Exam 1 Flashcards

Question

Monopoiesis

Answer 1

• the development of monocytes • CMP—> monoblast—> promonocyte—> monocyte—(in tissue)—> macrophage

Answer 2

• platelet formation in the bone marrow • involves the giant nucleated cell: megakaryocyte • nucleus undergoes endomitosis: copies, and enlarges DNA, but does not divide cytoplasm • cytoplasm fragments into thousands of platelets

Answer 3

They live by the sinusoids in order to send platelets into circulation

Answer 4

1. Myeloid tissue • produces most blood cell types • bone marrow • common myeloid progenitor (CMP) 2. Lymphoid tissue • abundance of lymphocytes • responsible for immune defenses of the body • thymus, lymph nodes, spleen, non-encapsulated lymph nodules • common lymphoid progenitor (CLP)

Answer 5

• B lymphocytes develop in bone marrow and spleen • T lymphocytes develop in bone marrow before maturing in the thymus • mature B & T lymphocytes populate other secondary lymphatic organs • CLP—> lymphoblast—> prolymphocyte—> B cells, T cells, NK cells

Answer 6

• bone marrow: B cells • thymus: T cells

Answer 7

• mucosa associated lymphatic tissue (nodular, non-encapsulated lymphatic tissue). Ex: tonsils, digestive, tract, respiratory, urinary, reproductive tracts • lymph nodes (encapsulated) • spleen (encapsulated)

Answer 8

• populated with lymphocytes • large lymphocytes: activated, NK cells • small lymphocytes: B cells, T cells

Answer 9

• lymphopoiesis • immune response: small lymphocytes (recirculate between blood and lymph, capable of responding to antigen)

Answer 10

• a component of lymphoid tissues • reticular cells (specialized fibroblasts) • macrophages (antigen, presenting cells) • dendritic cells (APCs— very efficient) • follicular dendritic cells (mesenchymal, not APCs)

Answer 11

1.) diffuse, lymphatic tissue found in GI, respiratory, urinary, reproductive. • loose or dense 2.) nodular lymphatic tissue found in GI, respiratory, urinary, reproductive. • represent local immune responses to antigens, characterized by solitary lymphatic nodules

Answer 12

• not enclosed by a capsule • primary: dark staining spherical balls of lymphocytes • secondary: contain a reaction (germinal) center

Answer 13

• germinal center indicates response to an antigen (T cell mediated) • immature B cell proliferation (larger cytoplasm makes it stain lighter in the center) • antibody production by plasma cells • accumulation of macrophages and follicular dendritic cells

Answer 14

1. Non-encapsulated lymph nodules 2. Tonsils of oropharynx 3. Peyer’s patches (ileum of small intestine) 4. Appendix

Answer 15

1. Trapping of antigen 2. Lymphocyte production in response to antigen: B cell proliferation 3. Destruction of antigen - no afferent lymphatic vessels

Answer 16

• only lymphatic organ located in the course of lymphatic vessels • only lymphatic organ that has lymphatic sinuses • only lymphatic organ that filters lymph (done by macrophages)

Answer 17

1. Capsule (dense CT) 2. Trabeculae (dense CT) 3. Stroma (cells and fibers, reticular) 4. Endothelial cells: line sinusoids

Answer 18

• lymphoid tissue, supported by reticular fibers and stromal cells • lymphocytes • lymphatic, nodules, including germinal centers, and tails that extend into the medulla as medullary cords

Answer 19

• lymphoid tissue, supported by reticular fibers and stromal cells • medullary cords and sinuses • cells: small lymphocytes • sinuses converge near hilum and drain into efferent lymphatic vessels

Answer 20

• between capsule and inner limits of germinal centers • contains majority B cells

Answer 21

• between germinal centers and medullary cords • majority T cells

Answer 22

• lined by endothelial cells with large intercellular gaps • slow, lymph flow- can trap metastatic cancer cells • lymphocytes, enter lymphatic sinuses and leave lymph node via efferent lymphatics at hilus

Answer 23

Afferent lymphatic vessels—> subcapsular sinus—> trabecular sinus—> paracortical sinus—> medullary sinus—> efferent lymphatic vessel—> aorta

Answer 24

1. Outer superficial cortex: simple, squamous endothelium 2. Deep paracortex: simple cuboidal endothelium, high endothelial venule (HEVs)

Answer 25

• site of passage of lymphocytes from blood vessels into lymphatic tissue • allow physical contact between APC and lymphocytes for activation— adaptive immune responses

Answer 26

afferent arterioles—> precapillary arterioles—> capillaries—> HEVs—> lymphatic tissue—> lymphatic sinuses—> efferent, lymphatic vessels

Answer 27

• lymph filter by macrophages • lymphocyte production • antibody production (plasma cells)

Answer 28

• intact skin • ciliary lung clearance • stomach PH • lysozymes in tears and saliva and ear wax

Answer 29

• natural killer cells • eosinophils • macrophages • mast cells • neutrophils • complement • C reactive protein • antimicrobial peptides • dendritic cells • natural killer cells

Answer 30

• T cells, B cells • Humoral- antibodies • dendritic/natural killer

Answer 31

•Fast, generally nonspecific reaction to foreign antigens • pattern, recognition receptors • complement cascades

Answer 32

• antigen specific response (B cell—> antibodies, T cell—> B cell helpers, and cytotoxicity/killing) • long term protective immunity

Answer 33

In the bone marrow—> hematopoietic stem cell—> myeloid progenitor cell (innate), and lymphoid progenitor cell (adaptive)

Answer 34

Are classified as innate because they are fast, primed, and ready. However, they come from a lymphoid progenitor cell, which is typically adaptive.

