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Flashcards in Exam 1 pt. 2 Deck (192):
1

a failure of the immune system to respond to usual stimuli

immunodeficiency

2

how is primary and secondary immunodeficiency obtained

primary- inherited
secondary- acquired

3

Exaggeration of the normal immune response to foreign substances

hypersensitivity

4

Immune response to self-antigens

autoimmunity

5

defects responsible for humoral immunodeficiencies

1. Infancy
2. X-liked Agammaglobulinemia
3. Common variable immune deficiency
4. Hyper IgM syndrome
5. Selective IgA deficiency

6

Infancy immunodeficiencies

-at birth, all circulating antibodies are maternal IgG
-3-6 months baby begins producing their own immunoglobluins
-mother’s antibodies decline before baby can make their own**
-Infants don't make memory T cells therefore need boosters!

7

another name for Bruton disease

X-liked Agammaglobulinemia (XLA)

8

Failure of cells to mature into B-cells, resulting in no plasma cells, low B-cells and no light chains produced for low antibody levels

XLA

9

what immunodeficiency initally presents with recurrent bacterial and viral infection sof the respirtatory and GI tracts and ears between 4months-2 yrs

XLA

10

treatment of XLA

replacement of pooled immunoglobulins
(IVIg)

11

B cell level normal but no plasma cells and low concentration of antibodies (IgG, IgA, IgM), autosomal

Common variable immune deficiency (inherited or acquired)

12

diagnosis and treatment of common variable immune deficiency

-diagnosis late childhood, early adulthood
-tx w/ replacement of pooled immunoglobulins

13

normal levels of IgM but can’t class switch from lack of CD40 on T cells and no other immunoglobulins present

Hyper-IgM syndrome

14

treatment of Hyper-IgM syndrome

-replacement of pooled immunoglobulins
-bone marrow transplant

15

most common primary immunodeficiency

Selective IgA deficiency
1:700 people

16

-only IgA is low and IgM and IgG levels are normal or high
-can have anaphylaxis to IgA introduced

Selective IgA deficiency

17

presents with increased sinus, respiratory, GI infections/inflammation and pneumonia

Selective IgA deficiency

18

defects responsible for congenital cell-mediated immunodeficiency

1. Severe combined immunodeficiency (SCID)
2. Thymic hypoplasia

19

defects responsible for phagocytosis

1. chronic granulomous disease
2. Chediak-Higashi syndrome

20

impaired T cell function often secondary impaired B cell function

SCID

21

x-linked: mutation in cytokine receptors (50%)
or
autosomal recessive: Chr 20, mutation in adenosine deaminase necessary for purine salvage (20%)

SCID

22

what happens if your body cannot recycle purine products

SCID
accumulation of purine is toxic to lymphocytes

23

presents in first weeks or months of life with recurrent infections, opportunistic infections, especially GI and respiratory

SCID

24

treatment of SCID

bone marrow transplant

25

another name for DiGeorge Syndrome

Thymic Hypoplasia

26

Underdevelopment of 3rd and 4th pharyngeal pouches in fetal development affecting:
-Thymus: low T cell education, low levels of T cells
-Parathyroid: calcium regulation, hypocalcemia
-Cardiovascular and facial defects

Thymic hypoplasia

27

autosomal dominant disease, Chr 22 gene deletion

Thymic hypoplasia

28

presents with suspectibilitiy to fungal and viral infections

thymic hypoplasia

29

treatment of thymic hypoplasia

fetal transplant of thymic tissue or BMT
-can improve w/ age if you make it to age 5

30

x-linked or autosomal where phagocytes can’t make O2 radicals, gp91 of NADPH oxidase defective, and granuoma formation

chronic granulomatous disease

31

presents at about 3 months with recurrent skin infection by bacteria or fungus

chronic granulomatous disease

32

lysosome traffic regulator gene mutation (LYST) causing cytoplasmic granules in leukocytes and platelets

Chediak-Higashi Syndrome

33

disordered vesicle transport:
-impaired fusion of lysosomes and phagosomes
-impaired secretion by cytotoxic T cels, NK cells and platelets (bleeding problems)
-Melanin not appropriately transferred to keratinocytes

Chediak-Higashi Syndrome

34

presents with albinism, and silvery hair with large granules

Chediak-Higashi Syndrome

35

large granules impair:

