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Pathology > Exam 2 (Chapters 5-6) Disease Notes > Flashcards

Exam 2 (Chapters 5-6) Disease Notes Flashcards

1
Q

How many spontaneous abortions are caused by chromosomal abnormalities?

A

50%

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2
Q

Sickle Cell Mutation

A

Point mutation from glutamic acid to valine

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3
Q

Example of mutation within noncoding sequence:

A

Hereditary anemias

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4
Q

Cystic Fibrosis Mutation Type

A

Three-base deletion (NOT A FRAMESHIFT MUTATION)

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5
Q

Example of a frameshift mutation:

A

Tay Sachs (four base insertion)

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6
Q

Diseases with Trinucleotide Repeats

A

CGG: Fragile X Syndrome/Tremor-Ataxia
GAA: Friedrich’s Ataxia
CAG: Huntington

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7
Q

Example of Pleiotropism

A

Sickle Cell - aside from the abnormal hemoglobin, it also causes “logjam” –> splenic fibrosis, organ infarcts, bone changes

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8
Q

Autosomal dominant disorders usually involve?

A

Structural proteins and receptors for metabolic pathways

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9
Q

Is Huntington dominant or recessive?

A

Dominant

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10
Q

Is Marfans dominant or recessive?

A

Dominant

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11
Q

Is Cystic Fibrosis dominant or recessive?

A

Recessive

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12
Q

Is Ehlers-Danlos Syndrome dominant or recessive?

A

Dominant (for most types)

Type VI and VIIc are autosomal recessive

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13
Q

Is Familial Hypercholesteria dominant or recessive?

A

Dominant

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14
Q

Is Alpha1-Antitrypsin dominant or recessive?

A

Recessive

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15
Q

Are Lysosomal and Glycogen Storage Diseases dominant or recessive?

A

Recessive

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16
Q

How are Agammaglobulinemia, Wiskott-Aldrich, and Fragile X syndrome inherited?

A

X-linked recessive

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17
Q

What is usually involved in autosomal recessive?

A

Enzyme proteins

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18
Q

Which diseases show a problem in receptor mediated endocytosis?

A

Familial Hypercholesterolemia

Cystic Fibrosis

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19
Q

Key Features of Marfans

A

Skeletal abnormalities: very tall, dolichocephalic, double jointed, scoliosis
Ocular changes: bilateral subluxation and dilation of lens (called ectopia lentis)
Cardiovascular lesions: mitral valve prolapse

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20
Q

Most common cause of death due to Marfans:

A

Aortic Dissection

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21
Q

Gene involved in Marfans:

A

FBN1 and FBN2

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22
Q

Treatment for Marfans:

A

Beta Blockers

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23
Q

What deficiency do all EDS types have in common?

A

COLLAGEN

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24
Q

Main feature of EDS with lysyl hydrolase deficiency?

A

Type VI - Kyphoscolios

Look for scoliosis and ocular fragility

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25
Q

Major symptoms/progressions of Familial Hypercholesterolemia?

A

Atherosclerosis and Xanthomas

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26
Q

Treatment for FH?

A

Statins to suppress intracellular cholesterol synthesis

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27
Q

Different between primary and secondary accumulations in lysosomal storage disease?

A

Primary: incomplete catabolism of metabolite causes accumulation within the lysosome

Secondary: impaired autophagy, damaged mitochondria accumulates and cell undergoes apoptosis

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28
Q

Deficiency and Accumulation of Tay Sachs

A

Deficiency: Hexosaminidase
Accumulation: GM2 gangliosides

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29
Q

Deficiency and Accumulation of Mucopolysaccharidoses

A

Deficiency: iduronidases
Accumulation: heparan sulfate, dermatan sulfate

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30
Q

Key features of Tay Sachs:

A

Cherry red macula
Motor incoordination
Death usually occurs 2-3 years

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31
Q

Deficiency in Niemann-Pick Types A and B

A

Sphingomyelinase

Gene is preferentially expressed from the maternal chromosome due to epigenetic silencing of paternal

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32
Q

Genes involved in Niemann-Pick Type C

A

MOST COMMON

NPC1 and NPC2

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33
Q

Most common lysosomal storage disease:

A

Gaucher Disease

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34
Q

Accumulations in Gaucher Disease

A

Glucocerebrosidase

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35
Q

Important features of Gaucher Type 1

A 
Pathologic bone fractures
No neurologic symptoms
Gaucher cells in the bone marrow
Splenomegaly
Pancytopenia
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36
Q

Important features of MPS

A

Hepatosplenomegaly
Coarse facial features
Mental retardation
Lysosomes show zebra bodies

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37
Q

Hurler Syndrome (MPS I-H)

