Combo 1

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What translocation and affected genes responsible for Mantle cell lymphoma?

(11;14)(q13;q32) CCND1: 11q13 IGH: 14q32

What translocation and affected genes responsible for Ewings sarcoma?

(11;22)(q24;q12) FLI1: 11q24 EWSR1: 22q12

What translocation and affected genes responsible for Follicular lymphoma?

(14;18)(q32;q21) IGH: 14q32 BCL2 18q21

What translocation and affected genes responsible for Prostatic adenocarcinoma?

(7;21) (p22;q22) (17;21) (p21;q22) TMPRSS2 (21q22.3) ETV1 (7p21.2) ETV4 (17q21)

What translocation and affected genes responsible for Burkitt lymphoma?

(8;14)(q24;q32) MYC: 8q24 IGH: 14q32

What translocation and affected genes responsible for Acute myeloid leukemia (AML)

(8;21)(q22;q22) (15;17)(q22;q21) AML: 8q22 ETO: 21q22 PML: 15q22 RARA: 17q21

What translocation and affected genes responsible for Chronic Myelogenous Leukemia (CML)

(9;22)(q34;q11) ABL: 9q34 BCR: 22q11

Class I HLA characteristics?

(A, B, and C) Expressed on all nucleated cells. Present endogenous antigens (viral) to Cytotoxic T cells. Highly polymorphic Composed of an alpha chain and B2 microglobulin (coded outsided of MHC) * B2 microglobulin is required for class I HLA to work, if missing then the HLA would just fold over itself* A1 and A2 domains form a cleft and bind to short peptides approximately 8-10 aa in length. Hydrophobic transmembrane region

Lactase-glucosylceramidase breaks down what?

(B-glycosidase complex (lactase) breaks down lactose) Low activity Rate-limiting enzyme for lactose absorption Hydrolyzes B-1,4 bond (found in lactose) Hydrolyzes B bond in glycolipids.

Sucrase-isomaltase breaks down what?

(Sucrase = sucrose, isomaltase-maltase = branch chains a-1,6 bonds like isomaltase, etc) Sucrase part breaks down sucrose. Isomaltase-maltase part breaks down a-1,6 branches (isomaltose)

What does glucoamylase break down?

(breaks down maltose, maltotriose, etc. to monosaccharides) Exoglucosidase: Specific for a-1,4 glycosidic bonds Hydrolyzes sequentially from nonreducing (the o between sugars) end to form monosaccharides Breaks down maltose, maltotriose Is heavily glycosylated to protect from digestion.

Trehalase breaks down what?

(trahalose) Cleaves trehalose (found in mushrooms, honey, and shrimp) Only enzyme that can cleave trahalose (a-1,1 bond) Trehalase deficiency has symptoms similar to a-amanitin poisoning (diarrhea, liver and kidney failure, death - this is that poisonous mushroom) Cleaves a-1,1 bond

Adaptive immunity characteristics

*B and T lymphocytes* - Highly specific - Extensive diversity - Memory - Self limiting

Clinical importance of stem cells (3)

*Bone marrow transplants* - Must carefully match MHC (major histocompatibility complex) to prevent graft rejection. *Graft vs host disease* (GVHD) *Gene therapy* - SCID (severe combined immunodeficiency - bubble boy) - ADA deficiency (Adenosine deaminase deficiency), replace the gene in HSC's (hematopoietic stem cells)

B lymphocytes

*Bone marrow* Membrane bound Ig (immunoglobulin), serves as receptor for antigen Develop into plasma cells and memory cells All clonal progeny from a given B cell secrete Ab (antibody) molecules with the same Ag (antigen) binding specificity. B cells can bind to anything; sugars, lipids, or proteins. Responsible for generating antibodies, plasma cells are terminally differentiated B cells. b cells become plasma cells whose job is to just secrete antibodies and then die.

T helper cells (TH cells)

*CD4+* Recognize antigen in associated with class II MHC (exogenous antigen) Activated following recognition of Ag-class II MHC on antigen presenting cells (APC's) Activated TH cells divide and give rise to clones of effector cells which secrete various cytokines and play a major role in B cell and TC cell activation and the inflammatory response - TH1- activates Tc, MØ (macrophage), drives isotype switching to IgG. - TH2- activates B cells, drives isotype switching to IgE - TH17- inflammation, extracellular bacterial and fungal infections.

Cytotoxic T cells (Tc cells)

*CD8+* Recognize antigen in association with class I MHC (endogenous antigens) Activated following recognition with Ag-class I MHC complex Secretes few cytokines Directly recognizes and kills target cells (virus infected and intracellular bacteria)

IgG

*Class switching occurs via TH1 cells and IFN-γ* IgG can participate in many immune functions including: - Opsonization - Antibody dependent cellular cytotoxicity (ADCC) - Activation of classical complement - Only antibody that can cross the placenta It is the predominant antibody in the serum It is a high affinity antibody and predominates during the secondary immune response 4 subisotypes IgG1, IgG2, IgG3 and IgG4

IgE

*Class switching occurs via secretion of IL-4 and IL-13.* Low levels in plasma Binds to mast cells and basophils and causes them to degranulate. Used to kill parasites. Responsible for type I hypersensitivity.

IgA

*Class switching occurs via secretion of TGF-β* and to a lesser extent IL-4, IL-10, iNOS, and retinoic acid. This occurs predominantly in the mucosa. Predominant antibody in the secretions: mucosal surfaces, saliva, tears, nasal fluids, sweat, colostrum (first form of milk produced in mammary glands) and breast milk In secretions present as a dimer, so it can bind 4 antigens. Protected in secretion by secretory piece

*Fixation* is usually done by a chemical or mixture of chemicals, permanently preserves the tissue structure for subsequent treatments. Specimens should be fixated immediately after removal from body. Fixation is used to: -Terminate cell metabolism - Prevent enzymatic degradation of cells and tissues by autolysis (self-digestion). - Kill pathogenic microorganisms such as bacteria, fungi, and viruses. - Harden the tissue as a result of either cross-linking or denaturing protein molecules.

*Fixation*

Activation of Macrophages induces what?

*Inflammation* 1. Phagocytosis 2. Production of cytokines 3. Recruitment of neutrophils 4. Diapedesis (the passage of blood cells through the intact walls of the capillaries, typically accompanying inflammation.) All 4 of these actions leads to *inflammation*.

Immune system cells

*Lymphoid* - B cells, T cells, Null cells (NK cells) *Mononuclear cells* - Macrophages (MØ) - Granulocytes -- Neutrophils, Eosinophils, Basophils, Mast cells - Dendritic cells

IL-2 characteristics

*Made by T cells.* Autocrine regulation Main function is activating cytotoxic T cells.

What does Il-4 do?

*Made predominantly by Th2 cells.* Essential for class switching (along with IL-13) to IgE. Activates Th2 pathway and inhibits Th0 and IFN-y (and therefore macrophage activation). Main function is B cell activation and lass switching to IgE. IL-4 can also induce eosinophil development and differentiation.

Natural killer cells (NK cells)

*No B/T cell markers* No specific receptor for antigen (Ig/TCR) Cytotoxic activity against a wide array of tumors Receptor for antibody (CD16)-ADCC Chediak-Higashi (autosomal recessive) No NK cells- increased incidence in lymphomas.

T lymphocytes

*Thymus* Membrane receptors for Ag (antigen), similar to Ig (TCR (T-cell receptor)) TCR (T-cell receptor) only recognizes Ag (antigen) in association with MHC (Major histocompatability complex) 2 major subsets (2:1) - TH (T- helper cells (high maintenance)) (CD4+) - TC (T- cytotoxic cells) (CD8+) These are the most important cells of the immune response. Can only recognize protein. Don't just go out and recognize antigen, every single antigen has to be handed to them called MHC (major histocompatability complex). Much more high maintenance to B cell. All T cells have CD3. CD4 found in TH. CD8 found in TC.

Nonessential amino acids are synthesized from four common metabolites, what are they?

- *Pyruvate* (alanine) - *Oxaloacetate* (aspartate, asparagine) - *a-Ketoglutarate* (glutamate, glutamine, proline, arginine*) - *3-phosphoglycerate* (serine, glycine, cysteine) *arginine essential only during growth (phenylalanine -> tyrosine) (Tyrosine and Cysteine conditional nonessential because phenylalanine and methionine needed to synthesis in the body respectively)

Liver's role in central receiving, recycling

- Compounds entering blood via digestive tract must go through liver 1st (enterohepatic circulation) - Retrieves usable portions - Removes toxic compounds - Can make many different molecules from many different precursors (e.g. cen convert all protein amino acids to glucose, FA, or KB)

Maple syrup urine disease symptoms

- Distinct sweet odor of urine - Poor feeding, vomiting - Lethargy - Abnormal movements - Delayed development - Seizures, coma, and death possible without treatment.

Affinity maturation

- In the course of a humoral response, the average affinity of the antibodies produced increases by 100-10,000 fold - This is the result of somatic hypermutation and the Ag selection of high affinity clones - Somatic mutation - point mutations, deletions, or insertions into the V,D, or J region of rearranged Ig genes - The majority of mutations occur in the variable regions - Higher affinity antibodies are positively selected, lower affinity antibodies are signaled to die by apoptosis So the reason IgG, IgA, and IgE have higher affinity than IgM is because of affinity maturation. During T cell dependent B cell response, B cells start proliferating in the germinal centers, dividing quickly and acquiring somatic mutations (point mutations, deletions, or insertions) in the variable region. The mutations that are good and increase binding affinity to antigen stay and those B cells divide and make copies of itself. Those that bind not so well, or just okay, get killed by apoptosis. When we get these high affinity antibodies the B cells class switch so that only the IgG, IgE, IgA ones have these high affinity antibodies.

