive Disorder
Affects 6% of the US population
A likely cause is a deficiency of the neurotransmitter serotonin, which affects mood, emotion, appetite, and sleep
Many antidepressant drugs are selective serotonin reuptake inhibitors (SSRIs) 88

89. Major Depressive Disorder
Figure 8.7 89

90. Bipolar Disorder Also called manic-depression
Affects 1% of the population
Associated with several chromosome sites
Its genetic roots are difficult to isolate 90

91. Schizophrenia
Loss of ability to organize thoughts and perceptions – withdrawal from reality
Worldwide – 1% affected
Typically early adult onset
Progression
- Difficulty paying attention, memory and learning difficulties, psychosis (delusions and hallucinations) 91

92. Schizophrenia
Disjointed drawings by schizophrenic patients display the characteristic fragmentation of the mind
Figure 8.8 92

93. Schizophrenia
A heritability of 0.8 and empiric risk values indicate a strong genetic component for schizophrenia 93

94. Schizophrenia
Dozens of genes may interact with environmental influences to cause this disease
One powerful candidate is infection during pregnancy
- Prenatal exposure to the influenza or herpes viruses 94

95. Autism Autism is a spectrum of disorders
- Characterized by loss of language, communication, and social skills, beginning in early childhood
- Seizures and mental retardation may occur
Autism affects 3-6 children out of every 1,000
- It strikes four times as many boys as girls 95

96. Autism More than 30 genes so far have been associated with autism
Two genes in particular may finally explain how autism develops
- They encode the cell adhesion proteins neurexins and neuroligins
- These proteins strengthen synaptic connections in neurons associated with learning and memory 96

97. Understanding Autism
Autism may arise from failure of synapses to form that enable a child to integrate experiences
Figure 8.9 97