Exam 2 Flashcards

Question

What does the alpha beta TCR recognize

Answer 1

Peptide antigens presented by MHC molecules

Answer 2

Six polypeptide chains which form CD3 complex and chain dimer (identical in all T cells); involved in transcription of signals into the T cell

Answer 3

Peptides, lipids, nd small molecules without presentation by MHC; tend to aggregate at epithelial surfaces (skin and mucosa of GI/GU tracts); sentinels that protect from microbes trying to enter through epithelia

Answer 4

Recognize glycolipids displayed by MHC-like molecule CD1; function not well defined

Answer 5

Alpha beta T cells

Answer 6

Promote attachement of T cells to APCs

Answer 7

IgM and IgD (antigen binding component of B cell receptor complex)

Answer 8

Develop into plasma cells (make abs); also in blood called plasmoblasts

Answer 9

Heterodimer of Igalpha (CD79a) and beta (CD79b) -> invariant; signal transduction; also contains type 2 complement receptor (CR2/CD21) -> recognizes complement products; CD40 (receives signals from helper T cells); *CR2 used by Epstein Barr virus to enter and infect B cells

Answer 10

Under epithelia and interstitia of all tissues

Answer 11

Immature dendritic cells located within the epidermis

Answer 12

Dendritic cells located in germinal centers in the spleen and LN; have Fc receptor for IgG and receptor for C3b; can trap antigen bound to abs or complement; plays a role in humoral response by presenting antigens to B cells and selecting the B cells that have the highest affinity for the antigen

Answer 13

Present peptides to T cells, effector cells in cell mediated immunity (t cells activate macrophages to make them better at killing ingested microbes), and effector cells in humoral immunity (destroy opsonized microbes)

Answer 14

Destroy irreversibly stressed cells (virus infected and tumor); do not express TCRs or Ig, have azurophilic granules; can kill without prior exposure; express CD16 and CD56 (markers); CD16 is a Fc receptor for IgG (can lyse IgG coated targets - called antibody dependent cell-mediated cytotoxicity)

Answer 15

``` Activating receptors: NKG2D family -> recognize surface molecules induced by stress Inhibitory receptors: recognize self class I MHC molecules (expressed on all healthy cells) ```

Answer 16

IL 2 and 15

Answer 17

Activates killing and secretion of IFN-y

Answer 18

Lack TCRs but produce cytokines similar to that made by Tcells; NK cells are an example; different subsets produce IL-5,17,22 and IFN-y; function as early defense, stress surveilance, and shaping adaptive response. By providing cytokines that influence differentiation of T cells

Answer 19

Where T and B cells mature; also called primary or central

Answer 20

Blood born antigens are trapped here by dendritic cells and macrophages

Answer 21

Cutaneous: located under epithelia of skin Mucosal: located in GI and respirator tracts (pharyngeal tonsils and Peyers patches)

Answer 22

B cells: follicles in the cortex; if recently responsed to an antigen, may have germinal center; contains follicular dendritic cells T cells: paracortex; contains dendritic cells

Answer 23

T cells: perioarteriolar lymphoid sheaths surrounding small arterioles B cells: follicles

Answer 24

Chromosome 6

Answer 25

Heterodimer of polymorphic alpha (heavy chain) linked to nonpolymorphic protein called beta2 microglobulin; alpha chains encoded by HLA-A,B, and C; extracellular region of alpha chain divided into three domains; alpha1 and 2 form a cleft for peptide binding (AA resides line the sides - explains why different class I alleles bind different peptides)

Answer 26

Peptides derived from proteins (viral and tumor antigens) located in cytoplasm and produced in the cell

Answer 27

Cytoplasmic proteins degraded in proteasomes and transported to ER where they bind to MHC I molecules; associate with beta2microglobulin that is transported to surface

Answer 28

Heterodimer of alpha and beta chain (both polymorphic); extracellular portion has alpha 1, alpha 2, beta 1, and beta 2; cleft formed by alpha 1 and beta 1 (this portion is where most differ)

Answer 29

Antigens internalized into vesicles, typically derived from extracellular microbes and soluble proteins

Answer 30

Proteins are proteolytically digested in endosomes or lysosomes; peptides associate with class II heterodimers in vesicles and transported to surface

Answer 31

TNF, complement components, lymphotoxin

Answer 32

TNF, IL-1,12,type I IFNs, IFN-y and chemokines

Answer 33

CD4 T cells; IL-2,4,5,17, IFN-y, TGF beta, IL-10

Answer 34

Marrow stromal cells, T lymphocytes, macrophages; ex: GM-CSF and IL-7

Answer 35

TNF antagonist

Answer 36

T cells just peptides | B cells: proteins, polysaccharides, and lipids

Answer 37

Given with protein antigen in vaccines; activates innate response; activates APCs to express costimulators and secrete cytokines that stimulate proliferation and differentiation of T cells; principal costimulators are B7 proteins (CD80 and 86) on APCs, recognized by CD28 on naive T cells

Answer 38

Triggered by costimulators; ensures that adaptive immune response is only induced by microbes; immune responses to tumors, signal 2 can be DAMPs from necrotic cells

Answer 39

Expressed on activated T cells; binds to CD40 on macrophages and B cells and activates them

Answer 40

IL-4 (B cells differentiate into IgE) | IL-5 (recruits eosinophils)

Answer 41

Some ab responses to protein antigens require T cells; B cells ingest protein and present them to T cells via Class II MHC; T cells stimulate B cells

Answer 42

Different classes IgG, IgA, IgE; isotope switching (induced by IFN-y, and IL-4); helper T cells also stimulate production of abs with high affinities for antigens (called affinity maturation)

Answer 43

Germinal centers, which are formed by proliferating B cells

Answer 44

Helper T cells that migrate into the germinal centers to stimulate isotype switching and affinity maturation

Answer 45

From mucosal epithelia in respiratory and GI tract

Answer 46

IgG; protect newborn

Answer 47

Most die by apoptosis

Answer 48

Th1: IFN-y and IL-12 Th2: IL-4 Th17: TGF beta, IL-6, IL-1, IL-23

Answer 49

Macrophages activation and IgG ab production

Answer 50

autoimmune and chronic inflammatory diseases (IBD, psoriasis, granulomatous inflammation)

Answer 51

Autoimmune and chronic inflammatory diseases (IBD, psoriasis, MS)

Answer 52

Heavy chain

Answer 53

Caused by Th2 cells, IgE abs, mast cells and other leukocytes

Answer 54

Ab mediated; secreted IgG and IgM abs injure cells by promoting their phagocytosis or lysis and injure cells by inducing inflammation; abs can also interfere with cellular function and cause disease without injury

Answer 55

Immune-complex mediated; IgG and IgM abs bind antigens in circulation and deposit on tissues, inducing inflammation; leukocytes are recruited and produce tissue damage by release of lysosomal enzymes and generation of free radicals; causes necrotizing vasculitis (fibrinoid necrosis)

Answer 56

Cell-mediated immune disorders; sensitized T lymphocytes (Th1,17, and CTLS) cause injury; causes perivascular cellular infiltrates, edema, granuloma ormation

Answer 57

Immediate reaction: vasodilation, vascular leakage, and depending on location, smooth m spasm or glandular secretions; subside in a few hours Late phase reaction: (common in allergic rhinitis and bronchial asthma) sets in 2 to 24 hours later and can last for several days; characterized by infiltration of eosinophils, neutrophils, basophils, monocytes, and CD4 T cells; mucosal epithelial cell damage

Answer 58

Autoimmune hemolytic anemia, Goodpasture syndrome

Answer 59

Lupus, glomerulonephritis, serum sickness, Arthur’s reaction

Answer 60

Contact dermatitis, MS, T1DM, TB

Answer 61

Enhances IgE production and acts on epithelial cells to stimulate mucus secretion

Answer 62

Bone marrow

Answer 63

Near BV and nerves and in subepihtlial tissues; explains why local immediate hypersensitivity reactions occurs at these sites

Answer 64

IL-8, codeine, morphine, adenosine, mellitin (bee venom), head, cold, sunlight

Answer 65

Have Fc IgE receptor and cytoplasmic granules; different because not present in tissues -> circulate blood in small numbers

Answer 66

Antigen binds to and cross links adjacent IgE abs; underlying Fce brough together which activates signal transduction pathways from cytoplasmic portion of receptors

Answer 67

Vasoactive amines (histamine), enzymes (neutral proteases: Chymase and tryptase and acid hydrolases -> cause tissue damage and lead to generation of kinins and complement); proteoglycans: heparin and chondroitin sulfate (package and store amines in granules)

Answer 68

``` Lipid mediators (leukotrienes, prostaglandin D2, and PAF): reactions in cell membrane activate phospholipase A2 to produce AA; *PAF not derived from AA -> causes platelet aggregation, release of histamine, bronchospasm, increased permeability, and vasodilation Cytokines: TNF, IL-1, chemokines (leukocyte recruitment -> late phase reaction), IL-4 (amplifies Th2 response) ```

Answer 69

Edema, mucus secretion, smooth m spasm

Answer 70

Allergic asthma; treatment requires broad spectrum of anti inflammatory drugs such as steroids instead of anti-histamine drugs which would just target the immediate reaction (ie: use for hay fever/allergic rhinitis)

Answer 71

Increased propensity to develop immediate hypersensitivity reactions

Answer 72

Higher serum IgE levels and more IL-4 producing Th2 cells; positive family history of allergy

Answer 73

5q31; include genes that encode for IL-3,4,5,9,13, and GM-CSF

Answer 74

Environmental factors

Answer 75

Immediate hypersensitivy reaction triggered b y non-antigenic stimuli such as temperature extremes and exercise; no Th2 or IgE; mast cells are abnormally sensitive to activation

Answer 76

Decrease in infections during early life; hygiene hypothesis -> early exposure to microbial antigens educates the immune system so that subsequent pathological responses against common allergens are prevented

Answer 77

Within minutes: itching, hives and skin erythema, followed by contraction of respiratory bronchioles, then laryngeal edema, vomiting, abdominal cramps, diarrhea, and laryngeal obstruction flow

Answer 78

Cells that are coated with IgG ab are killed by NK and macrophages which bind to the starter via their Fc fragment of IgG; cell lysis occurs

Answer 79

II; cells from incompatible donor react with an are opsonized by preformed ab in the host

Answer 80

II; IgG anti-Erythrocyte abs from the other cross the placenta and destroy fetal RBCs

Answer 81

Individuals produce abs to their own blood cells -> type II

Answer 82

Drug binds to the plasma membrane of RBCs -> abs produced agains the drug-protein complex; type II

