PATHO D115 Unit 2 Study Guide (Genes, Lifestyle, and Immunity) Latest Update (Download To Score An A)

Module: Genetic Influence on Patient Outcomes Chapter 4: Genes and Genetic Diseases Vocabulary Terms: • RNA o ribonucleic acid, a nucleic acid present in all living cells. Its principal role is to act as a messenger carrying instructions from DNA for controlling the synthesis of proteins, although in some viruses RNA rather than DNA carries the genetic information. o Uracil replaces thymine (A to U and C to G) o RNA is a single strand • DNA o Deoxyribonucleic Acid: a primary constituent of chromosomes o a self-replicating material that is present in nearly all living organisms as the main constituent of chromosomes. It is the carrier of genetic information. • Chromosomes o a threadlike structure of nucleic acids and protein found in the nucleus of most living cells, carrying genetic information in the form of genes. • Mitosis o The multi-step process in the cell cycle that allows a single cell to divide into two identical daughter cells:  Chromosomes condense  Spindle assembles  Chromosomes attach to spindle  Chromosomes align at cell equator  Spindle microtubules move apart  Nuclear membranes surround each set of chromosomes  Parent cell splits into two daughter cells • Transcription o The process by which RNA is synthesized from a DNA template forming messenger RNA from the base sequence specified by the DNA molecule. • Translation o The process by which RNA directs the synthesis of a polypeptide and aides into the formation of ribosomes. • Phenotype  Refers to the observable characteristics resulting from an organism’s genotype; genotype does not always specifically control phenotype due to the processes of epigenetics • Genotype o Refers to the overall genetic composition of a genome in an organism • Dominant o The allele whose effects are observable • Recessive o The allele whose effects are hidden.Two copies of these types of alleles are required to manifest a phenotype • Autosomal dominance o A way that a genetic trait or condition can be passed down from a parent to a child when one parent has a mutated gene on one of their autosomal chromosomes  A child who inherits this mutated gene has a 50% change of developing the condition in each pregnancy.  Men and women are equally likely to have the mutation  Sons and daughters are equally likely to inherit it • Autosomal recessive o A way a genetic trait, disorder, or disease can be passed down through families. o Occurs when a child inherits two copies of a mutated gene, one from each parent, on a non-sex chromosome. o The parents of this child usually do not have the condition and thus are referred to as carriers and can pass the mutated gene onto their children. • X-linked o A genetic condition that occurs when a gene on the x chromosome causes a trait or disorder. o They can be recessive or dominant and the inheritance pattern depends on the type of gene. • X-linked Dominant o A mutation in a gene on a single X chromosome can cause a condition in both males and females. o However, fathers cannot pass x-linked dominant conditions to their sons, but all daughters of affected fathers will be affected • X-linked Recessive o A mutation in a gene on the X chromosome causes the condition to be expressed in males and in females who are homozygous for the gene mutation. o Females with one copy of the mutated genes are carriers and are usually unaffected, or only mildly affected. o However, in some cases, female carriers can have medical problems. • Evaluation of pedigrees o Pedigree analysis is a vital tool in genetic evaluations. They allow us to determine genotypes, identify phenotypes, and predict how a trait will be passed on in the future. The information from a pedigree makes it possible to determine how certain alleles are inherited, whether they are dominant, recessive, autosomal, or sex-linked. • Incident rate o The number of new cases of a disease reported during a specific period (typically one year) divided by the number of individuals in the population.  Denominator is often expressed as persons-years.  Contrasted with the prevalence rate • Prevalence rate o Proportion of the population affected by a disease at a specific point in time. o Determined by both the incidence rate and the length of the survival period in affected individuals. • Relative risk o A common measure of the effect of a specific risk factor. Expressed as a ratio: increased rate of the disease among individuals exposed to a risk factor / incidence rate of the disease among individuals not exposed to a risk factor. Review Questions 1. What are genes composed of and where are they located? a. Genes are composed of sequences of DNA and are located in chromosomes. They are considered the basic unit of inheritance. 2. What are the four types of nitrogenous bases that constitute DNA? a. Adenine, cytosine, guanine, thymine (A, C, G, T) 3. How are new strands of DNA formed? a. DNA is a double helix model- twisted ladder with chemical bonds as its rungs. Nitrogenous bases pair together (Adenine to Thymine and Guanine to Cytosine) to form rungs. b. DNA must be able to replicate itself accurately during cell division so the genetic code can be preserved in subsequent cell generations. c. DNA replication: one protein unwinds the double helix, one protein holds the strands apart, and another protein (DNA Polymerase) travels along the single strand and pairs the nucleotides to the free end of the new strand, then perform a proofreading procedure to ensure each nitrogenous base is accurately paired. If it is not, it is excised and replaced. 4. How is the process of transcription regulated? a. Proteins called transcription factors bind to DNA sequences called transcription factor binding sites near genes to regulate the timing or transcription as well as specific tissues in which genes are actively transcribed. b. These factors can either activate or repress the expression of genes. 