1. impair fusion
2. impair degranulation
3. impair chemotaxis`

36

a primary complement pathway deficiency (alternative pathway) because missing regulators that tell C3 not opsonize own RBCs. So RBC get lysed by MAC(C5-C9)--> hemoglobin is released in urine

paroxysmal nocturnal hemoglobinuria

37

presents with anemia and red/brown urine

paroxysmal nocturnal hemoglobinuria

38

genetic mutation PIGA, Chr X
-dominant in the mutant clone

paroxysmal nocturnal hemoglobinuria

39

unable to synthesize the glycosylphosphatidylinositol anchor (GPI anchor)

paroxysmal nocturnal hemoglobinuria

40

absences of GPI anchor results in absences of what 3 proteins:

1. DAF/CD55
2. HRF
3. MIRL/CD59

41

Describe the spectrum of clinical presentations for patients with AIDS
(4)

-Begins with acute infection of flu-like symptoms, though symptoms may not appear for years (latent phase).
-Next can get lymphadenopathy, diarrhea, weight loss or meningitis, encephalopathy, neuropathy and dementia.
-Opportunistic infections occur (CMV, HSV, Pneumocystis pneumonia, toxoplasmosis, fungi, unusual mycobacteria, GI cryptosporidium.
- Also tumors – Kaposi’s sarcoma, non-Hodgkin’s lymphoma, cervical cancer.

42

causes of secondary immunodeficiencys

1. Loss of immunoglobulins (through nephron and urine or GI)
2. Impaired synthesis of immunoglobulins (from malnourishment, loss bone marrow, suppression of bone marrow or iatrogenic)

43

4 types of hypersensitivity

1. Immediate (type 1)
2. Antibody-Mediated (type 2)
3. Immune complex (T3)
4. T-Cell mediated (T4)

44

2 IgE bound to mast cells via Fc portion
-bind allergen and signal release of pre-formed inflammatory mediators (histamine, chemokines, preoteases, heparin) immediately

Type 1 (immediate)

45

what complement componenets are involved in type 1 hypersensitivity

C3a and C5a activate mast cells

46

ex of what hypersensitivity?
asthma
anaphylaxis
allergic reaction

immediate, T1

47

increase synthesis of prostaglandins and leukotrienes--> bronchoconstriction and abudant mucus secretion

asthma

48

drugs or metabolites bind normal body antigens making them look abnormal (hapten). This triggers complement cascade on cell and local tissue damage

Antibody-mediated hypersensitivity (T2)

49

ex of what hypersensitivity?
-drug-induced hemolytic anemia
-thrombocytopenia
-leukopenia

antibody mediated

50

ex of what hypersensitivity?
-pemphigus vulgaris--> antibody to dermal junction protiens
-good pasture--> antibody to glomerular and respiratory basement membrane

antibody mediated

51

antibodies can be autoantibodies to normal cellular protiens (mechanism for autoimmune diseases)
-infection causes mimicry

antibody mediated

52

Persistant deposition of antigen-antibody complexes in tissue.
- These can activate complement that destroys normal tissue or lodge in renal basement membrane

immune complex hypersensitivity, T3

53

ex. of hypersensitivity?
-tetanus, anti-venom
-post-streptococcal glomerulonephritis, lupus

immune complex hypersensitivity, T3

54

TH1 cells in skin were previously exposed to an antigen and upon repeat exposure a delayed rxn occurs. Inflammation, recruitment of lymphocytes and macrophages.

T-cell mediated, T4

55

ex. of hypersensitivity?
-tuberculin reaction (PPD)
-contact dermatitis
-poison ivy/oak

T-cell mediated, T4

56

Describe the mechanisms by which the body encourages tolerance of self-antigens (5)

1. hiding them from blood or lymph (vitreous humor, sperm)
2. educating T cells in thymus and B cells in bone marrow
3. Self-reacting B cells don’t have a T-helper to activate them
4. No co-stimulation of APCs by T cells that react to self (T cell anergy)
5. T-regs can secrete anti-inflammatory cytokines

57

How can tolerance fail and autoimmunity develop (7)