Answer 83

Ie: basement membrane and extracellular matrix; resultant injury due to inflammation; activate complement which recruits leukocytes, which are activated by their C3b and Fc receptors; this releases production of lysosomal enzymes (proteases that can digest basement membrane) and ROS; mechanism responsible in glomerulonephritis and vascular rejection in organ grafts; type II

Answer 84

Abs to cell surface receptors; Ie: myasthenia gravis -> abs to Ach receptors in motor end plates of skeletal mm causes m weakness; also, Graves’ disease -> ab to TSH receptor activates the receptor and results in hyperthyroidism

Answer 85

Platelet membrane proteins (GpIIb:IIIa); causes opsonization of phagocytosis of platelets -> bleeding

Answer 86

Targeted antigen -> proteins in intercellular junctions of epidermal cells (cadherin); causes ab mediated activation of proteases and disruption of cellular adhesions -> skin vesicles (Bullae) form (type II)

Answer 87

Noncollagenous protein in basement membrane of kidney glomeruli and lung alveoli; causes complement and Fc receptor mediated inflammation -> nephritis and lung hemorrhage (type II)

Answer 88

Streptococcal cell wall antigen; ab cross reacts with myocardial antigen -> inflammation and macrophage activation -> myocarditis and arthritis

Answer 89

II; targets insulin receptor -> ab inhibits binding of insulin

Answer 90

Intrinsic factor of gastric parietal cells -> causes neutralization of IF which causes decreased absorption of B12 -> abnormal erythropoiesis and anemia

Answer 91

Systemic, preferentially involving kidney, joints, and small vessels

Answer 92

- Formation of immune complexes: intro of a protein triggers production of abs, typically about a week after injection; complexes form - deposition of complexes (medium sized with slight antigen excess are most pathogenic); organs where blood is filtered at high pressure to form other fluid (urine and synovial fluid) are where they become concentrated and deposit - inflammation and tissue injury: imitation acute inflammatory reaction (approx 10 days after administration); causes fever, urticaria, joint pains (arthralgias), LN enlargement and proteinuria

Answer 93

IgG and IgM

Answer 94

Consumption of complement leads to decrease in serum C3 levels

Answer 95

Acute vasculitis, necrosis of vessel wall and intense neutrophilic infiltration; *fibrinoid necrosis (appears smudgy eosinophilic areas)

Answer 96

Localized area of tissue necrosis caused by acute immune complex vasculitis in the skin; can be produced by injection of an antigen in a previously immunized animal that contains circulating abs for that antigen

Answer 97

Delayed type hypersensitivity: tissue reaction to immune individuals; administration of an antigen results in cutaneous reaction within 24-48 hours (delayed)

Answer 98

``` Activation of T cells: naive CD4 T cells recognize antigen and produce IL2; if APC produces IL-12 -> Th1; if IL-1,6,or 23 then Th17 Responses of effector cells: repeat exposure to antigen, TH1 secretes IFN-y; causes macrophages to express more class II MHC which facilitates further presentation, secrete TNF, IL1 and chemokines to promote inflammation and IL12 to amplify Th1 response; Th17 produce IL-17 and 22 -> neutrophils and monocytes ```

Answer 99

Rheumatoid arthritis, MS, T1DM, IBD, psoriasis, contact sensitivity

Answer 100

Myelin; inflammation by Th1 and 17; myelin destruction by macrophages

Answer 101

CD4 mediated inflammatory reaction (delayed type hypersensitivity)

Answer 102

Intracutaneous injection of purified protein derivative (PPD) containing the antigen of tubercle bascillus; in a previously sensitized individual, injection causes redness and induration of the site in 8-12 hours, peak in 24-72 hours and then subsides

Answer 103

CD4 T cells and macrophages accumulated around venules, producing perivascular cuffing; in fully developed lesions -> venules show endothelial hypertrophy (cytosine mediated endothelial activation)

Answer 104

Strong Th1 cell activation and high levels of IFN-y

Answer 105

Environmental chemical binds to and modifies some self proteins -> peptides derived from these modified proteins are recognized by T cells and elicit the reaction; chemicals can also modify HLA molecules, making them appear foreign; same mechanism used for most drug reactions

Answer 106

T1DM, graft rejection

Answer 107

Presence of an immune reaction specific for some self antigen or self tissue, evidence that such a reaction is not secondary to tissue damage, and the absence of another well-defined cause of the disease

Answer 108

Autoimmune Hemolytic anemia, thrombocytopenia, atrophic gastritis of pernicious anemia, myasthenia gravis, Graves’ disease, good pasture syndrome

Answer 109

Rheumatoid arthritis, sjogren syndrome, and systemic sclerosis (scleroderma)

Answer 110

Immature self reactive T and B clones that recognize self antigens during their maturation in generative lymphoid organs are killed

Answer 111

When immature T cells recognize a self antigenmany die by apoptosis (negative selection or deletion); AIRE (autoimmune regulator) stimulates expression of peripheral tissue-restricted self ags in the thymus (mutation causes autoimmune polyendocrinopathy); some develop into Treg cells

Answer 112

When B cells recognize self antigens, many of the cells reactivate the machinery for antigen receptor gene rearrangement and begin to express new antigen receptors (receptor editing), if this does not occur, they undergo apoptosis

Answer 113

Self reactive T cells are rendered unresponsive; costimulators (B7) are weakly expressed on normal tissues; thus the self reactive T cells will not have the costimulation needed and become anergic; also,these cells receive inhibitory signals from CTLA4 (which has a higher affinity for B7 and are therefore more likely to bind)

Answer 114

Treat tumor immunotherapy; promotes response against tumors

Answer 115

If B cells encounter self antigen in peripheral tissues (especially in absence of T helper cells), B cells become usable to response and may be excluded from lymphoid follicles (resulting in their death)

Answer 116

CD4 cells that express high levels of CD25, the alpha chain of the IL-2 receptor, and FOXP3

Answer 117

IPEX (Immune dysregulation polyendocrinopathy, enteropathy, X-linked)

Answer 118

Secrete IL-10 and TGFbeta, also express CTLA-4, which may bind to B7 on APCs and reduce the amount of B7 that can bind to CD28

Answer 119

If T cells recognize a self antigen, they express a pro-apoptotic member of BCL family, called Bim without anti apoptotic members (antiapoptotic require full lymphocyte signaling to be activated); Bim triggers apoptosis by mitochondrial pathway; also CD4+ and B cells can die by Fas-FasL apoptosis (both are expressed on self reactive cells)

Answer 120

autoimmune lymphoproliferative syndrome (ALPS)

Answer 121

Brain, eye, testis; antigens do not communicate with blood or lymph; therefore if antigens released by trauma, causes prolonged immune response; mechanism for post-traumatic orchitis and uveitis

Answer 122

Ankylosing spondylitis

Answer 123

Celiac disease

Answer 124

MS, T1DM, rheumatoid arthritis and SLE

Answer 125

Encodes a protein tyrosine phosphatase; associated with T1DM, rheumatoid arthritis, and other autoimmune dz *gene most frequently implicated in autoimmunity; encodes for a phosphatase that is functionally defective and cannot control activity of RTK (excessive lymphocyte activation)

Answer 126

Crohn dz; cytoplasmic receptor; dz variant is ineffective at sensing gut microbes, including commensal bacteria, which results in entry of and chronic inflammatory responses against these organisms

Answer 127

Autoimmunity; binding of IgG/ab complexes to the Fc receptor on B cells turns the B cells off; thus, B cells can no longer be controlled d

Answer 128

Infections upregulate the expression of costimulators on APCs (breakdown of anergy b/c no self reactive T cells can react); also microbes can express antigens that have the same AA sequences as self antigens (molecular mimicry)

Answer 129

Rheumatic heart disease; abs against strep cross react with myocardial proteins and cause myocarditis

Answer 130

Stimulate polyclonal B cell. Activation, which can result in auto-ab production

Answer 131

Infections promote low level IL-2 production which maintains T reg cells

Answer 132

Associated wtih IBD, psoriasis, and akylosing spondylitis; receptor for IL-23 (induced by Th17); alters differentiation of CD4 to Th17 effector cells

Answer 133

An immune response against one self antigen cases tissue damage, releasing other antigens, resulting in activation of lymphocytes by these newly encountered epitopes

Answer 134

Blood vessels and connective tissue; therefore called collagen vascular diseases or connective tissue diseases

Answer 135

Women between the ages of 17-55, blacks and Hispanics; however, can manifest at any age

Answer 136

Abs to DNA, abs to histones, abs to non histone proteins bound to RNA, and abs to nucleolar antigens

Answer 137

Indirect immunofluorescence; can identify abs bound to a variety of nuclear antigens (DNA, RNA, proteins - called generic ANAs); pattern of fluorescence suggests type of ab present in patients serum

Answer 138

Malar rash, discoid rash, photosenstivity, oral ulcers, arthritis, serositis, renal disorder, neurological disorder, hematologic disorder, immunologic disorder, antinuclear ab

Answer 139

Flat or raised over malar eminences, tends to spare nasolabial folds

Answer 140

Erythematous raised patches with adherent keratitic scaling and follicular plugging; atrophic scarring can occur in older lesions

Answer 141

Nonerosive arthritis involving 2 or more peripheral joints, characterized by tenderness, swelling, or effusion

Answer 142

Persistent proteinuria >.5 g/dL or cellular casts (RBC, hemoglobin, granular, tubular or mixed)

Answer 143

Seizures in the absence of offending drugs or known metabolic derangement (ketoacidosis, uremia, or electrolyte imbalances) or psychosis in the absence of offending drugs or known metabolic derangements

Answer 144

Hemolytic anemia with reticulocytosis or leukopenia, lymphopenia, or thrombocytopenia on two or more occasions in the absence of offending drugs

Answer 145

- Homogeneous or diffuse nuclear staining: abs to chromatin, histones, and dsDNA - Rim or peripheral staining: abs to dsDNA and nuclear envelope proteins - Speckled pattern: *most common so least specific; abs to non-DNA nuclear constituents such as SM antigen, ribonucleoprotein, and SS-A/B reactive antigens - Nucleolar pattern: presence of few discrete spots within nucleus; abs to RNA *reported most often in patients with systemic sclerosis - Centromeric pattern: abs to centromeres; also seen in systemic sclerosis

Answer 146

dsDNA and smith antigen (speckled pattern and homogenous)

Answer 147

Prothrombin, annexin V, beta2 glycoprotein I, protein S, and protein C

Answer 148

Cardiolipin antigen -> used for syphilis testing

Answer 149

PTT in vitro (lupus anticoagulant); but in vivo, actually cause hypercoaguability

Answer 150

Nephritis; specific for SLE

Answer 151

Congenital heart block, neonatal lupus

Answer 152

- DNA topoisomerase I (linked to diffuse skin and lung disease; specific for systemic sclerosis) - Centromeric proteins (CENPs) ABC (linked to skin disease, ischemic digit loss, pulm HTN) - RNA polymerase III (linked to acute onset, scleroderma renal crisis, cancer)

Answer 153

- Histidyl aminoacyl-tRNA synthetase, Jo1 (linked to interstitial lung dz, Raynaud phenomenon) - Mi-2 nuclear antigen (linked to dermatomyositis, skin rash) - MDA5 (cytoplasmic receptor for viral RNA) - linked to vascular skin lesions, interstitial lung dz - TIF1-y nuclear protein (linked to dermatomyositis, cancer)

Answer 154

CCP (cyclic citrullinated peptides): specific for RA | Rheumatoid factor

Answer 155

DsDNA, smith, and phospholipids

Answer 156

May have inherited deficiencies in early complement (C2,4, or C1q); lack of complement can impair removal of circulating immune complexes by phagocytes -> this favors tissue deposition; deficiency in C1q causes defective phagocytic clearance of apoptotic cells

Answer 157

Dependent; produced in germinal centers; increased number of follicular helper T cells found in blood of SLE patients

Answer 158

Lymphocytes activation; high levels of circulating type I IFN correlates with disease severity; type I IFNs are antiviral cytokines normally produced by innate immunity (in SLE could be caused by nuclear DNA binding to TLRs and causing dendritic cells to produce IFN)

Answer 159

TNF family member that promotes survival of B cells; in some SLE patients, increased BAFF has been detected

Answer 160

May induce apoptosis and alter DNA in such a way that it becomes immunogenic (enhances recognition by TLRs); can also stimulate keratinocytes to produce IL-1

Answer 161

Hydralizine, procainamide, isoniazid, and D-penicillamine

Answer 162

Opsonize them and promote their phagocytosis and lysis

Answer 163

Cells that have engulfed denatured nucleus of another cell; present in lupus (as well as pericardial or pleural effusions)

Answer 164

Acute necrotizing vasculitis involving capillaries, small arteries, and arterioles can be present in any tissue; characterized by fibrinoid deposits; chronically, undergo vessel thickening and narrowing

Answer 165

Mesangium, basement membrane

Answer 166