Management of patient with liver cirrhosis

- Irreversible in later stages - Alcohol abstinence - Avoiding superimposed insults to live (up-to-date with vaccinations, avoiding hepatotoxins) -Management of symptoms and prevention of complications.

How are amino acids transported into cells from the blood

- Primarily by Na+ dependent cotransporters. - Different genes and amino acid composition, specificities similar to transporters in intestinal cells.

Mild to moderate intensity long-term exercise

- Release of lactate decreases over the course of the exercise due to aerobic use of glucose and fatty acid becoming predominant. - Liver maintains blood glucose via liver glycogenolysis and gluconeogenesis. Both glycogenolysis and gluconeogenesis stimulated by epinephrine (and glucagon in liver). -Muscle AMPK stimulates GLUT4 translocation (increase glucose uptake). After ~40 min, increased dependence on FA. - Liver glucose output decreases - FA dependence becomes greater w/ increasing exercise duration - Type I slow-twitch oxidative fibers Hormonal signals include decreased insulin and elevated glucagon, epinephrine, and norepinephrine. GH, cortisol, and TSH may also contribute.

Alcaptonuria symptoms

- Urine turns black when exposed to air. - Ochronosis, a buildup of dark pigment in connective tissues such as cartilage and skin, as well as in sclera of eyes. (Blue-black pigmentation usually appears after age 30.) - Often develop arthritis (spine and large joints) (early adulthood)

Free energy change of ATP-> ADP

-31 kJ/mol, occurs via hydrolysis

Cystinuria

-Defect in transport of amino acids, decreased resorption of amino acids in kidneys ( means more in urine). - Kidney stone formation due to insolubility of cystine.

Problems with amino acid metabolism: Phenylalanine and tyrosine (3)

-Inborn errors of metabolism - States required to test for these PKU, Alcaptonuria, and Tyrosinemia I PKU: defective phenylalanine hydroxylase (PAH) leads to hyperphenylalaninemia, irreversible mental retardation, delayed psychomotor skills, tremors, seizures, hyperactivity. lifelong dietary modification needed. Alcaptonuria: Homogentisate oxidase is defective, homogentisate accumulates, auto-oxidizes to a dark pigment that is excreted in urine. Tyrosinemia I: Genetic deficiency in fumarylacetoacetate hydrolase; fatal within first year of life. Phenylalanine + *Phenylalanine hydroxylase* (causes PKU) -> Tyrosine + PLP + *Tyrosine aminotransferase* (causes tyrosinemia II) -> p-hydroxyphenylpyruvate -> Homogentisate + *homogentisate oxidase* (causes alcaptonuria) -> -> *fumarylacetoacetate hydrolase* (causes tyrosinemia I) -> fumarate and acetoacetate

Monosaccharides

-fructose (some fruit, "soda pop") -Ribose (from DNA & RNA) - Glycerol (from triglycerides)

Lipases are regulated by?

-insulin (to allow FA uptake by tissues; LPL) -insulin counter-regulatory (lipolysis to release FA; HSL) Glucagon, epinephrine, cortisol HSL = hormone-sensitive lipase fed state = LPL fasting state = HSL exercise (HSL)

DIsaccharides

-lactose -sucrose -maltose

1. A-band (dark band): Everything that includes all the myosin. 2. H band: Contains myosin but no actin. 3. I band (light band): Contains actin but no myosin. 4. M band: Bunch of proteins that hold myosin in place. 5. Z disk or z line: Helps hold actin in place. 1 sarcomere is Z line to z line. 6. Connects cytoskeleton & extracellular matrix.

1. A-band 2. H band 3. I band 4. M band 5. Z disk or z line 6. Dystrophin protein

Assessing liver function via? (6)

1. ALT (alanine aminotransferase) and AST (aspartate aminotransferase) 2. Amino acids in serum 3. Urea 4. Bilirubin 5. Alkaline phosphatase (ALP) & y-glutamyl transferase (GGT) 6. Lipid profile, fasting blood glucose are also informative. - Cirrhosis patients tend to have higher fasting and postprandial (after a meal) blood glucose

6 different fates of glucose

1. Acetyl-CoA 2. Pentose Phosphate 3. Amino sugars (->glycosaminoglycans) 4. Glycogen 5. Lactate 6. Fructose, lactose.

T helper cell- Macrophage interaction

1. Antigen/MHC/T cell receptor complex formed. 2. Co-stimulatory molecules bind CD28 (on T cell) and B7 on (APC, macrophage in this case). 3. Cytokines are released by macrophage, specifically IL-1 or IL-12. 4. Upregulate IL-2 receptor after IL-1 or IL-12 received by T cell. Increase affinity of the IL-2 receptor for IL-2 molecules. 5. Make their own IL-2 molecules. IL-2 is by T cells for T-cells, T cells make it and T cells use it. T cells release IL-2 molecules to bind to the IL-2 receptor on its own surface. 6. When IL-2 molecules bind to IL-2 receptors it stimulates production of Interferon gamma (IFN-y). INF-y is a major cytokine that turns on macrophages and makes them upregulate everything. Also causes class switching to IgG. IL-2 is also essential for activating cytotoxic T cells (CD8). IgCAM and Integrin bind to each other (adhesion molecules) to facilitate this interaction. CTLA-4 is the downregulator of CD28. At the end of this process when we need to shut down CD28/B7 interaction we increase expression of of CTLA-4. TH1 response is equivalent to a type 4 hypersensitivity or delayed type sensitivity reaction.

5 roles of liver

1. Blood glucose homeostasis 2. Metabolism 3. Synthesis of proteins 4. Synthesis of N-containing molecules 5. Detoxification

What are the enzymes in urea cycle found in mitochondria

1. Carbamoyl Phosphate synthetase I (CPSI) 2. Ornithine transcarbamoylase

11 functions of the liver

1. Central receiving and recycling. 2. Synthesis/recycling of blood 3. Regulation of blood glucose 4. Synthesis, export of cholesterol and TG 5. Ketone body formation 6. Synthesis of nitrogen containing compounds 7. Detoxification 8. Ammonia depot, urea cycle 9. Nucleotide biosynthesis 10. Synthesis of glycoproteins, proteoglycans 11. Pentose phosphate pathway

What are some of the minor regulators of stimulating insulin release (3)

1. Certain amino acids 2. gastric inhibitory peptide 3. glucagon-like peptide (GLP-1) (epinephrin is minor inhibitor) (Glucose is major regulator- insulin release proportional to BG level)

What kind of peptides cleaved by chymotrypsin? Trypsin? Elastase?

1. Chymotrypsin- cleaves bulky, aromatic amino acids. 2. Trypsin- cleaves (+) charged amino acids. 3. Elastase- cleaves small, non-charged amino acids.

TCA intermediates used in other pathways? 1. Citrate 2. a-ketoglutarate 3. succinyl coa 4. malate 5. oxaloacetate

1. Citrate can be used in fatty acid synthesis. 2. a-ketoglutarate can be used in amino acid synthesis (or as neurotransmitter) 3. succinyl coa can be used in heme synthesis 4. malate can be used in gluconeogenesis 5. oxaloacetate can be used in amino acid synthesis.

What are the 7 nitrogen-containing compounds produced by the liver and what is their function

1. Creatine- Forms creatine phosphate in muscles (form of energy storage) 2. Glutathione- Protects against free radical injury (reduces peroxides) 3. Purines & Pyrimidines- Found in nucleotides 4. Sphingosine- Precursor of sphingolipids found in myelin (and other membranes) 5. Heme- Incorporated into hemoglobin. 6. Niacin - NAD, NADP coenzymes for oxidation reactions. 7. Glycine conjugates of xenobiotic compounds- Inactivation, target for urinary excretion.

Purines and pyrimidines uses (7)

1. DNA and RNA 2. Cofactors (NAD+, FAD, CoA) 3. Energy (ATP/GTP) 4. Activated intermediates in biosynthesis 5. SAM for methyl transfer 6. 2nd messengers (cAMP) 7. Allosteric regulators in metabolism. Purines and pyrimidines can be made from scratch or salvaged from existing bases.

Epinephrine pathway in muscle during glycogenolysis

1. Epinephrine stimulates adenylate cyclase which converts ATP to cAMP. 2. cAMP activates PKA. 3. PKA Activates phosphorylase kinase (glycogenolysis) via phosphorylation with ATP and inhibits glycogen synthase (glycogenesis) via phosphorylation with ATP. (Ca2+-calmodulin also activates phosphorylase kinase) 4, Phosphorylase kinase turns/activates phosphorylase b (inactive) to phosphorylase a (active) by phosphorylating it with ATP. (AMP also stimulates phosphorylase b to phosphorylase a activation) 5. Phosphorylase A turns glycogen into glucose 1-phosphase which then goes -> glucose 6- phosphate -> lactate or CO2 + H2O in muscle.

Sources that can produce Acetyl-CoA

1. Fatty acid, palmitate 2. Ketone body, acetoacetate. 3. Pyruvate (from glucose or alanine) 4. Ethanol

What 4 factors influence immunogenicity (illicit immune response)

1. Foreignness- the more different it is to us the better. 2. Molecular size- the bigger the immunogen (antigen) the better. 3. Chemical complexity- The more amino acids, etc. the better. 4. Susceptibility to Ag processing and presentation- Large, insoluble molecules are better.

Fasting state and glycogen degradation steps

1. Glucagon (liver) or epinephrine (muscle) signal G-protein. 2. Gas -> adenylate cyclase -> cAMP-> PKA. 3. PKA phosphorylates glycogen phosphorylase activating it. 4. Glycogenolysis is stimulated- glucose is released from the liver.

What can these glycolysis intermediates also produce: 1. Glucose 6-p 2. 1,3-bis-phosphoglycerate. 3. 3-phosphoglycerate. 4. Pyruvate. 5. Acetyl CoA

1. Glucose 6-p can produce five-carbon sugars or glycerol-P 2. 1,3-bis-phosphoglycerate can produce 2,3-bis-phosphoglycerate 3. 3-phosphoglycerate can produce 2,3-bis-phosphoglycerate or serine 4. Pyruvate can produce alanine. 5. Acetyl CoA can also produce fatty acids.