A

Autosomal recessive
Hepatosplenomegaly
Corneal clouding
Coarse facial features

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38
Q

Hunter Syndrome (MPS II)

A

X-linked

NO corneal clouding

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39
Q

Hepatic form of glycogen storage diseases:

A

Type I Glycogenosis - von Gierke disease

Autosomal recessive
Storage of glycogen in the liver
Hypoglycemia

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40
Q

McArdle Disease

A

Type V Glycogenosis

Muscle cramps after exercise
Deficiency in muscle phosphorylase

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41
Q

Type VII Glycogen Storage Disease

A

Deficiency in muscle phosphofructokinase

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42
Q

Pompe Disease

A

See symptoms in heart (cardiomegaly), liver, and muscle

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43
Q

Most common chromosomal disorder:

A

Trisomy 21 (Down Syndrome)

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44
Q

Most common cause of Down Syndrome:

A

Meiotic nondisjunction

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45
Q

Most common death for those with Down Syndrome?

A

Congenital heart disease - defects of the endocardial cushion, atrial defects, valve malformations

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46
Q

What are people with Down Syndrome more likely to develop?

A

Acute Leukemias

Most commonly: acute megakaryoblastic leukemia

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47
Q

Important Features of Edwards Syndrome:

A

Trisomy 18
Meiotic nondisjunction
Rocker bottom feet
Polydactyly

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48
Q

Important Features of Patau Syndrome:

A

Trisomy 13
Low set ears
Overlapping fingers

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49
Q

What two diseases make up the Chromosome 22q11.2 Deletion Syndrome?

A

DiGeorge Syndrome and Velocardiofacial Syndrome

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50
Q

Features caused by DiGeorge vs Velocardiofacial:

A

DG: immune defects and hypocalcemia due to parathyroids and thymus defects

VCF: heart, learning disability, facial features

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51
Q

What are people with the 22q11.2 deletion at risk for developing?

A

Psychotic illness - schizophrenia and bipolar disorder

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52
Q

Major genes in 22q11.2 deletion:

A

PAX9 and TBX1

These are expressed in the pharyngeal mesenchyme

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53
Q

On what day does the inactivation of X chromosomes via lionization happen?

A

Day 5.5 of embryonic life

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54
Q

Most common cause of hypogonadism in males vs females:

A

Klinefelters vs Turners Syndromes

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55
Q

Features of Klinefelters:

A

Abnormally long legs
Hypogonadism
Lack of secondary sex characteristics

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56
Q

Two mechanisms causing Klinefelters on the X chromosome:

A
  1. Uneven dosage compensation due to extra X’s

2. Gene for androgen receptor becomes insensitive to testosterone

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57
Q

Mechanisms for partial monosomy in Turners Syndrome:

A
  1. isochromosome of the long arm
  2. ring chromosome
  3. deletions of either the long or short arm
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58
Q

Most severely affected infants will appear at birth with:

A

Swelling of the dorsum of the hands and feet

Swelling of the nape of the neck (cystic hygroma)

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59
Q

Other main features of Turners:

A 
Short stature
Amenorrhea
Streak ovaries
Neck webbing
Looseness of skin on back of the neck
Congenital heart disease
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60
Q

Important gene in Turners:

A

SHOX

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61
Q

When do trinucleotide expansions happen in Fragile X vs Huntington?

A

FX: during oogenesis

HTN: during spermatogenesis

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62
Q

Morphologic hallmark of trinucleotide repeat diseases:

A

Accumulation of proteins in large intranucelar inclusions

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63
Q

Fragile X Syndrome is caused by a trinucleotide mutation in which gene?

A

FMR-1 (familial mental retardation 1)

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64
Q

Major features of Fragile X:

A

Macro-orchidism
Large everted ears
Mental retardation

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65
Q

Why do grandsons of normal transmitting males have a higher risk?

A

Amplification of the repeats happen during oogenesis, so the mothers will amplify the disease before passing it down

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66
Q

Why is Fragile X a loss-of-function disorder?

A

CGG repeats –> transcriptional silencing of FMR-1 –> lack of FMRP proteins

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67
Q

Mechanism behind Fragile X Tremor/Ataxia?

A

Toxic gain of function mechanism

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68
Q

Why is the Tremor/Ataxia verion considered toxic?

A

FMR1 gene is continuously transcribe and there is excess FMRP proteins and mRNA

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69
Q

Leber hereditary optic neuropathy is what type of disease? Main features?

A

Mitochondrial disease - neurodegenerative

Manifests as bilateral loss of central vision

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70
Q

Two diseases caused by genomic imprinting?