5. How many pairs of chromosomes do humans have? a. 23 pairs- 46 chromosomes in total 6. What are some of the most common types of chromosomal abnormalities? a. Aneuploidy- contain three copies of a chromosome and called “trisomic”. Monosomy refers to the presence of one copy of a chromosome i. Down Syndrome (3 of Chromosome 21) ii. Turner Syndrome (45 total chromosomes. Women only. Missing 1 Y chromosome. iii. Klinefelter Syndrome (XXY syndrome. Men only. Males with female features ie. Gynecomastia) b. Chromosomal deletions i. Cri du chat syndrome (partial deletion of chromosome 5) “cat cry syndrome” 7. How are pedigree charts utilized in genetics? a. Pedigree charts analyze modes of inheritance b. Summarizes family relationships and shows which members of a family are affected by a genetic disease. c. The chart begins with one individual in the family “the proband” who is the first person diagnosed or seen in a clinic. 8. How is gender determined from a genetic perspective? a. During meiosis, the SRY gene (Sex-determining region on the Y chromosome), which triggers male gonadal differentiation (in the 6th week of gestation) exchanges genetic material during the crossover to determine gender. 9. What common diseases are considered to be multifactorial? a. These are complex disorders that are influenced by multiple genes, lifestyles, and environmental factors b. Birth defects: neural tubes defects, cleft palate, club foot, pyloric stenosis c. Cancers: breast, ovaria, bowel, prostate, skin d. Metabolic diseases: diabetes, hypertension, high cholesterol e. Neurological diseases: Alzheimer’s disease, schizophrenia, bipolar disorder, autism spectrum disorder f. Heart diseases: coronary artery disease and congenital heart defects g. Others: asthma, depression, epilepsy, obesity, migraine headaches 10. Detail the criteria used to define multifactorial inheritance: a. Multifactorial inheritance describes biological traits or health problems that are caused by more than one factor, usually a combination of genetic and environmental factors i. Genes: a combination of genes from both parents or DNA sequence variations ii. Environmental factors: lifestyle factors like diet, physical activity, and stress management, as well as medical interventions like surgery and drugs. 11. How do monozygotic and dizygotic twins differ genetically? a. Monozygotic: identical twins- originate when the developing embryo divides to form two separate but identical embryos i. Natural clones ii. Originating from one egg b. Dizygotic: fraternal twins- result of double ovulation followed by the fertilization of each egg by a different sperm. i. No more genetically similar than siblings ii. It is possible for DZ twins to have two different fathers. 12. What are some well-known examples of imprinting? a. Imprinting: a baby inherits two copies of each autosomal gene: one from its mother and one from its father. b. Prader-Willi Syndrome: i. Deletion of about 4 million base pairs of the long arm of chromosome 15. ii. Inherited from the father! iii. Clinical features: short stature, hypotonia, small hands and feet, obesity, mild to moderate intellectual disability, hypogonadism. c. Angelman Syndrome: i. Deletion of about 4 million base pairs of the long arm of chromosome 15. ii. Inherited from the mother! iii. Clinical features: severe intellectual disability, seizures, ataxic gait. d. Beckwith-Wiedemann Syndrome: i. Overgrowth condition accompanied by an elevated risk of cancer ii. Large size for gestational age, neonatal hypoglycemia, large tongue, creases on the earlobe, omphalocele (birth defect of infant’s intestines). 13. How is the concept of probability applied to and used in genetics? a. Probability is a key tool in genetics that helps scientists understand and analyze heredity. It can be used to make predictions about the outcome of genetic crosses, calculate the risk of inheriting genetic diseases, and assess the strength of evidence in DNA profiling. 14. Which chromosome is affected in individuals with Down’s syndrome? a. Chromosome 21- “trisomy 21” 15. What are the clinical characteristics of Down’s Syndrome? a. Intelligence quotients (IQs between 25-70) b. Distinctive facial features: low nasal bridge, epicanthal folds, protruding tongue, flat- low-set ears. c. Poor muscle tone d. Short stature e. congenital heart defects 16. Identify the health challenges and risk factors associated with Down’s Syndrome i. Congenital heart defects (1/3 to ½ of live born Down Syndrome children) ii. Reduced ability to fight respiratory tract infections and increased susceptibility to leukemia contribute to reduced survival rate iii. By 40 years old, symptoms similar to Alzheimer's develop (Alzheimer's disease genes are located on chromosome 21). iv. ¾ of fetuses are spontaneously aborted or are stillborn (w/ D.S) v. 10-20% of infants born with D.S due during first 10 years of life vi. Average life expectancy is 60 years old. b. Risk factors for Down Syndrome i. Advancing age of mother who conceives 17. Identify the chromosomes affected in individuals with Turner syndrome i. Caused by the partial or complete absence of the second sex chromosome in females only! b. What are the clinical characteristics? i. Shorter than average height ii. Ovarian dysfunction iii. neck iv. Slightly puffy hands and/or feet v. Widespread nipples vi. Low set ears vii. Webbed neck viii. Low hairline ix. Minimal breast development x. Lack of pubic hair xi. Amenorrhea xii. High arches palate xiii. Small mandible xiv. Bicuspid aortic valve xv. Coarctation of aorta c. How are these individuals treated i. Hormone therapy to prevent ovarian failure, IVF for infertility issues. There is no cure. Treatment of individual symptoms can be successful. 