Glycogen metabolism start

1. Glucose enters cell. 2. Glucose converted to glucose-6-phosphate (via glucokinase in liver). 3. Glucose 6-phosphate -> glucose 1 phosphate via phosphoglucomutase (reversible). 4. Glucose 1-phosphate + UTP -> UDP-glucose (intermediate only used in synthesis pathway) 5. Glycogen synthesis.

Pancreatic B-cells and insulin release steps

1. Glucose in blood, taken up by B-cells via GLUT 2 transporters. 2. Metabolized which makes intracellular ATP levels rise. 3. Increased ATP/ADP ratio shuts down K+ channel 4. Membrane depolarizes. 5. Activates Ca2+ channels. 6. Increase Ca2+ stimulates fusion of vesicles and insulin release.

What are the only 3 enzymes that can fix nitrogen atoms onto an organic molecule?

1. Glutamate dehydrogenase 2. Glutamine synthetase 3. CPSI (Carbamoyl phosphate synthetase I, involved in production of urea)

2 main enzymes involved in glycogen degradation

1. Glycogen phosphorylase- cleaves nonreducing ends making glucose-1-phosphate. 2. Debrancher enzyme- cleaves the remaining branch (transferase) and attaches to primer glycogen (amylo-1,6 glucosidase) to be degraded by glycogen phosphorylase.

Glycogen synthesis steps

1. Glycogenin glycosylates itself using UDP-glucose to create primer. (reducing end attached to glucogenin) 2. Glycogen core + UDP glucose + glycogen synthase -> increasing glycogen core. (a-1,4 glycosidic bonds link glucosyl residues in long chain, lengthening glycogen primer) 3. Glycogen core + branching enzyme -> adding branches to glycogen core (a-1,6 branches every 8 to 10 residues). 4. Continued glycogen synthesis at all nonreducing ends. ======= -glucosyl units added from UDP-G to nonreducing ends by glycogen synthase -Glycogen synthase is regulated - Anomeric carbon of each glucose is attached via a-1,4-glycosidic bond to the hydroxyl on carbon 4 on terminal residue. -After 11 residues added, 6-8 cleaved by amylo-4,6-transferase (branching enzyme) and reattached by an a-1,6 bond). -Branching allows for increased sites for synthesis and degradation and enhances solubility

5 fat deposit sites in the human body.

1. Greater omentum- omental adipose tissue 2. Mesentery- mesenteric adipose tissue 3. Retroperitonea adipose tissue 4. Deep subcutaneous adipose tissue. 5. Superficial subcutaneous adipose tissue Both deep subcutaneous (visceral) and superficial adipose tissue increase when gaining weight. Subcutaneous doesn't keep up in vascularization as more fat deposited.

Urea cycle pathway

1. HCO3- (from CO2 + H2O) + NH4+ + 2 ATP + *carbamoyl phosphate synthetase I (CPSI)* --> Carbamoyl phosphate. (In mitochondria) 2. Carbamoyl phosphate + ornithine + *ornithine transcarbamoylase* --> citrulline (the amine group from carbamoyl phosphate is added to ornithine and the phosphate part is removed) (In the mitochondria). 3. Citrulline (moves into the cytosol) + Aspartate + ATP + *argininosuccinate synthetase* --> argininosuccinate. (cytosol) 4. Argininosuccinate + *argininosuccinate lyase* --> arginine removing fumarate in the process. (cytosol) 5. Arginine + H2O + *arginase* --> urea (excreted in urine) + ornithine (ornithine crosses into mitochondria to be used in step 2 and continue cycle).

Preparative phase of glycolysis enzymes

1. Hexokinase (glucose to glucose 6-phosphate, uses ATP) 2. Phosphoglucoisomerase. (glucose 6-phosphate to fructose 6-phosphate) 3. Phosphoglucokinase (F-6-phosphate to fructose 1,6 bisphosphate, uses ATP) 4. Aldolase (F-1,6-bis to dihydroxyacetone phosphate and glyceraldehyde 3- phosphate) 5. Isomerase (Dihydroxyacteone phosphate to glyceraldehyde 3-phosphate)

6 signs of liver damage

1. Increase in ALT, AST; may have increased Amino Acids in serum. 2. Jaundice (inefficient bilirubin glucuronidation) 3. Prolonged clotting times (liver not producing enough clotting factors) 4. Edema (liver not producing enough albumin) 5. Hepatic encephalopathy (less urea, excess ammonia) 6. Increased ALP and GGT may indicate some liver diseases

What do the complement pathways do?

1. Induce inflammation. Anaphylatoxins. 2. Lyse certain infectious agents (mainly neisseria because it has oligopolysaccharide instead of LPS via the MAC (membrane attack complex) which is C5-C9.) 3. Opsonize infectious agents (only complement that does this is C3b). 4. Clear immune complexes!! All of these pathways converge at C3 and result in a membrane attack complex (MAC). The larger proteins, B fragments (except for C2b) acquire enzyme activity- bind to surface. The smaller proteins (a fragments) have biological activity and are known as anaphylatoxins (degranulate basophils and mast cells releasing histamine, etc. and responsible for the anaphylactic response. Complements are also really good at lysing red blood cells, can cause massive hemolytic anemia if there are too much of them.

What are the 5 oxygen independent killing methods?

1. Inducible nitric oxide synthetase (iNOS) generates nitric oxide (NO) in both phagocytic cells and non-phagocytic cells. 2. Cathepsin G, a neutral protease (breaks down protein). 3. Lactoferrin (steals iron). 4. Lysozyme (breaks down peptidoglycan) 5. Defensins (punch holes) Not really strong enough to kill the bacteria, not enough to compensate if you have a defect in oxygen dependent killing.

Timeline of an immune response to an acute infection

1. Innate immune response 2. Induction of adaptive response 3. Adaptive immune response 4. Immunological memory

Insulin and glycogen synthesis pathway

1. Insulin allosteric inhibitor on glycogen phosphorylase a. 2. Inhibits cAMP therefore PKA inhibited. 3. Protein phosphatases are activated- dephosphorylate glycogen synthase (activate it) and glycogen phosphorylase (deactivate it) 4. Glycogenolysis inhibited, glycogen synthesis activated.

4 things fat tissue triggers

1. Insulin secretion from pancreas. 2. Heptatic glucose production in the liver 3. Glucose uptake and metabolism in the skeletal muscle 4. Leptin synthesis. Main functions of adipose tissue: glucose uptake, fat storage, and metabolism.

B cells vs T cells: 1. Interaction with antigen? 2. Binding of soluble antigen? 3. Involvement of MHC? 4. Chemical nature of Antigen? 5. Epitope properties?

1. Interaction with antigen? B cells: Binary complex of membrane antibody (mIg) and antigen. T cells: Ternary complex of TCR, antigen, and MHC. 2. Binding of soluble antigen? B cells: Yes T cells: No (has to be on MHC) 3. Involvement of MHC? B cells: No T cells: Yes 4. Chemical nature of Antigen? B cells: protein, polysaccharide, and lipid. T cells: protein only 5. Epitope properties? B cells: Accessible, hydrophilic, mobile peptides containing sequential or nonsequential aa. T cells: Internal linear peptides produced by antigen processing and capable of binding to MHC molecules.

Isotype vs allotypes vs ideotypes?

1. Isotype: also called classes includes IgG, IgA, IgE, IgM, and IgD. 2. Ideotypes: Variable region binding specificity (hypervariable regions). 3. Allotypes: Small allelic differences in the constant region genes (subtle differences within species). My IgG won't be the same as someone else's IgG because of this.

What are the 3 precursors for gluconeogenesis

1. Lactate (RBCs) 2. Amino acids (alanine) 3. Glycerol (adipose)

What are the location/function of the following lipases: 1. Lipoprotein lipase (LPL): 2. Hormone-sensitive lipase (HSL): 3. Pancreatic lipase:

1. Lipoprotein lipase (LPL): muscle and adipose tissue. Releases fatty acids from lipoproteins (chylomicron, VLDL, etc.) to allow tissue uptake. 2. Hormone-sensitive lipase (HSL): Inside adipose tissue. Allows fatty acid release from adipose tissue. 3. Pancreatic lipase: Duodenum of small intestine. Breaks down triglycerides (dietary lipids) into FAs and 2-MG

Amino acids converted to what in the liver? (5)

1. Liver proteins 2. Tissue proteins (A.A travel through blood to tissues) 3. Nucleotides, hormones, porphyrins. 4. NH3, urea 5. Pyruvate and citric acid cycle intermediates (gluconeogenesis, ketone bodies, or stored as glycogen, triglycerides)

What are macrophages called in the lungs? Connective tissues? Liver? Kidney? and Brain?

1. Lungs: alveolar macrophages 2. CT: histiocytes 3. Liver: kupfer cells 4. Kidney: Mesangial cells 5. Brain: Microglial cells

Overview of transport of carbohydrates (3 steps)

1. Monosaccharides are taken up by cells of the small intestine (apical side). 2. Pass through the cell and exit on the serosal/basal side and into the capillaries for distribution throughout the body. 3. Glucose is taken up by different tissues by different tissue-specific transporters (GLUT 1-5)

What are the 3 main pathways for glycogen metabolism in skeletal muscle? The 3 main stimulators for glycogenolysis in muscle?

1. Muscle contraction: ATP-> AMP-> glycogen phosphorylase b -> glycogen phosphorylase a 2. Nerve impulse ->Ca2+ -> Ca2+-calmodulin -> Phosphrylase kinase 3. Epinephrine -> cAMP-> PKA -> phosphorylase kinase Glycogenolysis in muscle stimulated by: AMP, Ca2+, or epi.

