Advanced Pathophysiology NSG 530 STUDY GUIDE FOR QUIZ #1

Study the process of meiosis – specifically what occurs when homologous chromosomes fail to separate Human cell can be categorized into gametes (Sperm & egg cells) and somatic cells, which include all cells other than gametes. Each somatic cell nucleus has 46 chromosomes in 23 pairs. These are diploid cells, and the individual’s father and mother each donate on chromosome per pair. New somatic cells are formed through mitosis and cytokinesis. Gametes are haploid cells: they have only 1 member of each chromosome pair, for a total of 23 chromosomes. Haploid cells are formed from diploid cells by meiosis. A somatic cell has 23 pairs of chromosomes In meiosis I, chromosomes in a diploid cell resegregate, producing four haploid daughter cells. It is this step in meiosis that generates genetic diversity. DNA replication precedes the start of meiosis I. During prophase I, homologous chromosomes pair and form synapses, a step unique to meiosis. In meiosis a haploid cell is created from a diploid cell. What are the 8 stages of meiosis in order? Aneuploidy is caused by nondisjunction, which occurs when pairs of homologous chromosomes or sister chromatids fail to separate during meiosis. The loss of a single chromosome from a diploid genome is called monosomy (2n-1), while the gain of one chromosome is called trisomy (2n+1). Know the risk factors for down syndrome Nondisjunction occurs when homologous chromosomes (meiosis I) or sister chromatids (meiosis II) fail to separate during meiosis..... The most common trisomy is that of chromosome 21, which leads to Down syndrome. Down syndrome is a chromosomal disorder Down syndrome Best known example of aneuploidy Trisomy 21 1:800 live births Mentally retarded, low nasal bridge, epicanthal folds, protruding tongue, poor muscle tone Risk increases with maternal age 35 People who have down syndrome are at a higher risk for developing Alzheimer disease because of involvement of chromosome 21. 1 in 800 to 1 in 1000 live births are affected with Down syndrome. RISK FACTORS – increases greatly with material age. Younger than 30 have a risk of 1 – 1000 to 1 in 2000. After 35 risk increases greatly. By 45 and older a risk of 3% to 5% of children born will have down syndrome. This increase in risk is caused by the age of maternal egg cells, which are held in an arrested state of prophase 1 from the time they are formed in the female embryo until they are shred in ovulations. Thus, an egg cell formed by a 45-year woman is inself 45 years old. This long suspended state may allow defects to accumulate in the cellular proteins responsible for meiosis, leading to nondisjunction. The risk of Down syndrome, as well as other trisomies, does not increase with paternal age. Genetic diseases caused by single genes usually are autosomal dominant, autosomal recessive or X-linked recessive X-linked recessive disease are seen more often in males than in females. If the cells have three copies of each chromosome triploidy is present. Loss of chromosome material usually has more serious consequences than duplication of chromosome material. A Barr body is an inactivated X chromosome that is seen in normal female cells. Study transmission factors associated with Huntington’s disease Recurrence risk for autosomal dominant inheritance like Huntington’s Disease. Recurrence risk for autosomal dominant inheritance would be 50% if one parent was heterozygous for the trait, 75% if both parents were heterozygous, and 100% if either parent was homozygous for the trait. Autosomal dominant inheritance pattern Huntington disease is a single-gene disorder. Huntington's disease is caused by an inherited defect in a single gene. Huntington's disease is an autosomal dominant disorder, which means that a person needs only one copy of the defective gene to develop the disorder Study Turner’s syndrome – specifically what karyotype is associated with it A sex chromosome aneuploidy (a cell that does not contain a multiple of 23 chromosomes) condition that lead to somewhat more serious problems is the presence of a single X chromosome and no homologous X or Y chromosome, so that the individual has a total of 45 chromosomes. The Karyotype is usually designated 45,X and it cases a set of symptoms know as Turner syndrome. Turner syndrome Females with only one X chromosome Characteristics: Underdeveloped ovaries (sterile) Short stature (~ 4'7") Webbing of the neck Edema Underdeveloped breasts; wide nipples High number of aborted fetuses X is usually inherited from mother Turner’s syndrome is a chromosome disorder Aneuploidy is usually the result of nondisjunction (an error in which homoloegous chromosomes or sister chromatids fail to separate normally during meisosis or mitosis) A karyotype or karyogram is an ordered display of chromosomes. A display of chromosomes ordered according to length and centromere locations is called a karyotype Study Klinefelte disorder. Specifically, what karyotype is associated with it Individuals with at least two X chromosomes and 1 Y chromosomes in each cell (47, XXY karyotype) have a disorder known as Klinefelter syndrome. Klinefelte is a chromosome disorder People who have the 47, XXY karyotype have klinefelte disorder Klinefelter syndrome Individuals with at least two Xs and one Y chromosome Characteristics Male appearance Develop female-like breasts Small testes Sparse body hair Long limbs Some individuals can be XXY and XXXY The abnormalities increase with each X Know the basics of CF (you should all know this well given our excellent discussion posts last week) but know if it’s dominant, recessive etc CF is autosomal recessive and a single gene disorder A recessive gene will be expressed only if it is present in two copies. The gene repressible for CF encodes a chloride ion channel in some epithelial cells. Defective transport of chloride ions lead to a salt imbalance that results in secretions of abnormally thick, dehydrated mucus. Some digestive organs, particularly the pancreases, become obstructed, causing malnutrition, and the lungs become clogged with mucus, making them highly susceptible to bacterial infects. Death from lung disease or heart failure occurs before 40 years of age in about half of person with CF. The important criteria for discerning autosomal recessive inheritance include the following. 