18. Which chromosomes are involved in individuals with Klinefelter syndrome? a. Produces extra sex chromosome (47) Referred to as XXY syndrome. Males have an extra X chromosome. Affects males only. b. What are the clinical characteristics? i. Males will have a male appearance but 1. Will be sterile (usually) 2. Half develop female-like breasts (gynecomastia) 3. Small testes 4. Sparse body hair 5. High pitched voice 6. Stature is elevated 7. Moderate degree of mental impairment may be present 19. Identify the types of genetic testing (carrier screening) available and their uses for disease screening, diagnosis, and treatment a. Genetic screening can detect and diagnose 5000 diseases b. Reveals the presence or absence of a disease but not the complete penetrance (what effect it will or will not have on the carrier) c. Gene therapy: harmful effects of a disease-causing mutation are corrected by altering the person’s DNA. i. Carrier screening: identifies heterozygous carriers for recessive diseases 1. Cystic fibrosis, sickle cell disease, Tay-Sachs d. Prenatal Diagnosis i. Amniocentesis-test that is performed around 16 weeks gestation, involves withdrawal of a small amount of amniotic fluid from uterus to detect chromosomal abnormalities 1. This fluid can detect single-gene disorders, neural tube defects (spina bifida), anencephaly. 2. This poses a risk for fetal loss ii. Chorionic villus sampling (CVS)- 10-12 weeks gestation extracting villous tissue from chorion. 1. Does not require invitro culturing of cells 2. Imposes slightly higher loss rate (approximately 1%) iii. Pre-implementation genetic diagnosis (PGD)- 8-12 celled embryos created by in-vitro, 1 or 2 cells are removed and tested for single cell abnormalities 1. This occurs before implantation iv. Analysis of fetal DNA in maternal circulation 1. 6-8 weeks gestation 2. Fetal cells can be found in the mother’s bloodstream 3. Minimal risk of harm to mother/fetus v. Presymptomatic diagnosis: hereditary diseases can be tested genetically before the person develops the disease 1. Used to diagnose the disease or minimize the risk of early disease vi. Testing for drug efficacy or sensitivity- testing genes for sensitivities to specific therapeutic drugs. 1. Used to guide drug dosages Learning Checks: 1. LEARNING CHECK: Which type of genetic disorder affects males more frequently than females? a. Autosomal recessive b. Sex-linked dominant c. Sex-linked recessive d. Autosomal dominant Since males have only one X and one Y, if the affected chromosome has the illness, it will be expressed 2. LEARNING CHECK: In which two conditions are chromosomal abnormalities the leading known cause? a. Fetal miscarriage b. Intellectual disability c. Respiratory disorders d. Cardiovascular disease e. Mental illness 3. LEARNING CHECK: What are three examples of prenatal diagnostic studies? a. Preimplantation genetic testing (PGT) b. Microscopy of cervical mucosa c. Amniocentesis d. Chorionic villus sampling (CVS) e. Drug-sensitivity testing These three tests are performed in vitro. CVS is a form of genetic testing that provides genetic information found in utero and is usually performed between weeks 11 and 14 of pregnancy. An amniocentesis is a form of genetic testing that evaluates the amniotic fluid and is usually performed during the second trimester between weeks 15 and 20. PGT is performed on the embryo prior to implantation. 4. LEARNING CHECK: Which genetic disorder is characterized by the presence of a zygote having one chromosome with a normal complement of genes and one chromosome with a missing gene? a. Turner Syndrome b. Klinefelter syndrome c. Down syndrome d. Cri du chat syndrome Cri du chat (translated to cry of the cat) is caused by DNA deletion. This term describes the cry often heard from a baby affected by the syndrome. It can present as a microcephalic, low birth-weight baby with a piercing cry. 5. LEARNING CHECK: How can an X-linked recessive disease skip generations? a. The disease can be transmitted through female carriers b. These diseases need only one copy of the gene in females c. Females are hemizygous for the X chromosome d. Mothers cannot pass X-linked genes to their sons e. Since females have two copies of the X chromosome, the mother may provide an unaffected X to a daughter or son. Furthermore, a daughter may not show signs of the disease because she has the other X (the only X the father can give to a female) to cancel it out. 6. LEARNING CHECK: Which type of risk is referred to as the ratio of the disease rate among the entire population to the disease rate in an unexposed population? a. Relative b. Casual c. Attributable d. Contingency e. Relative risk is a ratio of probability, not an actual occurrence of disease. 7. LEARNING CHECK: What are the empirical risks for most multifactorial diseases based on? a. Chromosomal testing b. Relative risks c. Direct observation d. Liability thresholds e. Many factors form lifestyle to genetics affect multifactorial diseases. Observation and evaluation of each case individually provides the most thorough and accurate assessment. 8. LEARNING CHECK: _____________ refers to the silenced gene of a gene pair. a. Imprinted  Module: Pathological Defense Mechanisms and Immunity Vocabulary Terms • Innate immunity (natural or native immunity) o The body’s first line of defense against harmful foreign substances, such as viruses and bacteria that enter the body • Human defense mechanisms (of innate immunity) o First: Physical/mechanical, and biochemical barriers and normal microbiome, o Second: inflammation • Physical/Mechanical/biomechanical barriers o Physical/mechanical: skin and membranous sheets lining the visceral organs. The normal turnover of these cells as well as the mechanisms for “washing” the surfaces may mechanically remove many infectious microorganisms and prevent their residence on the epithelial surfaces o Biochemical: epithelial derived chemicals on epithelial surfaces that trap and destroy microorganisms • Human Leukocyte Antigen o HLAs are genes in major histocompatibility complexes (MHC) that help code for proteins that differentiate between self and non-self. They play a significant role in disease and immune defense. They are beneficial to the immune system buy can also