Glycogen break down in muscle vs liver

1. Muscle- glycogen -> glucose 6-phosphate -> glycolysis. (stimulated in anaerobic glycolysis) 2. Liver- Glycogen -> glucose 6- phosphate -> glucose -> blood glucose. (stimulated by glucagon)

Mutations in innate immune receptors (5)

1. Mutation in signaling molecules effecting TLRs (Toll-like receptors) - Recurrent, severe bacterial infections (pneumonia) 2. Gain of function mutations in inflammasome - Gout - Atherosclerosis - Type II diabetes 3. NOD-2 mutations - IBD (irritable bowel disease) 4. IL-12 receptor deficiency - Recurrent infections with intracelluar bacteria (mycobacterium (like tuberculosis)) 5. IFN-y receptor deficiency - Recurrent infections with intracelluar bacteria (mycobacterium (like tuberculosis))

How can you treat hyperammonemia?

1. N-removing compounds. 2. Low protein diet. 3. Arginine supplementation (if block is afer argininosuccinate).

How much of every WBC type in human body?

1. Neutrophils the most ~50-70% 2. Lymphocytes at 20-40% 3. Monocytes at 1-6% 4. Eosinophils at 1-3% 5. Basophils at <1%

Liver cirrhosis symptoms

1. Portal hypertension - FIbrosis, reduced fenestrations 2. Thin-walled varices - From obstruction (shunting) of portal blood from liver, returns to heart via esophageal veins, makes the esophageal veins bigger. 3. Varices may rupture and cause bleeding into abdominal/thoracic cavity. 4. Increased ammonia in blood as bacteria metabolize blood proteins. 5. Hapatic encephalopathy (worsening of brain function due to liver not filtering toxins) 6. Jaundice and edema in abdomen

Regulation of the urea cycle? (3)

1. Regulated by substrate availability. Increase in arginine stimulates urea cycle. (feedforward regulation) 2. Allosteric activation of CPSI by N-Acetyl-glutamate (NAG). (as Arginine increases more NAG is formed). 3. Regulation of urea cycle enzyme synthesis. - Induced by high protein diet, fasting. Higher rate of ammonia production = higher rate of urea formation.

Summary of electron transport chain

1. Reoxidation of reduced coenzymes. 2. Consumption of O2 3. Formation of H2O 4. Stepwise release of free energy upon coenzyme oxidation 5. Coupled unidirectional pumping of H+ across membrane.

Effects of high protein meal (4)

1. Stimulate glucagon release 2. Stimulate insulin release to lesser extent. - stimulates AA uptake in tissues - increases protein synthesis 3. Gluconeogenesis enhanced 4. Reduced glycogen and TG synthesis

Enzymes can be regulated by> (4)

1. Substrate availability 2. Enzymes 3. Covalent modification of enzyme 4. Allosteric regulation (molecule binds to enzyme somewhere other than active site.)

What are the 3 major steps in urea cycle?

1. Synthesis of carbamoyl phosphate (in mitochondria) 2. Productin of arginine by urea cycle (cytosol) 3. Cleavage of arginine to produce urea. (cytosol).

Essential amino acids are required in the diet because generally humans are not capable of? (3)

1. Synthesizing branch chain amino acids. 2. Synthesizing aromatic amino acids 3. Incorporating sulfur into compounds.

Endogenous antigen processing and presentation. 1. How are viruses converted into 8-10 amino acids to fit inside class I HLA? 2. HLA molecules are in the ER and peptides are in the cytoplsm, how do the HLA molecules get loaded? 3. HLA class I + antigen are in the ER, how do they make it to the cell surface to present antigen to T cytotoxic cells?

1. Viral peptides are large, get degraded within proteosomes to fit inside the class I HLA. 2. TAP I and TAP 2 (transporters of antigen process) 3. Vesicular transport through the golgi to the surface.

Structure of glycogen (3)

1. a-1,4 glycosidic bonds with a-1,6 branches every 8-10 units. 2. Only one anomeric carbon per molecule of glycogen. 3. May be simultaneously degraded from all nonreducing ends.

Glucose 6 phosphate precursor of what (3)

1. glycolysis 2. pentose phosphate pathway 3. other pathways for synthesis of other sugars.

Lactose intolerance possible causes (4)

1. natural loss of lactose > age 7. 2. Injury to the intestinal mucosal cells 3. Gastroenteritis 4. Excess alcohol consumption.

How much acetyl coa, nadh, fadh2 from 16 carbon palmitoyl. How much ATP.

16/2 = 8 Acetyl Coa 1 NADH per cleave 1 FADH2 per cleave so 7 NADH and 7 FADH2 ATP produced: 2.5 ATP per NADH 1.5 ATP per FADH2 10 atp per acetyl coa So 7(2.5) + 7(1.5) + 8(10) = 108 ATP 110 - 2 ATP (FA activation) = 106 ATP total

How much ATP is used in FA activation by fatty acyl-CoA synthetase

2 ATP

Pyruvate dehydrogenase produces (energy)

2 NADH

How many NADH and FADH are produced in glycolysis and TCA cycle

2 NADH in glycolysis another 2 NADH in the PDC (linker step) and 6 in TCA cycle for a total of 10. FADH2 only made in TCA cycle and only 2 made.

Triglycerides first digested to what

2-Monoacylglycerol and FA

Micelle is what

2-monoglycerides + fatty acid + biles salts = micelles

1. Osteogenesis Imperfecta: - Affects Type I collagen - "Brittle bone disease"- risk factor for rheumatoid arthritis and osteoporosis. - Ligament and tendon weakness - Blue sclerae, progressive hearing loss. 2. Achondrogenesis Type 2: - Affects Type II collagen - Short stature, bone and joint - Typically lethal 3. Vascular Ehlers-Danlos syndrome - Affects Type III collagen - Fragile, thin skin and easily bruised. - Risk of arterial rupture.

3 common collagenopathies

1. *Mucous (ex, sub-lingual + stomach glands)* a. Secretions are viscous and slimy; extensive glycosylation of proteins (PAS +) b. Cells stain pale with H&E (secretions lost in prep) 2. *Serous (ex. Parotid gland + pancreas)* a. Secretions are watery; little to no glycosylation on proteins b. Apical cytoplasm is eosinophilic; perinuclear cytoplasm is basophilic (rER). 3. *Mixed* a. Submandibular gland b. Contain both mucous and serous cells c. Processing artifact: serous demilune (half-moons).

3 secretions of multicellular glands

What are the enzymes in urea cycle found in cytosol

3. Argininosuccinate synthetase. 4. Argininosuccinate lyase 5. Arginase

Antibody gene rearrangement

5 heavy chain classes (μ,δ,γ,α, and ε) 2 light chain classes (κ and λ) The heavy and light chains are encoded by multiple gene segments Variable (V), Diversity (D) and joining (J) segments compose the variable region of the heavy chain while only V and J segments are used to generate the light chains, No *D segment in the light chain*. Generates an incredible amount of diversity

Net reaction of TCA cycle per glucose (2 turns)

6 NADH 2 FADH2 2 GTP 4 CO2

Pentose phosphate pathway overall reaction produces what from 3 glucose-6-phosphates?

6 NADPH 3 CO2 2 Fructose 6-P 1 Glyceraldehyde 3-P

1. Protection (skin) 2. Absorption (intestines, kidneys) 3. Transport of nutrients/waste (along or across an epithelium) 4. Secretion (glands) 5. Excretion (kidneys) 6. Gas exchange (airway) 7. Selective barrier 8. Sensory receptors for special senses: -Olfactory epithelium, hair cells, taste buds, retina

8 functions of epithelial tissue

Normal level of blood glucose

80-100

Suffering from Rickets. Caused by vitamin D deficiency. Causes soft bones.

A 4-year old male presents to the clinic with a history of malnourishment. See images below for presentation. 1. What do you suspect the child suffering from? 2. What causes this disease?

White adipose tissue mass-- Lipoma

A 54 year old male presents with a soft, painless mass. Physical exam reveals the image below (left). The mass is excised and a biopsy reveals the histological specimen below (right). What is the most likely diagnosis?

(Left picture is normal, right picture is patient's bone biopsy) Osteoporosis caused the broken hip. Osteoporosis evident on the patient's bone biopsy. Treatment: Inhibit osteoclasts or activate osteoblasts via drugs.

A 72-year-old female presents to the emergency department following a recent fall. She fell off a curb at a local grocery store. 1. You suspect a hip fracture 2. What is going to be one of your main concerns? 3. Treatment?

Osteoarthritis. Most commonly affected are areas of weight bearing including hips, knees, lower lumbar, vertebrae, hands, and feet. Affects articular cartilage. Forms bone when trying to repair the articular fibers.

A 75 year old female presents to the clinic with complaints of chronic joint pain. Physical examination reveals joint deformity. What do you suspect? What are the most commonly affected areas? What is the disease *progression*?

Antibody dependent cellular cytotoxicity (ADCC)

A pathogen (virus) enters a cell and before it leaves the cell it will put its virus specific ligoproteins in/on the cell membrane. Then an antibody (IgG) attaches to the antigen (virus proteins) and then bring it to NK cells, macrophages, neutrophils, eosinophils, anybody with a receptor for IgG (aka CD16). The target cell is then killed, NK cells punch holes in it. It's mainly NK cells that do this but other cells can do it too, anyone with CD16 (receptor for IgG). Some viruses don't have to leave a cell to infect other cells like herpes, HIV, etc because they have cell fusion protein which will fuse cells together so the virus can travel between cells. These cells need to be killed by T cells.

What is any allosteric activator of muscle glycogen phosphorylase?

AMP

What does AMP activate/stimulate?

AMP activates glycogenolysis and glycolysis. Increase in AMP stimulates Phosphorylase b and PFK-1 in glycogenolysis pathway.