Answer 35

• protection in infected, stressed, and cancer cells • they are stimulated by innate cytokines • they are potent IFN-gamma and TNF-alpha producers • NK receptors function as kill or do not kill switches

Answer 36

Absence of self recognition. The presence of an activating signal will always be overridden by an inhibitory signals in the NK cell.

Answer 37

1. Granule-mediated: granzyme B (serine protease), perforin (oligomeric pore forming protein) — must be close contact 2. Death receptor-mediated: Fas:FasL, or TRAIL R:TRAIL • both involve apoptosis induction, programmed cell death

Answer 38

• fever, acute inflammation, endothelial expression adhesion molecules, chemokine secretion (WBC recruitment)

Answer 39

• induces, differentiation, and proliferation of Th2 helper cells. Class switching of IgM to IgE. Role in class one hypersensitivity reaction.

Answer 40

• fever, and acute phase protein production

Answer 41

• endothelial, activation, WBC, recruitment, vascular, leaking us, fever • cachexia in cancer, granuloma, maintenance in TB

Answer 42

Neutrophil chemotactic factors— cleanup on aisle eight. Clear infections.

Answer 43

NK cell activation, Th1 differentiation - Granuloma formation in TB

Answer 44

• innate defense against viruses via inhibition of protein synthesis, and induces ribonuclease to degrade mRNA. Activates NK cell killing functions.

Answer 45

• IL1 • IL4 • IL6 • TNF- alpha • IL8 • IL12 • IFN alpha/beta

Answer 46

• IL2: supports proliferation and differentiation of T cell, subsets and NK cells • IL3: supports growth and differentiation of bone marrow stem cells

Answer 47

IFN-gamma: produced in response to IL12, induces, macrophage, killing of phagocytosis pathogens. Induces IgG isotope switching inhibits Th2 differentiation

Answer 48

• IL4 • IL5 • IL10: Tregs to dampen immune response * IL11 • IL13

Answer 49

• extracellular, or lysosomal recognition • TLRs • c-type lectin receptors (CLRs)

Answer 50

• intracellular recognition • nucleotide-binding and oligomerization domain-like receptors • inflammasome • RIG-l like (RLRs), CCR7

Answer 51

• early control, and clearance of infectious pathogens the serum and membrane bound proteins • alternative, classical, lectin • all pathways converge at cleavage of C5 • form membrane attack complex for osmotic cell lysis

Answer 52

Selectins and integrins: adhesion molecules, that aid in leukocyte recruitment

Answer 53

NK cells—> target lysis. Killing via Fas:FasL, TRAIL

Answer 54

Macrophage/dendritic cell—> phagocytosis—> antigen, uptake, and presentation—> cytokine production—> chemotaxis Complement —> osmotic lysis of bacteria

Answer 55

• antibody mediated • B lymphocytes • antibodies, circulating in serum • primary defense against extracellular pathogens: bacteria and circulating viruses

Answer 56

• cell mediated • T lymphocytes • direct cell to cell contact or secreted soluble products (cytokines) • primary defense against intracellular pathogens: viruses and fungi, intracellular bacteria, tumor antigens, and graft rejection

Answer 57

Major histocompatibility complex MHC1: T cells B cells, macrophages, dendritic cells, neutrophils MHC2: B cells, dendritic cells, epithelial cells of thymus

Answer 58

Only T cells with TCR recognize self-MHC survive

Answer 59

T cells that react to strongly to self-MHC are eliminated

Answer 60

• dendritic cells • macrophages • Thymic epithelial cells, and B cells

Answer 61

• they are located in a common site of entry for foreign antigens • they express receptors that allow capture of antigens and processing of antigenic peptides • they express high levels of peptide MHCs, co-stimulatory molecules, and produce cytokines • they can present antigen and needed signals to both CD4 and CD8 T cells

Answer 62

Resident tissue APCs. They like to stay right at home.

Answer 63

In tissue but traffic to the lymph node: traveling salesman, displaying their goods

Answer 64

1. MHC 2. Co- receptor binding • both signals are required. If only one signal, the T cell becomes anergic and non-responsive to the antigen

Answer 65

• IFN-gamma • macrophages • macrophage activation • intracellular pathogens • autoimmunity, chronic inflammation

Answer 66

• IL4, IL5, IL13 • eosinophils • eosinophil and mast cell activation, alternative macrophage activation • helminths • allergy

Answer 67

• IL17, IL22 • neutrophils • neutrophil, recruitment, and activation • extracellular, bacteria, and fungi • autoimmunity, inflammation

Answer 68

• IL21, IFN-gamma, IL4 • B cells • antibody production • extracellular pathogens • autoimmunity (autoantibodies)

Answer 69

1. Receptor editing: replacement of self reactive, receptor with nonself reactive receptor 2. Clonal deletion: elimination of self reactive B cell clones 3. Clonal anergy: an antigen specific hypo responsiveness

Answer 70

The specific molecular target of which a complementary antibody binds to

Answer 71

Somatic hypermutation, affinity maturation, and class switching

Answer 72

IgA: dimer IgM: pentamer

Answer 73

1. Neutralization. 2. Opsonization 3. Complement activation 4. Antibody dependent cellular cytotoxicity (ADCC)

Answer 74

1. Activated helper T cell expresses CD40L, secretes cytokines 2. B cells are activated by CD40 engagement, cytokines 3. B cell proliferation and differentiation

Answer 75

• IgE, CD4+, Th2 • allergy, anaphylaxis, atopic • mast cells, eosinophils • IL4, IL5, IL13

Answer 76

• IgM, IgG against cell surface or extracellular matrix proteins • cellular destruction: opsonization, complement, ADCC, inflammation

