Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MFMII > Primary Immunodeficiencies > Flashcards

Primary Immunodeficiencies Flashcards

1
Q

how do mutant genes contribute to infection?

A

can provide the immune evasion needed by microbes to establish infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

how do mutant genes contribute to immunodeficiency

A

inadequate immune responses due to these genes result in an immunodeficient state and susceptibility to colonization and infection by microbes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what are primary immunodeficiency diseases?

A

inherited defects in genes for components of the immune system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what are secondary immunodeficiency diseases?

A

not due to defective genes, but diseases that develop as a consequence of environmental factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what environmental factors could contribute to secondary immunodeficiency diseases?

A

drug abuse, malnutrition, chronic disease, medication, age

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what are 3 warning signs of primary immunodeficiency?

A
  1. four or more new ear infections within one year
  2. two or more pneumonias within one year
  3. persistent thrush in mouth or fungal infection on skin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what 4 clinical features are suggestive of specific types of primary immunodeficiencies?

A
  1. recurrent bacterial infections
  2. recurrent viral infections
  3. recurrent/chronic infections of soft tissues
  4. angioedema, autoimmunity, recurrent pyogenic and neisserial infections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what primary immunodeficiency is indicated by recurrent bacterial infections

A

defect in antibody mediated (humoral) immunity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what results if there is deficiency in antibody mediated immunity?

A

recurrent bacterial infections involving encapsulated bacteria (strep pneumo, h influenzae, etc) or chronic enteroviral gasterenteritis and giardiasis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what primary immunodeficiency is indicated by recurrent viral infections?

A

defect in cell mediated immunity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what results if there is a deficiency in cell mediated immunity?

A

recurrent viral or mycotic infections like fungal pneumo, mucocutaneous candidiasis, PJP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what primary immunodeficiency is indicated by recurrent/chronic infections of soft tissues?

A

defect in phagocytic function (mostly neutrophils, maybe T cells)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what results if there is a defect in phagocytic function?

A

poor wound healing, soft tissue abscesses and granulomas of liver, lung, spleen, chronic gingivitis, periodontal disease, mucosal ulcerations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what primary immunodeficiency is indicated by angioedema, autoimmunity, recurrent pyogenic and neisserial infections?

A

defects in complement system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what causes angioedema and autoimmunity?

A

defects in regulatory proteins of complement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what causes recurrent pyogenic infections and autoimmunity?

A

defects in early components C1-4 of complement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what causes recurrent neisserial infections and autoimmunity?

A

defects in late components oC5-9 of complement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what causes humoral immunodeficiencies?

A

antibody synthesis is predominantly impaired

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

when do pt develop symptoms of humoral immunodeficiencies?

A

do not develop symptoms until over 1yo because of the disappearance of maternal IgG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

symptoms of humoral immunodeficiencies?

A

recurrent sinopulmonary infections with encapsulated bacterial pathogens like strep pneumo and h influenzae

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

pathogenesis of X linked (infantile) agamaglobulinemia? (XLA)

A

mutation in Bruton’s tyrosine kinase (BTK), which leads to lack of synthesis or production of nonfunctional protein –> lack of B cells in the blood and tissues (and plasma cells)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what does Bruton’s tyrosine kinase do?

A

triggers light chain rearrangement and BCR formation from pro-B cell to pre-B cell
(B cell differentiation, maturation, BCR signaling)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what impact does BTK have on B cells?

A

B cell maturation arrests early in development and there is normal levels of pro-B cells in bone marrow (just don’t have pre-B, immature or mature) HOWEVER lack of B cells (and plasma cells) in blood and tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what impact does XLA have on Ig?

A

there are severe deficiencies in IgM, IgA, IgE, IgG (no plasma cells to release)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

clinical presentation of XLA?