Exogenous antigen processing and presentation

APC phagocytosis a protein antigen. The phagocyte binds with a lysosome to create a phagolysosome which breaks apart the antigen into the appropriate length. The class II MHC can't bind while it is in the ER because there is a invarient chain attached to it which is a good thing because the class I MHC can bind in the ER so when infected with viruses the class I MHC would be expressed rather than class II MHC. So instead, the class II MHC will eventually fuses with the phagolysosome and the acidic lysosomal compartment chews up most of the invariant chain so that you are just left with a little clip molecule still blocking the chain. Then HLA-DM, a helper molecule, takes out that little clip and the class II MHC can finally bind to the antigen and express it on the cell surface, present it to T helper cells.

Which epigenomic regulatory gene mutation in 60% of ovarian clear cell carcinoma, and 30-40% endometrial carcinoma?

ARID1A: Nucleosome positioning/chromatin remodeling

Fuels used in skeletal muscle (6)

ATP by any means possible including: 1. Creatine phosphate (rapid) 2. Muscle glycogen (rapid) 3. Fatty acids (preferred) 4. Glucose 5. Ketone bodies 6. Some amino acids (including BCAAs)

How much do ATP, ADP, and AMP concentrations change during exercise?

ATP decreases 20% while ADP and AMP increase (AMP increases the most). Concentration of AMP, produced by adenylate kinase reaction, serves as a sensitive indication of decreasing ATP levels.

Steps in triacylglycerol resynthesis

ATP dependent. FA + ATP -> FA-AMP + CoASH (coenzyme A) -> FACoA + 2-Monoacylglycerol -> diacylglycerol + FACoA -> Triacylglycerol + ApoB-48 -> nascent chylomicrons

Mitchell hypothesis

ATP synthase + H+ gradient = oxidative phosphorylation

Oligomycin (interfere oxidative phosphorylation)

ATP synthase inhibitor Inhibits proton flow through the F0 component of the ATP synthase.

Where are monosaccharides absorbed?

Absorbed through intestinal epithelial cells into blood for distribution.

What can undergo spontaneous decarboxylation to make acetone?

Acetoacetate

Rate limiting step in synthesis of fatty acids

Acetyl CoA carboxylase

Fed vs fasting state and acetyl-CoA

Acetyl Coa= acetate + oxaloacetate. Fed: Acetyl CoA -> TCA cycle because you have enough oxaloacetate. Fasting: Acetly-CoA -> ketone bodies because not enough oxaloacetate for TCA.

MCAD (acetyl-coa dehydrogenase) deficiency

Acetyl-CoA dehydrogenase is the first enzyme to cleave in B-oxidation. Causes: reduced gluconeogensis (hypoglycemia) reduced ketone body production (hypoketotic) Reduced ureagenesis (Hyperammonemia) Overall causes neurological damage/hepatic encephalopathy Jamaican vomiting also affects this enzyme, hypoglycin is the compound in unripe fruit of ackee tree.

Acidic dye: *Eosin*, carries _net negative charge_ on its colored portion and is described by the general formula Na+dye-. Basic dye: Carries a _net positive charge_ on its colored portion and is described by the general formula dye+Cl-. *Hematoxylin* does not meet the definition of a strict basic dye but has properties that closely resemble those of a basic dye. The color of the dye is not related to whether it is basic or acidic. Basic dyes: Methyl green (green), methylene blue (blue), Pyronin G (red), and Toluidine blue (blue). Acidic dyes: Acid fuschsin (red), Aniline blue (blue), Eosin (red), and Orange G (orange). ================================ Basic dyes react with anionic components of cells and tissue (components that carry a net negative charge) such as the phosphate groups of nucleic acids, the sulfate groups of glycosaminoglycans, and the carboxyl groups of proteins. (Basophilia) At high pH (about 10) all 3 groups (phosphate, sulfate, and carboxyl) are ionized and seen. At slightly acidic/neutral pH (5 to 7) sulfate and phosphate groups seen. At low pH (below 4), only sulfate groups seen. ================================= Acidic dyes react with cationic groups in cells and tissues (components that carry a net positive charge), particularly with the ionized amino groups of proteins. (Acidophilia) Not as specific nor as precise as reactions with basic dyes. Acidic dyes sometimes used in combinations to color different tissue constituents like the Mallory staining technique:aniline blue (collagen), acid fuschsin (ordinary cytoplasm), and orange G (red blood cells). =============================== Basic dyes (basophilia) shows: 1. Heterochromatin and nucleoli of the nucleous. 2. Cytoplasmic components such as the ergastoplasm. 3. Extracellular materials such as the complex carbohydrates of the matrix of cartillage. Acidic dyes (acidophilia) shows: 1. Most cytoplasmic filaments, especially those of muscle cells. 2. Most intracellular membranous components and much of the otherwise unspecialized cytoplasm 3. Most extracellular fibers.

Acidic and Basic Dyes

What does Th2 activate and drive

Activates B cells, mast cells, and eosinophil, drives isotype switching to IgE

What does Th1 activate and drive?

Activates T cytotoxic cells and macrophages, drives isotype switching to IgG

Epinephrine does what in the muscles? Alpha and beta receptors?

Activates glycogenolysis and inhibits glycogen synthesis. Enhances the effects of glucagon in liver. Alpha receptors -> PLC -> IP3 and DAG-> Ca2+ and PKC Beta receptors -> cAMP -> PKA

FA import and oxidation steps

Activation of FA: ATP + CoA + fatty acid -> fatty acyl CoA. (enzymes for FA oxidation in mitochondrial matrix) Carnitine shuttle (intermembrane): Fatty acyl CoA transferred from outer mitochondrial membrane to mitochondrial matrix via Carnitine. Carinitine is exchanged for CoA to make Fatty Acyl carnitine which then can cross into matrix. FA Oxidation: Fatty acyl carnitine -> fatty acyl CoA in mitochondrial matrix. Beta oxidation of fatty acyl CoA produces FADH2, NADH, and acetyl-CoA

1. Attachment 2. Release 3. Bending 4. Force generation 5. Reattachment (same cycle for all muscles but duration of stages alters)

Actomyosin cross-bridge cycle

What are the linked human cancers to this product and where is this product found? Benzene

Acute myeloid leukemia Principal component of light oil; despite known risk, many applications exist in printing and lithography, paint, rubber, dry cleaning, adhesives and coatings, and detergents; formerly widely used as solvent and fumigant.

Major forms of underlying cancer and casual mechanism behind the paraneoplastic syndrome disseminated intravascular coagulation?

Acute promyelocytic leukemia and prostatic carcinoma Tumor products that activate clotting

What is somatic hypermutation

Adds to the diversity of the variable region. Allows immune system response to get better because after you bind to an antigen it refines the affinity of the antibody molecule.

What is one cause of SCID and how do you treat it?

Adenosine deaminase deficiency (ADA), treat it by replacing the gene in hematopoietic stem cells.

Adenylate kinase and atp production

Adenylate kinase turns 2 ADP to 1 ATP releasing 1 AMP in the process which then signals to AMPK, K-ATP, AMP-sensitive metabolic enzymes, and adenosine to decrease ATP consumption and stimulate ATP production.

Which adipokine decreases free FA

Adiponectin

Which 2 tissues increase GLUT 4 transporters on their surface in response to insulin?

Adipose and muscle

Adipose vs muscle in regards to LPL Km

Adipose has higher Km for Lipoprotein lipase- will require alot in blood in order for it to be absorbed by adipose tissue. Muscle has lower Km for LPL.

Adipokines

Adipose tissue produces hormones called adipokines. Different functions: - Help regulate appetite - Regulate adipocyte cell size - Act on cells of the immune system (promote inflammation) Few examples: - Adiponectin: decreases free FA, improves lipid and glycemic profile. Is an insulin sensitizing hormone- elevated levels is good. Those with obesity have lower levels of this hormone. -Leptin: Decreases food intake. Suppresses appetite. - Interleukin-6: pro-inflammatory

Major forms of underlying cancer and casual mechanism behind the paraneoplastic syndrome nonbacterial thrombotic endocarditis?

Advanced cancers Hypercoagulability

Fuel use during exercise

Aerobic fuel oxidation preferred Anaerobic glycolysis: - Initiation of exercise (few min) - Prior to increased blood flow. - Type IIB fast-twitch glycolytic fibers - Lowoxidative capacity - Strenuous activity - ATP demands exceed oxidative capacity.

Effects of training on muscle metabolism: aerobic vs resistance

Aerobic training: - Increase glycogen stores - Possibly use glycogen more efficiently with training - Increase mitochondrial size, numbers. Resistance training - Muscle hypertrophy to increase max force production - Strength, power, and endurance.

Pyruvate kinase deficiency

Affects RBC the most due to their reliance on glycolysis- causes hemolytic anemia. Believed to affect the Na+/k+ ATPase pump and other ATP dependent processes.

Deficiency in C3 causes what?

Affects both complement pathways. Causes recurrent bacteria infections, immune complex disease.

Deficiency in C5, C6, C7, C8, or C9 causes what?

Affects the MAC attack. Causes recurrent meningococcal and gonococcal infections.

Deficiency in C1q, C1r, C1s, C4, and C2 causes what?

Affects the classical pathway. Causes increase in immune complex diseases and increase in infections with pyogenic bacteria.

What is the major gluconeogenic amino acid

Alanine

What are the major N carriers in blood?

Alanine and glutamine (gln/Q). They transport amino acid nitrogen to liver via blood. Wouldn't want NH4+ to travel freely in your blood.