Answer 77

• circulating, antigen antibody complexes • complement activation • neutrophil, attraction, and lysozyme release • Ab:Ag bulky

Answer 78

• CD4+, CD8+, Th1, Th17 • cytokine mediated inflammation, macrophage, neutrophil, activation (CD4+) • direct target cell killing (CD8+, CTLs)

Answer 79

• CD21 • CD19 • CD3

Answer 80

• CD80/86 • CD28 • CD3- intracellular signal motif

Answer 81

TCR—> PLCgamma1—> calcineurin—> NFAT —> activation IL2—> T cell proliferation control

Answer 82

An immunosuppressant that is used to treat both T cell mediated, Auto immune disease and organ transplant Rejection. Acts by blocking the function of calcineurin. Prohibits T cell interaction with antigen.

Answer 83

This kinase cascade activates gene transcription through AP-1 Raf (MAPKKK) —> MEK (MAPKK) —> ERK (MAPK)

Answer 84

• activates transcription through NF-kB (important in many innate and adaptive immune processes- associated with pro-inflammatory an activation events rather than regulatory processes)

Answer 85

Secreted, low molecular weight proteins that regulate the immune response by exerting effects on cells that express the appropriate receptor. Typically cell to cell signaling.

Answer 86

• Cytokines that mediate chemotaxis in particular leukocytes via receptor engagement. Can regulate the expression, and/or adhesiveness of leukocyte integrins. • chemoattractants • chemokines: CCL(#), CXCL(#), XCL1, CX3CL1 • chemokine receptors: CCR(#), CXCR(#), XCR1, CX3CR1

Answer 87

1. Endocrine: far away cell, through circulation 2. Paracrine: nearby cell 3. Autocrine: self

Answer 88

Induces different biological effects, depending on the nature of the target cell type

Answer 89

Two or more cytokines that mediate similar function

Answer 90

Combined effect of two cytokines on cellular activity is greater than the additive effect of the two cytokines

Answer 91

The effect of one cytokine cancels out the effect of another

Answer 92

The effect of one cytokine on a target cell leads to the production of one or more additional cytokines from that target cell

Answer 93

Cytokines that are important in limiting the spread of viral infections

Answer 94

Large group of cytokines produced, mainly by T cells. Variety of functions, including causing neighboring cells to divide and differentiate.

Answer 95

Primarily involved in directing the division and differentiation of bone marrow, stem cells and precursors of blood leukocytes. Controls how many and what kind of leukocyte is to be produced

Answer 96

Chemotactic cytokine used to direct the movement of leukocytes around the body

Answer 97

Particularly important in mediating inflammation and cytotoxic reactions

Answer 98

Important in regulating cell division, and tissue repair

Answer 99

You will lose signaling from multiple cytokines important in T cell development, B cell and NK cell development, class switch recombination, and homeostasis (IL21, 15, 9, 7, 4, 2)

Answer 100

Area of the antibody where antigen binds

Answer 101

Part of the heavy chain of an antibody that has flexibility. It’s normal confirmation hides the compliment binding site to prevent unwanted, complement activation. Once antigen has been bound, it will open in this area and allow for immune response.

Answer 102

Light chain: one variable domain, and one constant domain Heavy chain: one variable domain, and 3-4 constant domains (x2)

Answer 103

• pentamer— connected by a J chain Light chain: one variable, one constant Heavy chain: one variable 4 constant

Answer 104

• dimer— connected by a J chain Light chain: one variable, one constant Heavy chain: one variable, one constant

Answer 105

• membrane bound on B cells (like IgM) • has tail pieces that have two more Constants on them. Hinge region is in between the normal chain and the tail pieces. Light chain: one variable, one constant heavy chain: one variable, one constant

Answer 106

• monomer Light chain: one variable, one constant Heavy chain: one variable, four constant

Answer 107

Kappa or Llamada. It may use one or the other, cannot use both. It does allow for flexibility during the cell modification. When class switching, the heavy chain gets replaced, but the light chain always stays the same.

Answer 108

• on the basis of slight differences in the amino acid, sequences of their H chain C regions. The five main classes of immunoglobulins are divided into sub classes based off of our genome 1. IgG: 1,2,3,4 2. IgA: 1,2 3. IgM: 1,2 4. IgD: 1 5. IgE: 1

Answer 109

• minor allelic differences in the sequence of immunoglobulins between individuals • determined by your parents in the usual Mendelian fashion • this is why we used pooled immunoglobulin serum for infusions

Answer 110

• each antibody will have a unique combining region made up of the hyper variable amino acids of its L & H chains.

Answer 111

The extra cellular spaces of the body— the tissue, fluids, blood, secretions by releasing antibodies into the fluids (humoral immunity)

Answer 112

Themselves survey the surface of the bodies sells looking for ones that have been changed or mutated (cell mediated immunity)

Answer 113

• Genetic rearrangement by mixing and matching one of each of the various genes segments for the heavy and light chains in a combinatorial matter • variation incorporated at the joining sites for the various segments of the heavy in light chains • hyper mutation in one of the gene segments of the heavy and light chains during proliferation of B cells • mixing, and matching heavy and light chains in a combinatorial manner

Answer 114

Lymphoid specific complex of two proteins, that catalyze DNA strand breakage and re-join to form signal and coding joints

Answer 115

Lymphoid specific protein that adds N region nucleotides to the joints between gene segments in the Ig heavy chain, and at all joints between TCR gene segments

Answer 116

Stabilize binding of RAG 1/2 to recombination signal sequences, particularly to the 23-bp RSS. Stabilized and introduced into the 23-bp spacer DNA by the RAG 1/2 proteins

Answer 117

Binds DNA coding and signal ends and holds them in protein-DNA complex

Answer 118

In complex with Ku proteins, recruits and phosphorylates Artemis

Answer 119

Opens the coding end hairpins

Answer 120

Stabilizes and activates DNA ligase IV

Answer 121

In complex with XRCC4, and cernunnos. Ligates DNA ends.