A
  1. recurrent infections in the sinuses and respiratory tract by pyogenic bacteria (strep pneumo, pseudomonas aeruginosa, h influenzae)
  2. otitis media, purulent conjunctivitis, bronchitis
  3. chronic diarrhea via giardia and enteroviruses
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

would immunization against H influenzae work in an XLA pt?

A

no because pt cannot develop their own Ab anyway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

how to diagnose XLA?

A
  1. flow cytometry to determine lack of B cells in peripheral blood (no BCR, no mature B cells)
  2. serology to see IgG, IgA, IgM 3 standard deviations below normal (IgG may be up due to maternal IgG)
  3. DNA sequencing to detect BTK mutation
  4. PCR shows lack of BTK mRNA
  5. western blot shows absence of BTK protein
  6. history of XLA (male relative)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

genetics of XLA

A

X linked

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

pathogenesis of Hyper-IgM syndrome

A

failure of B cells to undergo Ig class switch recombination because of X linked mutation of CD40 ligand or CD40. leads to low levels of IgG, IgA, IgE and HIGH levels of IgM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

what is the consequence of CD40L or CD40 mutation?

A

T cells do not express CD40L upon activation. normally CD40L on TFH cells bind to CD40 on B cells which leads to centroblast proliferation and AID (activation induced cytokine deaminase) for somatic hypermutation and class switch recombination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

when do symptoms for Hyper-IgM syndrome present?

A

during first 5 years of life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

symptoms of hyper-IgM syndrome?

A

increased frequency of pyogenic bacteria because of neutropenia (increases predisposition for pyogenic and opportunistic pathogen)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

what are hyper-IgM syndrome pt at increased risk of infection?

A

PJP pneumonia and chronic diarrhea/malabsorption due to cryptosporidium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

how do diagnose hyper-IgM syndrome?

A
  1. flow cytometry shows numbers of B and T cells are normal to elevated
  2. serology shows normal to high IgM and low levels of IgG and IgA
  3. DNA sequencing shows CD40L mutations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

pathogenesis of combined variable immunodeficiency (CVID)

A

B cell numbers are normal in the blood, but B cells have immature markers and their differentiation into plasma cells is defective.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

mutation of CVID

A
  1. inducible costimulatory molecule (ICOS) which means no IL-21 release and no differentiation into plasma cell
  2. TNF receptor family transmembrane activator and calcium modulator and cyclophilin ligant interactor (TACI) - (activates IL-21 receptor signaling)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

what is a secondary consequence of CVID?

A

1/3 pt show abnormal T cell numbers and function with a 2:1 CD8:CD4 ratio

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

clinical presentation of CVID?

A
  1. recurrent infections of sinuses and respiratory tract by pyogenic bacteria (s pneumo, m cattarhalis, p aeruginosa, h influenzae)
  2. otitis media
  3. chronic diarrhea (giardia)
  4. celiac disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

what is shown on the histology of CVID?

A

lymphoid tissues (LN, spleen, tonsils) may be enlarged due to reticular cell hyperplasia)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

how to diagnose CVID?

A
  1. see an antibody deficiency developing at more than 2yo and poor Ig development following vaccination
  2. flow cytometry shows numbers of B and T cells normal to elevated
  3. serology shows all Ig significantly reduced, IgG and IgA 2 SD below normal (some may only show sig decrease in one isotype)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

what is the most common Ab deficiency?

A

selective IgA deficiency (IgAD)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

pathogenesis of IgAD

A
  1. B cell differentiation abnormalities

2. mucosal immunoregulatory defects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

what does mucosal immunoregulatory defects cause?

A

proinflammatory IgG1/Th1 is produced while IgG4/Th2 and IgA are deficient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

what does B cell differentiation abnormalities cause?

A

defect in secretion of intracytoplasmic IgA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

what defect is present in 1/3 of patients with IgAD?

A

anti-IgA autoantibodies that bind IgA leading to its removal from the liver, high titers can lead to serum sickness and death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

clinical symptoms of IgAD

A

most cases are asymptomatic but sinusitis and diarrhea (giardia) are common

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

what GI diseases are associated with IgAD?