How are alanine, lactate, and glycerol used in gluconeogenesis pathway

Alanine and lactate form pyruvate. Glycerol forms Dihydroxyacetone phosphate (DHAP)

Liver's role in synthesizing blood proteins

Albumin: -55-60% total protein in blood (major blood protein) -Contributes to osmotic pressure and helps prevent edema. - Nonspecific transporter (e.g. steroid hormones, xenobiotic compounds, fatty acids, hydrophobic vitamins and drugs) - Hypoproteinemia can lead to edema due to decreased protein-mediated osmotic pressure in blood (examples of causes: Kwashiorkor syndrome, cirrhotic liver damage). Low levels of protein in blood and water seeps out of blood into surrounding tissues due to osmotic pressure. Clotting factors: If you have decrease in liver synthesizing proteins you will have less clotting factors. Glycoproteins: - Roles include protease inhibition, acute phase proteins in immune response, secretogogues for hormone release.

Treatment of gout

Allopurinol (inhibitor of xanthine oxidase) to decrease production of uric acid. Avoid diet rich in meat, seafood, fructose-sweetened drinks, alcohol.

Hepatocytes characteristics

Almost all metabolic pathways in the liver occur in hepatocytes. Long lifespan, low turnover Maintain constant liver mass (proportional to total body mass)

Tissue Macrophages

Alveolar macrophages - found in lung Histiocytes - found in connective tissues Kupfer cells - found in the liver Mesangial cells - found in the kidney Microglial cells- found in the brain

Glycolysis intermediates can be used to make?

Amino acids and fatty acids

Fate of amino acid carbon and nitrogen?

Amino acids containing carbon skeleton are used as fuel source. Nitrogen group is removed and excreted (waste).

What does ketogenic amino acids mean?

Amino acids that produce acetyl-CoA or acetoacetate (ketone bodies). Some amino acids are both glucogenic and ketogenic. Lysine and leucine are strictly ketogenic.

What are the intestinal cell enzymes

Aminopeptidases (close to N-terminus) Turns peptides into di- and tri- peptides + amino acids. Found in intestinal epithelial cell. Amino acids are then excreted into the blood.

Ornithine transcarbamylase deficiency (OTC) leads to accumulation of what?

Ammonia, glutamine, and carbamoyl phosphate.

i. *Cell body* - Nucleus - Cytoplasm ii. *Dendrites* - Periphery -> cell body - *Dendritic spines* iii. *Axon* - Cell body -> synapse - *Axon Hillock* - *Initial Segment of Axon* - *Myelin*

Anatomy of a Neuron

Zonula Adherens and Macula Adherens/Desmosomes -Serve to anchor cytoskeleton of adjacent epithelial cells - interact with actin (z.a) and intermediate filaments (m.a) -Provide structural and mechanical integrity

Anchoring junctions

Opsonization

Another way to recognize and respond to pathogens - May involve adaptive immune components such as IgG Phagocytes have membrane receptors for IgG and C3b - CD16 Enhance phagocytosis up to 4,000-fold. (Know IgG and C3b)

B cell development and activation stages/steps.

Antigen independent stage - occurs in the bone marrow - Involves the development of B cells from Hematopoietic stem cells through a series of defined intermediates Antigen dependent stage - Occurs in the periphery - Involves the development of mature B cells to memory and plasma cells. 1. Lymphoid stem cell can be a T cell, B cell, or NK cell. Once it commits to B cell, it goes into the Pro-B cell stage (progenitor). 2. At the Pro-B cell stage start Ig heavy chain gene rearrangement with RAG expression, Tdt, MHC II, and CD19, CD20, CD21, CD40. 3. After the heavy chain rearranges good it goes into the Pre-B cell stage which has characteristic *cytoplasmic Mu* (because its the first to be made). Light chain start rearranging in this stage, tdt isn't expressed here. 4. After light chain rearrangement, it enters the immature B cell stage which is characterized by *surface IgM*. RAG expression stops after the light chain rearrangement finishes in this stage. This is where selection happens, if it binds to itself it gets killed right in the bone marrow. If not then it moves into the periphery and onto the next stage. 5. Next it enters the mature B cell stage which is characterized by surface *IgM and IgD*. This is in the periphery. This is where it will test its antigen binding, if it binds antigen then goes to the next stage. It is naive until it binds to an antigen, has 1 month to find an antigen. 6. Becomes an activated/ blast B cell. Depending on which antigen it binds it either turns into a plasma cell which is characterized by *cytoplasmic Ig* or memory B cell which is characterized by surface IgG, IgA, or IgE.

Long cytoplasmic processes Core of microtubules (axoneme), anchored to basal bodies. *Specialized for: Motility (motile) and response to environment (primary)* Located on _respiratory epithelium_ , uterine tubes, etc.

Apical Modifications: Cilia characteristics

Short cytoplasmic processes Core of actin filaments, anchored to terminal web *Specialized for: absorption*, increases surface area. Located on epithelial cells of intestine, kidney, etc. "Brush border" (means it has microvili)

Apical Modifications: Microvilli characteristics

Also known as sterovilli Long, immotile microvilli (actin core) Limited to epididymis (absorptive) and hair cells of inner ear (mechanoreceptors)

Apical modifications: Stereocilia characteristics

What protein is essential component of chylomicrons?

ApoB-48

Superantigens

Are bacterial or viral proteins that bind outside of the peptide binding cleft on the TCR and MHC. This causes less specificity among the T cells so way more T cells are activated. From 1% normally to up to 25% with superantigens. With T cells you also get the B cells activated, cytokines, macrophages, etc all this combined to make the person go into shock. Toxic shock syndrome.

1. Multipolar neurons: have 1 axon and 2 or more dendrites (picture on the right) - Motor & interneurons 2. Bipolar neurons have 1 axon and 1 dendrite. (rare, middle picture) - Retina & CN VIII 3. Pseudounipolar (unipolar) neurons have one process, the axon divides close to the cell body into 2 long axonal branches. No dendrites. (left most picture) - Sensory neurons

Arrangements of neurons

*Superficial zone*- Is closest to the articular surface and contains elongated chondrocytes. *Intermediate zone*- Lies below the superficial zone and contains rounded chondrocytes. *Deep zone*- Characterized by small, round, chondrocytes that are arranged into columns. *Calcified zone*- Separated from the deep zone by a calcified line called the tidemark characterized by a calcified matrix and the presence of small chondrocytes. *No perichondrium*

Articular cartilage is divided into 4 zones

How does N enter urea cycle?

As NH4+ (released from glutamate in glutamate dehydrogenase with NAD+/NADP+ cofactors) and Aspartate (purine nucleotide cycle in brain and muscles)

In what form does pyruvate from glycolysis enter the TCA cycle in the mitochondria?

As acetyl-CoA

B. sublingual gland

As you are examining a 64 year old woman, you discover a mass in her mouth. A biopsy is taken and at the edges of the abnormal cells you see the image below. The mass is most likely located in: a. Buccinator muscle (in cheek) b. Sublingual Gland c. Tooth d. Cheek Mucosa e. Hard Palate

How is oxaloacetate synthesized

Aspartate + PLP in transamination reaction -> Oxaloacetate and vice versa. (NH3+ group removed from aspartate (transferred to a-ketoglutarate and makes glutamate) to make oxaloacetate) Oxaloacetate + PLP in transamination reaction -> Aspartate. (NH3+ group added to oxaloacetate (NH3+ group comes from glutamate to a-ketoglutarate reaction) to make aspartate) Oxaloacetate is part of TCA cycle

Largest & most populated neuroglial cell Communicate of neurons & blood vessels - Microenvironment (extracellular K+) Provide support to CNS neurons: 1. Mobilize waste and metabolites 2. Confine or metabolize NT's at synapse 3. Contribute to *Blood-brain barrier* Types: a. *Protoplasmic* b. *Fibrous*

Astrocytes

What converts disaccharides and oligosaccharides to monosaccharides and where does this occur?

At the brush border, glycosidases digest disaccharides and oligosaccharides to monosaccharides. 4 glycoproteins: 1. Glucoamylase 2. Sucrase-isomaltase 3. Trehalase 4. Lactase-glucosylceramidase

Purine biosynthesis (A, G)

Atoms are donated from Aspartate, glutamine, glycine, N10-formyl-FH4, and CO2. Energy required (ATP and GTP) N10-formyl-FH4 is molecule that transfers single C groups - Derived from folate (folate is needed for purine (and therefore DNA) synthesis). Aspartate, glutamine, Glycine provide the amide N to form purines, N10-formyl-FH4 adds single carbons to complete the rings. CO2 provides 1 carbon.

Pyrimidine biosynthesis (C, T, U)

Atoms are donated from aspartate, CO2, and glutamine. Base made first, then attached to R5P (ribose-5 phosphate)

Effector processes Transmit stimuli Cell body -> other neuron/cell Single axon per neuron - Branch to multiple targets *Axon hillock* *Initial segment of axon* - AP generates here Conduction velocity depends on axon size and *myelination* state

Axons

What does IL-7 do?

B and T cell development.

Which accessory molecules transduce the signals for B cell receptors? T cell receptors?

B cell receptors use Ig alpha and Ig beta to actually transduce the signal to initiate the activation process. T cell receptors use CD3 for the same purpose. Mutation in these accessory molecules would be that the B and T cells couldn't properly respond to antigens, differentiate them, etc.

B cell activation by a bacteria cell

B cell with its antibodies binds to the antigens on a bacterial cell. This initiates the Iga and Igb to signal to the SYK (B cell specific tyrosine kinase receptor) to phosphorylate which allows signals to reach the nucleus to change gene expression. Now CD19 role in this is receptor complex is that it is a coreceptor. When the coreceptors are ligated, you need less antigens to elicit a response (1000 vs 15 with coreceptor).

Clonal selection

B cells randomly made and only the ones that match the antigen will replicate itself and either become plasma cell or memory cells.

What are the lymphoid cells (lymphocytes)?

B cells, T cells, and NK cells B and T cells part of the adaptive response while NK cells part of the innate response.

Which ketone accumulated more in the blood as fasting continues?

B-hydroxybutyrate accumulates more than acetoacetate.