Answer 122

With XRCC4, activates DNA ligase IV

Answer 123

One V, one D, and one J Light chain: V, J Heavy chain : V, D, J

Answer 124

D + J —> DNA cut, ends joined —> V + DJ —> DNA cut, ends joined Primary RNA transcripts are alternatively processed using alt polyA sites and splicing

Answer 125

Gene rearrangement, but only with V and J segments, and only one constant gene domain. There is a kappa and lambda chain, while one is transcribed the other is silenced

Answer 126

RAG1 and RAG2 recombinases. They first bind splice signals to the right of a DNA segment and the left of a J segment, pull them together, and then cut and splice. If RAGs are knocked out, B and T cells fail to form

Answer 127

- sloppy - exonucleases chew away a few nucleotides after the DNA is cut but before two gene segments are joined. Therefore N region (where they are joined) is unpredictable - 2/3 times this does not work because it does not add/cut in lengths of 3 so there are frameshift mutations and nonsense codons that terminate transcription

Answer 128

- If a rearrangement is detected as faulty, the RAG genes are still active and can "try again" which sometimes results in a successful cell.

Answer 129

IgD and IgM on their external surfaces

Answer 130

membrane bound IgM and IgD to secretory IgM. This occurs at the level of processing of mRNA transcripts

Answer 131

Selection of the best fitting mutants after antigenic stimulation allows a gradual increase of affinity during an immune response

Answer 132

Activation- induced (cytidine) deaminase (AID) converts random cytosines in the variable gene regions to a uracil. C:G pair becomes a mismatch, and DNA polymerases come and fix it and replace it with single-base substitution mutations that may make the cell a better/worse antibody.

Answer 133

Stay the same: L chain, and VH domain Changes: C region of the H chain -- when the switch occurs, the DNA for the previous IgM/IgD gets excised, therefore you cannot go back once you go forward.

Answer 134

1. transport gases, hormones, nutrients, and waste products 2. regulates body temperature 3. protects against pathogens and fluid loss

Answer 135

Chloride and bicarbonate

Answer 136

The acellular liquid fraction after blood has been allowed to clot (HAS NO FIBRINOGEN) - THINK: fibrinogen is all taken up in the clots so you will no see it.

Answer 137

As fatty acids bound to albumin

Answer 138

Breast cancer treatment that affects microtubule stabilization, acting on M phase of the cell cycle and the microtubules cannot pull apart the dividing chromatin (no cell division). Can be carried into the cells by albumin

Answer 139

- synth: by hepatocytes - excreted into blood - Found: in the interstitial space

Answer 140

- Albumin Functions of albumin: Transportation, oncotic pressure regulation, antioxidant effects

Answer 141

Endogenous substances: Fatty acids (up to 7 at a time), steroids, L-tryptophan, copper, bilirubin, calcium, zinc Drugs: Warfarin, chlorpromazine, ibuprofen, naproxen

Answer 142

Albondin (gp60)

Answer 143

triple negative breast cancer ( basal subtype found in younger, more aggressive type)

Answer 144

- The contribution of dissolved colloids to osmotic pressure. In plasma, albumin contributes to 75% of the total oncotic pressure. - maintaining pressure is critical for filtering out fluid from the circulatory system and into lymphatic vessels in capillary beds.

Answer 145

- protein malnutrition - Prominent feature: swollen belly, edema, relating to albumin effects of oncotic pressure

Answer 146

hydrostatic pressure exceeds oncotic pressure and fluid leaves the capillary

Answer 147

Oncotic pressure exceeds hydrostatic pressure and fluid enters the capillary

Answer 148

- loss of oncotic pressure leading to interstitial edema. Rapid loss of fluid from the vasculature, with no way for reentry.

Answer 149

- exposed cysteines - the sulfur from Cys34 can be oxidized by reactive oxygen species - albumin also binds and sequesters copper (source of oxidative stress)

Answer 150

HPO4 2- accepting proton PR accepting proton

Answer 151

HCO3- from RBC via chloride antiporter

Answer 152

Hb (hemoglobin) HPO4 2-

Answer 153

1. Hydrogen ions 2. 2,3-BPG 3. Covalent binding of CO2

Answer 154

as pH decreases, hemoglobin's affinity for oxygen decreases and oxygen saturation decreases

Answer 155

Through the Rapport-Luberin shunt via a mutase enzyme for 1,3-BPG and a phosphatase enzyme to 3-PG

Answer 156

1. Phosphofructokinase-1 - activated by: AMP, fructose 2,6-BP - inhibited by: ATP, citrate

Answer 157

- Glutathione reduction

Answer 158

Hemolytic anemia in response to acute oxidative stress. This is because they cannot produce NADPH and therefore cannot produce reduced glutathione

Answer 159

Cytochrome-B5 methemoglobin reductase MetHbFe3+ seen with benzocaine anesthetic and G6PD

Answer 160

It will condense into dark inclusions visible within erythrocytes called Heinz bodies. Bite cells can also occur

Answer 161

when the production of methemoglobin exceeds the reducing power of the erythrocyte. --> hypoxia, cyanosis, death Treatment: Methylene blue ( electron acceptor in the NADPH methemoglobin reductase reaction)