``` Minimal mesangial lupus nephritis, mesangial proliferative, focal, diffuse, membraneous, advanced sclerosing *can advance to other stages; class I least common, class IV most common ```

Answer 167

Class I: characterized b y immune complex deposition in the mesangium, identified by immunofluorescence and EM, but without structural changes by light microscopy

Answer 168

Class II: characterized by mesangial cell proliferation, accompanied by accumulation of mesangial matrix and granular mesangial deposits of Ig and complement without involvement of glomerular capillaries

Answer 169

Class III: involvement of few than 50% of all glomeruli; can be segmental (only portion of glomeruli affected) or global (entire glomerulus); affected glomeruli exhibit swelling and proliferation of endothelial and mesangial cells associated with leukocyte accumulation, capillary necrosis, and hyaline thrombi; often extracapillary proliferation and focal necrosis and crescent formation; clinical presentation can range from mild hematuria and proteinuria to acute renal insufficiency; red cast cells common; can heal or progress

Answer 170

Class IV: *most common and severe; lesions similar to class III; half or more of glomeruli are affected; may be segmental or global (IV-s or IV-G); proliferation of endothelial, mesangial and epithelial cells (produces cellular crescents that fill Bowmans space); subendothelial immune complex deposition creates a wire loop (circumferential thickening of capillary Wall seen on light microscopy); immune complexes detected by EM and immunofluorescence; can progress to scarring; usually symptomatic (hematuria and proteinuria; also HTN common)

Answer 171

Class V: diffuse thickening of capillary walls due to deposition of subepithelial immune complexes, usually accompanied by increased production of basement membrane-like material; accompanied by severe proteinuria or nephrotic syndrome; can occur concurrently with diffuse or focal lupus nephritis

Answer 172

Class VI: characterized by sclerosis of more than 90% of glomeruli; represents end stage renal disease

Answer 173

Vascular degeneration of the basal layer of the pidermis; in dermis, variable edema and perivascular inflammation

Answer 174

Deposition of immune complexes and complement along dermoepidermal junction in involved and uninvolved skin; not diagnostic of SLE (may also be seen in scleroderma and dermatomyositis))

Answer 175

Infective endocarditis the vegetations are larger; rheumatic heart disease are smaller

Answer 176

More common in young patients with noteable disease and especially prevalent in those who ha ve been treated with corticosteroids

Answer 177

Splenomegaly, capsular thickening, and follicular hyperplasia; central penicilliary arteries can show concentric intimacy and smooth m cell hyerplasia producing onion-skin lesions

Answer 178

Increased formation of immune complexes and complement activation leads to hypocomplementemia; treated with corticosteroids or other immunosuppressants

Answer 179

Renal failure and inter current infections

Answer 180

Skin manifestations mimic SLE, but systemic manifestations are rare; characterized by skin plaques showing edema, erythema, scaliness, follicular plugging, and skin atrophy surrounded by an elevated border; usually affects face and scalp; ANAs involved but rarely have abs to dsDNA; immunofluorescence shoes depositin of Ig and C3 at the dermoepidermal junction, similar to SLE

Answer 181

Skin involvement, distinguished from discoid by: widespread, superficial, nonscarring; mild systemic symptoms consistent with SLE; association with abs to SS-A antigen and with HLA-DR3 genotype

Answer 182

Anti-TNF treatment (used to treat RA)

Answer 183

No, but tests positive for ANAs; those that do manifest symptoms such as fever, arthralgias, and serositis; renal and CNS involvement is highly uncommon

Answer 184

Abs to histones; dsDNA is rare

Answer 185

Characterized by dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) resulting from immunologically mediated destruction of lacrimal and salivary glands; can occur in primary form (isolated disorder) or in association with another autoimmune dz (secondary form) *RA most common associated disorder

Answer 186

Lymphocytic infiltration and fibrosis of lacrimal and salivary glands; CD4 helper cells and B cells/plasma cells

Answer 187

Rheumatic factor (ab to IgG), ANAs, *most impt -> abs against SS-A and SS-B (markers of disease) - those with SS-A more likely to have early onset of dz, longer duration, and extraglandular manifestations (cutaneous vasculitis and nephritis), however not diagnostic of the dz

Answer 188

HLA-B8, DR3, DRW52, | *DQA1, and DQB1 -> patients with SS-A and B abs, this is frequent

Answer 189

Periodical and perivascular lymphocyte infiltration; as time goes on, germinal centers may be present in larger salivary glands, ductal lining epithelial cells can show hyperplasia (obstructs ducts); later will see atrophy fibrosis and hyalinization; lastly replacement of parenchyma with fat

Answer 190

B cell lymphomas

Answer 191

Inflamed, eroded, and ulcerated corneal epithelium; atrophy of oral mucosa with inflammatory fissuring and ulceration, ulceration and perforation of nasal septum; blurring of vision, burning and itching, thick secretions accumulate in conjunctival sac, difficulty swallowing, decreased ability to taste, epistaxis, enlargement of parotid gland, recurrent bronchitis and pneumonia is

Answer 192

Women between ages of 50 and 60

Answer 193

Synovitis, diffuse pulmonary fibrosis, and periphery neuropathy; more common with high titers of SS-A abs; glomerular lesions highly rare; however defects in tubular function are seen (renal tubular acidosis, uricosuria, and phophaturia -> associated with tubulointerstitial nephritis)

Answer 194

Lacrimal and salivary gland enlargement due to any cause including sarcoidosis, lymphoma, and other tumors

Answer 195

Biopsy of the lip to examine minor salivary glands

Answer 196

B cell clones can gain a growth advantage (presumably due to acquisition of somatic mutation); dominant B cell. Clones is indicative of development of marginal zone lymphoma (hashimoto thyroiditis is also associated with this lymphoma)

Answer 197

Characterized by chronic inflammation due to autoimmunity, damage to small blood vessels, and progressive interstitial and perivascular fibrosis in the skin and multiple organs; remains in skin for many years but ultimately progresses to visceral; death from renal, cardiac, or pulmonary failure or intestinal malabsorption

Answer 198

Diffuse scleroderma: widespread skin involvement at onset with rapid progression and early visceral involvement Limited scleroderma: skin involvement is confided to fingers, forearms and face; visceral involvement occurs late; relatively benign

Answer 199

Combination of calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia(dilated small bv) (CREST syndrome)

Answer 200

Autoimmune responses, vascular damage, collagen deposition

Answer 201

CD4 and Th2 cells -> IL-13 and TGFbeta stimulate collagen deposition; also inappropriate activation of humoral immunity (ANAs produced)

Answer 202

Microvascular disease consistently present early on; may be primary lesion; intimal proliferation is evident in digital arteries, capillary dilation with leaking, and nail fold capillary loops are distorted in early course and eventually disappear; * have telltale signs of endothelial activation (ie: increased levels of vWF) and increased platelet activation; repeat injury and platelet aggregation causes release of PDGF and TGFbeta causing perivascular fibrosis; vascular smooth m shows increased adrenergic receptors as well

Answer 203

Accumulation of M2 macrophages, hyperresponsiveness of fibroblasts to cytokines released by infiltrating leukocytes, scarring following ischemic damage caused by vascular lesions; *evidence that patients have abnormality with fibroblasts that cause them to produce excessive collagen

Answer 204

Sclerotic atrophy usually begins distally (fingers) and works proximally (shoulders, neck, face); histo: edema and perivascular infiltrates containing CD4 cells w/ swelling and degeneration of collagen; with progression, increasing fibrosis of the dermis and thinning of epidermis; sometimes leads to autoamputation; face becomes drawn mask

Answer 205

PRogressive atrophy and collegeneous fibrous replacement of the muscularis (most severe in esophagus) -> lower 2/3 develops rubber-hose-like inflexibility -> leads to GERD and Barrets metaplasia; loss of villi in small bowel (malabsorption)

Answer 206

Inflammation of synovium associated with hypertrophy and hyperplasia of synovial soft tissue in the early stages; fibrosis later; reminiscent of RA, but joint destruction is not common; in some patients, inflammatory myositis (indistinguishable from polymyosistis) may develop