What are the 3 ketone bodies

B-hydroxybutyrate, Acetoacetate, and acetone (released in breath, fruity)

BG levels and hormone response

BG <80 mg/dL (4.4 mmol/L) - Reduction in insulin secretion BG <70 mg/dL (3.9 mmol/L) - Increased secretion of glucagon and epinephrine BG <67 mg/dL (3.7 mmol/L) - Secretion of norepinephrine and growth hormone (GH) BG <65 mg/dL (3.0 mmol/L) - Secretion of cortisol BG <55 mg/dL (3.0 mmol/L) - Autonomic symptoms develop BG <50 mg/dL (2.8 mmol/L) - Cognitive function is impaired

Cells adhered to basement membrane, composed of basal lamina and underlying reticular connective tissue. (Not made up of epithelial tissue) *Functions of basal lamina*: Cell attachment, compartmentalization, filtration, tissue scaffolding, regulation + signaling Cells anchored to underlying connective tissue via *junctions* (hemidesmosomes, focal adhesions) *Basal infoldings* increase cell surface area (transport, etc.) (Picture is of the basal portion of a kidney tubule cell showing basal infolding)

Basal domain characteristics

Antibody structure

Basic structure - 2 identical heavy chains - 2 identical light chains Heavy and Light Chains - variable and constant regions - disulfide bonds link the chains together - light chains have 2 domains, 1V and 1C - heavy chains have 4-5 domains, 1V and 3-4 C

1. Abundant, basophilic granules 2. Granules: - Azurophilic (primary)- lysosomes; myeloperoxidase, acid hydrolases, etc. - Specific (secondary) - heparin, histamine, heparin sulfate, leukotrienes, IL-4, IL-13 3. Bind IgE, secreted by mast cells.

Basophil key points

Why does the body excrete N as urea?

Because NH3 is toxic to the brain.

Why is the favored form in the body NH4+?

Because the pKa of ammonia (NH3) is 9.3, the favored form in the body at physiological pH is ammonium (NH4+).

What is bilirubin?

Bilirubin is one of the heme degradation products. When RBCs destroyed, bilirubin released and can be found in blood. Billirubin accumulation = jaundice (yellowing of skin and whites of eyes). Gallbladder can cause gallbladder to be obstructed which means bile salts can't be secreted into GI which gives stool a light clay-colored appearance (no bile salts in it). Often caused by liver and gallbladder disorders (elevated bilirubin)

Constant regions, antigen dependent vs antigen independent.

Biological function of antibodies comes from the constant region. Some biological functions mediated by the constant region are antigen independent like IgG crossing the placenta or IgE binding to mast cells. Some are antigen dependent. In antigen dependent functions, a cryptic site on the constant region is exposed after antigen binding and causes a conformation change in the antibody molecule after formation of the Ag-Ab complex.

This tumor marker is found in what tumor types? TP53 mutants in urine?

Bladder cancer

What is the associated neoplasm and etiologic agent in chronic cystitis

Bladder carcinoma Schistosomiasis

Disorders of the urea cycle

Blocks in urea cycle increase glutamine levels; alpha-ketogluterate levels become too low to fix more N, ammonia levels rise. -Accumulation of ammonia is very toxic to CNS. Extent of elevation in glutamine and NH4+ depends on the defective enzyme. High levels of ammonia and glutamine lead to brain swelling; elevated glutamine opens MPTP, leads to cell death; lower glutamate means less excitatory neurotransmitter synthesis resulting in lethargy and reduced CNS activity. Hyperammonemia- can cause irreversible brain damage and mental retardation. - Diagnose early, treat aggressively with N-removing compounds, low protein diet. -If block is after argininosuccinate, arginine supplementatin can help. Most common defect is Ornithine transcarbamylase deficiency (step 2).

This is a blood smear of a patient with homozygous sickle cell disease. There are several sickle cells, a nucleated RBC and Howell-Jolly body (nuclear material in RBC (appears purple) -> damaged spleen)

Blood smear from 16 year old female. What seems off?

The number of small lymphocytes is greatly increased, suggesting a B-cell or T-cell leukemia.

Blood smear from a 40 year old female with chronic fatigue. Observations?

Controls communication between blood & brain - Protecting CNS from toxins, immune cells, & fluctuating levels of circulating substances Specialized *endothelial cells* with continuous tight junctions Neuroglial cells associated: - Astrocytes -- Support barrier --- *Glial limitants* -- Buffer (K+) O2, CO2, some lipid-soluble molecules pass free (ethanol, steroids, etc. ) Transmembrane carrier proteins actively transport specific macromolecules (like glucose, amino acids, nucleosides, vitamins).

Blood-brain barrier

1. *Intramembranous*: simpler; no cartilage precursor - Flat bones of skull, face, mandible, and clavicle 2. *Endochondral*: cartilage precursor - Long bones and bones of the axial skeleton that bear weight (ie- vertebrae).

Bone formation is classified into 2 types

Derived from osteoblasts Similar to osteoprogenitor cells Flat cells seen on the surface of quiescent bone Considered Periosteal and endosteal cells

Bone lining cells

Cleaves proteins attaching synaptic vesicles to presynaptic membrane Less/No ACh release into cleft ↓ response to stimulus

Botox = *Botulinum Toxin*

Dendrites (D) Golgi cells (G) Gray matter - Granule cell layer (Gr) - Molecular layer (Mol) White matter(WM) Purkinje Cells are not the same as Purkinje Fibers

Brain

Leptin triggers the brain to release what and what do they do

Brain releases: Neuropeptide Y which causes: Decrease NPY secretion, decreased food intake, decreased body weight, increased sympathetic tone, increase energy expenditure. Normalization of glucose and insulin. Endocrine hormones: When leptin levels high, releases- glucocorticoids, insulin, and TNF-a/IL-1. When leptin levels low, releases catecholamines, T3/T4, cAMP, and androgens.

This tumor marker is found in what tumor types? CA-15-3

Breast cancer

Major forms of underlying cancer and casual mechanism behind the paraneoplastic syndrome "disorders of the central and peripheral nervous system"

Breast carcinoma- no mechanism listed

Major forms of underlying cancer and casual mechanism behind the paraneoplastic syndrome "hypertrophic osteoarthropathy and clubbing of the fingers"

Bronchogenic carcinoma and thymic neoplasms Unknown

Major forms of underlying cancer and casual mechanism behind the paraneoplastic syndrome myasthenia gravis

Bronchogenic carcinoma and thymic neoplasms immunologic

Major forms of underlying cancer and casual mechanism behind the paraneoplastic syndrome dermatomyositis?

Bronchogenic carcinoma, breast carcinoma. Immunologic

Functions in thermogenesis (newborn to 10 yo) Abundant mitochondria (cytochrome oxidase), blood vessels, and sympathetic innervation. Brown adipocytes are multilocular and smaller than white adipocytes *Locations:* a. Upper back b. Shoulder c. Thorax d. Abdomen

Brown adipose tissue

Thermogenin

Brown adipose tissue has thermogenin which is thermogenic- is an ETC uncoupler- allows protons to sneak back into matrix which decreases ATP production. Lose energy through heat. Helps to keep warm- most adipose tissue is white as we reach adulthood. Babies have brown fat.

How can macrophage function be enhanced?

By T helper cytokines which increase their phagocytic activity, give them higher levels of class II MHC on the cell surface, and in turn increased ability of macrophages to activate T helper cells.

How is fructose metabolized

By conversion to intermediates of glycolysis: Dihydroxyacetone-P and Glyceraldehyde-3-P Occurs mainly in liver. Rate limiting enzyme of fructose metabolism: Aldolase B (cleaves fructose 1-P) (in liver) (not rate limiting in glycolysis) Uses Aldolase A in muscle Fructose can also be converted to Fructose-6-P (in glycolysis intermediate) in muscle and adipose via hexokinase when glucose is low.

How does the body capture energy as ATP?

By oxidizing fuel, fatty acids in low oxidized state while ketone bodies are already in a high oxidized state therefore you get more energy out of fatty acids than ketone bodies (glucose in the middle).

What does a deficiency in C1-INH cause?

C1-INH (C1 inhibitor) normally inhibits the classical pathway of complement system. A C1-INH deficiency causes hereditary angioedema. You have overuse of C1, C4, and C2 which causes edema at mucosal surfaces so the most obvious sign is that the patients face is swollen but it happens everywhere.

What initiates the MAC attack?

C5 convertase

14-year-old male who had grand mal seizure at school Mild left-sided muscle weakness (face, arm, leg); CVA suspected; cleared spontaneously within a few days Slight mental retardation; downward partial dislocation of lenses of both eyes (corrected surgically); slight waddling gait last few years Increased length of long bones, slight scoliosis Diagnosis

CAT scan consistent with small infarct in right cerebral hemisphere. Decreased mineralization of skeleton (osteopenia) and high Met and HCy (homocystein), low Cys in blood

What stimulates gallbladder, pancreas secretions?

CCK (cholecystokinin)- Hormone produced by intestinal cells and secreted when stomach contents enter intestine.

What is the CD marker for macrophages?

CD14

NK cells characteristics

CD16 and 56 Responsible for killing viral infected and transformed cells (ADCC) Non-specific Activation of NK cells leads to degranulation - perforin (punch holes in membrane of target cells and fills it full of toxin components which makes the target cell die.) Apoptosis - Fas on the NK cell binds with Fas on the target cell and induces the target cell to commit suicide

What is the CD marker for NK cells?

CD16 and CD56

Which adhesion molecule is important in getting WBC into tissues from the blood?

CD18 which is activated by IL-8 (cytokine) and initiates tight binding of the WBC to the vascular endothelium.

What is the CD marker for B cells?

CD19, CD20, and CD21

What is the CD marker for all T cells?

CD3

What is the CD marker for stem cells?

CD34

What is the CD marker for T helper cells?

CD4

What is the CD marker for APC's (antigen presenting cells) and what are the APC's?

CD40 Macrophages, dendritic cells, and b cells.