have detrimental effects. • Normal microbiome o Normal microbiome: microorganisms that are colonized on internal and external body surfaces that contribute to the human body’s innate protection against pathogenic microorganism • Inflammatory response o Activated to protect the body from further injury, prevent infection of the injured tissue, and promote healing. Rapid activation of biochemical and cellular processes that is relatively nonspecific, with the similar responses being initiated against a wide variety of causes of tissue damage  Occurs in tissues with a blood supply (vascularized)  Is activated rapidly (within seconds) after damage occurs  Depends on the activity of both cellular and chemical components (including plasma proteins)  Is nonspecific- it takes place in approximately the same way regardless of the type of stimulus or whether exposure to the same stimulus has occurred in the past • Wound healing stages o Stage 1: hemostasis  occurs immediately, blood vessels constrict to stop bleeding, blood clots form o Stage 2: inflammation  occurs within 4 days, neutrophils and macrophages work to remove debris, infection prevention o Stage 3: Proliferation  occurs within 2 weeks, wound rebuilds connective tissue for protection, granulation of the skin is promoted, tissue repair o Stage 4: Remodeling  occurs anywhere from 24 days to 1 year, new epithelial tissue forms (new, healthy skin) • Adaptive immunity (acquired or specific immunity): inflammation associated with infection usually initiates and adaptive process that results in a long-term and very effective immunity to the infecting microorganism. Has memory and more rapidly targets and eradicates a second infection with a particular disease-causing microorganism • Antigens: a molecules that can react with binding sites on antibodies or antigen receptors on B and T cells • Immunogens: cells that will induce an immune response, resulting in the production of antibodies or functional T cells. • Clonal diversity: the first phase of the immune response that occurs before birth when a large population of T and B cells are produced. These lymphocytes have the capacity to recognize almost any foreign antibody found in the environment. • Clonal selection: the second phase of the immune response that begins at birth and proceed throughout the life as the individual encounters new antigens. This phase produces effector cells and memory cells that provide long-term specific protection against infectious microorganisms. • Antibody function: protection against infection either directly or indirectly. o Directly: antibody can cause neutralization: inactivation or blocking the binding of an antigen to a receptor o Agglutination: clumping insoluble particles that are in suspension o Precipitation: making a soluble antigen into an insoluble precipitate of infectious agents and their toxic products o Indirectly: antibodies activate several components of innage immunity, including complement and phagocytes • Major histocompatibility complex: glycoproteins on the surface of all human cells (except RBCs). Control the quantity and quality of an immune response • Passive immunotherapy: countermeasure against pathogens in which preformed antibodies are given to the individual. • Infectious Diseases: true pathogens: bypass normal defenses and cause infection. Infection is usually dependent on adequate numbers of microorganisms rather than a compromise of the host’s defenses. • HIV: A retrovirus that infects and depletes a portion of the immune system (helper T cells) causing the individual to be extremely susceptible to life-threatening infections and malignancies. HIV causes AIDS. • Antimicrobials: prevent growth (bacteriostatic) or directly kill (bacteriocidal) microorganisms. o Inhibit the production and function of the cell wall o Block DNA replication o Inhibit DNA replication o Inhibit protein synthesis o Interfere with folic acid metabolism Chapter 7: Innate Immunity: Inflammation and Wound Healing 1. What are the 3 lines of human defense? What happens during each? a. First line: i. Natural barriers: physical, mechanical, and biochemical ii. Physical and mechanical 1. Skin and low temp/pH of skin 2. Linings of GI, GU and respiratory tracts 3. skin and membranous sheets lining the visceral organs. The normal turnover of these cells as well as the mechanisms for “washing” the surfaces may mechanically remove many infectious microorganisms and prevent their residence on the epithelial surfaces iii. Biochemical 1. Sweat, saliva, tears, and earwax 2. epithelial derived chemicals on epithelial surfaces that trap and destroy microorganisms b. Second line: i. Inflammation 1. Causes: infection, mechanical damage, ischemia, nutrient deprivation, temperature extremes, radiation 2. Rapidly initiated 3. No memory cells 4. Nonspecific: takes place the same way regardless of stimulus 5. Signs: redness, heat, swelling, pain, loss of function 6. Vascular response: blood vessel dilation, increased vascular permeability and leakage, WBC adherence to inner walls of vessels and migration through the vessels 7. Purpose: prevent and limit infection and further damage, limit and control inflammatory process, interact with components of the adaptive immune system, prepare the area of injury for healing. c. Third line: i. Adaptive (acquired) immunity: antibodies or T cells are produced after either a natural exposure to an antigen or after immunization 2. How do acute and chronic inflammation differ? a. Acute inflammation i. The systemic effects of inflammation are fever and increases in levels of circulating leukocytes and plasma proteins (acute-phase reactants) b. Chronic inflammation i. Lasts 2 weeks or longer ii. Often related to unsuccessful acute inflammatory response iii. Characteristics: 1. Dense infiltration of lymphocytes and macrophages 2. Granuloma formation 3. Epithelioid cell formation 4. Giant cell formation iv. The body may wall off and isolate the infection to protect against tissue