Answer 207

Vascular lesions; resembles malignant hypertension, but scleroderma only involves vessels 150-500 micrometers in diameter and doesn’t always involve HTN; 50% of patients die of renal failure

Answer 208

May involve pulm HTN (pulm vasospasm secondary to pulm vascular endothelial dysfunction) or interstitial fibrosis

Answer 209

Pericarditis with effusion, myocardial fibrosis, thickening of intramyocardial arterioles

Answer 210

Female to male ratio is 3:1; peak incidence in 50-60 yrs old; distinct features: skin thickening, Raynauds, dysphasia, ab pain, malabsorption, anemia, resp difficulties, malignant hypertension; more severe in black women; pulm death has been main cause since renal treatments have improved

Answer 211

DNA topoisomerase I (anti-Scl 70) - more likely to have pulm fibrosis and PVD; and anticentromere ab: tend to have CREST syndrome -> limited involvement of skin; live longer

Answer 212

Dermatomyositis, polymyositis, and inclusion body myositis

Answer 213

Have clinical features that are a mix of SLE, systemic sclerosis, and polymyositis; characterized by high titers of abs to ribonucleoprotein particle-containing U1 ribonucleoprotein; present with synovitis of fingers, Raynaud and mild myositis; renal involvement modest; good response to steroids; can evolve into classic SLE or scleroderma

Answer 214

Includes polyarteritis nodosa; necrotizing inflammation of walls of any bv

Answer 215

Mikulicz (enlargement and fibrosis of salivary and lacrimal glands), diesel thyroiditis, idiopathic retroperitoneal fibrosis, autoimmune pancreatitis and inflammatory pseudo tumors of the orbit, lungs, and kidneys; most often effects middle aged and older men

Answer 216

Anti-b cell reagent

Answer 217

T cells of recipient recognize donor MHC molecules on APCs in the graft (dendritic cells in the donor organs are most impt for initiating antigraft response); CD8 and CD4 cells recognize molecules

Answer 218

Recipient T cells recognize MHC antigens of the graft being presented by the recipients APCs; generates CD4 cell that enter the graft -> delayed hypersensitivity reaction; CD8 cells that are generated cannot kill graft cells because they recognize graft antigens presented by host APCs and cannot recognize graft cells directly

Answer 219

Allografts

Answer 220

CD4 cells react by secreting cytokines and causing inflammation; causes increased vascular permeability and local accumulation of mononuclear cells; graft injury is caused by activated macrophages

Answer 221

Lymphocytes in the vessel wall secrete cytokines that induce local inflammation and stimulate the proliferation of vascular endothelial cells and smooth m cells

Answer 222

Preformed abs against the donor antigens are present in the circulation of the recipient ie: someone who has previously rejected a transplant, multiparous women who develops abs against parental HLA antigens (reject from husband or children), prior blood transfusion

Answer 223

Anti donor abs produced after transplantation; cause injury by complement dependent cytotoxicity, inflammation, and ab dependent cell mediated cytotoxicity; initial target seems to be graft vasculature

Answer 224

Develops without preceding acute rejection and primarily affects vasculature; abs detected but not readily identified within the graft; not well understood

Answer 225

Within minutes to hours becomes cyanotic, mottled, and flaccid, may excrete few drops of blood urine; Ig and complement deposited in vessel walls causing injury and fibrin-platelet thrombi, neutrophils accumulate; glomeruli undergo thrombotic occlusion of capillaries and fibrinoid necrosis occurs; kidney cortex undergoes necrosis (infarction) and has to be removed

Answer 226

Within days, weeks, months, or even years; T cell or B cells can predominate depending on individual

Answer 227

Tubulointerstitial: type I, interstitial inflammation with infiltration of tubules (tubulitis), both CD4 and CD8 cells present Vascular: type II; endotheliitis; necrosis of vascular walls(type III), swollen endothelial cells; important to recognize because in absence of humoral rejection, patients respond well to immunosuppressive therapy

Answer 228

Nephrotoxic so can cause histological changes like arteriolar hyaline deposits

Answer 229

Dominated by vascular changes; intimal thickening w/inflammation, glomerulopathy w/ duplication of basement membrane, peritubular capillaries; have mononuclear infiltrated include NK and plasma cells

Answer 230

Steroids, mycophenolate mofetil (inhibits lymphocyte proliferation), tacrolimus (predecessor is cyclosporine; inhibitor of phosphatase calcineurin which activates TF, NFAT)

Answer 231

EBV induced lymphomas, HPV induced squamous cell carcinomas, and kaposi sarcoma

Answer 232

Occurs within days to weeks; major manifestation results in involvement of the immune system of the skin, liver, and intestines; generalized rash, destruction of small bile ducts (jaundice) and mucosal ulceration of gut (bloody diarrhea); tissue not heavily infiltrated by lymphocytes; CD8 and CD4 cells of donor responsible

Answer 233

Extensive cutaneous injury, destruction of skin appendages, fibrosis of dermis (Resembles sclerosis), cholestatic jaundice (chronic liver disease), esophageal strictures, involution of thymus and depletion of lymphocytes in LN (recurrent infections)

Answer 234

Removing T cells from donor; however, in HSC transplants for leukemia patients, will cause recurrence of tumors and increased risk of graft failure and EBV related B cell lymphoma

Answer 235

Immunodeficiency; *infection with cytomegalovirus is impt -> induced pneumonia can be fatal

Answer 236

Primary: genetic Secondary: acquired

Answer 237

- leukocyte adhesion deficiency type I: defect in synthesis of beta2 chain shared by LFA-1 and Mac-1 integrins - leukocyte adhesion deficiency type II: absence of sialyl Lewis X (ligand for E and P selectin) -> caused by defect in fucosyl transferase * both of these cause recurrent bacterial infections due to inadequate granulocyte function

Answer 238

*chediak-higashi syndrome; AR; defective fusion of phagosomes and lysosomes; causes neutropenia (decreased neutrophils), defective granulation, delayed microbial killing; peripheral blood smears reveal leukocytes containing giant granules; abnormalities in melanocytes (albinism), cells of the nervous system, and platelets (bleeding disorders); defective gene encodes for LYST, which regulates lysosomal trafficking

Answer 239

*chronic granulomatous disease; susceptible to bacterial infections; defects in genes encoding for phagocyte oxidase (generates superoxide anion); most common are x-linked defect in one of the membrane components (gp91phox) and AR defects in genes encoding cytoplasmic components (p47phox and p67phox)

Answer 240

Defects in TLR3 (for viral RNA) -> recurrent herpes simplex encephalitis Defects in MyD88 -> adaptor protein downstream; destructive bacterial pneumonia’s

Answer 241

Recurrent bacterial or viral infections; but patients usually have no symptoms because alternative pathway can still function; but can cause SLE-like autoimmune disease

Answer 242

(Properdin and factor D); associated with pyogenic infections.

Answer 243

Recurrent neisserial infections (gonococcal and meningococcal)

Answer 244

C1r, C1s, factor XII, and kallikrein system; unregulated activity of kallikrein leads to increased production of bradykinin

Answer 245

SCID: defects in humoral and cell-mediated immune responses; infants present with thrush, diaper rash and failure to thrive; some develop morbilliform rash after birth (maternal T cells cross placenta and attack fetus); susceptible to Candida albicans, pneumocytosis jiroveci, pseudomonas, cytomegalovirus, varicella; without HSC transplant, death occurs within 1st year

Answer 246

X-linked; *more common in boys; mutated gamma chain subunit of cytokine receptors for IL-2,4,7,9,11,15,and21; IL-7 required for survival of lymphoid progenitors (T cell precursors); T cells decreased, B cell numbers normal but ab synthesis decreased; also deficient in NK cells (lack of IL-15)

Answer 247

Most common cause results from deficiency of adenosine deaminase (ADA); accumulation of deoxyadenosine toxic to immature lymphocytes; also proposed mechanisms: mutation in recombinant activating genes (RAG) ->blocks development of T and B cells; mutations of Jak3, and mutations of kinases or calcium channels

Answer 248

In gamma mutation and ADA deficiency: thymus is small and devoid of lymphoid cells; former, thymus has lobules of undifferentiated epithelial cells (Fetal thymus); later: remnants of Hassals corpuscles can be found

Answer 249

Development of T cell lymphoblastic leukemia

Answer 250

Characterized by failure of B cell precursors to develop into mature B cells; caused by mutations in cytoplasmic TK (Bruton TK) located on long arm of Xq21.22; Btk is associated with Ig receptor complex -> needed to transduce signals; mutation causes inability for pre-b cell to deliver signals and maturation stops; light chains are not produced

Answer 251

About 6 months, when maternal abs have depleted; manifests as recurrent bacterial infections of upper respiratory tract

Answer 252

Haemophilus influenzae, streptococcus pneumoniae or staphylococcus aureus; they are normally opsonized by abs and cleared; *also viral infections especially enteroviruses (echovirus, poliovirus, and coxsackievirus); giardia lamblia (intestinal protozoan resisted by IgA) also seen in this disorder; *intracellular infections, however, are handled quite well

Answer 253

B cells absent, all classes of Igs are decreased, pre B cells (CD19 marker) w/o Igs are in normal numbers, germinal centers, peyer’s patches, the appedix and tonsils are all underdeveloped; plasma cells absent; T cell mediated reactions normal

Answer 254

Breakdown of self-tolerance

Answer 255

Ig replacement therapy

Answer 256

T cells; poor defense against viral and fungal infections

Answer 257

T cell zones of lymphoid organs (paracortical areas of LN and periarteriolar sheaths of spleen) are depleted, Ig levels can be normal or reduced

Answer 258

TBX1 -> required for development of the branchial arch and great vessels; involved by loss-of-function mutations that lack the 22q11 deletion in DiGeorge

Answer 259

Mutation in TF that are required for class II MHC gene expression; this prevents development of CD4 cells and then B cells cant be activated -> results in combined immunodeficiency

Answer 260

X-linked form: mutation of gene encoding CD40L on Xq26 AR form: loss-of-function mutations invovling either CD40 or activation-induced cytidine desminase (AID) -> DNA editing enzyme required for Ig switching and affinity maturation

Answer 261

High IgM, no IgA or IgE, low levels of IgG; B and T cells normal; recurrent pyogenic infections (opsonizing IgG abs is low); those with CD40L mutations are susceptible to pneumonia caused by the intracellular organism, pneumocystis jiroveci because cannot activate macrophages; IgM can react w/ blood cells and cause autoimmune hemolytic anemia, thrombocytopenia, and neutropenia