A

Prader-Willi and Angelman’s

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71
Q

Features of Prader-Willi

A 
Mental retardation
Short stature
Hypotonia
Hyperphagia - can't stop eating, high BMI
Hypogonadism
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72
Q

Why are those diagnosed with Angelmann’s referred to as “happy puppets”?

A

Mentally retarded, with inappropriate laughter

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73
Q

Prader-Willi vs Angelmann Imprinting:

A

PW: maternal chromosome imprinted, rely on paternal but that gets deleted

A: paternal chromosome imprinted, rely on maternal, but that gets deleted

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74
Q

Genes in Prader-Willi vs Angelman:

A

PW: SNORP
A: UBE3A

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75
Q

What does FISH stand for?

A

Fluorescence in Situ Hybridization

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76
Q

Importance of NOD-like Receptors (NLRs)

A

Cytosolic reeptors
Recognize products of necrotic cells, ion disturbances, microbial products
Signal via the inflammasome complex

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77
Q

Inflammasome Complex

A

Activates caspase-1 –> IL-1 –> recruits leukocyte and induces fever

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78
Q

Mutations in TLRs vs NLRs

A

TLR: immunodeficiency syndromes
NLR: autoinflammatory syndromes

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79
Q

C-type Lectin Receptors: (CLRs)

A

Found on macrophages and DCs

Detects fungal glycans

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80
Q

RIG-like Receptors (RLRs)

A

Found in the cytosol of most cell types

Detects viral nucleic acids

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81
Q

GPCRs:

A

On neutrophils, macrophages, and leukocytes

Recognize N-formylmethionyl residues on bacteria

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82
Q

Mannose Receptors

A

Recognize microbial sugars

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83
Q

Best antiviral defense secretion:

A

Type 1 interferon

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84
Q

Enzyme in developing lymphocytes that mediates recombination:

A

RAG-1 and RAG-2

Defects here = no mature lymphocytes

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85
Q

What do NK-T cells do?

A

Recognize glycolipids displayed by CD1

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86
Q

Proteins found on the B cell receptors:

A

Iga and Igb, Type 2 complement receptor (CD21), and CD 40

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87
Q

Which cells are most important as APCs for activating T cells?

A

Dendritic Cells

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88
Q

Immature DCs within the epidermis are called:

A

Langerhan Cells

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89
Q

Follicular DCs are found where? and do what?

A

Found in germinal centers of lymph nodes

Select B cell with highest affinity for antigens
Can also trap antigens with C3b

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90
Q

What are the main targets of NK cells?

A

Viruses and tumor cells (irreversibly stressed and abnormal cells)

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91
Q

What markers are used to identify NK cells?

A

CD16 (responsible for ADCC) and CD56

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92
Q

How are NK cells regulated?

A

They have inhibitory and activating receptors

IL-2 and IL-15 stimulate proliferation
IL-12 activates killing and secretion of IFNy

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93
Q

Genes for HLAs are found where?

A

On chromosome 6

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94
Q

Class I MHC Molecules use which HLAs?

A

HLA-A, HLA-B, and HLA-C

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95
Q

Class II MHC Molecules use which HLAs?

A

Encoded for in the HLA-D region:

HLA-DR, HLA-DQ, and HLA-DP

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96
Q

What are colony stimulating factors?

A

Cytokines that stimulate hematopoiesis

Examples: GM-CSF and IL-7

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97
Q

Condition where you’d rather inhibit cytokines?

A

RA = with TNF antagonists

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98
Q

Condition where you’d rather administer cytokines?

A

Boosting hematopoiesis and defense against viruses

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99
Q

What type of antigen stimulates a T-independent response from B cells?

A

Polysaccharides and Lipids - stimulate IgM

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100
Q

Which cytokines induce isotype switching?

A

IFNy and IL-4

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101
Q

What is caused by Type I hypersensitivities?

A

Allergies, anaphylaxis, and atopy

Caused by production of IgE by Th2 cells/B cells

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102
Q

Main type of cell in Type II hypersensitivity?

A

B cells - make IgG and IgM antibodies to activate complement/phagocytosis

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103
Q

Main type of cell in Type III?

A

Immune Complexes - antigens and antibodies that cause inflammation and fibrinoid necrosis

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104
Q

Main type of cell in Type IV?

A

T cells - Th1, Th17, and CTLs (CD4 and CD8)

Delayed type of hypersensitivity

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105
Q

Order of cell appearances in Type I?

A

Immediate reaction: predominantly mast cells

Late-phase reaction: mostly eosinophils, activated T cells

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106
Q

What are the preformed mediators secreted by mast cells?

A

Vasoactive amines (Histamine), Enzymes (proteases), and Proteoglycans (heparan and chondroitin sulfate)

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107
Q

Which secondary mediators are made de novo in mast cells?