damage by formation of a granuloma 3. What are the phases of wound healing and the process that takes place during each? a. Phase 1: Inflammation i. Coagulation and infiltration of cells that participate in inflammatory process 1. Platelets contribute to clot formation 2. Neutrophils and macrophages clear wound of debris 3. Fibrin serves as clots (scabs) b. Phase 2: Proliferation and New Tissue Formation (Proliferation) i. Macrophages invade and dissolves the fibrin clots, synthesize collagen and stimulate epithelialization. ii. Granulation tissue grows into the wound from surrounding healthy connective tissue- giving the wound the red granular appearance. iii. Wound contraction occurs- reconstruction of new tissue. Wound begins to close 6-12 days after injury c. Phase 3: Remodeling and Maturation i. Begins several weeks after injury and is normally complete within two years ii. Continuation of cellular differentiation, scar formation, and scar remdeling iii. Maturation phase: recovering normal tissue structure that can persist for years 4. How does the inflammatory response differ in neonates? a. Neonates have a less robust inflammatory response than adults and children. They can develop severe system inflammatory responses, such as sepsis. Their immune systems are still developing and have distinct immune components and functions. i. Anti-inflammatory responses- could be delayed responses against harmful pathogens which can cause more severe disease ii. Phagocytes: less responsive to PAMP stimulation (pathogen-associated molecular patterns) which can result in deficient adhesion and extravasation iii. Monocytes: decreased expression can impair antigen presentation and lead to decreased adhesion and infiltration to inflamed tissues iv. T- cells- neonates have much lower numbers of T-cells compared to adults 5. How and why does aging affect innate immunity? a. Impaired or delayed inflammation likely as a result from chronic illnesses such as diabetes and cardiovascular disease b. Medications may interfere with wound healing c. Infections are more common in the older adult (lungs, skin, urinary tract) d. Diminished immune function Chapter 8: Adaptive Immunity 6. Describe the process of adaptive immunity a. Works together with inflammation b. Recognizes foreign substances i. Antigens, pathogens, noninfectious environmental agents, drugs, vaccines, transfusions, transplants c. Provides long-term protection d. Is slower than innate, but more specific e. Has memory 7. How do active immunity and passive immunity differ? a. Active immunity: i. Antibodies or T cells are produced after either a natural exposure to an antigen or after immunization ii. Is long lived b. Passive Immunity: i. Preformed antibodies or T lymphocytes are transferred from a donor to a recipient ii. Occurs naturally or artificially iii. Is temporary or short-lived 8. Discuss the five different immunoglobulins and their biologic function a. IgG i. Most prevalent ii. Most of protective activity against infection iii. Crosses placenta- protects newborn during first 6 months of life b. IgM i. Largest ii. First antibody produced during the initial, or primary, response to antigen c. IgA i. Mostly in secretions ii. Most of protective activity in body secretions d. IgD i. Not known well ii. Functions as one type of B-cell antigen receptor e. IgE i. Most rare ii. Mediator of many common allergic responses iii. Defends against parasitic infections Chapter 9: Alterations in Immunity and Inflammation 9. What terms are collectively known as hypersensitivity reactions? a. Allergy: exaggerated response against an environmental antigen b. Autoimmunity: misdirected response against the host’s own cells c. Alloimmunity: directed against beneficial foreign tissues (transfusions/transplants) 10. Identify the 4 types of hypersensitivity reactions, their rate of development, class of antibody involved, principal effort cells, and examples of disorders for each class a. Type I: IgE mediated i. Immediate ii. IgE iii. Mast Cells iv. Seasonal allergic rhinitis b. Type II: Tissue-specific reactions i. Immediate ii. IgG/IgM iii. Macrophages in tissues iv. Autoimmune thrombocytopenic purpura, Graves disease, autoimmune hemolytic anemia c. Type III: Immune complex mediated i. Immediate ii. IgG/IgM iii. Neutrophils iv. Systemic lupus erythematosus d. Type IV: cell mediated/delayed i. Delayed ii. None iii. Lymphocytes/macrophages iv. Contact sensitivity to poison ivy and metals (jewelry) 11. What are some causes of autoimmune diseases? a. Sequestered antigens, infectious diseases with molecular mimicry, neoantigens, survival of a forbidden clone, or defective peripheral tolerance 12. What are some examples of alloimmune disorders? Why do these occur? a. Transplant and transfusion rejections b. Transient neonatal alloimmunity: fetus expressing parental antigens not found in the mother (Rh factor) c. These reactions occur because the body recognizes these antigens as “non-self” and initiates an immune response to destroy them, typically due to a mismatch between the donor and recipient’s blood group antigens or other tissue-specific markers. 13. Explain the relationship between HLA alleles and diseases. a. HLA alleles determine an individual’s susceptibility to specific infectious agents or the capacity of that individual to mount an immune response against specific antigens. Therefore, that individual may have an inappropriate or exaggerated immune response againse a microorganisms resulting in a hypersensitivity reaction. 14. Identify which HLA alleles have been linked to common diseases encountered in primary care (Type 1 diabetes, graves diseases, rheumatoid arthritis, systemic lupus erythematosus, etc) 15. What are the clinical manifestations and pathophysiologic mechanisms of systemic lupus erythematosus. Why is the disease so difficult to diagnose? Which labs are commonly run? a. Chronic multisystem inflammatory disease b. Deposition of circulating immune complexes containing antibody against the host’s DNA c. Eleven findings are common, the presence of at least four indicates SLE d. ANA(antinuclear antibody)- substantial number of falst positives. 