Review for path Flashcards

Question

What are the causes of trisomy 21?

Answer 1

95% due to trisomy nondisjunction associated with maternal age. 4% due to Robertsonian translocation between chromosome 21 & 14 or 22

Answer 2

Edwards syndrome. Clinical features: Clinical features Prominent occiput, Intellectual disability, low set ears, overlapping fingers, short neck, congenital heart diseases, renal malformations, limited hip abduction, rocker feet

Answer 3

patau syndrome. Clinical features Microcephaly, intellectual disability, microphthalmia, cleft lip/palate, polydactyl, cardiac defects, renal defects, umbilical hernia, rocker feet

Answer 4

Cri du chat. Clinical features Microcephaly, round faces, characteristic cry of a kitten, mental retardation

Answer 5

``` DiGeorge syndrome. Deletion in 1 chromosome id detected by FISH Clinical features Cardiac Abnormal faces Thymic aplasia Cleft palate Hypocalcemia CATCH!!! ```

Answer 6

Rearrangement of genetic material giving rise to visible structural changes Changes are transmitted only infrequently since most are incompatible with survival

Answer 7

Missense or point mutation frameshift Nonsense

Answer 8

Alters the code in a triplet of bases leading to replacement of 1 amino acid by another. Two types: Conservative or Non- conservative ex. Sickle cell mutation

Answer 9

change in the DNA sequence that leas to a stop codon. Ex. beta thalassemia

Answer 10

Small deletions or insertions involving the coding sequence leads to alteration in the reading frame of the DNA strand NO frameshift: If the number of nucleotides involved is 3 or a multiple of 3 YES frameshift: If the number of nucleotide bases involved is OTHER THAN A MULTIPLE OF 3 Trinucleotide Repeat Ex. Fragile X

Answer 11

these are defects that reduce activity or there may b e a reduce amount of normal enzyme and causes a metabolic block.

Answer 12

Accumulation of the substrate, decreased amount of end product, failure to inactivate a tissue damaging substrate.

Answer 13

Marfans EDS, Familial hypercholesterolemia

Answer 14

it is a structural protein defect: disrupted microfibril assembly through a missense mutation. It has a variable clinical presentation, ranging from mild to severe systemic disease.

Answer 15

it is with the Fibrillin -1. it is secreted by fibroblast. there is a mutation of the FBN1 gene at chromosome 15q21.

Answer 16

Tall stature, lax joints, tapered fingers, dislocated lens, aortic arch aneurysms. it occurs every 1 in 5000 with the transmission through autosomal dominant.

Answer 17

components of the extracellular matrix consisting primarily of fibrillin, essential for the integrity of elastic fibers.

Answer 18

Mutation in the FBN-2 gene

Answer 19

Congenital Contractural Arachnodactyly (CCA) is characterized by a Marfan-like appearance (tall, slender habitus in which arm span exceeds height) and long, slender fingers and toes Contractures of major joints (knees and ankles) at birth; Hip contractures, adducted thumbs, and club foot may occur

Answer 20

Structural protein defect: defective collagen synthesis Autosomal dominant and autosomal recessive Gene: ADAMTS2, COL1A1, COL1A2, COL3A1

Answer 21

``` Classical ( type1 and 2 - Type V Procollagen, COL5A1 and A2) : characterized with skin hyper extensibility, joints and ligament hyper mobility, widened atrophic scarring. Hyper mobility (type 3 - tension X and TNX-B): characterized by joint hyper mobility Vascular (type 4 - Type 3 Procollagen and COL3A1) Excessive Brusing, Arterial Fragility Kyphoscoliosis ( type 6 Lysyl Hydroxylase 1, LH-1 (PLOD1)) characterized by scleral Fragility, Hypotonia ```

Answer 22

Receptor Protein Defect: LDL Receptor defect Causing: elevated Plasma LDL levels, impaired cholesterol transport across liver cells, accumulation of cholesterol leading to Xanthomas, increased risk of Myocardial Infarction “Scavenger System” for cholesterol clearance includes phagocytosis by Macrophages (foamy macrophages)