A

Leukotrienes, Prostaglandin D2 (causes bronchospasm), and Platelet-Activating Factor (recruits platelets)

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108
Q

Treatment for immediate vs late-phase Type I reaction:

A

Immediate: anti-histamine

Late-phase: anti-inflammatory (steroids)

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109
Q

Which type of hypersensitivity has autoantibodies?

A

Type II

110
Q

Mechanism behind Type II:

A

Opsonization and Phagocytosis

111
Q

Examples of conditions where we see Type II?

A

Blood transfusions
Erythroblastis Fetalis
Autoimmune hemolytic anemia
Drug reactions

112
Q

What type of hypersensitivty are Myasthenia Gravis and Graves’ disease?

A

Type II

113
Q

What is Goodpasture Syndrome? Type of hypersensitivity?

A

Pulmonary-renal disease - attacks self tissues causing nephritis and lung hemorrhage

Type II Hypersensitivity

114
Q

Main clinical manifestations of Type III?

A

Affects the kidneys (glomerulonephritis), joints (arthritis) and vessels (vasculitis)

115
Q

Prototypic examples of Type III?

A

Acute Serum Sickness

116
Q

Why is organ damage a Type III response?

A

The high pressure of blood flow pushes immune complexes to be concentrated and deposited

117
Q

How can you measure the progress of the active phase of Type III?

A

C3 levels - it will decrease as it is being consumed

118
Q

Common disorders caused by Type III?

A

SLE, glomerulonephritis, reactive arthritis, serum sickness

119
Q

What is the prototypic example of Type IV?

A

Delayed Type Hypersensitivity (DTH)

120
Q

If the macrophages continue to be activated, what happens?

A

First form epithelioid cells –> granulomas

To prevent this, give an IFNy antagonist

121
Q

Disorders caused by Type IV?

A

RA, MS, T1D, IBD, psoriasis, and contact sensitivity

122
Q

Central tolerance for T cells:

A

As they mature in the THYMUS, those that recognize self antigens are either killed by apoptosis or made into regulatory T cells

123
Q

Central tolerance for B cells:

A

As they mature in the BONE MARROW, those that recognize self antigens either undergo receptor editing or are killed by apoptosis

124
Q

Mechanisms of peripheral tolerance:

A

Anergy
Suppression by regulatory T cells
Deletion by apoptosis

125
Q

Immune-Privileged Sites:

A

Eyes, testis, and brain

126
Q

What diseases is PTPN22 associated with?

A

RA, T1D, and IBD

Due to a functionally defective phosphatase

127
Q

What disease is NOD2 associated with?

A

Crohn’s

Receptor is ineffective at sensing gut microbes

128
Q

What diseases is CTLA4 associated with?

A

T1D and RA

T cell responses are inhibited by regulatory T cells

129
Q

What disease is ATG16 associated wit?

A

IBD - involved in autophagy

130
Q

Examples of molecular mimicry:

A

Rheumatic heart disease –> antibodies against strep also share sequences with myocardial proteins

EBV and HIV –> causes polyclonal B cell activation which may create autoantibodies

131
Q

Mechanisms of injury behind SLE:

A

Formation of multiple autoantibodies leads to immune complexes being deposited all over

Self-tolerance fails

132
Q

Most popular SLE symptoms:

A

Malar rash, photosensitivity, arthritis (nonerosive), renal disorders (proteinuria), specific antibodies found in serum, inflammation of serosal membranes, Liebman-Sacks verrucous endocarditis

133
Q

SLE predominantly affects:

A

Women mostly

Blacks and Hispanics at higher risk

134
Q

Most widely used testing for detecting ANAs is:

A

Indirect Immunofluorescence

135
Q

Which antibodies are diagnostic for SLE?

A

Anti-Smith antigen and Anti-DNA for double stranded

136
Q

Why might SLE patients test falsely positive for syphilis?

A

Because 30-40% of SLE patients also have antiphospholipid antibodies

137
Q

Though many factors may cause SLE, what specific locus has been linked?

A

HLA-DQ

138
Q

Environmental factors that may cause SLE:

A

Exposure to UV light: exacerbates the disease, may induce apoptosis and production of IL-1

Gender bias: SLE partly attributed to sex hormones

Drugs: hydralazine, procainamide, isoniazid

Microbiome

139
Q

Treatment for SLE:

A

Corticosteroids or immunosuppressive drugs

140
Q

Most common cause of death due to SLE:

A

Renal failure and recurrent infections

141
Q

Chronic Discoid Lupus

A

Mostly involves skin - characterized by skin plaques on face and scalp

See depositions of C3 and Ig

142
Q

Subacue Cutaneous Lupus

A

Also involves skin mostly - widespread rash that is superficial and nonscarring

Ab for SS-A

143
Q

Drug-Induced Lupus

A

May develop after administering certain drugs (like isoniazid or anti-TNF therapy for RA)

Renal and CNS are NOT affected
Ab for histones is high

144
Q

6 Types of Kidney Lesions in SLE:

A

1: least common - only seen in electron microscopy
2: no involvement of glomeruli
3: less than 50% glomeruli affected
4: most common and most severe
5: diffuse
6: represents end stage renal disease

145
Q

Main features of Sjogren Syndrome?