Answer 262

Encompasses group of disorders in which the common feature is hypogammaglobulinemia (generally all classes but sometimes just IgG); both sporadic and inherited forms; normal B cells that cannot differentiate into plasma cells; some have defect in BAFF receptor which promotes differentiation of B cells or ICOS which is homologous to CD28

Answer 263

Resemble X-linked agammaglobulinemia because no abs produced; recurrent sinopulmonary pyogenic infections and herpesvirus infections; *affects both sexes equally and onset is later than agammaglobulinemia; B cell areas are hyperplastic; high frequency of autoimmune disease; risk of lymphoid malignancy and increase in gastric cancer

Answer 264

*european descent; low levels of secretory and serum IgA; can be acquired (associated with viral infection - measles) or genetic; asymptomatic; mucosal defense weakened (infections occur in resp, GI, and GU tracts); those with defects in IgG2/4 are particularly prone to infections; prone to AI dz (SLE) and resp allergy

Answer 265

Can have severe anaphylactic reaction; IgA behaves like foreign substance

Answer 266

Inability to eliminate EBV leading to infections mono and development of B cell tumors

Answer 267

Gene encoding an adaptor molecule called SLAM-associated protein (SAP) that binds to surface molecules involved in activation of NK cells and T and B cells; defects result in susceptibility to viral infection; also cannot form germinal centers (don’t make follicular helper T cells) and don’t produce high affinity abs

Answer 268

Th1: atypical mycobactterial infections Th17: chronic mucocutaneous candidiasis and bacterial infections of the skin (Job syndrome)

Answer 269

X-linked dz characterized by thrombocytopenia, eczema, and vulnerability to recurrent infection resulting in early death; thymus is normal, but there is progressive loss of T cells in blood and T zones of LN; do not make abs to polysacch ags and response to protein is low; IgM low, IgG normal; IgA and E elevated; prone to B cell lymphoma

Answer 270

Gene encoding Wiskott-Aldrich syndrome protein (WASP) located at Xp11.23; linked membrane receptors to cytoskeleton; involved in cell migration and signal transduction

Answer 271

HSC transplant

Answer 272

AR disorder characterized by abnormal gait, vascular malformations (telangiectasia), Neuro deficits, increased incidence of tumors and immunodeficiency

Answer 273

Chromosome 11 - encodes ATM (ataxia telangiectasia mutated) that is related to PI-3 kinase; senses DNA damage and activated p53 by phosphorylation; generation of receptors may be abnormal because can’t repair damaged DNA

Answer 274

HIV Irradiation and chemo: decreased BM precursors for all leukocytes Involvement of BM by cancer: reduced site of leukocyte development Malnutrition: metabolic deragnements inhibit maturation and function Removal of spleen: decreased phagocytosis of microbes

Answer 275

MSM, IV drug abusers, hemophiliacs, recipients of blood and blood components, heterosexual contacts of other high risk groups, Newborn

Answer 276

Sexual contact, parent real inoculation, passage of virus from infected mothers to their newborn

Answer 277

- direct inoculation into bv injured by trauma | - infection of dendritic cells or CD4 cells within the mucosa

Answer 278

Herpes, chancroid, and syphilis; gonorrhea and chlamydia are also cofactors because of increased inflammatory cells in semen (increase viral load in semen)

Answer 279

Hemophiliacs, IV drug abusers, blood transfusion recipients

Answer 280

- in utero by transplacental spread - during delivery through infected birth canal - after birth by ingestion of breast milk

Answer 281

Administration of antiretroviral therapy to pregnant women

Answer 282

HIV-1 and 2 (HIV 1 most common in US)

Answer 283

Spherical, electron dense core surrounded by lipid envelope derived from host; core contains: p24 (major capsid protein), nucleocapsid protein p7/p9, two copies of viral genomic RNA, and 3 viral enzymes - protease, reverse transcriptase and integrate; viral core surrounded by p17; gp120 and 41 stud the envelop *critical for infection

Answer 284

Gag, pol, env; gag and pol -> precursors to yield mature proteins; also contains accessory genes -> tat, rev, vif, nef, vpr, and vpu(regulate synthesis of infections viral particles)

Answer 285

M (major)*most common, O (outlier), and N(neither)

Answer 286

Immune system and CNS

Answer 287

Required for initiation of transcription; bind host TF, binds tat

Answer 288

P17 (promotes viral assembly at cell surface), p24 (binds cyclophilin A), p7 (RNA binding protein), p6 (interacts with VPR, terminal. Steps of notion building)

Answer 289

Uses CD4 as receptor and chemokines as coreceptors (gp120 binds) -> CCR5, CXCR4; R5 strains preferentially infect monocyte/macrophages (M-tropic) and X4 strains infect T cells (T-tropic); R5 typically found in acute infection, then T-tropic accumulates

Answer 290

Gp120 binds CD4 which leads to a conformational change resulting in formation of new recognition site on gp120 for coreceptors; then binding to coreceptors causes conformational change in gp41 that results in exposure of hydrophobic region (inserts into cell membrane of target cell) -> fusion of viral cell with host cell; virus core then can enter

Answer 291

Block the receptors so HIV cant bind to coreceptors

Answer 292

Reverse transcriptase -> cDNA; in quiescent T cells will remain in linear form, in dividing T cells cDNA circularizes, enters nucleus, and integrates into host genome; can be latent or can be transcribed and form viral particles which bud from the membrane and lead to death of infected cell

Answer 293

Naive T cells -> they contain active form of an enzyme called APOBEC3G that introduces mutations in the HIV genome; its a cytidine deaminase that introduces cytosine to uracil mutations in viral DNA; this inhibits further DNA replication; activation of T cells converts the enzyme to an inactive state; HIV also can combat this by producing Vif which binds APOBEC3G

Answer 294

If an environment antigen is recognized by these cells, IkB is phosphorylated which allows NF-kB to translocate to the nucleus which can bind to the LTR region of HIV genome; HIV DNA is transcribed which leads to production of virions and lysis of cell

Answer 295

Chronic activation of uninflected cells (responding to HIV or other microbes -> activation-induced cell death); non-cytopathic HIV infection activates inflammasome pathway (pyroptosis); destruction of composition of lymphoid tissues, can infect thymus progenitor cells or accessory cells that secrete cytokines needed for CD4 maturation, fusion of infected cells with in infected cells (form giant cells; usually just X4)

Answer 296

HIV-1 can infect terminally differentiated, non-dividing macrophages with the help of vpr gene -> allows nuclear targeting of HIV pre-integration complex through the nuclear pore; macrophages resistant to cyotpathic effects (replicate virus but do not bud); act as portal of infection (impt in pathogenesis of dz); can be used to transport to other parts of the body (CNS)

Answer 297

Lymphopenia, decreased T cell function, polyclonal Bcell activation, altered monocyte or macrophage function (decreased class II HLA expression)

Answer 298

Follicular (reservoirs; trap HIV with anti-HIV abs -> infect T cells) and mucosal (infected and transport to LN) dendritic cells; dendritic cells have lectin receptor that directly bind HIV

Answer 299

Gp41 can promote Bcell growth and diff; HIV infected macrophages produce IL-6 which stimulates proliferation of B cells; both T dependent and independent ab responses are suppressed; therefore, are susceptible to encapsulated bacteria like S pneumoniae and H. Influenzae

Answer 300

Exclusively M-tropic

Answer 301

Caused indirectly by viral products and soluble factors produced by infected microglia -> TNF, IL-1 and ; also NO induced in neuronal cells by gp41 has been implicated

Answer 302

Acute retroviral syndrome, middle chronic phase (asymptomatic), clinical AIDS

Answer 303

Mucosal tissues affected (have large number of T cells), few infected cells detectable in blood, associated with damage to mucosal epithelium, defects in mucosal barrier function; followed by dissemination of virus and development of host immune responses (dendritic cells -> LN); within days after exposure, viral replication can be detected in LN -> viremia; humoral and cell-mediated responses 3-7 wks; HIV specific CD8 cells detected @ same time viral load begins to fall (12 wks)

Answer 304

Occurs 3-6 weeks after exposure and resolves spontaneously in 2-4 weeks; self-limited acute illness with nonspecific symptoms (sore throat, myalgias, fever, weight loss, fatigue)

Answer 305

HIV-1 RNA levels in the blood (measure viremia)

Answer 306

At the end of the acute phase, viral load and immune response reach an equilibrium; steady-state viremia; predictor of rate of decline of CD4 cells

Answer 307

9-12 weeks

Answer 308

Phase of clinical latency; HIV replication and cell destruction continues in LN and spleen; CD4 cells steadily declines; host defenses begin to wane and HIV RNA levels increase; coreceptor switch is associated with a more rapid decline

Answer 309

Fever >1 month, fatigue, weight loss, diarrhea, generalized LAD, opportunistic infections, secondary neoplasms, and neurological dz emerge

Answer 310

7-10 years

Answer 311

Chronic phase is telescoped to 2-3 years after infection

Answer 312

Untreated HIV-1-infected individuals who remain asymptomatic for 10 years or more with stable CD4 counts and low levels of plasma viremia (less than 500)

Answer 313

Have undetectable plasma viremia (<50 RNA)

Answer 314

Oral candidiasis

Answer 315

Retina and GI

Answer 316

Manifests early in the course of AIDS

Answer 317

Meningitis

Answer 318

Affects CNS: causes progressive multifocal leukoencephalopathy

Answer 319

Kaposi sarcoma, anal cancer in men, cervical cancer in women, B cell lymphoma

Answer 320

Caused by oncogenes DNA viruses -> kaposi sarcoma herpesvirus, EBV (B cell lymphoma), HPV (cervical and anal cancer)

Answer 321

Vascular neoplasm; HAART has drastically reduced incidence; characterized by proliferation of spindle-shaped cells that express markers of both endothelial cells and smooth m; chronic inflammation infiltrates; not malignant; linked to rare B cell lymphomas called primary effusion lymphoma and multi centric castelman disease

Answer 322

Has decreased the incidence rate overall, but are still 10 fold more likely than the general population to develop lymphoma.