Answer 23

Types Class I mutations: relatively uncommon, complete failure of synthesis of the receptor protein (null allele) Class II mutations: fairly common, the receptor protein is synthesized, but its transport from Endoplasmic Reticulum to Golgi Apparatus is impaired Class III mutations: affect the LDL-binding domain of the receptor Class IV mutations: Receptors fail to internalize after binding

Answer 24

Transport Protein Defect: impaired transport system for chloride ions Leads to serious injury to the lungs and pancreas, viscid mucous secretions block airways and ducts, meconium ileus, steatosis, infertility Mutations in transmembrane conductance regulator (CFTR) gene at chromosome locus 7q31.2 CFTR gene inheritance is Autosomal Recessive

Answer 25

Single gene mutation causes multiple phenotypic changes

Answer 26

Phenylketoruria

Answer 27

Inborn error of metabolism Caused by any mutation (pretty much) in the gene that codes for phenylalanine hydroxylase Normally converts phenylalanine to tyrosine Mutation will result in diminished or absent conversion Phenylalanine concentrations will hit toxic levels and cause systemic tissue damage

Answer 28

When one of the lysosomal enzymes is missing, complete breakdown of the molecule is not possible. This leads to the accumulation of the incompletely digested molecule within the cell. The lysosomes and subsequently the cell and the organ increase in size. Normal cellular function is compromised significantly.

Answer 29

Ex: Gaucher disease Most prevalent lysosomal storage disorder. Deficiency of glucocerebrosidase, which is a lysosomal enzyme. Inherited in an autosomal recessive manner. Accumulation of glucocerebroside in the cells of the bone marrow, liver, and spleen. Hallmark of Gaucher disease, a lipid-filled macrophage containing the undigested glucosylceramides that accumulates

Answer 30

Mucopolysaccharidoses are a group of disorders caused by a deficiency of the lysosomal enzymes normally required for the degradation of glycosaminoglycans (mucopolysaccharides). The glycosaminoglycans are dermatan sulfate, heparin sulfate, keratin sulfate, and chondroitin sulfate. There are 10 subtypes of this disorder, all but 1 of which are transmitted as autosomal recessive.

Answer 31

There is a hereditary deficiency of one of the enzymes involved in the synthesis or degradation of glycogen. As in most enzyme deficiencies, the majority of the subtypes are transmitted as autosomal recessive. In the hepatic forms of the condition, enzyme deficiency results in organomegaly, principally hepatomegaly, and impaired glucose release into the circulation, leading to hypoglycemia

Answer 32

Ex: Type I aka Von Gierke Disease Deficiency of glucose-6-phosphatase Enzyme required for the conversion of glucose 6-phosphate to glucose, Glucose 6-phosphate & glycogen accumulates within the liver (hepatocytes) Defects in Receptors and Transport Systems

Answer 33

Found in places that prevent microbe entry: epithelial barriers of skin, GI & respiratory tracts Cells: neutrophils, macrophages, NK cells

Answer 34

Cells: lymphocytes and their products “Immune system” and “immune response” refer to adaptive immunity Two types: Humoral & Cellular

Answer 35

Humoral B cells Antibody mediated Antibodies provide protection against extracellular microbes in the blood, mucosal secretions, and tissues

Answer 36

T cells Cell mediated T lymphocytes are important in defense against intracellular microbes Cytotoxic T cell: kill directly Helper T cells: activate macrophages to kill

Answer 37

Type of antigen presenting cell Ingest microbes and other particulate antigens Display peptides for recognition by T cells which then activate the macrophages to kill microbes

Answer 38

Mature in thymus DO NOT detect free circulating antigens 95% only recognize peptide fragments of protein antigens bound to major histocompatibility complex (MHC) Function by interacting with other cells To kill infected cells To activate phagocytes or B cells Peptide antigens presented by self MHC molecules are recognized by the T cell receptor (TCR), TCR is a heterodimer composed of disulfide-linked a and b protein chains

Answer 39

Mature in bone marrow A type of antigen presenting cell Present peptides to helper T cells and receive signals that stimulate antibody responses to antigens Found in Follicles of lymph nodes, spleen, tonsils, mucosal tissues and bone marrow Antigens IgG: crosses maternal membrane in pregnancy IgM IgA: major isotope in mucosal secretion IgE: found attached to surfaces of Mast cells IgD: expressed on the surfaces of B cells but is not secreted

Answer 40

Cell types that are specialized to capture microbial antigens and display these to lymphocytes

Answer 41

Types: dendritic cells, macrophages, B cells

Answer 42

Cells that are in the innate immunity that are not expressed high variable and colonially distributed receptors for antigens. they don't have adverse specificities.

