Immunodeficiencies Flashcards
(118 cards)
1
Q
Asplenia increases susceptibility to
A
encapsulated bacteria
2
Q
asplenic pt.s should be counseled to…
A
- receive vaccines for encapsulated bacteria
2. take antibiotics prophylactically in they begin to experience symptoms of respiratory infection
3
Q
Dx of NK cell deficiency
A
flow cytometry
4
Q
Viral susceptibilities with NK defects
A
varicella zoster
herpes virus
cytomegalovirus
epstein-barr virus
5
Q
Bacterial susceptibilities with NK defects
A
mycobacterium (opportunistic pathogens)
6
Q
fungal susceptibilities with NK defects
A
trichophytan
7
Q
NEMO deficiency…
A
defect in protein IKKgamma required for NFkB–> leads to lack of expression of cytokine/chemokines and leads to increases susceptibility of infection
8
Q
Defects in NFkB signaling affect which cell signaling path way
A
(INNATE SIGNALING PATHWAY)–> via TLR’S
9
Q
Susceptibilities associated with NEMO
A
recurrent bacterial and viral infections
10
Q
Tx for NEMO
A
bi-weekly injections of gamma globulin from a healthy donor; bone marrow transplant
11
Q
LAD deficiency
A
defect in CD18 (subunit of LFA-1) that results in defective migration of phagocytes into tissues
12
Q
LAD def. –> susceptible to
A
encapsulated bacteria
13
Q
clinical indicator of LAD deficiency
A
delayed sloughing of umbilical cord
14
Q
CGD is caused by
A
defective NADPH oxidase and inability to perform the oxidative burst–> cannot make toxic ROS’s
15
Q
CGD leads to
A
chronic granuloma formation –> inability to kill phagocytosed bacteria
(chronic bacterial and fungal infections)
16
Q
Glucose 6 phosphate dehydrogenase deficiency
A
defective G6-P leading to impaired oxidative burst–> very similar effects as CGD
17
Q
MOP deficiency
A
inability to make HOCL–> ineffective bacteria killing
18
Q
Chediak Higashi syndrome
A
defective vesicle fusion–> recurrent/ persistent bacterial infections and formation of granulomas
19
Q
Neutropenia (basic definition)
A
low neutrophil count
20
Q
susceptibilities with neutropenia
A
bacterial infections especially normal flora microbes
21
Q
Cause of severe congenital Neutropenia (kostmann syndrome)
A
AR defects in GM-CSF or its receptor GM-CSFR
22
Q
Cause of cyclic neutropenia
A
defect in the gene that encodes elastase (ELA-2)
this disease is cyclic every 2-4 weeks and alsts about a week
23
Q
Neutropenia causes
A
elevated levels of ALL ANTIBODY ISOTYPES
*continued activation of B cells–> infections never really gets cleared
24
Q
Primary immunodeficiencies with associated neutropenias
A
X linked hyper IgM
X linked agammaglobulinemia
WHIM syndrome
Griselli syndrome
25
In general defects in any of the compliment proteins will lead to?
susceptibility to extracellular bacteria
26
In general, defects in compliment regulatory proteins can cause? (2)
susceptibility to encapsulated bacteria (loss of C3)
or
autoimmune-like disease--> compliment destroys RBC's via excessive MAC formation
27
Defects of components C5-C9 leads to susceptibility to
Neisseria
| *no MAC formation
28
Deficiencies of C1, C2, C4
Immune complex disease--> small immune complexes created by antibody binding to its antigen is usually further opsonized by activation of the classical compliment cascade, promoting uptake and destruction of these small immune complexes
29
C3 defects lead to
susceptibility to encapsulated bacteria
30
Factor D, properdin factor P defects lead to what immune susceptibility?
susceptibility to encap. bacteria and Neisseria, but no immune complex disease
31
Factor I
reduced cleavage of C3b of C4b
| *similar to C3 deficiency bc the result is depletion of C3
32
DAF and CD59 deficiencies lead to -->
paroxysmal nocturnal hemoglobulinemia
33
Paroxysmal Nocturnal Hemoglobulinemia is caused by
defects in GPI glycosylphosphatidylinositol
* DAF and CD59 cannot bind to host cell membrane and therefore cannot prevent the MAC from forming in the Host Cell--> RBC's lyse
* a form of hemolytic anemia
34
CINH deficiency
HANE--> buildup of anaphylatoxins
35
MBL deficiency causes
inability to activate the lectin pathway ( a secreted PRR)--> leads to sever bacterial infections (acute phase response in hindered)
36
clinical presentation for MBL deficiency
pt.'s experience recurrent severe infections
37
C1 INH controls
spontaneous activation of C1 that always occurs--> w/o the inh. the system will constantly run and anaphylatoxins will buildup
38
Tc for C1inh defiiency
monthly injections of C1INH
39
a rare, acquired, potentially life-threatening disease characterized by complement-induced intravascular hemolytic anemia, red urine (due to hemoglobin in the urine), and thrombosis
Paroxysmal Nocturnal Hemoglobulinemia
40
CD59 and DAF requires
surface expression of GPI anchor
41
Tx for PNH
allogenic bone marrow transplantation is the only cure
| *Compliment component C5 specific monoclonal Ab "eculizumab"--> aids in reducing thrombosis but is not curative
42
Inherited Antibody deficiencies
```
X-linked agammaglobulinemia (XLA)
Pre-B Cell receptor (lambda 5)
X-linked hyper IgM syndrome
selective IgA
selective IgG
```
43
Antibody deficiencies lead to...
susceptibility to extraceullular bacteria, especially encapsulated bug that are resistant to phagosytosis
44
Dx for Ab def.
monthly injections of gamma globulin from healthy donor
| *all forms are susceptible to extracellular bateria and virions )unable to neutralize
45
XLA is cause by
| X linked agammaglobulinemia
defect in B cell development
*defective BTK--> no signal transduction in the bone barrow--> improper B cell development/ B CELLS DONT SURVIVE BONE DEVELOPMENT
46
Do pt.s with XLA have a humoral immune system
HELL NAW
47
Pre-BCR (lambda 5) deficiency is from
mutation of lambda 5 gene (so chromosome 22)
--> non-functional surrogate light chain which result sin the inability of developiong B cells to produce a proper BCR--> they all undergo apoptotic death in germinal centers
48
X linked Hyper Igm is caused by?
defect in CD40 or CD40L or AID
49
defect in CD40L (defect in helper T cell function)--> results in
B cells and macrophages cannot receive the second signal of activation
50
AID deficiency results in
no isotype switching or somativ hypermutation
51
which is more desirable AID or CD40 deificiency
AID--> still be able to produce and activate effector T cells that could supply the second signal of activation
52
antibodies produced in some one with X linked hyper Igm syndrome
almost all of them will be IgM and the Igm levels will be lower than in some one who is immunocompetent
53
"Those individuals who cannot activate B cells will not have..."
germinal centers in secondary lymphoid tissues
54
Selective IgA deficiency cause?
unknown, likely heterogenous
55
Most pt.'s with Selective IgA are healthy until
exposed to parasite pathogens
56
People with Selecitve IgA deficiency are at risk of producing...
*they do not make any IgA
IgA-specific hypersensitivity fllowing blood transfusions
| life threatening anaphylactic response
57
Selective IgG deficiency cause?
unknown, likely heterogenous
58
Most rare, yet important IgG deficiency
IgG1--> susceptible to many bacterial pathogens
| * all subtypes of IgG can be deficienct
59
content of IgG circulating in adult blood that is IgG1
60-70%
*20-30% is IgG2
60
the most common immunodeficiency
Common Variable Immunodeficiency
61
common features of CVID
a group of 150 primary immunodeficiencies that have common features including:
HYPOGAMMAGLOBULINEMIA reduced ab levels (but all different etiologies)
62
clinical presentation of CVID
recurring infections mainly bacterial and/or viral pathogens involving ears, eyes, sinuses, nose bronchi, lungs skin, Gitracts, joints, bones, CNS, parotid glands etc
63
hypogammaglobulinemia means
low serum levels of gamma glonulins
| * a subset of which is antibodies
64
CAUSES of CVID are usually ______ but do not appear until ______
genetic
| 2nd or 3rd gnerations of life
65
clinical triad for Ataxia telangiectasia
```
cerebellar defects (ataxia)
spider angiomas (telengiectasia)
IgA of IgE deficiency
```
66
prenatal finding associated with AT
elevated AFP
67
Cause of AT
inherited defect in ATM gene ( a gene that encodes DNA repair enzyme)
68
Ataxia Tangleictasia can result in....
B and T cell deficiencies
Low numbers if lymphocytes (especially T cells)
Very low levels of IgA and IgE (mostly IgA)
69
IL-12 signaling deficiency results in
inability to generate TH1 responses
| inability to fully activate macrophages
70
IL-12 deficient pt.'s make much less
IFN gamma
71
Clinical presentation of IL-12 deficient pt.'s
recurrent susceptibility to disseminated mycobacterial infections
72
hyper IgE syndrome is also known as
Job's Syndrome
73
What causes Job's syndrome
genetic deficiency of STAT-3 function that results in reduced production of IFN gamma by TH1 cells and neutrophils that fail to respond to chemotactic signals
74
Two syndromes that cause
1. very little IFN gamma production
2. inability to activate TH1 responses
1. IL-12 signaling deficiency
| 2. Hyper IgE/Job's syndrome
75
Clinical findings of Job's syndrome
1. high Ige in blood
2. eczema
3. Recurrent abcesses with Staph aureus
4. coarse facial features
FATED
facies, abcesses, retained primary teeth, IgE, Dermatologic problems
76
Hyper Ige polarizes immune responses toward
TH2 phenotype--> leads to increases IgE
77
Chronic mucocutaenous candidiasis Cause
T cell dysfunction, undefined cytokine deficiency
78
Clinical presentation of Chronic Mucocutaneous Candidiasis
persistent superficial infection of the skin, mucous membranes, and nails with candida organisms
79
CD8 dysfunction can be caused by
TAP transporter deficiency
CD8 alpha chain defect
Non-Sense mutation of perforin
80
TAP defects result in
| *sometimes calles BARE LYMPHOCYTE SYNDROME (MHC CLASS 1)
low levels of MHC 1 molecules
defective responses to intracellular pathogens
VERY LOW NUMBER OF CD8 T CELLS BECAUSE FEW ARE POSITIVELY SELECTED IN THYMIC DEVELOPMENT
81
CD8 ALPHA CHAIN DEFECT
SAME PHENOTYPE AS TAP DEFECTS
| *HIGHLY SUSCEPTIBLE TO INTRACELLULAR BACTERIA
82
non-sense mutation of perforin causes
1. dramatically or totally reduced CTL activity
2. pt.'s have NORMAL numbers of CD8 t cells
3. CTL's are unable to induce programmed cell death
83
Perforin mutations also affect which cell type
NK cells
84
Defect in CD4 T cell function can result in______
SCID phenotype
| * b cell responses require an effector t cell for activation
85
CD4 t cells are important to ____ mediate and _____ mediate immune responses
antibody
| cell-mediated
86
Bare Lymphocyte Syndrome (SCID)
lack of expression of MHC II
| *unable to mount cd4 responses or B cell responses
87
Wiskott-Aldrich Syndrome (WAS)
| SCID PHENOTYPE
defect in cytoskeletal reorganization that is required for T cells to deliver cytokines and other signals to B cells and macrophages
88
causes cell-crosstalk deficiency
Wiskott-Aldrich Syndrome
89
Adenosine Deaminase or Purine nucleotide phosphorylase deficiency both result in (SCID)
accumulation of toxic nucleotide catabolites that kills all lymphocytes during their development
90
COmmon Gamma chain deficiency results in
SCID
```
FAILURE OF T CELLS TO PROLIFERATE
NO T CELLS OR B CELLS
-->Gamma chain is signaling component of
IL2, 4, 7, 9, 15
--> gamma chain interacts with JAK3
```
91
JAK 3 DEFICIENCY
```
FAILURE OF T CELLS TO PROLIFERATE
NO T CELLS OR B CELLS
-->Gamma chain is signaling component of
IL2, 4, 7, 9, 15
--> nteracts with GAMMA CHAIN
```
92
T CELL GROWTH FACTOR
IL2
93
B CELL GROWTH FACTOR
IL7
94
CD3 DEFICIENCY RESULTS IN
| SCID
no CD4+ or CD8+ T cells; no T cell function:.
95
CD3 DEFICIENCY CAN RESULT FROM
nonfunctional CD3 delta, epsilon, or zeta chain
96
DiGeorge syndrome results from
small deletion in chromosome 22 (q11.2
97
Characteristics of Digeorge syndrome
| SCID
congenital heart disease (40%), palatal abnormalities (50%), learning disabilities (90%), hypocalcemia (50%), mild differences in facial features
98
complete digeorge syndrome (SCID)
athymic
| *very few t cells if any
99
Tx for digeorge synrome
thymic transplant, no tx for other features
100
ZAP 70 deficiency (SCID)
pt.'s have absence of CD8 T cells, but normal number of NON-FUNCTIONAL CD4 t cells
101
Cause of Zap 70 def.
genetic defect that prevents expression of function zap70
102
what is zap 70
tyrosine kinase that associates with phosphorylated ITAMs during t cells development
*ZAP 70 is required for signaling via the TCR
103
Tx for ZAP-70 deficiencty
bone marrow transplant
104
Cause of OMENN syndrome
mis-sense muatation that results in partially active RAG enzymes
105
result of OMENN syndrome (SCID)
absence of B cells and low numbers of oligoclonal autoreactive T cells
*susceptible to all types of infections and also suffer from autoimmune disease that attacks skin and GI as well
106
tx for OMENN syndrome
bone marrow transplant
107
SYMPTOMS OF OMENN SYNDROME
erythroderma, desquamation, alopecia, chronic diarrhea, failure to thrive, lymphadenopathy, and hepatosplenomegaly
108
Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED)
a genetic deficiency of (AIRE) that is expressed in the thymic medulla
*impaired negative selection of thymocytes
109
Clinical presentation of APECED
problems in numerous glands (polyglandular) including hypoparathyroidism, hypogonadism (with sex gland failure), adrenal insufficiency, type 1 (insulin-dependent) diabetes, and latent hypothyroidism, total baldness (alopecia totalis), keratoconjunctivitis, tooth enamel hypoplasia, candidiasis (yeast infection), juvenile-onset pernicious anemia, gastrointestinal problems (malabsorption, diarrhea)
110
transcription factor that regulates expression of several hundred host-tissue specific genes by epithelial cells in the thymic medulla
AIRE
111
Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked Syndrome (IPEX) results from
deficiency of FoxP3 expression by Tregs
| *early onset autoimmunity to a variety of host tissues due to lack of Treg cell function
112
Clinical triad associated with IPEX
1) watery diarrhea,
2) eczematous dermatitis
3) endocrinopathy (type 1 diabetes)
113
Tx for IPEX
aggressive immunosuppresion and/or bone marrrow transplant
114
Autoimmune Lymphoproliferative Syndrome (ALPS) is characterized primarily by what physical findings
lymphadenopathy and splenomegaly
115
What causes ALPS
| Autoimmune Lymphoproliferative Syndrome
*mutation in Fas, FasL, or Caspase 10
immune cells failing to undergo apoptotic death following an immune response; causes overpopulation of secondary lymphoid tissues
116
PRESENTATION OF ALPS
| Autoimmune Lymphoproliferative Syndrome
autoimmune hemolytic anemia and neutropenia, thrombocytopenia (decreased platelets in the blood), lymphadenopathy, splenomegaly; also, often have large number of CD4- CD8- T cells
117
TX OF ALPS
| Autoimmune Lymphoproliferative Syndrome
IMMUNOSUPRESSION
| IV-Ig
118
Classical presentation of DiGeorge syndrome
```
*CATCH 22*
Cardiac Abnormality (especially tetralogy of Fallot)
Abnormal facies
Thymic aplasia
Cleft palate
Hypocalcemia/Hypoparathyroidism.
22ND chromosome
```
