Primary ImmunoDeficiencies Flashcards
Histopathology and laboratory abnormalities of: B Cell Deficiencies
Often absent or reduced Follicles and germinal centers in Lymphoid organs
Reduced serum Ig Levels
Histopathology and laboratory abnormalities of: T cell deficiencies
Reduced T cell zones in lymphoid organs
Reduced DTH to common antigens
Defective T cell proliferative responses to mitogens in vitro
Warning signs of Immunodeficiency Disorder
Eight or more ear infectionsin one year.•
Two or moreserious sinus infectionsin one year.•
Two or more bouts of pneumoniain one year.•
Two or more deep-seated infections, or infections in unusual areas.•
Recurrentdeep skin or organ abscesses.•
Needfor iv antibiotic therapyto clear infection.•
Infectionswith unusual or opportunistic organisms.•
Family history of primaryimmunodeficiency.
Recurrent Sinopulmonary Bacterial infections
screen Humoral Immunity
Recurrent Viral or fungal infections
Screen Cellular Immunity
Recurrent skin abscesses or fungal infections
Screen Phagocyte defect
Bacteremia or meningitis with encapsulated bacteria?
Screen for complement deficiency
Testing for PID: Differential CBC
T cell, B-cell T/B cell defects
Testing for PID: DTH skin Test
T cell defects
Testing for PID: Serum IgG, IgM, IgA
Hummoral immunodeficiency
Testing for PID: Ab testing to specific Ag after immunization
Humoral immunodeficiency
Testing for PID: Total Hemolytic complement assay
Complement deficiency
Testing for PID: Nitroblue tetrazolium test
Phagocytic disorder
Adenosine Deaminase Deficiency (ADA)
SCID disease
happens after the progenitor cells
T-,B-,NK-
Low Igs
Autosomal Recessive
Metabolic function of T-cells due to an accumulation of toxic deoxyadenosine
Avoid all live Viral Vaccines
treatment HSCT
Characteristics of SCID diseases
Defficiencies in both T cell and B cells
Severe lymphopenia
Severe opportunistic infections
Chronic diarrhea and failure to thrive
Purine Nucleoside Phosphorylase (PNP) deficiency
T-,B-,NK+/-
Exception to SCID
SCID
Normal Ig levels
Autosomal recessive
SCID disease
Accumulation of intracellular deoxyguanosine triphosphate (dGTP)
decrease in peripheral T cells
Early neuro disorders, hemolytic anemia, thyroid disease, arthritis, and lupus
treatment HSCT
Artemis Deficiency
T-,B-,NK+
SCID
Low Ig levels
Autosomal recessive and radiosensitive
Artemis important in repairing VDJ rearrangement double strand breaks
diarrhea candidiasis and pneumocystis jiroveci pneumonia
treatment HSCT
RAG1/RAG2 deficiency
T-,B-,NK+
SCID
Low Ig levels
Autosomal Recessive
Impaired VDJ recombination and leads to defects of the pre-TCR and pre-BCR
diarrhea, candidiasis, pneumocytis jiroveci pneumonia
treatment HSCT
OMENN syndrome
lesser version of RAG1/RAG2 deficiency because has partial function
Severe erythoderma, splenomegaly, eosinophilia, high IgE
Deficiency of Jak3
T-,B+,NK-
Form of SCID
low Ig levels
Autosomal Recessive
Defect in IL-2 receptor signaling
Mutation in Janus Kinase 3
treatment HSCT
X linked Btk Kinase Deficiency
T+,B-,NK+
No Igs
Defect in rearrangement of the Ig heavy chains
IgG IgA and IgM are absent or very low
Affects pre-B cell so stuck in Pre-B cell
Isolated IgG subclass Deficiencies
T+,B+,NK+
IgG sublcass very low
normmal IgM and IgA
Defect in several genes
increase in IgG4 which is none in healthy people
Asymptomatic but recurring viral/bacterial infections in respiratory tract
Low IgG2 and poor responses to polysaccharide Ags
Autosomal recessive
IgA Deficiency
T+,B+,NK+
No IgA but everything else is normal
Happens in the periphery affecting IgA secreting plasma cells
recurrent infections via encapsulated bacteria
If given a IVIG can have Anaphylaxis due to anti-IgA IgG in the body
Autosomal higher in male
Digerorge Syndrome
T-,B+,NK+
Normal Ig level
Tcell deficiency
Microdeletion in 22q11.2 region
Cardiac anomalies, hypocalcemia, hypoplastic thymus
undeveloped thymus
Autosomal dominant
Hyper IgM Syndromes (HIGM)
T+,B-+NK+
group of diseases characterized by impaired Ig class switching and somatic hypermutation
Normal number of peripheral B cells and low numbers of CD27-positive memory B cells
High IgM and low IgG and IgA
X linked recessive for 2/3 on CD40L
Autosomal CD40 on B cell deficiency 1/3 cases
mutation in the CD40L gene
Transient Hypogammaglobulinemia of Infancy
T+,B+,NK+
Low IgG/IgA and IgM is normal
Intrinsic IgG production delayed for up to 36 months
Normal after 2-4 years
Increased susceptibility to sinopulmonary infections
Common Variable Immune Deficiency (CVID)
T+,B+/-,NK+
Defect in Ab production associated with hypogammaglobulinemia
recurring pyogenic sinopulmonary infections
Number of B cells are normal but cant mature and differentiate into plasma B cells
Autosomal Recessive
Low IgA and IgG and sometimes IgM
Heterogeneous group of diseases
Common y Chain Deficiency (yC or IL-2Ry)
SCID
T-,B+,NK-
Very Low Igs but has IgM
X linked Recessive
Growth factors for Gamma Chain is mutated
issue with IL-2Ry
No functional B cells since T cells unable to help
Failure to thrive, severe thrush, oppurtunistic infections and chronci diarrhea
treatment HSCT
IL-7R alpha chain Deficiency
T-,B+,NK+
SCID
Very low Igs but have some IgM
Autosomal Recessive
Key role in early T cell development
Candidiasis, chronic diarrhea, Pneumocytstis Jiroveci pneumonia, severe viral infections
treatment HSCT
Bare Lymphocyte Syndrome type 2 (BLS II)
CD4 T-, CD8 T+,B+,NK-
Autosomal Recessive
no MHC class II expression on proffessional APCs
Mutations for transcription factors that regulate MHC II genes
Variable HypoGammaglobulinemia (IgA and IgG2
death and recurrent infections
treatment HSCT
MCH Class I deficiency
Mutation in TAP 1 molecule
CD4 T cells are normal
CD8 cells are deficient
Recurring Viral Infections
Autosomal recessive
CD3 Complex deficiencies
T-,B+,NK+
Low Igs usua;;y normal
Deficiency in the CD3 subuntits(delta gamma epsilon and zeta)
Autosomal recessive form of SCID
Decreased T cell numbers and lymphopenia
failure to thrive, oppurtunistic infections. chronic diarrhea
HSCT
no live vaccines
Defect in IL-12 and IFN-y pathway
No Th1 cells
Th1 doesnt produce IFN-y which leads to selective susceptibility to intracellular pathogens
such as atypical mycobacteria
Th17 deficiency
Mutatons in genes encoding for IL-17 and IL-17R, or transcriptional factors STAT1, STAT3, and AIRE
Unusual susceptibility to chronic mucocutaneous candidiasis
Hyper IgE syndrome
IPEX (Immunodysregulation, polyendocrinopathy and enteropathy, x linked syndrome)
Self reactive T effector cells are not inhibited
Mutation in FOXp3 in Treg cells
ALPS (Autoimmune Lymphoproliferative Syndrome)
defects in Fas, FasL, caspase-8 or caspase-10 genes which leads to resistance in effector T cell Apoptosis
Wiskott-Aldrich Syndrome (WAS)
T-,B+,NK+
Low IgM, normal Ig, Elevated IgA and IgE
X linked Disorder
Mutation in the Wiskott-Aldrich Syndrome Protein (WASP)
T cell lymphonia
Decreased effectiveness of NK cell but not number
thrombocytopenia, eczema, cellular and humoral immunodeficiency, autoimmune disease, and malignancy.
Recurring encapsulated Bacteria
NK cell Deficiencies (NKD)
Present with multiple servere or disseminated viral infections
Mutations in Multiple genes
NK cells must represent the major immunologic abnormality of the patient
Classical (CNKD): GATA2, lack of NK cells
Functional (FNKD): Perforin deficiency
Chronic Granulomatous Disease (CGD)
Phagocytic disorder that forms granulomas
Enzyme deficiency in NADPH oxidase
Fail to generate superoxide and O2 radicals
recurring infection with catalase positive organisims (staphylococci)
Glucose 6 phosphate Deficiency
Phagocyte disease
x linked recessive
Anemia
Lack substrate for NADPH
Asymptomatic
Tendancy to form grnulomas
Leukocyte Adhesion Deficiency (LAD)
Neutrophil count twice as normal
recurrent infections of the oral, genitalia, skin, intestine, and respiratory tract
Defect in Adhesion on LAD integrins
Mutation in B2 integrins
affects CD11 and CD18
Slow wound healing failure to fform pus delayed detachment of the umbilical cord severe bacterial infections early death
Chediak Higashi Syndrome
Autosomal Recessive disorder
wheelchair bound
abnormal giant granules that dont contain Cathepsin G and elastase
affects chemotaxis and degranulation
Azurophilic giant cytoplasmic inclusions
partial Albinism
2 phases:
- infections
- Lymphoproliferative syndrome and hepatosplenomegaly
No NK activity
Factor H deficiency
Alternative complement pathway
hemolytic uremic syndrome
or glomerulonephritis
C1 and C4 deficiency
Systemic Lupus Erythematosus (SLE) and rheumatoid arthritis (RA)
complexes arent cleared from the blood and lead to build up cause sites of inflammation
Deficiency in C1-Inhibitor
Hereditary Angioedema (HAE)
Recurrent swelling in the extremities, face, lips, larynx, and GI tract
over activation of CP pathway and swelling due to inabillity to stop the kinin generating pathway
production of bradykinin which leads to vaso dilation
C8 complement Deficiencies
Autosomal recessive
increased susceptibility to Neisserial Infections
Paroxysmal Nocturnal Hemolobinuria (PNH)
Failure to regulate MAC complex
Somatic mutation that causes a deficiency in gycosylphosphatidylinositol (GPI)
important to anchor down DAF (CD55) and CD59
causes intravascular hemolysis
Deficiency in TLR
Myd88 deficiency results in impaired signaling except for TLR3
sever infections caused by pyogenic bacteria
normal resistance to other common bacteria, fungus and viruses
Patients lack fecers due to low amounts of TNF-a, IL-1, and IL-6
TLR 3 deficiency
Autosomal dominant
increased susceptibility to HSV encephalitis