Answer 162

Deformation of the fluid is proportional to the stress applied to it. (ex. water and plasma) - Blood is non-newtonian because it is more resistant to movement from small forces than large forces

Answer 163

Amount of red blood cells

Answer 164

JAK/STAT receptors. Ligand binding causes JAKs to phosphorylate the receptors, recruiting STAT proteins which dimerize, translocate to the nucleus, and activate transcription of target genes

Answer 165

SOCS expression

Answer 166

1. Bcl-XL (anti-apoptotic) 2. cyclin D (G1-S checkpoint)

Answer 167

Polycythemia

Answer 168

a disease caused by overproduction of red blood cells. The increased viscosity of blood increased the risk for thrombosis - typically sporadic somatic mutation, rarely inherited

Answer 169

1. phlebotomy 2. Hydroxyurea (inhibits ribonucleotide reductase and inhibits hematopoiesis)

Answer 170

- no afferent lymphatic vessels - efferent lymphatic vessels in capsule and CT - site for differentiation of T cells - largest in fetal life and gets smaller over time - Endodermal epithelial cells --> epithelioreticular cells and Thymic (Hassall's corpuscles)

Answer 171

Common lymphoid progenitor cells (CLP)

Answer 172

- Two lobes enclosed by CT capsule (divided by CT trabeculae or septae) - between sternum/heart - Cortex and medulla within each lobe

Answer 173

Cortex: stains darker Medulla: stains lighter, thymic corpuscles in medulla (round, eosinophilic)

Answer 174

1. Epithelioreticular cells 2. Macrophages 3. Lymphocytes (various stages of maturation) -- No CT or reticular fibers in the cortex

Answer 175

- interconnected processes form a closely packed cellular network that supports and forms a barrier around the differentiating t-cells - large, faintly stained nucleus - do not produce reticular fibers - express MHCI and MHCII -APCs to thymocytes for education - produce thymic hormones - helps form blood-thymus barrier with desmosomes

Answer 176

- phagocytic - destroys abnormally developing T cells - Stained with PAS (periodic acid ship staining) because they do not stain with H&E

Answer 177

- epithelioreticular cells - larger lymphocytes (more differentiated) - some connective tissue cells and reticular fibers - Thymic corpuscles (Hassall's- concentric wrapped epithelioreticular cells)

Answer 178

- regulate dendritic selection of a specific lineage of T cells (FoxP3+)

Answer 179

- internal thoracic and inferior thyroid arteries

Answer 180

- prevents antigens in blood stream from entering the thymic cortex - Components: endothelial cells with tight junctions, basal lamina, perivascular CT, epithelioreticular cells with desmosomes

Answer 181

- largest lymphatic organ - no afferent lymphatic vessels - efferent lymphatic vessels present - no lymph sinuses

Answer 182

- artery and vein - efferent lymphatic vessels - sympathetic nerve fibers - thick capsule with some smooth muscle - thick CT trabeculae - splenic pulp, white and red

Answer 183

- occupied by lymphoid cells - periarterial lymphatic sheath (PALS) surrounding white pulp artery - contains primarily T cells - Splenic lymphatic nodules - scattered throughout length of the PALS - contains primarily B cells

Answer 184

- occupied by myeloid cells - splenic sinuses (sinusoids) - Splenic cords (billroth cords)

Answer 185

- vascular passageways lined by specialized endothelial cells

Answer 186

- located between sinuses - contains: RBCs, granulocytes, lymphocytes, macrophages, dendritic cells, plasma cells, reticular cells and fibers

Answer 187

- zone between the red and white pulp - small blood vessels dump their blood into this area (slow flow rate) - traps antigen for presentation to lymphocytes - macrophages help to clear antigen by phagocytosis

Answer 188

- consist of elongated and narrow endothelial (rod-like) - endothelial cells supported by an anastomosing ring of basement membrane and reticular fibers that encircle the sinusoid like the hoops of a barrel

Answer 189

Terminal capillaries opens into the sinuses

Answer 190

Terminal capillaries open into red pulp

Answer 191

- APCs to initiate immune response - Activation and proliferation of B and T lymphocytes - Production of Abs against antigen present in circulating blood (plasma cells) - Removal of macromolecular antigens from the blood (macrophages, neutrophils)

Answer 192

- removal and destruction of senescent, damaged, and abnl erythrocytes and platelets - Retrieval of iron from erythrocyte hemoglobin - Formation of erythrocytes during early fetal life - storage of blood, esp RBCs

Answer 193

- arbovirus (+) ssRNA flavivirus - Africa and South America - urban cycle (humans and mosquitos) - sylvan cycle (monkeys and mosquitos) - capillary fragility and disruption of blood clotting system. Leads to localized bleeding and shock

Answer 194

- RNA virus, icosahedral nucleocapsid, enveloped, ss(+)RNA, class 4, flavivirus

Answer 195

- Vector: Aedes mosquito - cytolytic and destroys the cells it infects - elevated: TGF-beta, TNF-alpha, IFN-gamma, IL-6 - in liver: infiltrate of CD4+ and CD8+ and NK cells (councilman bodies)

Answer 196

-severe systemic disease, flu-like symptoms, loss of liver, kidney, and heart function, hemorrhagic fever, shock. Mortality of infected is 50% Lab tests: immunofluorescence, RT-PCR, ELISA, NO LIVER BIOPSY Treatment: supportive care, vector control, vaccination

Answer 197

- one of 4 related (+)ssRNA flavivirus - transmitted by Aedes mosquito - non-vector transmission through blood transfusion, organ transplantation, and needle stick injuries - BREAKBONE FEVER (severe muscle/joint pain) - Where? Southeast Asia and India. (also in South America, Central America, and Carribean/Mexico) - Mild flu-like infection but can occasionally become Dengue Hemorrhagic Fever (usually during second isotype exposure)