16. What causes an immune deficiency? a. The failure of the immune or inflammatory mechanisms to protect the body at their normal capacity, resulting in increased susceptibility to infections. 17. What are autoinflammatory diseases characterized by? a. Abnormally high levels of inflammation secondary to mutations in control of inflammasome activation or in defects in cellular receptors of cytokines designed to decrease inflammation. 18. What are some causes of Acquired immunodeficiencies? a. Normal physiologic conditions: i. Pregnancy ii. Premature infants iii. Infancy iv. Aging b. Psychologic stresses, dietary insufficiencies, malignancies, chronic diseases, chromosomal abnormalities, environmental agents, physical trauma medical treatments, infections, lifestyles 19. How are deficiencies in immunity treated? a. Gamma-Globulin therapy: IM or IV administration of immune gamma-globulin to treat B-cell deficiencies b. Transplantation and Transfusion- stem cells through bone marrow or umbilical cord c. Soluble Immune Modulators: restore t-cell function d. Gene therapy Chapter 10: Infection 20. What are the four distinct phases of infectious disease? a. Incubation period: the period from initial exposure to the onset of symptoms. This can last several hours to years b. Prodromal stage: the occurrence of initial symptoms, which are often very mild and include a feeling of discomfort and tiredness c. Invasion period: invasion is father and affects other body tissues d. Convalescence: recovery occurs and symptoms declines, or the disease is fatal, or has a period of latency 21. Describe some direct and indirect ways for transmission of infectious disease a. Direct contact with infections of another individual: skin lesions of impetigo (staph), fungal (athlete’s foot), scabies (mites), lice (head or body), oral herpes, and STIs. b. Vertical transmission: the spread of microorganisms from mother to child across the placenta (toxoplasma gondii), ascending the birth canal from vaginal colonization or during delivery (, gonorrhea, hep B, HIV) or through breast milk (staph aureus, HIV). c. Horizontal transmission: the spread of organisms from one person to another d. Indirect: from contact with contaminated materials (ex. Bacterial infection inoculated on catheter insertion) e. Respiratory transmission-microorganisms that are inhaled from airborn droplets of an infected individual post cough/sneeze or inhalation of spores (environmental) f. Fecal-oral (salmonella and giardia) g. Zoonotic (rabies) from animals h. Vector-born- insect bites 22. Detail characteristics of HIV including causes, transmission, risks, treatments, etc. a. Cause: i. Retrovirus that infects and depletes the body’s helper T cells, reducing the effectiveness of the immune system, and making the individual extremely susceptible to life-threatening infections and cancers b. Transmission i. Blood or blood products, intravenous drug use, sexual activity, maternalchild transmission before or during birth c. Diagnosis: i. various clinical conditions and lab testing, CD4 +T-cell numbers are at or below 200 cells (depending on age), atypical or opportunistic infections/cancer d. Clinical manifestations: i. Early stages: may be asymptomatic ii. Window period: infectious by asymptomatic iii. Fatigue, headache, muscle aches, fever, severe weight loss/anorexia, ulcerative lesions iv. May remain asymptomatic for years e. Treatment: i. Antiretroviral therapy (ART): three or more drugs- usually two or more target reverse transcriptase and one is from a different class of drugs ii. Does not cure, but slows progression iii. Prevention is not currently possible and no vaccine has proven effectiveness 23. What are some effective countermeasures for infectious disease transmission? a. Environmental infection control measures b. Antimicrobials i. Prevent growth (bacteriostatic) ii. Directly kill microorganisms (bacteriocidal) c. Antivirals i. Sometimes less successful because viruses use host enzymes d. Antibiotic resistance e. Horizontal gene transfer f. Enzymatic inactivation of antibiotics g. Aminoglycoside-modifying enzymes (AMEs) h. Multi-drug-resistant transporters (MDRs) i. Proteins that prevent antibiotic cell access i. Target bypass i. Resistance mechanism 24. Describe how vaccinations activate the immune system. How do they lead to immunity of disease? a. The purpose of vaccination is to induce active immunologic protection before exposure to the risks of debilitating or fatal infection b. For each vaccine, an initial immunization protocol is developed to produce large numbers of memory cells and a sustained protective secondary immune response in the greatest number of individuals 25. Why is a vaccination safer than suffering from the primary infection prevented by the vaccine? a. Getting vaccinated introduces infectious diseases to your body in a controlled way so your immune system can develop antibodies and memory cells can store information about the disease. If the individual becomes infected again, the immune system will already have antibodies to initiate an immunologic response to combat the disease. Learning Checks: 1. LEARNING CHECK: What is the primary reason that some older adults have impaired inflammation and wound healing? b. The complement is deficient c. The number of mast cells is insufficient d. The circulatory system cannot adequately perfuse tissues e. The underlying chronic illness exists f. A generalized inflammatory response seen in chronic illness depletes the body’s reserves to fight against illness. 