1. Genetic susceptibility = certain HLA types
2. molecular mimicry (bacteria cross reactivity)
3. T-regs are down regulated
4. APCs induced to express co-stimulatory molecules
5. tissue damage letting out antigens that were hidden
6. or local inflammation causes protein break-down that makes new antigen from dead cells
7. imperfect lymphoctye education

58

what predisposes you to autoimmunity

1. genetics
2. environmental factors (drugs, estrogen, UV radiation, mimicry)

59

HLA B27 predisposes you to

ankylosing spondylitis

60

HLA DR2 predisposes you to

Goodpasture syndrome, SLE

61

HLA DR3 predisposes you to

Hashimoto's throiditis, myasthenia gravis, SLE

62

HLA DR3 and DR4 predisposes you to

DM 1

63

antibodies found in systemic lupid erythematous

1. Antinuclear antibodies (DNA, histones, nucleolar antigens, nonhistone proteins bound to nucleic acids)
2. autoantibodies to RBC, platelets, and some WBCs.
3. antiphospholipid antibodies (causes thrombosis

64

antibodies found in sclerosis

1. antinuclear antibodies
2. Autoantibodies to antitopoisomerase/anti-SCL 70 and anticentromere
3. Autoantibodies to skin and connective tissue (makes a lot of collagen)

65

How are free radicals made

1. Generated by oxidative stress
2. radiation exposure
3. production by mitochondria
4. production neutrophils and macrophages

66

Metabolic pathways that remove free radicals

1. superoxide dismutase to make H2O2 which catalase makes to H2O
2. Other antioxidants include Glutathione peroxidase

67

Apoptosis or Necrosis?
pathologic only

necrosis

68

Apoptosis or Necrosis?
occurs in cell groups

necrosis

69

Apoptosis or Necrosis?
it is energy dependent

apoptosis

70

Apoptosis or Necrosis?
occurs in single cells

apoptosis

71

Apoptosis or Necrosis?
fragmentation of DNA by endonucleases, protein degradation

apoptosis

72

Apoptosis or Necrosis?
lysosome intact

apoptosis

73

Apoptosis or Necrosis?
lost cell membrane intergrity

necrosis

74

Apoptosis or Necrosis?
impaired ion homeostasis, cytoskeletal degradation, nonspecific DNA breakdown

necrosis

75

Apoptosis or Necrosis?
cell shrinkage, chromatin condensation, cell fragmentation

apoptosis

76

Apoptosis or Necrosis?
cell swelling, blebs, lysis, increased eosinophilia

necrosis

77

Apoptosis or Necrosis?
presents with inflammation

necrosis bc unconfined leakage

78

most common form of coagulative necrosis

infarcts (loss blood supply)

79

type of necrosis?
-makes ghost cells with loss of nuclear staining (karyolysis) and loss of cytoplasmic detail
-Inflammatory infiltrate and then a loss of structure of cells

coagulative necrosis

80

causes of caseous necrosis

tuberculosis

81

type of necrosis?
Amorphous cell debris, structureless like cheese. Often with fungi and bacteria

caseous necrosis

82

type of necrosis?
Enzymes from WBC in response to infection, with lack of support stroma in brain*

liquefactive necrosis

83

what happens to tissue in liquefactive necrosis

liquefies into empty space

84

type of necrosis?
only seen microscopically leaking from damaged vessel walls, deposition of immune complexes and fibrin from damaged vessel walls.

fibrinoid necrosis

85

type of necrosis?
like coagulative but with added putrefaction due to bacteria. Black is from iron (dead tissue that becomes infected)

Gangrenous necrosis

86

type of necrosis?
enzymatic lysis of fatty acids + Ca2+ = soap. Inflammation and macrophages come to clean it up causing inflammation (often in pancreas)

fat necrosis

87

types of necrosis (6)

1. Coagulative
2. Caseous
3. Liquefactive
4. Fibrinoid
5. Gangrenous
6. Fat

88

calcification due to cell injury with normal levels of blood calcium

Dystrophic calcification

89

ex of dystrophic calcification

1. atheromatous plaques
2. abnormal heart valves
3. necrosis can’t regulate intracellular Ca2+).