A

Dry eyes (blurry vision), dry mouth (dysphagia), destruction of lacrimal and salivary glands, parotid gland enlargement

146
Q

Primary form of Sjogren is called?

A

Sicca Syndrome

147
Q

Important antibodies in Sjogren?

A

Anti-SS-A (Ro) and Anti-SS-B (La)

148
Q

Who is most susceptible to Sjogren?

A

Women, ages 50-60

149
Q

How is Sjogren diagnosed?

A

With a biopsy of the lip

150
Q

Lymph nodes are hyperplastic in Sjogrens. What type of cells are seen?

A

Initially: polyclonal T and B cells
Later: B cells take over, putting them at risk for marginal zone lymphoma (5%)

151
Q

Two types of scleroderma and the differences:

A

Diffuse: widespread skin involvement, rapid progression and early visceral involvement

Limited: skin involvement on forearms, fingers, and face

  • late visceral involvement
  • may develop CREST syndrome
152
Q

What is involved in CREST syndrome?

A 
C: calcinosis
R: Raynaud's phenomenon
E: esophageal dysmotility
S: sclerodactyly
T: telangiesctasia (spider veins)
153
Q

Pathogenesis of Scleroderma

A

Autoimmunity: CD4+ T cells, Th2
Vascular damage
Fibrosis (myocardial and interstitial lung fibrosis)

154
Q

In patients with systemic sclerosis, death is usually caused by what?

A

Renal failure, cardiac failure, or malabsorption syndrome

155
Q

Who is more susceptible to developing scleroderma?

A

Female to male ratio is 3:1

Most aged 50-60 years old

156
Q

Clinical features and progressions of systemic sclerosis:

A

Raynaud phenomenon
Dysphagia (90%)
Mild proteinuria (30%)
Malignant hypertension –> may progress renal failure

157
Q

What causes malabsorption syndrome in systemic sclerosis?

A

Loss of villi in the intestines

158
Q

Mixed Connective Tissue Disease

A

Mixture of features from SLE, systemic sclerosis, and polymyositis

Characterized by antibodies to U1RNP

Symptoms: pulmonary hypertension, interstitial lung disease, and renal disease

159
Q

IgG4-Related Diseases

A

Tissue infiltrates dominated by IgG4 plasma cells
Storiform fibrosis: looks like a wheel
Increased serum IgG4

mostly affects middle-aged men and older men

160
Q

Difference between direct and indirect pathways of rejecting a graft?

A

Direct: uses both Class I and II MHC molecules

Indirect: only uses Class II MHC molecules and causes a delayed type hypersensitivity (type IV)

161
Q

When is hyperacute rejection likely?

A

When the patient already has preformed antibodies (presensitized):

  • previously rejected transplant
  • multiparous women
  • previous blood transfusion
162
Q

When does acute antibody-mediated rejection occur?

A

Antidonor antibodies are produced after transplantation

Initial target: graft vasculature

163
Q

How does chronic antibody-mediated rejection happen?

A

Develops insidiously

Primarily affects the vascular components

164
Q

Drugs used for immunosuppressive therapy:

A

Steroids, mycophenolate mofetil (inhibits lymphocyte proliferation), tacrolimus (inhibits T cells), IVIG

165
Q

Major risk of immunosuppression:

A

Susceptibility to opportunistic infection by the polyoma virus –> kidney specific, causes graft failure

166
Q

Rejection patients also at risk for developing:

A
  • EBV-induced lymphoma
  • HPV-induced squamous cell carcinoma
  • Kaposi sarcoma
167
Q

For polyoma or other viruses after rejection, treatment includes:

A

Decreasing the levels of the immunosuppressive drug to allow the immune system to fight off the virus

168
Q

Graft v Host Disease is most commonly seen after what?

A

HSC transplantation

169
Q

Acute GVHD presents as:

A

Occurs within days to weeks

Presents with skin (rash), liver (jaundice), and intestines (bloody diarrhea)

170
Q

Chronic GVHD presents as:

A

Occurs within months to years

Presents with skin (fibrosis of dermis), liver (chronic liver disease), GI (esophageal strictures), involution of thymus

171
Q

When are primary immunodeficiencies seen?

A

In infancy, from about 6 months to 2 years

Telltale sign of this: recurrent infection

172
Q

Leukocyte adhesion deficiency 1:

A

Mutations in CD11/CD18 integrins

See recurrent infections due to inadequate granulocyte

173
Q

Leukocyte adhesion deficiency 2:

A

Absence of Sialyl Lewis C - E and P selectins cannot bind

See recurrent infections

174
Q

Chediak-Higashi Syndrome

A

Inherited defect in phagolysosome function - unable to kill microbes

175
Q

Chronic granulomatous disease

A

Activated macrophages –> granulomas

X-linked (most common) and autosomal recessive both have a defect in phagocyte oxidase

176
Q

Myeloperoxidase Deficiency

A

Defective MPO-H2O2 system

177
Q

Defect in TLR 3

A

Receptor for viral RNA

178
Q

Affected infants with SCID present as:

A

Prominent thrush, extensive diaper rash, failure to thrive

May also present with a morbiliform rash (looks like measles, sign of GVHD)

179
Q

How is the most common form of SCID inherited?

A

X-linked

180
Q

How is the autosomal form of SCID inherited?

A

Autosomal recessive

181
Q

Treatment for SCID:

A

HSC transplantation

182
Q

X-linked Agammaglobulinemia is characterized by?

A

Failure of B cell maturation

Marked decrease of B cells in circulation

183
Q

How does XAG present?

A

Appears around 6 months of age after maternal antibodies are gone
Starts with recurrent bacterial infections
Almost always caused by: H. influenzae, S. pneumoniae, and S. aureus

184
Q

What else is XAG susceptible to?

A

Enterovirus and Giardia lamblia

185
Q

Treatment for XAG?

A

Replacement therapy with immunoglobulins

186
Q

DiGeorge Syndrome is characterized by:

A

T cell deficiency due to failure of the 3rd and 4th pharyngeal pouches development

187
Q

Common presentation/symptoms of DiGeorge:

A

Lack of T cell mediated immunity
Hypocalcemia
Congenital defects of heart and vessels
Mouth, ear facies

188
Q

Bare Lymphocyte Syndrome

A 
Mutations in transcription factors required for class II MHC molecules
B cells don't receive proper signaling
Leads to combined immunodeficiency
189
Q

Hyper IgM Syndrome is caused by:

A 
CD40/CD40L mutation
Most people (70%) have the X-linked form
190
Q

What bacterial infection are patients with Hyper IgM susceptible to?

A

Pneumocystis jiroveci - pneumonia

191
Q

Common Variable Immunodeficiency

A

Common feature is low levels of immunoglobulins

But they will have normal levels of B cells (these areas may be hyperplastic)

192
Q

Isolated IgA Deficiency

A

Occurs in about 1 in 600 European descent
Have extremely low levels of IgA
Most people are asymptomatic
Symptomatic people have recurrent sinopulmonary infetions

193
Q

Overall defect of Isolated IgA deficiency:

A

Impaired differentiation of naive B cells to IgA producing plasma cells

194
Q

What causes X-linked Lymphoproliferative Syndrome?

A

Inability to eliminate EBV leading to a fulminant infectious mononucleosis and development of B cell tumors

195
Q

XLS is due to a mutation in which protein?

A

SLAM-associated protein (SAP)

SLAM = signaling lymphocyte activation molcule

196
Q

How is Wiskott-Aldrich characterized?

A

X-linked disease
Thrombocytopenia, eczema, recurrent infections
Mutations in the WASP gene/protein

197
Q

How is Wiskott-Aldrich treated?

A

HSC transplantation

198
Q

What are the symptoms of Ataxia Telangiectasia?

A

Abnormal gait, spider veins, neuro deficits, tumors, immunodeficiency
Defective isotype switching - primarily IgA and IgG2
Mutated protein is called ATM

199
Q

Common causes of secondary immunodeficiency?

A

HIV, radiation/chemo, leukemias, malnutrition, removal of spleen, drugs or severe infection

200
Q

How does radiation/chemo cause secondary immunodeficiency?

A

Decreased bone marrow precursors for leukocytes

201
Q

How does malnutrition cause secondary immunodeficiency?

A

Metabolic derangments inhibit lymphocyte maturation

202
Q

How does removing the spleen cause secondary immunodeficiency?

A

Decreased phagocytosis

203
Q

What is the most common secondary immunodeficiency?

A

AIDS

204
Q

Dominant mode of transmission for HIV/AIDS?

A

Sexual Transmission

205
Q

How is sexual transmission enhanced?

A

By the presence of STIs

206
Q

How is HIV passed on between mother and child?

A
  1. In utero
  2. During delivery
  3. After birth by breast milk
207
Q

Which strains of HIV are more common geographically?

A

HIV-1: US, Europe, Central Africa

HIV-2: West Africa, India

208
Q

HIV virus core contains:

A

p24 (major capsid protein)
p7/p9 (nucelocapsid protein)
Two copies of viral RNA
Three viral enzymes (protease, reverse transcriptase, and integrase)

209
Q

What is the viral core surrounded by?

A

p17

210
Q

What studs the viral enveope?

A

Two glycoproteins: gp120, gp41

211
Q

HIV-1 Genome contains which three important genes typical of retroviruses?

A

gag, poly, and env

212
Q

Two major targets of HIV?

A

Immune system and the central nervous system

213
Q

What is considered the hallmark of AIDS?

A

Profound immune deficiency, primarily affecting cell-mediated immunity

214
Q

What molecule does HIV use to infect cells?

A

CD4 molecule (on many cells)

215
Q

What is the importance of CCR5 and CXCR4?

A

HIV has two strains:
CCR5: used by the R5 strains, which are M-tropic
CXCR4: used by X4 strains, which are T-tropic

216
Q

Polymorphisms in CCR5 can lead to…?

A

Resistance of the HIV infection - happens in 1% of the white population

217
Q

In 90% of HIV cases, which strain is dominant?

A

R5 strain; X4 will accumulate gradually over time though

218
Q

Virus in quiescent cells versus dividing cells:

A

Q: cDNA will stay in the cytoplasm
D: cDNA circularizes and moves to the nucleus, incorporates into host DNA

219
Q

Why is HIV ineffective at infecting naive T cells?

A

Naive T cells still have the APOBE3G enzyme activated which inhibits DNA replication of the HIV virus

This becomes inactivated in mature T cells

220
Q

What accessory gene in HIV allows it to inactivate APOBE3G?

A

Vif gene - binds to the enzymes and degrades it

221
Q

How can the HIV virus be activated again after being in a latent phase?

A

Stimulation by antigen or cytokine will release NF-kB and can activate it
HIV is capable of activating these mechanisms on its own

222
Q

What causes the depletion of CD4+ T cells in HIV?

A

Mainly the direct cytopathic effects of the replicating virus

223
Q

What are the giant cells formed in HIV called?

A

Syncytia - specific to the T-tropic, X4 strain

224
Q

If HIV activates the inflammasome pathway, what happens next?

A

Cell undergoes pyroptosis

225
Q

What percentage of CD4+ T cells in the lymph nodes are latently infected?

A

0.05%

226
Q

What are other big effects caused by HIV?

A

Lymphopenia
Decreased T-cell function
Polyclonal B activation
Altered Monocyte/Macrophage functions

227
Q

What is the vpr gene responsible for?

A

Allowing the HIV-1 strain to infect and multiply in terminally non-dividing macrophages

228
Q

Why are macrophages considered reservoirs for HIV?

A

Because they don’t die once they’re infected - allow HIV to replicate within them

229
Q

Why are follicular dendritic cells potential reservoirs?

A

These can trap the virus once it has been coated with antibodies and remain in the germinal centers of lymph nodes

230
Q

What does polyclonal activation of B cells lead to?

A

Germinal center B cell hyperplasia

231
Q

What are the predominant cell type in the brain once infected with HIV?

A

Macrophages/microglia

232
Q

Acute retroviral syndrome is caused when?

A

Presents during the initial spread of the virus along with the initial host response
See a lot of non-specific, flu-like symptoms
Appears in 40-90% of those infected
Occurs about 3-6 weeks post infection
Resolves spontaneously 2-4 weeks later

233
Q

How can the extent of viremia be measured?

A

Levels of HIV-1 RNA - the lower the viral load, the better

234
Q

According to the CDC, when is it considered AIDS?

A

No matter the viral load, if there is a constitutional (widespread) disease, neuro disease, or neoplasm, it is considered AIDS

235
Q

When there are few or no clinical manifestations, it’s called:

A

Clinical Latency Period

236
Q

Mechanisms HIV uses to avoid immune response:

A

Switch between CCR5 and CXCR4
Destroy CD4+ T cells
Antigenic variation
Down regulate Class I MHCs

237
Q

Without treatment, how long before HIV becomes AIDS?

A

7-10 years

238
Q

What is the most common presenting symptoms of AIDS?

A

Pneumonia caused by Pneumocystis jiroveci

239
Q

Most common fungal infection in AIDS?

A

Candidiasis

240
Q

Which parasite is responsible for CNS lesions?

A

Toxoplasma gondii

241
Q

What doe the JC virus cause?

A

Multifocal leukoencephalopathy

242
Q

What are some of the oncogenic DNA viruses?

A

Kaposi sarcoma
EBV –> B cell lymphoma
HPV –> cervical and anal carcinoma

243
Q

What is the mechanism behind AIDS patients developing Kaposi Sarcoma?

A

Caused by the KSHV or HHV8 virus
Shows proliferation of spindle shaped cells
Produces a cyclin D homologue

244
Q

What other diseases are linked to Kaposi Sarcoma?

A

Primary effusion lymphoma

Multicentric Castleman disease

245
Q

Lymphoma and AIDS prevalence

A

5% of AIDS patients will present with lymphoma

another 5% will develop it at some point

246
Q

Two mechanisms behind developing lymphoma after HIV infection:

A
  1. Unchecked proliferation of B cells after profound T cell depletion –> primary effusion lymphoma
  2. Germinal center B cell hyperplasia during early HIV infection - not associated with EBV or KSHV
    - caused by activation-induced deaminase (AID)
247
Q

Agressive B cell tumors that may occur:

A

Burkitt lymphoma
Diffuse large B-cell lymphoma

Both are associated with MYC and BCL6

248
Q

Hodgkin Lymphoma

A

B cell tumor associated with pronounced tissue inflammation

249
Q

Oral Hairy Leukoplakia

A

EBV driven squamous cell proliferation of the oral mucosa

Appears as white patches on the side of tongue

250
Q

HAART stands for:

A

Highly active antiretroviral therapy

251
Q

After using HAART, what happens to T cells?

A

They can return to normal levels after a few years of treatment

252
Q

Complications with HAART treatment:

A
  1. Some people develop IRIS = immune reconstitution inflammatory syndrome
  2. Side effects: lipoatrophy (loss of facial fat), lipoaccumulation (centrally), insulin resistance, elevated lipids
253
Q

Main mechanism behind amyloidosis:

A

Extracellular deposits of misfolded fibrillary proteins are responsible for tissue damage

254
Q

What do the fibrils bind to?

A

Proteoglycans and glycosaminoglycans like heparan sulfate and dermatan sulfate

255
Q

AL (amyloid light chain) proteins are made up of:

A

Complete immunoglobulin light chains or amino-terminal fragments of light chains

Most are lambda light chains, but can be kappa

Secreted by plasma cells

256
Q

AA (amyoid-associated) proteins are made up of:

A

Unique non-Ig proteins made by the liver

Derived from a larger precursor, SAA which causes secondary amyloidosis

257
Q

Beta-amyloid portein (AB) is found in which disease?

A

Alzheimer’s

258
Q

Rarer amyloids include:

A

TTR (transthyretin): mutant forms cause familial amyloidosis, normal forms can cause senile forms

B2-microglobulin: component of MHC Class I, identified as AB2m in amyloidosis

Prion proteins: disease of the CNS

259
Q

Primary Amyloidosis is associated with?

A

Plasma cell disorders (like multiple myeloma) - due to clonal proliferation
Major amyloid protein: AL

260
Q

Secondary/Reactive Systemic Amyloidosis is associated with?

A

Chronic inflammatory conditions; often seen with RA

Major amyloid protein: AA

261
Q

Hemodialysis Amyloidosis is associated with?

A

Chronic renal failure

Major amyloid protein: AB2m

262
Q

Familial Mediterranean Fever

A

Autosomal recessive, autoinflammatory syndrome caused by excess IL-1
Major amyloid protein: AA
Found in Armenian, Sephardic Jews, Arabs

263
Q

In other heredofamilial amyloidosis, what is the major amyloid protein?

A

Mutant TTRs

264
Q

Localized Amyloidosis?

A

Major amyloid protein: AL

265
Q

Endocrine amyloid is associated with?

A

Endocrine tumors, specifically medullary carcinoma

Amyloid proteins are derived from polypeptide hormones

266
Q

Amyloid of Aging (2 types)

A
  1. Senile systemic amyloidosis: deposition of amyloid in the elderly (70s/80s), involvement of the heart
    Amyloid is derived from normal TTR
  2. Cardiac amyloidosis: another form that affects the heart, but amyloid comes from a mutant TTR
267
Q

Amyloid is most often deposited where?

A

In the glomeruli of the kidney

268
Q

Differences in deposition of the spleen:

A
  1. Sago spleen = splenic follicles

2. Lardaceous spleen = walls of splenic sinus

269
Q

Other organs affected in amyloidosis:

A

Macroglossia - enlarged tongue
Carpal ligament in hemodialysis patients
Liver - normal functioning by may be enlarged

270
Q

Most common sites biopsied for amyloidosis:

A

Kidney, rectal, or gingival tissues

Pathology (2 decks)

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