2. LEARNING CHECK: Which cells are the body’s primary defense against parasite invasion? g. T lymphocytes h. Eosinophils i. B lymphocytes j. Neutrophils k. A generalized inflammatory response seen in chronic illness depletes the body’s reserves to fight against illness 3. LEARNING CHECK: Which characteristic is the most important determinant of immunogenicity when considering the antigen? a. Foreignness b. Complexity c. Size d. Quantity e. Immunogenicity is primarily based on the ability to recognize something foreign 4. LEARNING CHECK: How are erythrocytes destroyed when mismatched blood is administered, causing ABO incompatibility? a. Phagocytosis in the spleen b. Complement-mediated cell lysis c. Phagocytosis by macrophages d. Natural killer cells e. The complement pathway is activated in response to blood incompatibility 5. LEARNING CHECK: Which four infections are considered fungal infections? a. Ringworm b. Candida c. Cholera d. Athlete’s foot e. Aspergillus f. Infection with a fungus is called mycosis and includes dematophytes (e.g., tineas, which refers to several skin mycoses, including ringworm and athlete’s foot) and yeasts, which include candida and aspergillus. 6. LEARNING CHECK: When is the earliest after sexual transmission of HIV that lab results can detect infection? a. 2-4 months b. 1-2 days c. 4-10 days d. 4-8 weeks e. Lab testing can detect HIV RNA 4-10 days after sexual transmission, whereas HIV antibody testing may take 23-90 days to result in a positive test. Repeat testing may be needed to rule out a false negative test due to testing too soon after exposure, especially if a high likelihood of exposure is suspected. 7. LEARNING CHECK: What is a characteristic of exotoxins? a. Released during bacterial growth b. Able to initiate the complement and coagulation cascades c. Contained in the cell walls of gram-negative bacteria d. Released during the lysis of bacteria Module: Other Influences on Patient Outcomes Chapter 5: Genes, Environment-Lifestyle, and Common Diseases Vocabulary Terms: • Incidence rate: the number of new cases of a diseases reported during a specific period (usually 1 year) divided by the number of individuals in the population. Expressed as “persons/years” • Prevalence rate: proportion of the population affected by a disease at a specific point in time. It is determined by both the incidence rate and the length of the survival period in affected individuals • Multifactorial inheritance: inheritance caused by many genetic and environmental factors where the traits tend to follow a normal, or bell-shaped, distribution in populations. • Twin studies: consist of comparisons between monozygotic and dizygotic twins. If both members of a twin pair share a trait, they are said to be concordant. If they do not share the trait, they are discordant. • Adoption studies: studies of adopted children used to estimate the genetic contribution to a multifactorial trait. • Congenital malformations: multifactorial disorders present at birth Review Questions: 1. How do the incidence and prevalence rate differ? a. Incidence rate: the number of new cases of a diseases reported during a specific period (usually 1 year) divided by the number of individuals in the population. Expressed as “persons/years” b. Prevalence rate: proportion of the population affected by a disease at a specific point in time. Varies from population to population 2. How is relative risk used in relation to disease processes? i. Increased rate of disease among individuals exposed to a risk factor divided by the incidence rate of the disease among individuals not exposed to the risk factor. 3. What are some examples of diseases that correspond with the liability model? a. Pyloric stenosis, neural tube defects, cleft lip with or without cleft palate, club foot, and some congenital heart diseases. 4. What are empirical risks and how do they affect disease? a. Risks based on direct observation of data b. Because each multifactorial disease has different numbers and types of risk factors, empirical recurrence risks vary for each disease 5. How do multifactorial disease and single-gene disease differ? a. Recurrence risks for multifactorial diseases can change substantially from one population to another because gene frequencies as well as environmental factors can differ among populations. 6. Define a gene-environment interaction. a. A genetic predisposition may interact with an environmental factor to increase the risk for a disease to a much higher level than either factor would alone. 7. What are some common diseases that are categorized as multifactorial in nature? a. Coronary heart disease b. Hypertension c. Cancer d. Breast cancer e. Colorectal cancer f. Diabetes (type I and type II) g. Obesity h. Alzheimer’s i. Alcoholism j. Bipolar Disorder k. Schizophrenia Learning Checks: 1. Which dietary lifestyle choice has been associated with a decreased risk for developing colon cancer? a. Decreased consumption of artificial food coloring b. Increased consumption of dairy products c. Decreased consumption of high-fat foods d. Increased consumption of foods containing vitamin c 2. Which cancer is an individual who has worked with asbestos for over 40 years most likely to develop? a. Stomach b. Leukemia c. Lung d. Bladder 3. Which statement is true regarding ultraviolet (UV) light? a. The principal source of ultraviolet radiation (UVR) is tanning beds b. It can cause the formation of sarcomas c. The degree of damage is not affected by the light’s wavelength d. It causes basal cell carcinoma and squamous cell carcinoma e. UV light causes basal cell carcinoma and squamous cell carcinoma when the UVB rays hit DNA strands, causing thymine base pairs that are side by side to pair together, becoming thymine dimers. These thymine dimers lead to cell death or cancer. 