Answer 198

- RNA virus, icosahedral nucleocapsid, enveloped, ss(+) non-segmented genome (class IV), flavivirus

Answer 199

- second serotype exposure is very dangerous because it is similar enough to the first that the body does not make new antibodies for it but the antibodies for the first serotype do not work quite right. The virus gets uptaken by dendritic cells but is not neutralized --> rapid replication and more virus. Very sick

Answer 200

- 25% experience a self-limiting febrile illness with mild to moderate hematological and biochemical abnormalities. - can also have: vascular leakage, coagulation abnormalities, and liver and CNS involvement -Lab tests: immunofluorescence, RT-PCR, ELISA, direct isolation of the virus - Treatment: supportive care, vector control, and vaccination

Answer 201

- (+)ssRNA virus - transmitted by the Aedes albopictus mosquito - causes symptoms similar dengue fever in individuals with the complication of severe CHRONIC joint pain (years post infection) - severe cases can have neurological impairment and/or hemorrhagic fever

Answer 202

- RNA virus, icosahedral nucleocapsid, enveloped, ss(+) non-segmented class 4, togaviridae, alphavirus

Answer 203

- causes symptoms similar dengue fever in individuals with the complication of severe CHRONIC joint pain (years post infection) - severe cases can have neurological impairment and/or hemorrhagic fever Lab tests: immunofluorescence, RT-PCR, ELISA, direct isolation of the virus Treatment: supportive care and vector control measures (no vaccine)

Answer 204

- RNA virus - transmitted by Fruit bat reservoirs- contact with fruit bat, monkeys, tissues/secretions, infected humans - Endemic in Africa (west and central) - 5 serotypes: ZEBOV, SEBOV, BEBOV, CIEBOV, REBOV

Answer 205

RNA virus, helical/pleomorphic nucleocapsid, enveloped, ss(-)RNA, non-segmented genome (class 5), filovirus

Answer 206

- necrosis in liver, spleen, lymph nodes, and lungs - hemorrhage causes edema and shock - mortality rate: 40% - no vaccination, supportive care

Answer 207

-(-)ssRNA arenavirus, primarily found in West Africa - 20% of cases result in a severe hemorrhagic syndrome - reservoir found in multimammate rat (rodent) - virus spreads via aerosoled rat droppings, eating contaminated foods - 95% spontaneous abortion rate in pregnant women

Answer 208

- RNA virus, helical nucleocapsid, enveloped, ss(-)RNA, segmented genome, class 5, arenavirus, mammarenavirus

Answer 209

-STD, direct contact - vaccine available - wart disease - effects E6 (increases turnover of p53 degradation) and E7 (promotes E2F to drive cell cycle and replication forcing cell proliferation) --> leads to malignancy

Answer 210

- dsDNA, class 1, circular genome, icosahedral nucleocapsid, nonenveloped, papovaviridae

Answer 211

dsDNA, group 1, linear genome, icosahedral nucleocapsid, enveloped, herpesvirus (gamma)

Answer 212

- usually asymptomatic primary infection - Kaposi sarcoma derived from lymphatic and vascular endothelial cells - Dark purpuric rash on the skin - most common in immunocompromised pts (AIDs, HIV) - associated with primary effusion lymphoma and multicentric castleman's disease (cancers of B cells) Lab tests: tissue biopsy (spindle shaped tumor cells), PCR, Warthin-Starry silver staining Treatment: ganciclovir (against lytic virus), IFN-alpha (leukocytic effects), no vaccine

Answer 213

Early Pro-B (DJ H chain recombo, start V-DJ recombo) --> Late Pro-B (V-DJ H chain recombo) --> Pre-B (H chain solidified, several rounds of cell division, VJ L chain recombo) --> Immature B (mIgM expression, negative selection, deletion, receptor editing, check auto-reactivity)

Answer 214

- membrane bound IgM - the signaling chains CD79a, CD79b (aka Ig-alpha, Ig-beta)

Answer 215

- progenitor B cell, earliest stage of antigen-independent B cell development. Express CD43, CD19 (works with CD21, CD81), and RAG1/2. Also c-Kit which binds to stem cell factor expressed on bone marrow stromal cells- inducing proliferation) - 3 groups: 1.) Early pro-B: TdT only 2.) intermediate pro-B: TdT and CD45R 3.) Late pro-B: CD45R and downregulate TdT and RAG 1/2

Answer 216

- receptor for cell growth and differentiation - remains expressed on the surface throughout the remainder of B cell ontogeny

Answer 217

- divided into large mitotically active pre-B cells and small, non-dividing pre-B cells - Both large and small express IgM - Large has successfully rearranged the Ig heavy chain genes - large--> small, they rearrange their Ig light chain and upregulate RAG1/2 again

Answer 218

- IgM chain, 1 variable and 4 constant - Surrogate light chain (lambda5, Vpre-B)

Answer 219

- Finals stage - successfully rearranged their light chain and express IgM - RAG1/2 downregulated - immature--> mature = express both IgM and IgD on the surface - exit bone marrow and migrate to periphery - TRANSITION PHASE

Answer 220

- Cross checking phases to ensure the B cell is not too autoreactive, and that it responds appropriately to antigen

Answer 221

- occurs in bone marrow (clonal deletion) - Limits development of antibody-mediated autoimmunity (apoptosis or editing) - some negative selection occurs in the periphery (not every self-reactive B cell is eliminated in the marrow because not every self-antigen is expressed there)