A

celiac disease, pernicious anemia ( B12), ulcerative colitis, enteritis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

what may be more common in pt with IgAD?

A

Rheumatoid Arthritis, SLE, food allergies and asthma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

how to diagnose IgAD?

A

serology will show a pt older than 4yo with IgA of less than 10mg/dL with normal levels at 70-400mg/dL (normal IgG and IgM)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

pathogenesis of transient hypogammaglobulinemia of infancy

A

as maternal IgG is catabolized, the infant IgG production cannot maintain adequate levels.
levels drop to >2 SD from normal age levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

what is significant about a 6mo old child?

A

this is the lowest point of maternal IgG serum concentration and newborn IgG production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

how to treat transient hypogammaglobulinemia of infancy ?

A

generally no treatment is required and it fixes itself

there is no genetic component

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

what immunodeficiencies are humoral immunodeficiencies?

A
  1. infantile agammaglobulinemia
  2. Hyper IgM syndrome
  3. common variable immunodeficiency
  4. IgA deficiency
  5. transient hypogammaglobulinemia of infancy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

what is an important cell-mediated immunodeficiency?

A

DiGeorge syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

pathogenesis of DiGeorge syndrome

A

abnormal migration of neural crest cells that form the 3rd and 4th pharyngeal arches during the 4th week of gestation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

what are the 3rd and 4th pharyngeal arches responsible for?

A

development of thymus, parathyroid gland, heart and face

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

genetic abnormality in DiGeorge syndrome?

A

microdeletion of chromosomal region 22q11.2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

clinical presentation of DiGeorge

A

thymic hypoplasia, T cell deficiency, hypoparathyroidism, hypocalcemia, facial dysmorphism, cardiac defects

59
Q

what physical deformities are found in pt with DiGeorge?

A

short stature, mild to moderate learning difficulties, speech and language delay, eyes slanted up or down, cleft lip and palate, small jaw and upper lip, low set ears or abnormally folding ears

60
Q

what do pt with partial DGS present with?

A

low T cell numbers, elevated CD4:CD8 T cell ratios, low numbers of naive T cells in the blood

61
Q

what do pt with complete DGS present with?

A

no detectable thymus or T cells, usually die because of opportunistic infections

62
Q

what is a thymic shadow?

A

the widening of the superior mediastinal shadow by a prominent thymus seen on frontal film of infants

63
Q

how to diagnose DiGeorge syndrome?

A
  1. flow cytometry/cell counts show extremely reduced CD3+ Tcells (less than 500/microL)
  2. CXR or MRI shows absence or extreme reduction in size of thymic image
64
Q

what is required for a definitive diagnosis of DGS?

A

T cell deficiency/thymic absence WITH 1. cardiac defects 2. hypocalcemia or 3. deletion of 22q11.2

65
Q

what are the combined humoral and cellular immunodeficiencies

A
  1. severe combined immunodeficiency (SCID)
  2. bare lymphocyte syndrome
  3. MHC class II deficiency
  4. ataxia-telangiectasia
  5. wiskott aldrich syndrome (WAS)
66
Q

what 3 problems are associated with SCID?

A
  1. deficiencies in cytokine receptors
  2. defects impacting differentiation of progenitor cells
  3. deficiencies of purine salvage enzymes
67
Q

what is the most common form of SCID?

A

lack of common gammaC chain

is X linked

68
Q

what is the importance of common gammaC chain?

A

this chain is the signaling chain for the receptors of cytokines IL-2, IL-4, IL-7, IL-11, IL-15

69
Q

what is a signaling molecule for gammaC chain receptors?

A

JAK-3, so may see same SCID phenotype if JAK-3 is deficient

70
Q

what occurs if there is a mutation in RAG 1,2,3 genes?