Answer 323

- Unchecked proliferation of B cells infected with oncogenic hyperpesviruses in the setting of profound T cell depletion (T cells required to restrain proliferation of these B cells) - Germinal center B cell hyperplasia in the setting of early HIV infection: mutations in oncogenes MYC (Burkitt lymphoma) and BCL6 (large B cell lymphoma)

Answer 324

Oral hairy leukoplakia (white projections on the tongue)

Answer 325

Patients with advanced AIDS who are given antiretroviral therapy develop clinical deterioration even with CD4 levels increasing and decreased viral load

Answer 326

Lipoatrophy (loss of facial fat), lipoaccumulation (excess fat deposition centrally), elevated lipids, insulin resistance, peripheral neuropathy, premature CV, kidney and liver dz

Answer 327

Associated with inherited and inflammatory disorders in which extracellular deposits of fibrillar proteins and responsible for tissue damage and functional compromise; fibrils formed by misfolded proteins which are normally soluble in folded form -> bind proteoglycans and glycosaminoglycans (notable serum amyloid P component)

Answer 328

Encroaches on and produces pressure atrophy of adjacent cells

Answer 329

Congo red stain -> shows green apple areas

Answer 330

- AL (amyloid light chain): made up of complete Ig light chains, the aminotermial fragments of light chains, or both; most lambda chains; made from plasma cells; associated with plasma cell tumors - AA (amyloid associated): derived from liver (non Ig); derived from serum amyloid-associated protein (bound to HDL); assoc with chronic inflammation *secondary amyloidosis - beta amyloid: core of cerebral plaques in Alzheimer’s; derived from amyloid precursor protein

Answer 331

- Transthyretin (TTR): normal serum protein that binds and transports thyroxine and retinol; mutant forms deposit in disorders called familial amyloid polyneuropathies; Normal ttr is also deposited in heart of aged individuals (senile systemic amyloidosis) - beta2 microglobulin: component of MHC I molecules; identified in patients on long term dialysis - prion dz

Answer 332

Primary: associated with plasma cell disorder Secondary: occurs as complication of chronic inflammatory dz

Answer 333

Plasma cell disorders; caused by clonal proliferation of plasma cells that synthesize an Ig prone to form amyloid; ie: patients with multiple myeloma (secrete Ig and Bence-Jones proteins)

Answer 334

Systemic; composed of AA protein; secondary amyloidosis; complicates RA, ankylosing spondylitis and IBD; heroin abusers also at risk; also occur with renal cell carcinoma and Hodgkin lymphoma; SAA produced an enzyme defect prevents its breakdown

Answer 335

- AR called familial Mediterranean fever; autoinflammtory syndrome (excessive production of IL-1); attacks of fever accompanied by inflammation of serosal surfaces; gene encodes pyrin; largely in Armenian, Sephardic Jewish, and Arabic origins; amyloid fibril made up of AA proteins - AD: deposition of amyloid in peripheral and autonomic nerves; made up of mutant TTRs

Answer 336

Black; increased risk of cardiomyopathy due to amyloidosis

Answer 337

Primary: heart, GI, resp, peripheral nerves, skin tongue Secondary: kidneys, liver, spleen, LN, adrenals, thyroid

Answer 338

Organ is enlarged and appears gray and waxy

Answer 339

Amyloid deposition is extracellularly and begins between cells; can then encroach on the cells and destroys them; green color (seen under polarized light) caused by crossed beta pleated configuration

Answer 340

At first: non specific (light headed, syncope, weight loss, weakness); Renal involvement -> proteinuria (can become nephrotic syndrome); renal failure common cause of death CHF can occur; restrictive cardiomyopathy

Answer 341

- disorders related to mutations in single genes with large effects; highly penetrant (those with mutation is associated with the dz in a large proportion) -> follow classic Mendelian pattern of inheritance - chromosomal disorders: high penetrance - complex multigenic disorders: more common; caused by interactions btw multiple variant forms of genes and environmental factors; no single susceptibility gene is sufficient to produce dz; only when several polymorphisms present (multigenic or polygenic); *low penetrance Ie: DM, HTN, autoimmune dz

Answer 342

Single nucleotide replacement that causes a different amino acid to be sequenced; if substituted AA is similar to original AA, called conservative

Answer 343

Sickle mutation; CTC (GAG in mRNA) (glutamic acid) is changed to CAC (GUG in mRNA) (valine)

Answer 344

Point mutation in beta globin; CAG replaced with UAG (stop codon); short peptide is degraded -> beta thalassemia

Answer 345

Reading frame in tact -> an abnormal protein lacking or gaining one or more AA synthesized

Answer 346

Frameshift mutation -> incorporation of a variable number of incorrect aa with premature stop codon

Answer 347

CF; results in lack of aa 508 (phe)

Answer 348

CGG within the gene called familial mental retardation 1 (FMR1)

Answer 349

They are dynamic, meaning the degree of amplification increases during gametogenesis

Answer 350

Includes disorders resulting from triplet repeat mutations, mutations in mitochondrial DNA, and those in which transmission is affected by genomic imprinting or gonadal mosaicism

Answer 351

- Four-base insertion in hexosaminidase A gene -> causes tay Sachs dz in ashkenazi Jews - Single base deletion in ABO locus leading to O allele

Answer 352

Homo: disorder is always fully expressed Hetero: only some are HbS and therefore red cell sickling only occurs under unusual circumstances (exposure to low oxygen) -> called sickle cell trait

Answer 353

Same mutant gene may lead to many end effects (sickle cell example) -> sickle cell leads to logjam in difft organs

Answer 354

Same trait may be produced via mutations in different loci; Ie: childhood deafness

Answer 355

AR, AD, X linked

Answer 356

- generally, one affected parent - some proportion of patients do not have affected parents -> caused by new mutation; siblings not affected or at risk ; seems to occur in older fathers - can have incomplete penetrance (have gene but are phenotypically normal) - age of onset can be delayed (ie: Huntington’s)

Answer 357

A trait is seen in all individuals carrying the mutant gene but is expressed differently; ie: neurofibrotosis type 1

Answer 358

When a mutant allele impairs the function of a normal allele; ie: collagen formation

Answer 359

AD pattern

Answer 360

Parents usually not affected, siblings have 25% chance (recurrence risk for each birth), if mutant gene occurs with a low frequency in population, likely the affected individual is product of a consanguineous marriage

Answer 361

Complete penetrance, onset early in life, new mutations rarely occur, but are not detected (they would be heterozygote), many of mutated genes encode enzymes (in heterozygotes have half normal and half defective)

Answer 362

Neuro: Huntington’s, neurofibromatosis, myotonic dystrophy, tuberous sclerosis Urinary: polycystic kidney dz GI: familial polyps is cold Hematopoietic: Hereditary spherocytosis, vW dz Skeletal: Marfan, enhlers danlos, OI, achondroplasia Metabolic: familial hypercholesterolemia, acute intermittent prophyria

Answer 363

Metabolic: CF, PKU, galactosemia, homocytinuria, lysosomal storage dz, alpha antitrypsin, Wilson, hemochromatosis, glycogen storage dz Hematopoietic: sickle cell, thalassemia Skeletal: enhlers danlos, alkaptonuria Endo: conventional adrenal hyperplasia Nervous: neurogenic muscular atrophied, fried rich ataxia, spinal muscular atrophy

Answer 364

Men with Y mutations are usually infertile

Answer 365

X-linked; predisposes to hemolysis in patients receiving certain types of drugs; heterozygous female can show trait because some RBCs can have the normal allele inactivated

Answer 366

Vitamin D resistant rickets

Answer 367

MSK: duchenne MD Blood: hemophilia, chronic granulomatous dz, glucose 6PDH Immune: agammaglobulinemia, wiskott-Aldrich Metabolic: diabetes insipidus, lesch-nyhan syndrome NErvous: Fragile X syndrome

Answer 368

NOT enzymes -> structural proteins and receptors

Answer 369

Lack of melanin production

Answer 370

Hemoglobinopathies: defects in structure of glowing Thalassemias: mutations that affect amount of globin chains synthesized

Answer 371

Antimalarial drug, primaquine -> causes severe hemolytic anemia

Answer 372

Eyes, skeleton, CV

Answer 373

- loss of structural support in microfibril rich connective tissue - excess activation of TGF beta signaling

Answer 374

FBN1 (FBN2 -> congenital contractural arachnodactyly); most are missense mutations; inhibits polymerization of fibrillin fibers (dominant negative effect); reduction of fibrillin below a certain threshold weakens tissue (haploinsufficiency))

Answer 375

Bone overgrowth and myxoid changes in mitral valves; normal microfibrils sequester TGF beta; MMPs are also activated causing further breakdown of ECM

Answer 376

Long-headed; *marfans

Answer 377

Tall, flexible, bossing front eminence, prominent supraorbital ridges, kyphosis, scoliosis, or rotation/slipping of lumbar vertebrae; chest is either pectus excavatum or carnatum

Answer 378

Bilateral subluxation or dislocation (outward and upward) of the lens (ectopia lentis); *very uncommon in any other dz

Answer 379

Mitral regurgitation, elongation of chordae tendinae, aortic dissection, mitral valve prolapse

Answer 380

Involvement of 2 of 4 organ systems (skeletal, CV, ocular and skin) and minor involvement of another organ

Answer 381

Beta blockers (decrease aortic wall stress)

Answer 382

kyphosclosis (VI) -> defect in lysyl hydroxylase Dermatosparaxis (VIIc) -> defect in procollagen peptidase * the rest are AD

Answer 383

Rupture of colon and large arteries (vascular), ocular fragility with rupture of cornea and retinal detachment (kyphoscoliosis), and diaphragmatic hernia (classic)

Answer 384

Abnormalities of type III collagen (COL3A1 gene); heterogenous because 3 distinct mutations can cause this variant; some affect rate of synthesis of pro alpha chains, some affect secretion of type III proollagen, and some lead to structural abnormalities

Answer 385

Arthrochalasia and dermatosparaxis; this step involves cleavage of. Noncollagen peptides at N and C terminus of procollagen via peptidases; defect in arthrochalasia type -> mutations in COL1A1/2; leads to formation of pro alpha 1/2 chains that resist cleavage; dermatosparaxis type -> mutation of procollagen N peptidase gene

Answer 386

Genes for type V collagen (COL5A1/2)

Answer 387

EDS-like syndreom; affects synthesis and fibril formation of type VI and I collagen

Answer 388

Leaves the liver via VLDLs (rich in TAGs, low cholesterol esters) -> blood -> cleaved by LPL to IDL (low TAG, high cholesterol esters; has apo B-100 and E) -> can be taken up by liver by receptor mediated transport via LDL receptor and recycled to VLDL OR converted to LDL (removes TAGs and apo E)