4. What cancer does exercise have a convincing impact on reducing? a. Stomach b. Liver c. Endometrial d. Colon e. Exercise-induced myokines cause apoptosis of colon cancer cells 5. Low healthcare literacy is recognized as a major risk factor in blood pressure control and has been shown to have adverse effects on health outcomes a. True b. False i. By providing patient education at the appropriate literacy level, improved health outcomes may result 6. One of the goals of the National Action Plan to Improve Health Literacy is to incorporate research and evidence-based plans of treatment from childhood through university-level education in a manner consistent with an individual’s literacy level. a. True b. False i. Ensuring the individual can understand all elements of a treatment plan is crucial for understanding and compliance 7. What is a red flag for low healthcare literacy? a. Medication noncompliance b. Ability to identify medications on sight c. Asking questions about health d. Adherence to medical appointments i. Low literacy often leads to perceived noncompliance to medical instructions, including medication instructions. Ensuring the patient fully understands all instructions in critical for understanding. UNIT 2 QUIZ 1. Amniocentesis is recommended for pregnant women with certain health histories. Which health history would result in an amniocentesis recommendation? a. Those who had a late menarche b. Those who have experienced in vitro fertilization c. Those who have a family history of genetic disorders d. Those who have a history of chronic illness i. Amniocentesis is indicated for pregnant women who have a family history of genetic disorders because it is performed to detect chromosome abnormalities, genetic disorders, and neural tube defects. 2. Studies have identified several genes that play a role in the prevention of obesity. What do these genes influence? a. Metabolization of fat b. Sense of satiety c. Regulation of appetite d. Absorption of fat i. Research has shown that genetic mutations may cause alterations in the regulation of appetite 3. Which concept is data reporting that sickle cell disease affects approximately 1 in 600 black Americans an example of? a. Prevalence b. Incidence c. Ratio d. Risk i. Prevalence tells us how often disease is seen in a population, which includes all people with the disease at a given time, at any stage in the disease progression. 4. What describes a chromosomal defect caused by Prader-Willi syndrome? a. One that is related to maternal alcohol abuse b. One that is inherited from the father c. One that is initiated by postnatal exposure to a virus d. One that is transferred from mother to child i. Prader-Willi syndrome is caused by a disorder of a portion of chromosome 15. Normally, a portion of this chromosome is inherited from both parents. With Prader-Willi syndrome, the chromosome inherited from the father is problematic 5. Which action is a purpose of the inflammatory process? a. Prevent infection of the injured tissue b. Create immunity against subsequent tissue injury c. Provide specific responses toward antigens d. Lyse cell membranes of microorganisms i. The inflammatory response is a defense mechanism designed to remove damaged tissue so the body can heal. 6. Which leukocytes are elevated in response to acute inflammatory reactions when considering white blood cell differentials? a. Neutrophils b. Eosinophils c. Monocytes d. Basophils i. Neutrophils are one of the first responders to acute inflammations, and an increase in neutrophils demonstrates an acute inflammatory response. 7. Which type of immunity is produced by an individual after either natural exposure to the antigen or after immunization against the antigen? a. Active-acquired immunity b. Passive-innate immunity c. Passive-acquired immunity d. Active-innate immunity i. Active-acquired immunity or naturally acquired active immunity occurs when an individual is exposed to a live pathogen and develops the disease or becomes immune as a result of a vaccine 8. Which characteristics do atopic individuals have that make them genetically predisposed to develop allergies? a. Greater quantities of histamine b. More histamine receptors c. Deficiency in epinephrine d. Greater quantities of IgE i. The greater quantities of IgE in atopic individuals make them genetically predisposed to develop allergies. IgE mediates the immune response to allergens; therefore, the more IgE one has, the stronger the response can be to an allergen. Think of it as having more soldiers in the army to fight the war. 9. A healthcare professional is conducting community education on vaccinations. Which statement about vaccines should the professional include in the presentation? a. Most bacterial vaccines contain attenuated organisms b. Most viral vaccines are made by using dead organisms c. Vaccines require booster injections to maintain life-long protection d. Vaccinations provide effective protection against most infections i. Most vaccines require a booster to increase immunity. The initial effects of a vaccine may diminish over time, and boosters improve protection against disease. 10. Which term describes an agent’s ability to produce disease? a. Virulence b. Immunogenicity c. Pathogenicity d. Infectivity Genetics, Lifestyle, and Disease Management Vocabulary Terms • Differential Diagnosis • Definitive Diagnosis • Plan of Care • Referrals • Health literacy barriers • Patient education Review Questions 1. How do you incorporate genetic factors into formulation of differential/definitive diagnosis, plan of care and referrals? 2. How do you assess for health literacy barriers? What are some common health literacy barriers? a. The provider should be practice with cultural sensitivity and be educated on the cultural norms of the patient population they are caring for so they can incorporate these nuances into their communication and care planning. By addressing how genetics and lifestyle influence disease within the patient’s cultural framework, healthcare providers foster better engagement and understanding. 3. How do you address health literacy barriers when formulating a plan of care and patient education? a. Provide education that is tailored to the patient’s literacy level. Patients are better able to understand the significance of lifestyle adjustments in managing their condition. This empowers them to make informed, positive health decisions that complement medical treatments.