Answer 43

Inhibitory and activatting

Answer 44

Inhibitory: recognize self MHC I molecules, which are expressed on all healthy cells

Answer 45

Activating: recognize molecules that are expressed or upregulated on stressed or infected cells or cells with DNA damage

Answer 46

Inhibitory

Answer 47

Infections (ESP viral) and stress= reduced expression of MHC I molecules, thus: Releasing the NK cells from inhibition Increased engagement of ACTIVATING receptors

Answer 48

are a broad and loose category of small proteins (~5–20 kDa) that are important in cell signaling. They are released by cells and affect the behavior of other cells. Cytokines can also be involved in autocrine signaling. Synthesized and secreted in response to external stimuli: microbial products, antigen recognition, or other cytokines Secretion typically is transient and controlled by transcription and post-translational mechanisms

Answer 49

Innate Immunity and Inflammation | TNF, IL-1, Chemokines, IL-12, IFN-g, IL-6, IL-23, IL-17 (Recruits Neutrophils)

Answer 50

IL-2 (Stimulates T cell Proliferation), IL-4 (Proliferation and Differentiation of Lymphocytes, Stimulates B cells to Differentiate into IgE-secreting Plasma cells), IL-5 (Activates Eosinophils), IFN-g (Activates Macrophages, Stimulates B cells to produce antibodies), IL-13 (Activates Mucosal Epithelial Cells, Activates Macrophages to Secrete Growth Factors) Hematopoiesis Stimulation: Colony Stimulating Factors

Answer 51

Cell-mediated immunity and inflammation Induced by: IL-12, IFNγ Triggered reaction: macrophage activation, stimulation of IgG production Host defense against: intracellular microbes viruses, bacteria Role in disease: immune-mediated chronic inflammation diseases (often autoimmune)

Answer 52

Antibody-mediated immunity Induced by: IL-2 Triggered reaction: stimulation of IgE production, activation of mast cells and eosinophils Host defense against: helminthic parasites Role in disease: allergies, asthma

Answer 53

Extracellular bacteria on skin, lining of intestine Induced by: IL-17, IL-22, chemokines Triggered reaction: recruitment of neutrophils, monocytes Host defense against: extracellular bacteria, fungi Role in disease: immune-mediated chronic inflammation diseases (often autoimmune)

Answer 54

Type I: Immediate IgE mediated hypersensitivity Initiation time: 20-30 minutes Phases Exposure to allergen phase Th2, CD4 + T cell activation leads to B cell production of IgE IgE binds to Fc receptors on mast cells Immediate phase: mast cell degranulates releasing histamine, vasodilation, vascular leakage, smooth muscle contraction, broncho spasm Late phase (hours, days): eosinophils, PMNs, T cells Ex: acute allergic reaction, systemic bee venom, drug anaphylaxis S/sx: itching, urticaria (hives), skin erythema, bronchoconstriction, mucus hypersecretion, laryngeal edema, abdominal cramps, hypotension, anaphylactic shock

Answer 55

Type II Antibody-mediated cytotoxic hypersensitivity Initiation time: 5-8 hours Antibodies bind to fixed tissue or cell surface antigens OPSONIZATION of cells by antibodies PHAGOCYTOSIS of opsonized cells COMPLEMENT FIXATION (cascade of C1q, C1r, C1s, C2, C3, C4, C5….. ) Antibodies bind Fc Receptors of Leukocytes Ex: Good pasture Syndrome, Pemphigus Vulgaris LYSIS: destruction of cells by membrane lysis ANTIRECEPTOR Antibodies disturb receptor function Anti-TSH Receptor Anti-Ach Receptor Ex: Graves Disease, Myasthenia Gravis