A

these genes are involved in BCR and TCR rearrangements to if they are lacking, no B or T cells

71
Q

what occurs if there is a mutation in ZAP-70?

A

large numbers of CD4 cells but few CD8, and neither proliferate when activated

72
Q

what is omenn’s syndrome?

A

defect of TCR complex or CD3 that produces SCID phenotype

73
Q

what genes are related to differentiation of progenitor cells?

A
  1. RAG 1,2,3
  2. ZAP-70
  3. TCR/CD3
74
Q

what is adenosine deaminase (ADA)

A

immature T cells express high levels of ADA which breaks down adenosine and 2’ deoxyadenosine to inosine

75
Q

what if ADA is deficient?

A

there is an accumulation adenosine and 2’deoxyadenosine in the cell

76
Q

what occurs if 2’deoxyadenosine builds up in the cell?

A

turns into deoxyadenosine triphosphate which inhibits ribonucleotide reductase thereby impairing DNA synthesis == inability to proliferate
ALSO PROMOTES CHROMOSOME BREAKS SO WILL SEE SEVERE LYMPHOPENIA IN SCID PT

77
Q

when do pt present with SCID symptoms?

A

initiate by 4mo

78
Q

survival of SCID?

A

survival beyond first year is rare without aggressive therapy bc no T or B cells – stem cell therapy, exposure to pathogens eliminated (bubble boy)

79
Q

clinical presentation of SCID

A

persistent lung infections especially PJP pneumonia, chronic diarrhea, severe mucocutaneous candidiasis, failure to thrive

80
Q

histology seen for SCID

A

absence of all lymphoid tissue and absence thymic shadow

81
Q

how to diagnose SCID

A
  1. flow cytometry shows severely low numbers of lymohocytes (immature B and T cells)
  2. serology shows decrease in all Ig
  3. absent response to skin tests and activation of mononuclear cells to mitogens
  4. CXR or MRI shows absent thymic shadow and all lymphoid tissue
82
Q

what is the definitive diagnosis of SCID

A

genetic evaluation of the defect underlying SCID phenotype

gammaC, ZAP70, TCR, CD3, RAG

83
Q

pathogenesis of bare lymphocyte syndrome

A

deficiency in MHC class I = HLA-A, HLA-B, HLA-C and beta2 microglobulin along with a loss of expression of TAP-1 and 2 or TAPbinding protein

84
Q

what does TAP-1 and 2 do

A 
transporters associated with Ag processing, required for construction of MHC class I molecules. without these molecules no Ag can enter the ER for leading onto the alpha chain or MHC class I. 
NO MHC I ON CELL SURFACE AND NO CD8 IF NO TAP
85
Q

clinical presentation of bare lymphocyte syndrome?

A

persistent infections are common especially with PJP and pyogenic bacteria

86
Q

how to diagnose bare lymphocyte syndrome?

A
  1. flow cytometry shows lymphopenia, poor mitogenic responses of CD8
  2. serology shows decrease in all IgG
87
Q

definitive diagnosis of bare lymphocyte syndrome?

A

genetic evaluation of the defect underlying. decreased CD8, decreased all Ig means MHC I

88
Q

what HLA molecules are deficient in MHC class II deficiencies?

A

HLA-DP
HLA-DQ
HLA-DR

89
Q

pathogenesis of MHC class II deficiencies?

A

mutations are associated with transcription factors that promote MHC class II gene expression (CIITA, RFX)

90
Q

what is seen in MHC class II deficiency?

A
  1. nearly absent CD4 cells

2. lack of differentiation of B cells into Ab producing plasma cells

91
Q

how to treat MHC II deficiency?

A

stem cell transplant required or death occurs by 2nd decade of life

92
Q

clinical presentation of MHC II deficiency?

A

persistent infections common esp with candida albucans, cryptosporidium parvum leading to malabsorption and failure to thrive. pulmonary infections also frequent.