1. Males and females are affected in equal proportions. 2. Consanguinity (marriage between related individuals) is sometimes present especially for rare recessive disease/ 3. The disease may be seen in siblings of affected individual but usually not in their parents. 4. On average one fourth of the offspring of carrier’s parents will be affected. Know the difference between adaptive (specific immunity) and Innate Immunity Innate immunity is something already present in the body. INNATE IMMUNITY Physical barriers: Innate, or nonspecific, immunity is the defense system with which you were born. It protects you against all antigens. Innate immunity involves barriers that keep harmful materials from entering your body. These barriers form the first line of defense in the immune response. Examples of innate immunity include: Innate immunity also comes in a protein chemical form, called innate humoral immunity. Examples include the body's complement system and substances called interferon and interleukin-1 (which causes fever). If an antigen gets past these barriers, it is attacked and destroyed by other parts of the immune system. Adaptive immunity is created in response to exposure to a foreign substance. Once activated against a specific type of antigen, the immunity remains throughout the life ...... Adaptive immune system is composed of B cells and T cells a. Purposes: Destruction of infectious microorganisms that are resistant to inflammation Long-term, highly effective protection against future exposure to the same microorganism Overview of human defenses Characteristics Physical and Biochemical Barriers and the Human Microbiome Innate Immunity Adaptive (Acquired) Immunity Level of defense First Line of defense against infection and tissue injury Second line of defense, occurs as response to tissue injury or infection (inflammatory response) Third line of defense, initiated when innate immune system signals cells of adaptive immunity Timing of defense Constant Immediate response Delay between primary exposure to antigen and maximal response, immediate against secondary exposure to antigen Specificity Broadly specific Broadly specific Response is very specific toward antigen Cells Epithelia cells Microbiome Mast cells, granulocytes (Neutrophils, eosinophils, basophils) monocytes/macrophages, natural killer (NK) cells platelets, endothelial cells. T lymphocytes, B lymphocytes, macrophages, dendritic cells Memory No memory involved No memory involved Specific immunologic memory by T and B lymphocytes Active molecules Defensins, cathelicidins, collectins, lactoferrin, bacterial toxins Complement, clotting factors, kinins, cytokines Antibodies, complement, cytokines Protection Protection includes anatomic Physical barriers (i.e. skin and mucous membranes) Epithelial Cell -Derived chemicals: Cell and secretory molecules (e.g. lysozymes, low pH of stomach and urine), and ciliary activity Normal Microbiome Protection includes vascular responses, cellular components (e.g. mast cells, neutrophils, macrophages), secretory molecules or cytokines, and activation of plasma protein systems. Clotting system Protection includes activated T and B lymphocytes, cytokines, and antibodies. Study immune reactions. You will be given a scenario and asked to specify if it’s IgE, Tissue specific, cell mediated, immune complex…so know your immune reactions Immunoglobulin E (IgE) is an antibody that is produced by the body’s immune system and is associated with allergic responses, including asthma, and to a lesser degree with immunity to parasites. The total IgE test may be used to screen for and detect allergic diseases. Least concentrated of the immunoglobulin classes in the circulation Mediator of many common allergic responses Defender against parasites a. Provides protection from large parasites Initiates an inflammatory reaction to attract eosinophils b. When produced against innocuous environmental antigens, they are a common cause of allergies Fc portions of IgEs are bound to mast cells The tissue-specific genes are a group of genes whose function and expression are preferred in one or several tissues/cell types. Identification of these genes helps better understanding of tissue–gene relationship, etiology and discovery of novel tissue-specific drug targets. Tissue Specific Promoters are active in a specific type of cells or tissues such as B cells, monocytic cells, leukocytes, m acrophages, muscle, pancreatic acinar cells, endothelial cells, astrocytes, lung... Cell-mediated immunity is an immune response that does not involve antibodies, but rather involves the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. Action by the immune system involving T cells (T LYMPHOCYTES) and concerned with protection against viruses, fungi, TUBERCULOSIS and cancers and rejection of foreign grafted material. Cell-mediated immunity is not primarily effected by ANTIBODIES. Immune complex is the term used to refer to the combination of an antibody with its antigen. Immune complexes must be removed from tissues and kept from accumulating in the circulation and forming deposits throughout the body. Failure to clear immune complexes can lead to autoimmune disease. Study color blindness and risk factor for developing it (look for more in book). Color deficiency is usually a hereditary condition. The trait is passed on the X chromosome, and because males only have one X chromosome, it is easier for them to inherit color vision deficiency. A mother who carrier’s one normal X chromosome and one X chromosome with a mutation of red and/or green pigments is not affected, but her son has a 50% chance of having a color vision deficit. Fathers cannot pass it to their sons, because they supply only a Y chromosome to the genetic mix, but they can pass the gene to their daughters who carry the gene but do not manifest a color deficit. Abnormal color vision also may be caused by color blindness and is an X-linked genetic trait. Color blindness affects 6 to 8% of the male population and about 0.5% of the female population. Although many forms of color blindness exist, most commonly the affected individual cannot distinguish red from green. In the most severe form individuals see only shades of grey, black, and white.