Answer 389

NPC1/2; released to cytoplasm for membrane synthesis; this suppresses cholesterol synthesis within the cell by inhibiting 3-hydroxy-3-methyglutaryl coenzyme A (HMG CoA) reductase, activates acyl-coenzyme A (favors storage of excess cholesterol), and suppresses synthesis of LDL receptors (protects from excessive uptake)

Answer 390

LDL receptor: cant uptake LDL OR IDL; causes accumulation of LDL and excess production of LDL

Answer 391

Scavenger receptors -> receptor for chemically. Altered LDL; increased transport in hypercholesterolemia; responsible for presence of xanthomas and atherosclerosis

Answer 392

Class I: uncommon; complete failure of synthesis of receptor protein Class II: common; encode receptor proteins that accumulate in ER b/c misfolded Class III: affect LDL binding domain of receptor Class IV: bind LDL normally, but fail to localize in coated pits and LDL not internalized Class V: pH-dependent dissociation of receptor and bound LDL fails to occur; trapped in endosome and fail to recycle

Answer 393

Inhibit HMG CoA and thus lead to increased synthesis of LDL receptors

Answer 394

Catabolism of substrate is incomplete; accumulation of partially degraded material

Answer 395

Impaired autophagic; accumulation of autophagic substrates such as polyubiquinated proteins and old mitochondria -> can cause generation of ROS and apoptosis

Answer 396

Enzyme replacement therapy; substrate reduction therapy (reduce the production of the substrate that cant be broken down), exogenous competitive inhibitor of the enzyme can bind to mutant enzyme and act as folding template that assists proper folding and prevent its degredation (called molecular chaperone therapy)

Answer 397

Spleen and liver; contain many macrophages which are very rich in lysosomes

Answer 398

Group of 3 lysosomal storage diseases caused by inability to catabolism GM2 gangliosides; requires 3 polypeptides encoded by 3 genes

Answer 399

Most common form of GM2 gangliosidosis; results from mutation in alpha subunit locus on chrom 15 that causes severe deficiency of hexosaminidase A; prevalent among Ashkenazic Jews; infants normal at birth, manifest symptoms at 6 mo; motor and mental deterioration, muscular flaccidity, blindness, dementia, cherry red spot in macula, 1-2 yrs -> vegetative state, death at 2-3 years; unfolded protein response -> possible chaperone therapy

Answer 400

Neurons in central and autonomic NS, retina; (though GM2 accumulates in many tissues); neurons are ballooned w/cytoplasmic vacuoles; stains for fat are positive; destruction of neurons, proliferation of microglia, accumulation of lipids in phagocytes of brain; ganglion cells in retina swollen

Answer 401

Sphingolipodoses

Answer 402

Sulfatidoses

Answer 403

Sphingomyelinase; type A: sever in infantile, Neuro impairment, visceral accumulations of sphingomyelin, wasting and early death; type B: organomegaly but no CNS involvement; survive into adulthood *common in Ashkenazi Jews; gene expressed on maternal chromosome as a result of epi genetic silencing of paternal gene (usually AR but those who inherit mutant allele from mom can get dz)

Answer 404

Missense mutation -> complete deficiency of sphingomyelinase; causes foaminess of cytoplasm; stain for fat; lipid-laden foam cells widely distributed in spleen, liver, LN, BM, tonsils, GI, and lung;

Answer 405

splenomegaly but not hepatomegaly; in brain, gyri shrunken and sulci widened; retinal cherry spot seen; protruberant abdomen; symptoms start at 6 mo -> followed by failure to thrive, vomiting, fever, generalized LAD, and deterioration of psychomotor function; feat within 1-2 years

Answer 406

Mutation in NPC1/2 (1 more common); causes primary defect in non-enzymatic lipid transport; NPC1 is membrane bound - NPC2 is soluble; both transport free cholesterol from lysosomes to cytoplasm; heterogenous; may present as hydros fetalis and stillbirth, neonatal hepatitis, or chronic characterized by progressive Neuro damage (most common) *ataxia, vertical supranuclear gaze palsy, dystonia, dysarthria, psychomotor regression

Answer 407

Sulfatidose class; cluster of AR disorders resulting from mutations in gene encoding for glucocerebrosidase (normally cleaves glucose residue from ceramide) *most common lysosomal storage disorder; glucocerebroside accumulate in phagocytes (Formed from catabolism of glycolipids from membranes of senescent leukocytes and RBCs)

Answer 408

Not just by burden of storage material: also by activation of macrophages and secretion of IL-1,6, and TNF

Answer 409

- Type I: most common, chronic nonneuronopathic form; storage of glucocerebrosides limited to phagocytes throughout body, but not brain; *splenic and skeletal involvemtns; Jews; reduced levels of enzyme activity; longevity shortened slightly - Type II: acute neuronopathic; infantile acute cerebral pattern; no enzyme activity; hepatosplenomegaly; dominated by CNS involvement; early death - Type III: intermediate; systemic involvement of t yep I, but also have CNS involvement beginning in early adulthood

Answer 410

spleen, liver, BM, tonsils, peyers patches, thymus, LN

Answer 411

Don’t appear vacuolated, but instead have a fibrillar type of cytoplasm (like crumpled tissue paper); have one or more dark eccentrically placed nuclei

Answer 412

Type I** causes bone erosion

Answer 413

No lipid accumulation in neurons -> cytokines released from neighboring phagocytes damage neurons; gaucher cells seen in virchow Robbins spaces

Answer 414

Type I: symptoms appear in adult; splenomegaly (thrombocytopenia and pancytopenia secondary), bone pain, Type II and III: convulsions, progressive mental deterioration, liver, spleen, LN also affected

Answer 415

Recombinant enzyme replacement therapy; HSC transplant (defect resides in mononuclear phagocyte cells originating from marrow)

Answer 416

Group of syndromes resulting from deficiencies of enzymes involved in degredation for of mucopolysaccharides (glycosaminoglycans)

Answer 417

Dermatomes sulfate, heparan sulfate, keratan sulfate, and chondroitin sulfate

Answer 418

All are AR except Hunter syndrome which is X-linked recessive

Answer 419

Coarse facial features, clouding of cornea, joint stiffness, mental retardation, urinary excretion of accumulated mucopolysaccharides; hepatosplenomegaly, skeletal deformities, valvular lesions, subendothelial arterial deposits, lesions in the brain

Answer 420

Phagocytic cells, endothelial cells, smooth m cells and fibroblasts; sites of involvement are spleen, LN, liver, BM, bv and heart

Answer 421

Niemann pick and MPSs

Answer 422

MPS I: deficiency of alpha 1 iduronidase; most severe; affected children normal at birth, develop HSM by age 6-24 mo, growth is retarded, coarse facial features, skeletal deformities, death by age 6-10 due to CV complications

Answer 423

MPS II: absence of corneal clouding, milder clinical course

Answer 424

Glucose converted to glucose 6 p via hexokinase; glucose6P-> G1P via phosphogluctomutase -> uridine diphosphoglucose -> polymer built to form glucose molecules linked by alpha 1,4 bonds

Answer 425

Enzymes break off G1P until 4 glucose residues remain leaving a branched oligosaccharide called limit dextrin; can be further degraded by debranching enzyme; *also degraded in lysosomes by acid Maltase

Answer 426

Hepatic forms, myopathic forms, and form associated with deficiency of acid maltase or lack of branching enzyme

Answer 427

Ie: deficiency of glucose 6 phosphatase (von gierks; type I): form of hepatic hypoglycemic glycogen storage disease; hepatic enlargement and hypoglycemia dominate in any of these disorders; renomegaly also seen; hyperlipidemia; bleeding tendency

Answer 428

In skeletal mm, glycogen used as source of energy during activity; ATP generated by glycolysis which leads to production of lactate; if enzymes that fuel this pathway are deficient, muscular weakness occurs; ex: deficiency of muscular phosphorylase (McArdles: type V) or muscle PFK (type VII); present with m cramps after exercise and low lactate levels after exercise; serum creatinine kinase elevated

Answer 429

Associated with glycogen storage in many organs and death early in life; acid maltase -> type II (Pompe) *cardiomegaly most prominent feature

Answer 430

Stop dividing cells in metaphase with mitotic spindle inhibitors (cycle is) and then stain the chromosomes

Answer 431

Total # of chromosomes, sex chromosome complement, description of abnormalities in ascending numerical order; ie: male with trisomy 21: 47, XY, +21

Answer 432

Nondisjunction (either have extra or one less chromosome) -> results in trisomy or monosomy and anaphase lag (one homologous chromosome in meiosis or one chromatid in mitosis lags and is left out of the cell nucleus) -> results in one normal cell and one will monosomy

Answer 433

Turner sydrome; have combination of cells that are 45,X and 47, XXX

Answer 434

Special kind of deletion; produced when break occurs at both ends of a chromosome with fusion of the damaged ends (46,XY,r(14)); usually results in serious consequences

Answer 435

Two breaks within single chromosome and reinsertion of the inverted intervening segment; when it involves only one arm -> paracentric; if breaks are on opposite sides of centromere -> pericentric; fully compatible with normal development

Answer 436

Results when one arm is lost and the remaining arm is duplicated; identical information in both arms; most common in live births is long arm of the X -> i(X)(q10); associated with monosomy for genes on short arm of X and trisomy on long arm of X

Answer 437

Segment of one chromosome is transferred to another; balanced reciprocal translocation -> single breaks in 2 chromosomes which exchange material (normal but at increased risk for producing abnormal gametes); robertsonian (centric fusion) -> translocation btw 2 acrocentric chromosomes (breaks close to centromere); produces one long and one short chrom (small usually lost) -> normal but can lead to abnormal progeny

Answer 438

In ovum -> correlation with mothers age

Answer 439

- Robertsonian translocation of long arm of 21 to another acrocentric chromosome; cases are commonly familial - also could be mosaics -> mixture of cells with 46 and 47 chromosomes; results from mitotic nondisjunction of chrom 21 during embryogenesis; milder depending on proportion of normal cells * in both of these cases, maternal age serves no importance

Answer 440

Flat face, oblique palpebral fissures, epicanthic folds *evident at birth

Answer 441

- Congenital heart disease: Latium primum, atrial septal defects, AV valve malformations, ventricular septal defects - atresia of esophagus and small bowel - increased risk of developing acute leukemia: acute megakaryoblastic leukemia - older than 40 -> develop neuropathologist changes characteristic of Alzheimer’s - abnormal immune responses that predispose them to serious infections, particularly of the lungs and thyroid autoimmunity - intestinal stenosis, gap btw first and second toe, hypotonia, umbilical hernia, simian crease, abundant neck skin