Answer 222

- Tonic signaling from BAFF in the follicle

Answer 223

- Secondary lymphoid organs - From precursors in bone marrow - highly diverse V region - Somatic hypermutation capable - Requires T cell help - High levels of IgG - possibly responds to carb antigens - Responds to protein antigens - Yes memory - Surface IgD on naive B cells - Has CD19/CD21, IgM, IgD, CD23

Answer 224

in the germinal center

Answer 225

CD40+CD40L (B+T, respectively) - causes: entry into the germinal center for class switching, IgM bearing memory cells from primary response, and Focus cells secreting IgM

Answer 226

- immunodeficiency resulting from an inherited genetic defect in the immune system - Present at birth and creates help problems early on in life

Answer 227

1. 4+ ear infections in one year 2. 2+ sinus infections 3. 2+ months of abx treatment with little effect 4. 2+ pneumonias 5. failure to gain weight or grow 6. recurrent skin/organ abcesses 7. persistent thrush in mouth or fungal infection in skin 8. need for IV abx to clear infections 9. 2+ deep-seated infections including septicemia 10. a family hx of PI

Answer 228

- trouble with adhesion to the endothelial cells for WBC entry to tissue (all WBCs stay in the blood rather than getting to infection) - LFA-1 protein (integrin) is bad, usually from a defect in CD18 - symptoms include: recurrent sickness, very high WBC count, IV abx can resolve symptoms - REBUCK SKIN WINDOW TEST IS DONE (disrupt skin and see what cells come over hours) - treatment: bone marrow transplant

Answer 229

- failure of phagocytes to produce hydrogen peroxide and superoxide - is mostly problematic with catalase + organisms (staph aureus, aspergillus spp, Chromobacterium violaceum, pseudomonas, nocardia, etc) -

Answer 230

- p21 - gp91(most common, X-linked) - p47 - p67

Answer 231

-DHR assay with PMA-activated neutrophils - DHR: dihydrorhodamine: reduced by H2O2, will fluoresce - Patient with CGD will have no right shift and no fluorescent effect - gp91 x-linked males: 100% non-fxnal neutrophils, female carriers: 50% fxnal, 50% fluorescence

Answer 232

- teenage male - severe shortness of breath, aspergillus fungal pneumonia - normal IgG, IgA, IgM, normal WBC response - failed DHR assay - end up with granulomas: giant cells with macrophage center that cannot rid of antigen, and t cell wall around it, engulfing it

Answer 233

- a defect in intracellular vesicle trafficking - usually from gene LYST - trafficking issues occur everywhere in the body: granule vesicle problems, melanocyte melanosome-->keratinocyte problems, neuronal CNS trafficking problems - on histology you will see neutrophils with "stuck" granules

Answer 234

- Newborn/young child - recurrent ear infections - cellulitis, lymph node infections - bruising easily/mild nosebleeds: platelet maturation is bad - albinism - sensitivity to bright light - NORMAL: WBC, serum Ig levels, and DHR test - GIANT CYTOPLASMIC GRANULES IN LEUKOCYTES - treatment: bone marrow transplant (will only fix immune problems, not other bodily trafficking problems)

Answer 235

- Chediak-Higashi syndrome - causes abnormal organeller protein trafficking, aberrant fusion of vesicles, and failure of transport

Answer 236

vesicles that normally participate in platelet aggregation. Dysfunction of them is seen in Chediak-Higashi syndrome

Answer 237

- glycine - succinyl CoA - Ferrous (2+) iron

Answer 238

- porphyrias - defects in heme breakdown causing jaundice

Answer 239

- Eyrthroid cells ( for O2 delivery in hemoglobin) - Liver (for redox enzymes like cyp 450)

Answer 240

First step: Succinyl CoA + glycine --delta-ALA synthase--> delta-ALA Last two steps: Protoporphyrinogen IX --protopor. oxidase--> protoporphyrin IX --ferrochelatase and Fe2+--> heme

Answer 241

The production of delta-aminolevulinic acid by delta-aminolevulinic acid synthase - this enzyme is inhibited by negative feeback inhibition via Heme. This can be problematic when part of the pathway is blocked because there is no way to shut it off and it builds up intermediate products

Answer 242

- pyridoxal phosphate (PLP, vitamin B6) as a cofactor - dietary deficiency = microcytic anemia due to impaired heme synthesis

Answer 243

- duodenum

Answer 244

- catalyzes the decarboxylation of glycine and joins it to succinate, creating 5 carbon d-ALA - expressed ubiquitously and is responsible for HEPATIC heme synthesis. - on chromosome 3 - negative feedback regulation by Heme at the level of mRNA stability and protein import to the mitochondria

Answer 245

- catalyzes the decarboxylation of glycine and joins it to succinate, creating 5 carbon d-ALA - expression is restricted to ERYTHROID LINEAGE - on X chromosome (X-linked disease) - positively regulated by iron and iron pool availability by regulating access of mRNA to ribosomes

Answer 246

- Acute intermittent porphyria (caused by a loss of porphobilinogen deaminase - hemin is a form of heme

Answer 247

- ALAS2: 5' untranslated region of mRNA containing a stem loop - in the absence of iron, IRE-BP prevents the initiation of translation (aconitase) - iron binding displaces IRE-BP allowing for translation (aconitase) - therefore, heme is only made via ALAS2 when there is iron available

Answer 248

- inherited mutations that decrease ALAS2 activity - RBCs present as small (microcytic), and pale (hypochromic) - causes an increase in the uptake and accumulation of iron, promoting damage via ROS