What is the CD marker for activated T helper cells?

CD40L

What is the CD marker for T cytotoxic cells?

CD8

What is the INK4/ARF family and what are the main functions?

CDKN2A-C: P16/INK4a binds to cyclin D-CDK4 and promotes the inhibitory effects of RB. P14/ARF: Increases P53 levels by inhibiting MDM2 activity.

Overview of pyrimidine synthesis

CPS-II (first step in synthesis converts glutamine + CO2 + 2 ATP -> Carbamoyl phosphate) reaction similar to the CPSI reaction in the urea cycle. - Occurs in cytosol (not mitochondria) - Uses glutamine instead of NH4+ -Regulated step Note that orotate is an intermediate. Uses ATP

Regulation of pyrimidine synthesis

CPS-II is Inhibited by: UTP Stimulated by: PRPP

Location of the carnitine shuttle (3)

CPTI: outer mitochondrial membrane CPTII and translocase: inner mitochondrial membrane.

Which epigenomic regulatory gene mutation found in 40% of diffuse large B cell lymphoma?

CREBBP/EP300: histone acetylation

Effector cells in cell-mediated immunity

CTL = Cytotoxic T cell

T cell receptor

Can only bind one antigen, is always membrane bound and never secreted, and can only recognize things bound on MHC.

Pathway when OTC is defective, clinical diagnosis?

Carbamoyl -> orotate -> pyrimidines and urine. Pyrimidine synthesis pathway becomes flooded with OTC defect. Excess orotate is produced and excreted in the urine. This excess urinary orotate is indicative of a problem in the urea cycle.

What does glucogenic amino acids mean?

Carbon skeletons converted to some product of glucose breakdown. These amino acids produce pyruvate or intermediates of the TCA cycle. Considered glucogenic because they can lead to production of glucose in the liver. Some amino acids are both glucogenic and ketogenic. Lysine and leucine are strictly ketogenic.

What is the associated neoplasm and etiologic agent in osteomyelitis

Carcinoma in draining sinuses bacterial infection

This tumor marker is found in what tumor types? carcinoembryonic antigen

Carcinomas of the colon, pancreas, lung, stomach, and heart

Cells *DO NOT DIVIDE* little capacity for repair past childhood Fibroblasts in connective tissue form scar tissue - Replace dead cells -> release troponin Surrounding cells respond with *hypertrophy* (No satellite cells here)

Cardiac muscle repair

*Appositional* - Forms at the surface of existing cartilage - New cells derived from perichondrium *Interstitial* - Forms within an existing cartilage mass - New cells form from existing chondrocytes

Cartilage growth

Cartilage is composed of chondrocytes Chondrogenesis: - Aggregation of mesenchymal cells into a chondrogenic nodule - Differentiate into chondroblasts - Chondroblasts secrete cartilage matrix - Become chondrocytes - Surrounding mesenchymal tissue forms perichondrium

Cartilage is composed of?

Glucose and diabetes

Cataracts -Glucose increases rate of sorbitol, fructose formation. -Glucose & fructose increase nonenzymatic glycation of lens protein.

Glutamine synthetase role in cells around portal vein?

Catches NH3 that escaped from urea production and adds it to glutamate to form glutamine. *Uses ATP*

Dilated region of neuron Large, central *Nucleus - Nucleolus* *Perinuclear cytoplasm* - *Nissl bodies* -- rER & free ribosomes - Golgi apparatus - Mitochondria - Lysosomes - Microtubules - Neurofilaments - Transport vesicles - Inclusions

Cell body (soma)

Cell mediated immunity

Cell mediated immunity deals specifically with things that are intracellular like viruses and some bacteria. Cell mediated immunity goal is to always destroy the host cell that harbors the virus, etc. Intracellular bacteria and parasites or fungi induce delayed type hypersensitivity via Th1 and macrophage activation.

Osteoprogenitor cells Osteoblasts Bone lining cells (periosteal and endosteal cells) Osteocytes Osteoclasts

Cell types

Injury induces *axonal degeneration* CNS is unable to regenerate due to restrictions: - Inefficient clearance of myelin debris -- Restriction of sufficient number of macrophages by: --- *blood-brain barrier- macromolecule* ---- Disrupted at site of injury -- Inefficient phagocytic activity by: --- *Microglia cells* -- Clearance can take months-years - Formation of *astrocyte-derived scar* (plaques) -- Fills space left by degenerated axons.

Central Nerve Injury

I. Composition A. Brain & spinal cord B. White matter C. Gray matter II. Meninges A. Dura mater B. Arachnoid mater C. Pia mater III. Blood-brain barrier IV. Nerve injury

Central Nervous System

Often heavy metal staining or immunocytochemica methods necessary i. Oligodendrocytes ii. Astrocytes iii. Microglia iv. Ependymal cells

Central Neuroglia

What is the associated neoplasm and etiologic agent in chronic cervicitis

Cervical carcinoma Human papillomavirus

Location: Heart *Striated muscle* - Striated arrangement Involuntary muscle - *Autonomic* control Difference from skeletal muscle: - Individual *mononucleated* cells - Cells do not run length of muscle -- Attach linearly via *Intercalated discs* -- Cells branch

Characteristics and classifications of cardiac muscle

Composed of cells and extra-cellular matrix (ECM) ECM composed of fibers and ground substance Function is a reflection of composition *Locations:* Fascia, tendons, ligaments, supportive layers of vessels/nerves/muscles/organs

Characteristics of connective tissue

- Composed of cells and a basement membrane - Lines cavities and covers surfaces - Three distinct surface domains - Cells adhered to one another via cell junctions (form selective barrier) - Renewed continuously through mitosis. - *Avascular* *Absent from: articular cartilage, anterior surface of iris, enamel of teeth.*

Characteristics of epithelial tissue

*Pseudostratified Epithelium* Simple epithelium All cells attach to basement membrane (just 1 cell that stretches goes from apical to basement) *Locations*- Trachea, bronchi, ductus deferens, epididymis Secretion and conduit Absorption and conduit Will find cilia on these pseudostratified epithelium

Characteristics of this tissue type:

*Transitional Epithelium* (urothelium) Stratified epithelium Specialized for distention- cells flatten and "unfold" (cells at the top termed 'umbrella cells') *Locations*: Lower urinary tract (minor calyces, ureter, bladder, proximal urethra). (Barrier, distensible property)

Characteristics of this tissue type:

Release of chemical substance (*neurotransmitters*) from presynaptic cell into synaptic cleft Affect ion channels on postsynaptic cell -> transmit impulse

Chemical synapse

What are mitogens

Chemical/molecules that are capable of inducing cell division in a high % of B and T cells. Activate many clones, not just cells bearing specific receptors (polyclonal activators). Many are sugar binding proteins called lectins which bind to glycoproteins on cell surface. Some activate B cells, T cells, or both. Concanavalin A - T cell Phytohemaglutinin- T cells Pokeweed mitogens- B and T cells Non-lectin (2 most important mitogens) - LPS- B cells - EBV (epstein barr virus)- B cells

What is the associated neoplasm and etiologic agent in Opisthorchis, cholangitis

Cholangiocarcinoma, colon carcinoma Liver flukes (opisthorchis viverrini).

Chromogranin A marker for

Chromogranin A is a protein that is found in neuroendocrine cells, which are mainly present in the pancreas (i.e., islet cells), gastrointestinal tract, lungs, and adrenal glands. The biopsy of this patient's ileal mass shows numerous small cells of similar shape and size (monomorphic cells) arranged in a rosette pattern that is typical of a carcinoid tumor. Chromogranin A, synaptophysin, and neuron-specific enolase can be used as an immunostain to confirm the neuroendocrine origin of this tumor.

What does a deficiency in NADPH oxidase cause

Chronic granulomatous disease

Microtubules Kartagener's syndrome and Young's syndrome (bronchiectasis, rhinosinusitis and reduced fertility.)

Cilia made of? What diseases are characteristic of cilia disorder?

What are the 3 classes of HLA (MHC), which chromosome is it found in, and general characteristics.

Class I (A, B, and C) - Cytotoxic T cells. Class II (DP, DQ, and DR) - Helper T cells. Class III- Non-classical HLA (don't worry about). All 3 classes found on chromosome 6 They are highly polymorphic (high allelic differences and variability). Expression is co-dominant (one from mom and one from dad and they are coexpressed).

What is the difference between the classical, lectin, and alternative pathways?

Classical pathway: Antibody binds to specific antigen on pathogen surface. Need at least 1 IgM (which is pentameric) or 2 IgG (monomeric) to initiate. Needs antibody so this is adaptive immune system. Lectin pathway: mannose-binding lectin binds to pathogen surface. Initiates when a complement binds to carbohydrates on bacteria and initiates this pathway. Happens innately. Alternative pathway: Complement proteins coming from the liver, spleen, and macrophages spontaneously lyse (C3 to C3a and C3b) then if C3b binds to the pathogen surface because of attraction to it's (example) LPS, etc, this pathway is triggered. Happens innately.

- *Long bones* - Short bones - Flat bones - Irregular bones Compact vs spongy bones

Classification of bones

Based on: 1. Cell type 2. ECM/ground substance characteristics 3. Function Classifications: 1. *Embryonic Connective Tissue* a. Mesenchyme b. Mucous CT 2. *Connective Tissue Proper* a. Loose CT b. Dense CT (regular, irregular) 3. *Specialized Connective Tissue* - Bone - Cartilage - Adipose - Blood - Hemopoietic - Lymphatic

Classification of connective tissue

1. Number of cell layers: - Simple - Stratified 2. Cell morphology: - Squamous - Cuboidal - Columnar 3. Apical modifications: - Keratinized/ non-keratinized - Ciliated

Classification of epithelial tissue (3)

Simple columnar: -Small intestine and colon (absorption and secretion. -Stomach lining and gastric glands (secretion) -Gallbladder (Absorption)