Answer 442

Those involved in mitochondrial energy pathways, folate metabolism, and CNS development; thought to be overexpression of genes

Answer 443

Edwards syndrome: trisomy and mosaic type; prominent occiput, mental retardation, micrognathia, low set ears, short neck, overlapping fingers, congenital heart defects, Renal malformations, limited hip abduction; rarely survivable past 1st year

Answer 444

Patau syndrome: trisomy, translocation, and mosaic type; renal defects, rocker-bottom feet, cleft lip and palate, microcephaly and mental retardation, microphthlamia, polydactyly, cardiac defects, umbilical hernia; not survivable past 1st year of life

Answer 445

DiGeorge and velocardiofacial syndrome

Answer 446

Facial dysmorphism (prominent nose, retrognathia), cleft palate, CV anomalies, and learning disabilities

Answer 447

Psychotic illnesses: schizophrenia, bipolar | ADHD also seen

Answer 448

TBX1: T box TF

Answer 449

Downs, digeorge, velocardiofacial

Answer 450

Lyonization of X chromosome and modest amount of genetic material carried by Y chromosome

Answer 451

Short arm of Y chromosome

Answer 452

Azoospermia

Answer 453

Male hypogonadism that occurs when there are two or more X chromosomes and one or more Y chromosomes; rarely diagnosed before puberty; increase in length btw soles and the pubic bone (appearance of elongated body), eunuchoid body habit is w/long legs, small atrophic testes and small penis; lack of secondary sex characteristics (deep voice, hair), gynecomastia, mean IQ lower, but not mental retardation

Answer 454

T2DM; mitral valve prolapse; osteoporosis and fractures due to sex hormonal imbalance; *breast cancer, extragonadal germ cell tumors, and autoimmune dz

Answer 455

Hypogonadism

Answer 456

High FSH, low testosterone; high estradiol

Answer 457

Testicular tubules can be atrophied and replaced by pink, hyaline, collagenous ghosts, leydig cells appear prominent

Answer 458

47,XXY; results from nondisjunction of either parent

Answer 459

Genes that escape lyonization -also, in this syndrome, X chromosome with shorter CAG repeat is inactivated therefore they are less sensitive to androgens (longer CAG repeats encode for testosterone receptors that are less sensitive)

Answer 460

45,X: either missing chromosome, abnormalities of X chromosome or mosaics

Answer 461

- most common: isochromosome of the long arm 46,X,i(X)(q10) resulting in loss of short arm - deletion of portions of both long and short arms -> ring chromosome 46,X,r(X) - deletion of portions of short or long arm 46X,del(Xq) or Xp

Answer 462

- 45,X/46,XX - 45,X/46XY - 45,X/47,XXX - 45,X/46,X,i(X)(q10)

Answer 463

Gonadal tumor (gonadoblastoma)

Answer 464

Swelling of dorsum of hand and foot. Due to lymph stasis and swelling of the nape of the neck (distended lymph channels producing cystic hygroma); swellings subside but leave b/l neck webbing and looseness of skin on the back of neck

Answer 465

Congenital heart disease; left sided CV abnormalities (preductal. Coarctation of aorta and bicuspid aortic valve) *most impt cause of increased mortality; pigmented neck, broad chest, cubitus valgus -at puberty, don’t develop secondary sexy characteristics, short stature, amenorrhea (last two establish diagnosis) *turner sydrome most impt cause of primary amennorhea; can also develop hypothyroidism and glucose intolerance, obesity, and insulin resistance

Answer 466

Growth hormone is often used to treat these patients, but this would worsen insulin resistance

Answer 467

Dad; problem with gametogenesis

Answer 468

Develop normally in early embryogenesis, but because lack one X chromosome, begin to deplete rapidly and complete loss by age 2; menopause occurs before menarche (streak ovaries)

Answer 469

Short stature homeobox (SHOX) -> active in both chromosomes

Answer 470

Genetic sex: presence or absence of Y chromosome GOnadal: histological characteristic of gonads Ductal: presence of derivatives of mullerian or wolffian ducts Phenotypic or genital: appearance of external genitalia

Answer 471

Hermaphrodite is presence of both ovarian and testicular tissue; pseudo is disagreement between gonadal and phenotypic sex

Answer 472

Sex of transmitting parent; in fragile X -> occurs during oogenesis, in Huntington’s occurs during spermatogenesis

Answer 473

- loss of function (fragile X); repeats occur in noncoding regions - toxic gain of function (Huntington and spineocerebellar ataxia); repeats occur in coding regions - toxic gain of function mediated by mRNA (fragile X tremor-ataxia syndrome); noncoding parts affected

Answer 474

CAG -> codes for polyglutamine tracts; characterized by neurodegeneration, typically striking in midlife; abnormal protein impairs function of normal (dominant negative) or acquire new pathophysiologic toxic activity; proteins can also aggregate and cause ER stress response *morphologic hallmark = accumulation of aggregated mutant proteins in large intranuclear inclusions

Answer 475

Familial mental retardation 1 (FMR1)

Answer 476

Males: mentally retarded, long face with large mandible, large everted ears and large testicles (macro-orchidism), hyperextensible joints, high arched palate, mitral valve prolapse *affects males most

Answer 477

- males can be carriers: have the gene but are not affected; referred to as normal transmitting males - females are affected - risk depends on position in pedigree (brothers have less risk than of grandsons) - anticipation: observation that clinical features worsen with each successive generation

Answer 478

GAA in the intron; causes loss of protein function

Answer 479

Small repeats (55-200 CGG repeats) in normal trasmitting males and carrier females

Answer 480

When inherited by carrier male -> doesn’t really transform; when inherited by carrier females, high probability of dramatic amplification *during process of oogenesis, premutations converted to mutations by triple amplification; explains unusual inheritance pattern

Answer 481

Repeats in UTR of FMR1 gene causes DNA methylation resulting in transcriptional silencing; FMRP not made; FMRP most abundant in brain and testis

Answer 482

- Selectively bind mRNAs associated with polysomes and regulates their intracellular transport to dendrites; it binds to mRNAs that encode for proteins that regulate synaptic function - translation regulator: at synapses, FMRP suppresses protein synthesis from bound mRNAs in response to signaling through group I metabotropic glutamate receptors; thus, reduction in FMRP results in translation of these mRNAs which changes function of synapses

Answer 483

PCR detection of repeats

Answer 484

CGG premutations in FMR1 that cause a diseases; causes premature ovarian failure (before age 40), transmitting males exhibit progressive neurodegenerative syndrome starting in 6th decade, intention tremors and cerebellar ataxia (can progress to Parkinson’s); FMR1 gene is transcribed instead of methylated -> accumulate in nucleus and form inclusions -> recruit RNA binding proteins

Answer 485

- exert effects mostly on CNS, skeletal m, cardiac m, liver, and kidneys - heteroplasmy: each mit contains thousands of copies of mtDNA and thus mutations can affect some but not all of copies; tissues can harbor both wild type and mutant; minimum # of mutant but appear before causing oxidative dysfunction that gives rise to disease (Threshold effect)

Answer 486

Lender hereditary optic neuropathy: neurodegenerative disease, manifests as progressive b/l loss of central vision; first noted between ages 15-35; leads to blindness

Answer 487

Maternal: maternal allele is silenced and vice versus

Answer 488

In ovum or spleen before fertilization

Answer 489

DNA methylation at CG nucleotides, histone H4 deacetylation and methylation

Answer 490

Characterized by mental retardation, short stature, hypotonia, profound hyperplasia, obesity, small hands and feet, and hypogonadism; caused by deletion of band q12 in long arm of chromosome 15 of the paternally derived chromosome

Answer 491

Deletion of q12 on chromosome 15 of the maternal chromosome; mentally retarded, ataxic gait, seizures, inappropriate laughter (happy puppets)

Answer 492

Patients with prader Willi without the deletion have shown two maternal copies of chromosome 15 (Does not have set of non-imprinted genes so has dz); angelman syndrome without deletion -> have two sets of paternal chromosome 15

Answer 493

Ubiquitin ligase (UBE3A)

Answer 494

No single gene; SNORP family (encodes small nucleolar RNAs involves in modifications of ribosomal RNAs) -> loss of SNORP function

Answer 495

AD, but more than one child is often affected; gonadal mosaicism thought to be responsible -> mutation occurs postzygotically during early embryonic development (germ cells have defect but somatic cells don’t; can then transmit to children)

Answer 496

Constitutional: present in all cells of the effected individual (CFTR) Somatic: restricted to specific tissue types (KRAS in cancers)

Answer 497

Multiple congenital anomalies, suspicion of metabolic syndrome, unexplained mental retardation or delay, suspected aneuploidy (features of downs), suspected monogenic disease

Answer 498

Amplified DNA mixed with a DNA pol, primer, nucleotides, and four dead end nucleotides labeled with different fluorescent tags; size separation by electrophoresis -> sequence read and compared to normal sequence to detect mutations

Answer 499

Same set up as Sanger but instead of terminator nucleotides it involves cycling individual nucleuotides one at a time into the reaction; if one or more are incorporated into the strand, pyrophosphatase is released and involved in rx with luciferase that produces light; more sensitive than Sanger; sometimes used for cancer biopsies

Answer 500

Uses DNA probes that recognize sequences specific to particular chromosome regions; used to detect abnormal chromosome number, subtle microdeletoins, or complex translocations, and gene amplification

Answer 501

Detect anomalies too big for PCR and too small for FISH; uses pair of probes that hybridizes with DNA; probes create template to be amplified by PCR *CFTR

Answer 502

Detection of trinucleotide repeats

Answer 503

Can be used to detect genetic anomalies without prior knowledge of the chromosomal regions affected

Answer 504

Test DNA and normal DNA are labeled with 2 diff fluorescent dyes; then cohybridized to array with DNA probes; if two samples equal, all spots will be yellow, if not equal will skew towards red or green

Answer 505

To uncover copy number abnormalities in pediatric patients when the karyotype is normal but a structural abnormality is still suspected

Answer 506

SNPs and repeat length polymorphisms (mini satellite and micro satellite repeats) -> used for PKD1 in polycystic kidney dz; also used for paternity and criminal investigations

Answer 507

Used to perform linage studies of complex dz (diabetes, HTN); large cohoes of patients with and without a disease are examined across entire genome for common genetic variants or polymorphisms that are over expressed in pts with dz; also used for height, hair color, etc

Answer 508

CpG islands.

Answer 509

Treat it with sodium bisulfite which converts unmethylated cytosine to uracil; methylated cytokines protected and remain unchanged