Answer 249

- ALAS2 mutations that lead to a GOF, or increase in activity - results in the accumulation of intermediates of heme synthesis - porphyrins accumulate in skin and cause photosensitivity when they are oxidized to free radicals by UV light - some patients develop liver disease -ALAS2 hyperactivity can look like ferrochelatase deficiency

Answer 250

- defects in heme production characterized by the accumulation of porphyrinogens that cause neuronal, GI, and skin problems

Answer 251

neurological and GI symptoms (NO SKIN)

Answer 252

Neurological and GI symptoms ALONG WITH skin blistering with sun exposure - types of porphyria: ALA-dehydratase, Acute intermittent, Hereditary, and variegate

Answer 253

- nutritional deficit - viral infection - drug exposure

Answer 254

- affect the liver, skin, and nervous system - types of porphyrias: Porphyria cutanea tarda, erythropoietic protoporphyria, congenital porphyria, and x-linked erythropoietic protoporphyria

Answer 255

- negative feedback on delta-ALA synthase by heme - intermediates accumulate rapidly

Answer 256

caused by an inherited mutation of the d-ALA dehydratase. Very rare inborne error of metabolism - characterized by: acute attacks of abdominal pain, and neuropathy

Answer 257

- Lead (Pb) acts as a non-competitive (active site binder- decreasing Vmax, not changing km) inhibitor of delta-ALA dehydratase - endogenous lead binding protein PbBP is protective against this - Characterized by: GI symtpoms, CNS symptoms

Answer 258

- most common porphyria - characterized by neuropsych disturbances and abdominal pain - caused by inherited defects in porphobilinogen deaminase - women 4x more affected than men (estrogen?) - dark urine, measured PBG deaminase activity in RBCs for diagnosis

Answer 259

- GIVOSIRAN - liver targeted RNA that is converted to siRNA that directs the RISC nuclease to the ALAS1 (LIVER) mRNA (causes interruption, decrease in ALAS1 mRNA, delta-ALA, and porphobilinogen

Answer 260

- most common NON-ACUTE porphyria - caused by deficient activity of uroporphyrinogen decarboxylase (UROD) - Type 1: sporadic - Type 2: familial, heterozygous for UROD mutation - more commonly seen in men because of alcohol use

Answer 261

- over production of an inhibitor of UROD - production of inhibitor is induced by stresses such as HCV infection, drugs, ethanol, and oxidative stress

Answer 262

- blistering of the skin after precipitating event (toxin exposure) - urine color is orange, and fluoresces under UV light due to the accumulation of uroporphyrin - New growth of hair on the face (hirsutism)

Answer 263

- blood letting

Answer 264

- Molecular oxygen - reduced NADPH - it is then transported to the liver with albumin - Biliverdin is GREEN (from O2 and heme oxygenase) - Bilirubin is YELLOW (from NAPDH and biliverdin reductase)

Answer 265

Glucuronate. In the liver, two glucuronates are added to bilirubin to form bilirubin diglucuronide (can be excreted in the bile ducts)

Answer 266

- occurs immediately after birth due to an increase in hemolysis and immature glucoronate conjugating system

Answer 267

- occurs if there is excessive red blood cell destruction

Answer 268

- occurs if the liver is not functioning (can be from damage via alcohol overconsumption) - block of 2 UDP-GlcUA --> 2 UDP

Answer 269

- caused by a disturbance in bile drainage due to a gallstone or a tumor, etc

Answer 270

- increased red cell breakdown or decreased conjugated capacity in the liver - Direct = conjugated (bilirubin diglucuronide) - indirect = unconjugated (Bilirubin)

Answer 271

- inherited deficiency in bilirubin-UDP-glucuronate transferase (UGT1A1) - Crigler & Najjar

Answer 272

- encodes a family of proteins with different substrate specificity. Their job is to add glucuronate to molecules to make them more excretable - UGT1A1 specifically adds a glucuronate to bilirubin. if this does not happen, Kernicterus occurs (treatment with phenobarbital to increase transcription from the A1 promoter)

Answer 273

Brain damage from a high level of bilirubin in a baby's blood. It can cause athetoid cerebral palsy and hearing loss. Kernicterus also causes problems with vision and teeth and sometimes can cause intellectual disabilities.

Answer 274

• chikungunya • dengue fever • yellow fever • Zika virus • lymphatic filariasis

Answer 275

• malaria (Plasmodium falciparum) • lymphatic filariasis

Answer 276

• Japanese encephalitis • lymphatic filariasis • west Nile virus

Answer 277

P 53 becomes ubiquitinated and targeted for degradation at the proteosome. P53 is targeted to ubiquitin ligase

Answer 278

• high risk, HPV strains bind to RB with higher affinity • blocks the ability of RB to hold E2F in check • E2F allows for the expression of genes that allow for the progression through S phase

Answer 279

Inactivates p53 and the RB tumor suppressor pathways

Answer 280

Viral interferon regulatory factor

Answer 281

Glycoprotein H (structural proteins/has been shown to have some anti-P 53 effects)

Answer 282

Activates NFKB, promoting cell survival and allows for the production of anti-apoptotic genes

Answer 283

Induce entry into the S phase by counteracting the effects of p21 and p27

Answer 284

Chemokine receptor, that facilitates trafficking when binding of an antigen pattern recognition receptor

Answer 285

Proerythroblast (blast cell) —> basophilic erythroblast —> polychromatic erythroblast —> orthochromatophilic erythroblast —> reticulocyte —> erythrocyte • gradually get smaller • orthochromo= condensed nucleus, extrusion

Answer 286

Blast cell —> promyelocyte (azurophilic, 2x size) —> myelocyte (multicolored granules) —> metamyelocyte (kidney bean nucleus) —> band cell (c shaped nucleus)