93
Q

diagnosis of MHC II deficiency?

A
  1. flow cytometry shows normal CD3+ T cells (inc. CD8) but extremely low CD4 T cells (nearly absent)
  2. serology shows extremely low all Ig
94
Q

definitive diagnosis MHC II deficiency?

A

genetic evaluation

95
Q

pathogenesis of ataxia telangiectasia

A

deficiency of DNA repair enzymes (ATM responsible for double strand break repair)

96
Q

what does ATM mutation result in ?

A

enzyme deficiency results in generalized defect in tissue maturation with particular impact upon brain capillary vessels (causes dilation)

97
Q

what does dilation of brain capillaries impact in ataxia telangiectasia?

A

involve cerebellum, causing motor difficulties (ataxia)

98
Q

histology of ataxia telangiectasia

A

thymic hypoplasia

99
Q

clinical presentation of ataxia telangiectasia in early childhood

A

progressive cerebellar ataxia (impaired balance and coordination) and telangiectasia that first appears as dilated conjunctival vessels (bloodshot eyes)

100
Q

clinical presentation of ataxia telangiectasia in late childhood?

A

recurrent sinopulmonary infections initiate leading to bronchiectasis

101
Q

diagnosis of ataxia telangiectasia

A
  1. flow cytometry shows a T cell deficiency (didn’t develop right)
  2. serology shows decrease in all Ig (double stranded break repair is important in B cell development)
102
Q

pathogenesis of Wiskott Aldrich Syndrome (WAS)

A

loss of function mutation or lack of synthesis of WASP (wiskott aldrich syndrome protein)
X LINKED DISEASE

103
Q

what does WASP do?

A

plays role in actin polymerization and cytoskeleton rearrangement - helps keep cells size and even distribution of shape

104
Q

what occurs if WASP is deficient?

A

cells demonstrate abnormal size, shape and function, which is most apparent in platelets and lymphocytes

105
Q

what do platelets look like in WAS?

A

small and aggregate, so they are destroyed in the spleen causing thrombocytopenia (WAS platelets look like specks)

106
Q

what other conditions are seen in WAS and why?

A

severe eczema and autoimmunity because of abnormal expression of Th2 responses (cytokines)

107
Q

clinical presentation of WAS?

A

eczema, thrombocytopenia, frequent infections, bleed and bruise easily l

108
Q

what viral infections are seen most often in WAS?

A

HSV, VZV, molluscum contagiosum

109
Q

what bacterial infections are seen most often in WAS?

A

pygogenic bacteria like strep pneumo, h influenzae, neisseria meningitidis

110
Q

what occurs later in life in WAS patients?

A

more opportunistic infections develop

111
Q

what autoimmune conditions are often seen in WAS patients?

A

autoimmune hemolytic anemia, rheumatoid arthritis

112
Q

what is the most frequent cause of death in WAS patients?

A

hemorrhage

113
Q

diagnosis of WAS?

A
  1. flow cytometry shows normal lymphocyte counts
  2. serology shows abnormal shaped and small platelets and thrombocytopenia, decreased IgM (other isotypes may be normal or decreased)
  3. ELISA shows lymphocyte function decline over time
114
Q

definitive diagnosis of WAS

A

genetic evaluation of WASP for mutation or absence of WASP mRNA

115
Q

what are the phagocyte deficiencies ?

A
  1. chronic granulomatous disease

2. Chediak-Higashi syndrome

116
Q

what is the most frequent phagocyte deficiency?

A

chronic granulomatous disease, but it is still rare

117
Q

pathogenesis of CGD

A

X linked form is the result of a mutation in gp1991phox (alpha chain phosphoprotein of cytochrome b558) protein

118
Q

what is gp1991phox protein

A

alpha chain phosphoprotein of cytochrome b558 which provides electron for NADPH to convert O2 to superoxide (ROS)

119
Q

what is the result of mutation of gp1991phox protein?