90

psammoma body is indicative of

dystrophic calcification

91

calcification from calcium in normal tissue with elevated blood calcium levels (hypercalcemia)

metastatic calcification

92

Occurs from increased parathyroid hormone, hyperparathyroid tumors, destruction bone (Paget’s), Vitamin D disorders (sarcoidosis, intoxication), renal failure (phosphate retention)

metastatic calcification

93

types of systemic amyloid

1. AL amyloid
2. AA amyloid
3. Alpha-beta amyloid (AB)

94

fibrils of protiein
-which layer as B-sheet chains
-chains wound together to form fibrils

amyloid

95

what is amyloid stained with

congo red

96

extracellular amyloid deposition that disrupts normal function

amyloidosis

97

most common type of amyloid

AL amyloid

98

from too many antibodies made by plasma cells* (light chains)

AL amyloid

99

cerebral plaques in Alzheimer disease

AB amyloid

100

serum amyloid produced by liver when there is inflammation anywhere in body

AA amyloid

101

what amyloid is specific to the brain

AB amyloid

102

genetic defects in SAA protein favor precipitation of what amyloid

AA amyloid

103

effects prom amyloidosis

1. effects kidney filtration
2. cardiac abnormalities/arrhythmias
3. enlarged liver and spleen

104

types of genetic abnormalities which can lead to genetic diseases

1. Abnormal number of chromosomes
2. Deletion/duplication
3. Disorder of gene expression
4. Mutation or alteration in single gene
5. Repeat expansion

105

this type of genetic abnormality are usually syndromic (consist of constellation of findings which are characteristic)

Chromosomal abnormalities

106

Are the gain or loss of most chromosomes usually viable?

no
~50% of spontaneous abortuses have an abnormality in chromosome number

107

having 3 chromosomes

trisomy

108

having 1 chromosome

monosomy

109

having an extra copy of every chromosome is

triploidy

110

Complications associated with trisomy

*higher chance of miscarriage

111

how does trisomy happen?

non-disjunction during meiosis where sister chromosomes don't separate like they should

112

clinical features and possible complications associated with trisomy 21

-down syndrome
-CHD
-Early Alzheimer disease
-GI atresia
-Risk for acute leukemias
-facies

113

most common live-born abnormality of chromosome number

trisomy 21
*almost all are true trisomy

114

-Edward Syndrome
(most die in neonatal)
low ears, micrognathia, abnormal hands and feet

Trisomy 18

115

-Patau syndrome
cleft lip and palate, polydactyly, poor brain development

Trisomy 13

116

X, very short, neck webbing, often mosaics so cause 1/3 ammenorrhea

45, X
Turner Syndrome

117

XXY, long legs, female like shape and breasts, hypogonadism (infertility)

47, XXY
Klinefelter syndrome

118

XXX, some learning problems, puberty earlier

XXX syndrome

119

XYY, delay learning, larger than average

XXY Syndrome

120

common laboratory methods to evaluate chromosomal number and microdeletions

1. FISH (Fluorescence in situ hybridization
2. aCGH (array comparative genomic hybridization)
3. Karyotype
4. PCR
5. Nex gene sequencing

121

characterized by deletion a chromosome or part of a chromosome

deletion of a set of genes

122

deletion of an area of 22q

DiGeorge Syndrome

123

deletion of an area of 5p

Cri-du-chat syndrome

124

deletion of an area of 17p

Smith-Magenis Syndrome

125

arget DNA tagged with fluorescent tag and studied under a fluorescent microscope

FISH

126

molecular cytogenetic method for analysing copy number variations (CNVs) relative to ploidy level in the DNA of a test sample compared to a reference sample, without the need for culturing cells

array comparative genomic hybridization (aCGH)

127

disorder where some genes are always turned on or off from a specific parent (imprinting)

disorder of gene expression

128

-Non-disjunction leads to a trisomy zygote
-if the early trisomic zygote is "rescued" and leads to 2 chromosomes from the same parent, this can result in what kind of disorder

imprinting disorder

129

imprinting disorders (2)

1. Prader-Willi Syndrome
2. Angelman Syndrome

130

if both chromosome 15's are from mother, that is functionally equivalent to a parental deletion (loss of the imprinting effects of the paternal gene)- leads to

Prader-willi syndrome
(PWS)

131

presents with:
short stature, small hands and feet
hyperphagia (obesity)
mild mental retardation

Prader-Willi Syndrome

132

if both chromosome 15's are from father, that is functionally equivalent to a maternal deletion (loss of the imprinting effects of the maternal gene)- leads to