Answer 56

Type III Immune complex-mediated hypersensitivity Initiation time: 2-8 hours Antibodies bind to antigens these complexes circulate and deposit in: kidneys, blood vessels, skin, joint fluid (synovium) Vasculitis if it occurs in blood vessels Glomerulonephritis if it occurs in renal glomeruli Arthritis if it occurs in the joints Compliment activation and acute inflammation

Answer 57

``` Type IV Cell-mediated hypersensitivity Initiation time: 24-72 hours Cells involved: CD4+ Th1 & Th17, CD8+ cytotoxic T cells Ex: TST reaction Direct antigen contact with cells Granuloma formation Contact dermatitis ```

Answer 58

Occurs within minutes hours of transplant Occurs when preformed antidonor antibodies are present in recipient circulation Early lesions point to an antigen-antibody reaction Accumulation of neutrophils within arterioles, glomeruli, and peritubular capillaries Fibrinoid necrosis of arterial wall/necrosis of renal cortex

Answer 59

Occurs within Days of transplant Cell mediated and antibody mediated reactions Acute cellular rejection and acute rejection vasculitis Acute cellular rejection – interstitial mononuclear cell infiltration (lymphocytes), edema and hemorrhage Acute rejection Vasculitis – alterations in the intima of the arteries – thickened by – proliferating fibroblasts, monocytes & macrophages – luminal narrowing / immunoglobulin and complement deposits on the wall

Answer 60

Occurs over a period of 4-6 Months after transplant Vascular changes – intimal Fibrosis of cortical arteries – renal Ischemia – interstitial fibrosis, tubular atrophy and shrinkage of renal parenchyma Chronic cell mediated rejection, interstitial mononuclear cell infiltrates, plasma cells and numerous eosinophils

Answer 61

Hashimoto Thyroiditis, Autoimmune Hemolytic Anemia, Multiple Sclerosis, Autoimmune Orchitis, Goodpasture Syndrome, Autoimmune Thrombocytopenia (Itp), “Pernicious” Anemia, Insulin Dependent Diabetes Mellitus, Myasthenia Gravis, Graves Disease

Answer 62

SLE, RA, Shjogren syndrome

Answer 63

It is the human leukocyte system in the MHC

Answer 64

It is located on Chromosome 6

Answer 65

``` Class I (A, B & C) antigens are expressed on all nucleated cells and platelets Class II (DR, DP & DQ) antigens are expressed only on APCs ```

Answer 66

Each person expresses a unique MHC antigenic profile on his or her cells HLA matching is important in transplantation Any cell displaying some other HLA type is "non-self" and is “foreign”, resulting in the rejection

Answer 67

At the site of microbe entry, epithelia serve as physical barriers to infections and eliminate microbes through production of peptide antibiotics and the actions of intraepithelial lymphocytes The microbes encounter phagocytes and neutrophils, rapidly recruited from the blood into the tissues being invaded The microbes also encounter resident macrophages which ingest microbes and destroy them In response to recognition of microbes, phagocytes, dendritic cells, and many other cell types secrete cytokines Promote inflammation and enhance protective immune responses Immune Cells Recognize bacterial and viral components through Toll-like Receptors (TLRs) Natural Killer (NK) Cells Kill virus-infected cells and produce the macrophage-activating cytokine IFN-γ If the microbes enter the blood, many plasma proteins recognize the microbes and are activated Their products kill microbes and opsonize (coat) the microbes for phagocytosis Microbes are captured by dendritic cells that are resident in and under epithelia Protein antigens are proteolytically digested in the APCs to generate peptides that are displayed on the surface of the APCs bound to MHC molecules Antigen-bearing dendritic cells then Migrate to draining Lymph Nodes

Answer 68

the principle co-stimulators for T cell are B7 molecules

Answer 69

Signal one: through T cell receptor Signal two: through B7 molecules If T cell fails to receive signal two, cell dies by apoptosis If second signal is not provided, T cells can be tricked to not respond causes CA

Answer 70

Antigen recognition in lymphoid organs T cell proliferation and differentiation Differentiated effector and memory T cells enter circulation Migration of effector T cells to site of antigen Results CD4+ effector T cells & phagocytes= macrophage activation: killing ingested microbes Cytokine secretion= inflammation CD8+ T cells & infected cell with microbe in cytoplasm= killing of infected cell