A

NADPH oxidase is not functional, so there is a failure to generate superoxide and H2O2, so intracellular killing of pathogens is defective. both neutrophils and macrophages affected

120
Q

what cell type is affected in CGD?

A

macrophages and neutrophils

121
Q

what diseases are CGD highly susceptible to?

A

catalase positive bacteria like staph aureus, staph epidermidis, klebsiella, salmonella, nocardia

122
Q

clinical presentation of chronic granulomatous disease?

A

recurrent bacterial and fungal infections, frequently in lungs, LN, liver, skin and soft tissues. will present with generalized lymphadenopathy and hepatosplenomegaly.

123
Q

where are infections most frequent in CGD?

A 
lungs
LN 
liver
skin 
soft tissues
124
Q

what are CGD infections characterized by?

A

formation of microabscesses and granulomas

125
Q

what is commonly seen on exam in CGD?

A

generalized lymphadenopathy and hepatosplenomegaly

126
Q

what are the results of tissue cultures in CGD?

A

microbes are sequestered so tissue cultures are negative but Ig are elevated

127
Q

diagnosis of CGD?

A
  1. flow cytometry shows oxidative burst by neutrophils and expression of NADPH or products
  2. serology shows increased Ig (IgA and/or IgG and/or IgM)
128
Q

pathogenesis of Chediak-Higashi syndrome

A

deficiency of lysosome trafficking regulator (LYST), so phagosomes do not fuse with giant secondary lysosomes

129
Q

what does LYST do?

A

lysosome trafficking regulator is essential for assembly of cytoplasmic granules and their fusion with phagosomes to form the phagolysosome, also release of melanin from melanosomes

130
Q

what is the result of deficient LYST?

A

phagosomes do not fuse with giant secondary lysosome, so defect leads to multiple lysosome fusion with few enzymes, and lack of melanin transport and pigmentation

131
Q

what cells are affected by LYST

A

intracellular killing by phagocytes is slow and inefficient, and NK cell function is impaired

132
Q

what do pt with Chediak-Higashi syndrome present

A
  1. oculocutaneous albinism (light colored eyes, skin, hair)
  2. unexplained fevers and peripheral neuropathy (seizures, weakness, gait disturbance)
  3. bruise easy (abn platelets)
  4. recurrent bacterial and viral infections leading to hepatosplenomegaly and lymphadenopathy
133
Q

how to diagnose Chediak-Higashi syndrome

A
  1. see giant lysosomes in neutrophils under microscopy

2. ELISA = impaired killing by phagocytes

134
Q

what molecules are impacted in early complement activation deficiencies?

A

lack of synthesis of C1, C2, and/or C4

135
Q

infections that early complement deficiencies are susceptible to?

A

pyogenic bacteria

136
Q

what do all complement deficiencies’ lymphoid tissues, B cell and Ig look like?

A

Lymphoid tissues are normal
B cell numbers are normal
Ig levels are normal to elevated

137
Q

what autoimmune conditions are pt with early complement deficiencies susceptible to?

A

SLE (systemic lupus erythematosus)

138
Q

what is the genetics of early complement activation deficiencies

A

autosomal dominant

139
Q

what is the genetics of C3 deficiency?

A

autosomal recessive

140
Q

what molecules are impacted in C3 deficiency?

A

lack of synthesis of C3

141
Q

what infections are C3 deficient pt susceptible to?

A

pyogenic bacteria

142
Q

what autoimmune conditions are pt with C3 deficiencies susceptible to?

A

vasculitis, glomerulonephritis

143
Q

what molecules are impacted in late complement deficiencies?

A

lack of synthesis of C5,C6, C7, C8 and/or C9.

144
Q

what infections are late complement deficiencies susceptible to ?

A

polysaccharide encapsulated bacteria, especially neisseria. bc these need Ab to lyse the bacteria. (MAC complex)

MFMII (29 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions