Overview of Primary Immune Deficiencies (PID) Flashcards
1
Q
What are Primary Immune Deficiencies and how do they compare to secondary immune deficiencies?
A
- PIDs are intrinsic defects in the immune system that are usually but not always inheritied
- secondary immune deficiencis are due to extrinsic factors that suppress the immune response (drugs or HIV)
2
Q
When should you suspect PID?
A
- too many infections, or infections that won’t go away (>2 pneumonias or a lot of sinus infections)
- Weird infections or locations of infections (lung/liver abscess, or Pneumocystis jerovecii)
- Early onset immunity, weird patters of autoimmunity or immunodysregulation (eg IB in a baby)
3
Q
WHat are some things that lead to secondar immunodeficiencies?
A
- infections
- malnutrition
- malignancies
- metabolic
- loss of lymphocytes or antibodies
- immunosuppresants
- collagen vascular disease
4
Q
What are the two things that tests of immune function measure?
A
- Number or quantitiy (are there enough PMNs)
- Function (do the PMNs work)
5
Q
What cell surface protein(s) do all T cells have?
A
CD3- all T cells
6
Q
What cell surface protein(s) do naive T cells have
A
CD3+CD45RA
**A for nAive**
7
Q
What cell surface protein(s) do memory T cells have
A
CD3+CD45RO
**O for MemOry**
8
Q
What cell surface protein(s) do helper T cells have
A
CD3+/CD4+
helper T cells
9
Q
What cell surface protein(s) do Cytotoxic T cells have?
A
CD3+CD8+
10
Q
What cell surface protein(s) do all B cells have
A
CD19 or CD20
All B cells
11
Q
NK Cell markers
A
CD3-/CD56+
12
Q
What are the clinical manifestations of neutrophil defects?
A
- onset early in infacny/childhood
- severe bacterial infections
- abscesses
- gingival/peridontal disease
- Poor wound healing/lack of pus
- common pathogens: catalase + organs
- staphylococcus, aspergillus, nocardia, burkholderia (CGD or CF)
13
Q
List 3 examples of diseases that are neutrophil defects
A
- chronic granulomatous disease (CGD)
- congenital/cyclic neutropenia
- Leukocyte adhesion deficiency
14
Q
What is the workup when neutrophil defects are suspected?
A
- Initaial
- NUMBER: CBC with differential- look at abosolute numbers of WBCs including the absolute neutrophil count (ANC)
-
FUNCTION: Dihydroorhodamine test (DHR)
- sometimes Nitroblue tetrazolium (NBT)-older
- Secondary
- chemotaxis
15
Q
WHat is the clinical manifestation of a complement defect?
A
- any age
- “classical” complement pathway defects are most common
- Two types:
- Early (C2, C4) Defects
- autoimmune disease most common presentation (SLE, glomerulonephritis)
- Sinopulmonary infections, sepsis, increased susceptibility to S. pneumoniae, H. influenzae
- Late (C5-C9 defects)
- increased suseptibility to Neisseria infections
- Early (C2, C4) Defects
16
Q
describe early and late complement defects
A
- Early (C2, C4) defects
- autoimmune disease is the most common presentation
- often see sinopulmonary infections, sepsis, increased susceptibiloty to S. pneumoniae, H. influenzae
- Late (C5-C9) defects
- increased susseptibility to Neisseria
17
Q
What is the workup if you suspect a complement defect
A
- Initial
-
CH50 (functional assay for all of the classical complemts)
- if there is a complement deficiency CH50=0 usually, but if it is just a problem with complement consumption (ie Lupus) then CH50 is low but not 0.
-
CH50 (functional assay for all of the classical complemts)
- Secondary
- do individual component testing is CH50 is low. If if is not zero suspect complement consumption problem (ie Lupus)
*
- do individual component testing is CH50 is low. If if is not zero suspect complement consumption problem (ie Lupus)
18
Q
What is the clinical manifestation of a B-cell/ Antibody defect? and examples
A
- Antibody deficiencies are the most common PID (50%)
- Agammaglobulinemias usually presnet in first year or two of life; CVID at any age
- you would see: recurrent sinopulmonary bacterial infections, infections with encapsulated organisms like (H. flu, S. pneumo and mycoplasma sp.) chronic GI infections, malabsoprtion and FTT
Ex: XLA, CVID
19
Q
What is the work up for a B-cell/Antibody Defect?
A
- Quantitative immunoglobins (IgG/A/M/E) -note can be influenced by secondary immunosuppression
- vaccine titiers-if low reimmunize and measure titier 4 wks later
- consider
- lymphocyte substs
- CH50
- sweat chloride
20
Q
What is teh clinical manifestation of a T cell or combined T cell/B cell Defect?
A
- Recurrent severe infections: viruses Idisseminated CMV, EBV, Varicella), Funal (candidiasis) bacteria, opportunistic pathogens (P. jiroveci, mycobacteria)
- poor growth/FTT/chronic diarrhea
- SCID-onset first year of life usually after maternal antibodies wane
- combined B/T: SCID
21
Q
WHat is the workup if you suspect T-cell/combined defects?
A
- CBC w differential: a low absolute lymphocyte count (ALC) can be a helpful clue
- Lymphocyte susbset enumeration (flow cytometry)
- Numbers ot T/B/NK cells, memory and naive T cells
- Quantitative IgGs (IgM, IgG, IgA)
- T cell proliferation
22
Q
Example os combined B cell and T cell and the screening?
A
SCID
- Screen:
- Lymphocyte susbsets (T and B cells/NK cells) by flow cytometry; T proliferative response to mitogens (PHA)
23
Q
Example of a T cell immunodeficiency
A
DiGeorge Syndrome
Test:
Lymphocyte susbsets: FISH for 22.q11.2 deletion, RT-PCR for TBX1 gene
DNA chromocome microarray (preffered)
24
Q
Examples of antibody immunodeficiency
A
XLA, CVID
TestL IgG, IgA and IgM-not IgG subclasses
25
Example of PMN immunodeficiency
CGD
## Footnote
Dihydroorhodamine (DHR) test
26
Example of complement deficiency
C2 (early), C5-9 (late)
## Footnote
TestL CH50
27
describe the molecular basis of X-Linked SCID and what does this mean?
* mutation in the common gamma chain of the IL-2 receptor. This s a common component for other Il receptors too!
* Therefore they lack T cells and NK cells, and B cells are present but not functional
* naive T cells are reduced in all forms of SCID
28
clinical manifestation of SCID
onset in infancy, neumonia ( P. jiroveci) otitis media, trush, intractable diarrhes, FTT
bone marrow transplant can help!
29
Diagnostic test for SCID. screening and confirmatory
screening test: CBC, lymphopenia
confirmatory: lymphocyte enumeration ( T cells, naive/memory, B cells, NK cells)
30
Describe the newborn screening test for SCID
* While making a T cell receptor T cells uncergo rearrangement resulting in small fragments of nonreplicating DNA being released called ***_TRECs_***
* these TRECs when measure by ***_RT-PCR_*** are a marker for numbers of ***_normal naive T cells_***
## Footnote
***_If TRECs are low suspect SCID!_***
31
What causes DiGeorge syndrome?
* Microdeletion in chromosome 22q11.2 leading to defect in 1st to 6th pouches: deletion TBX1 gene is a common cause
* Common!
32
Clinical manifestations of DIGeorge Syndorme
* CATCH 22
* Cardiac Defects
* Abnormal Facies- low set ears
* THymic hypoplasia
* CLeft palate
* HYpocalcemia
* 22nd chromosome
* Chronic infection/autoimmunity
* T cell abnormalities: low T cell counts
* Antibody deficiency
33
How do you diagnoseDiGeorge syndrome?
DNA microarray (copy number variation), FISH
RT-QPCR for hploinsufficiency TBX1 (CHF)
34
Clinical manifestation of XLA
* recurrent otitis, sinusitis, pneumonia
* Early dx/Rx to prevent bronchiectasis
* encapsulated bacteria (S pneumo and H influenzae) and mycoplasma
* sever enteroviral infections
* onset early infancy or childhood in most
mutations in Btk result in failure to differntiate B cells
35
Screening for XLA
IgG, IgA, IgM-best screening test for ALL Ab deficiencies
36
Clinical manifestations for Common Variable Immunodeficiency (CVID)
* most common PID
* onset at any age
* infections: RTI most common
* Pulmonary disease: **bronchiectasis and interstitial lung disease** this typically the cause of death
37
How do you diagnose CVID
* **decrease in IgG and low IgA** and/or IgM
* absent isohemagglutinins and poor response to vaccines
* exclude primary Ab deficiency (XLA) or secondar Ab deficiency
38
manifestation of IgA Deficiency
* most common AB deficiency
* low IgA but ormal IgG and IgM
* no phenotype sometime GI infectiions
39
Specific Antibody deficiency manifestation
* recurrent sinopulmonary infections
* normal IgG, IgA and IgM and normal T cell fucntin
* Abnormal specific antibody reponse to immunization especiall Polysaccharides-have all the right toll djust can't really elicit response. will grow out of it
40
What are the lab tests for diagnosing Antibody deficiencies
* serum IgG, IgA, IgM
*
41
Compare lab results of XLA to CVID
XLA: decrease in all isotypes
CVIDL decrease in 2 of 3 isotypes INCLUDING IgG
Both XLA and CVID have poor specific Ab response to vaccines
\*\*Do PCR to diagnose Ab deficiency
42
Manifestation of Chronic Granulomatous Disease (CGD)
* hepatic absess without obvious source in young child
* infection w catalase + bacteria
43
DIagnosis of CGD
DHR
Note some people can be carriers bc its often X-linked
44
WHat is the best screening for all classical compement deficiencies?
CH50