Angelman Syndrome

133

presents with:
severe mental retardation-poor speech development
ataxia (the loss of full control of bodily movements), seizures
inappropriate laughter, always smiling

Angelman Syndrome

134

Disorder: Change in DNA sequence leads to change in RNA which leads to change in the protein

gene mutation or alteration in a single gene

135

point mutation that results in premature stop codon

nonsense mutation

136

point mutation that causes a change in 1 amino acid

missense mutation

137

point mutation that changes the reading fraem (usually results in premature stop later)

frameshift mutation

138

only need to inherit ONE copy of bad gene to get disease. Often structural protein- changes how it interacts with other proteins

Autosomal dominant

139

need to inherit TWO copies of the mutated gene to get disease. often enzyemes- become nonfunctinoal

autosomal recessive

140

what type of inherited genetic disorder?
Achondroplasia
Marfan syndrome (Fibrillin)

autosomal dominant

141

what type of inherited genetic disorder?
Familial Adenomatous Polyposis
BRCA 1/2 Familial Breast Cancer Syndrome
Neurofibromatosis

autosomal dominant

142

what type of inherited genetic disorder?
cystic fibrosis
Tay-Sachs
Sickle cell anemia
Thalassemia

Autosomal recessive

143

what type of inherited genetic disorder?
Phenylketonuria
Galactosemia
Glycogen storage diseases
Lysosomal storage diseases

autosomal recessive

144

Discuss population screening for CF

-CF screening offfered to all women/couples planning pregnancy
-screening detects 23 most common CF mutation (over 1000 mutations known)
-A NEGATIVE screening result reduces the likeelihood that a patient is a carrier, but does not make it zero***

145

what causes cystic fibrosis

mutation in CFTR, the gene that encodes for a chloride transport channel in the cell membrane
- defect in this channel leaddsto thick secretions in lung and pancreas (therefore chronic bronchiectaiss, lung infections, pancreatitis)

146

what type of inherited genetic disorder?
Hemophilia
Fragile X
Duchenne Muscular Dystrophy

X-linked disease

147

How does repeat expansion occur

Regions of genes have repeated sequences, some right before or in genes, when DNA is replicated, easy to make slippage errors and create more repeats

148

what does it mean? Repeat expansion deases exhibit anticipation

anticipation
-repeat gets longer in next generation and more severe disease
-can be preferentially passed by 1 parent

149

what type of inherited genetic disorder?
Fragile X syndrome
Huntington Disease
Myoclonic Dystrophy
Spinocerebellar Atrophy
Freidrich Ataxia

Repeat expansion

150

next to FMR1, over 200 repeats is bad and lead to down regulation of gene causing long face and mandible, large ears, macro-orchidism (abnormally large testes)***

Fragile X syndrome

151

above 35 repeats bad WITHIN a gene, leads to large non-functional protein that causes neurodegenerative disease (progressive motor, cognitive, and psychiatric abnormalies)

Huntington Disease

152

number of mutations needed for "pre-mutation" of Huntington Disease

27-35

153

What type of genetic mutation causes Huntington Disease

-Repeat expansion
-Autosomal Dominant

154

start with small amount of DNA and amplify using primers

PCR

155

designed to sequence many genes at the same time

Next Generation Sequencing
**A methodology (platform) not a test

156

pros and cons of next generation sequencing

pros: (can do a lot more faster)
-simutaniously evaluate many genes
-reduced turnaround times compared to sequential testing
Cons:
-may get incidental findings
-relatively new technology in clinical diagnostics

157

common causes of acute inflammation (5)

1. Infection (bacterial, viral, funal)
2. Hypersensitivity
3. Physical agents (trauma radiation, thermal damage)
4. Chemicals
5. Other reasons for necrosis (infarction)

158

key players in acute inflammation

neutrophils

159

ex of hypersensitivity rxns that cause acute inflammation

allergic rhinitis, drug rxn, serum sickenss, TB rxn

160

classic symptoms of acute inflammation.

-rubor (red)
-calor (warm)
-tumor (swollen)
-dolor (painful)
-functio laesa (impaired function)

161

describe progression of acute inflammation (5 steps)

-Hyperemia due to relaxation of precapillary sphincters and vasodilation from histamine, PGE, and NO
-increased vascular permeability (endothelial cells contract and create gaps)
-Exudation
-slowing of blood flow (stasis)
-movement of cells into plasmatic zone

162

how does hyperemia relate to acute inflammation sx

warmth and redness from vasodilation and increased blood flow from histamines

163

how does increase vascular permeability relate to acute inflammation sx

Histamine leaks out of damaged endothelial cells and creates toxins, heat, and corrosive chemicals

164

how does exudation relate to acute inflammation sx

movement of fluid and proteins into the tissue cause edema

165

how do neutrophils get into the tissue during acute inflammation (4 steps)

1. Margination
2. Adhension
3. Transmigration- move through vessel wall
4. Chemotaxis- attracted to injury site

166

loss plasma and slowing flow, neutrophils move to edge of vessel

margination

167

surface adhesion molecules on endothelium are expressed more and neutrophils roll until stably adhered

adhension

168

three steps of phagocytosis

1. Molecule is flagged or opsonization and neutrophil adheres to it
2. Engulfment by specific binding
3. Degradation (phagolysosome creates oxygen radicals, H2O2, bleach or lysozyme, acid, lactoferrin to kill)

169

Subtypes of acute inflammation

1. Suppurative/purulent
2. serous
3. Fibrinous

170

Subtype of acute inflammation?
mostly cellular components, often infectious (pus)

suppurative/purulent

171

Subtype of acute inflammation?fluid with large amounts of fibrinogen an dothe proteins

fibrinous

172

Subtype of acute inflammation?
low protein fluid, often "sterile inflammation"

serous

173

beneficial effects of inflammation

1. vasodilation (increase delivery of nutrients)
2. edema (dilute toxins)
3. phagocytosis

174

harmful effects of inflammation

1. digestion of normal tissue
2. swelling (loss of anatomic fxn/ impaired flow)
3. predisposition to infection

175

3 type of cells

1. Labile
2. Stable
3. Permanent

176

what type of cell?
high rate of division, stem cells present, completely recover
-favor resolution/regeneration

labile

177

what type of cell?
don’t divide after birth, minimal stem cell, no recovery
-favor organization/repair

permanent

178

what type of cell?
slow division, stem cells present, limited recovery from injury
-favor organization/repair

stable

179

ex of what type of cell?
cardiac muslce
neurons

permanent

180

ex of what type of cell?
GI tract
skin
bone marrow

labile

181

ex of what type of cell?
hepatocytes
renal tubular cells

stable

182

complete restoration of tissue, usually from minimal damage, labile** tissue, good vascular drainage.

resolution

183

Growth of granulation tissue (capillaries, fibro and myofibroblast, collagen) and some scars, usually tissue with poor regeneration (stable/permanent cells**) or large area of damage, poor drainage and lots of fibrin present

organization

184

these factors favor:
1. minimal tissue damage
2. tissue with high regenerative capacity
3. rapid removal of causa agent
4. good local vascular drainage

resolution

185

these factors favor:
1. tissue with limited regenerative capacity
2. large amounts of fibrin
3. large area of damage
4. poor local vascular drainage

organizaiton

186

Primary causes of chronic inflammation

-infectious disease
-foreign body reaction
-autoimmune
-granulomatous dsiease (chrohns, sarcoid)

187

Steps from an injury to the formation of a scar

1. usually stable or permanent cells
2. granualtion tissue
3. proliferation of capillaries and macrophages come
4. fibroblasts and myofibroblasts
5. Collagen secretion
6. Wound contraction
7. formation of a scar

188

Explain the reasons that acute inflammation may progress to chronic inflammation

1. Usually begins as suppuration (abscess) or organization but no resolution of problem
2. offending agent is not removed or there are repeated episodes of acute inflammation

189

Subtype of chronic inflammation in which macrophages are the most promiment cell, lymphocytes are still present

granulomatous inflammation

190

cells and mediators involved in acute inflammation

Neutrophils, eosinophils, basophils, mast cells, histamine, prostaglandins, leukotrienes, IL-1, TNF

191

cells and mediators involved in chronic inflammation

Lymphocytes, plasma cells, monocytes, and macrophages

192

chronic inflammation always leads to ___ and can lead to ____

always leads to fibrosis
can lead to amyloidosis