14) Immunodeficiency Flashcards
primary vs secondary immune deficiency syndromes
primary – deficiency is cause of disease
secondary – deficiency is a sx of disease
primary immunodeficiencies are categorized based on…
the expressed defect
SCID
severe combined immunodeficiency diseases
T and B cell defect
SCID patient suscpetible to…
any infection, especially…
- CMV
- Pneumocystis jiroveci
- Candida
T- B+
(2 types)
X-linked SCID: T cells ↓ and B cells don’t function (lack of T cell ILs)
autosomal recessive SCID: same clinically; JAK3 mutation
T- B-
(2 types)
adenosine deaminase deficiency: T/B cells don’t develop; skeletal abnormalities; toxic waste buildup
recombinase deficiency: Rag genes cannot rearrange; maturation stops at pre-T/B
Omenn syndrome
recombinase deficiency (SCID) with partial Rag activity
acts like graft-vs-host disease
infiltrates of T-cells, eos, and hyper-IgE in GI/skin
T+ B+
(3 types)
SCID with normal T/B numbers and abnormal function
- bare lymphocyte syndrome
- Wiskott-Aldrich syndrome
- Ataxia telangiectasia
MHC is lacking; T-helpers do not get presented with Ag
bare lymphocyte syndrome
reversed CD4:CD8 ratio (more CD8)
thymic epithelials cannot select CD4+ cells
bare lymphocyte syndrome
triad of Wiskott-Aldrich syndrome
- thrombocytopenia with small plts
- recurrent bacterial infections
- allergic rxn, hyper-IgE, food allergies, eczema
patients unable to respond to polysaccharide Ag
Wiskott-Aldrich syndrome
lifespan of 3 years without tx
cure is BM transplant
Wiskott-Aldrich syndrome
staggering gait + spiderlike vascular dilation
Ataxia telangiectasia
lymphopenia, thymic hypoplasia
↓ IgA, IgE, IgG
increased susceptiblity to malignancies
Ataxia telangiectasia
in T-cell immunodeficiencies, Ab may be lacking because…
lack of functional T-helpers
patients with T-cell immunodeficiencies susceptible to…
viruses
bacteria
fungi
protozoa
thymus and parathyroid do not form
↓Ca and lack of T-cells
no IgG (no class switching)
congenital thymic aplasia
(DiGeorge syndrome)
cardiac disease
chronic infections
congenital thymic aplasia
(DiGeorge syndrome)
selective defect in T-cells
no cell-mediated response to C. albicans
chronic mucocutaneous candidiasis
pre-B cells do not mature, so no Ig
severe, repeated bacterial infections when mom’s Ab is gone (5-6 months)
Bruton’s agammaglobulinemia (x-linked infantile agammaglobulinemia)
repeated infections with…
H. influenzae
S. pneumoniae
Bruton’s agammaglobulinemia (x-linked infantile agammaglobulinemia)
Bruton’s agammaglobulinemia tx
IV IgG
cannot make IgG from 2 months to 2 years
↓ T-cell number and function
transient hypogammaglobulinemia
↓↓ IgG and IgA
peaks at 1-5yo and 15-20yo
common variable immunodeficiency disease (CVID)
recurrent pyogenic infections in resp/GI tracts
increased autoimmune disease, cancer
common variable immunodeficiency disease (CVID)
most common Ig deficiency and diseases
IgA
sinopulmonary infections, celiac disease
severe infections with polysaccharide encapsulated organisms (H. influenzae, Pneumococcus)
IgM deficiency
2 T/B interaction disorders
- hyper-IgM syndrome
- Duncan’s syndrome
no class switching; ↑ IgM, ↓ IgG, IgA, IgE
boys 1-2 yo with recurrent resp infections
hyper-IgM syndrome
CD40 ligand defect on T-cells
hyper-IgM syndrome
T-cells not able to control B-cell proliferation during EBV infection
results in Burkitt’s lymphoma if pt survives
Duncan’s syndrome (x-linked lymphoproliferative disease)
WBCs cannot interact with endothelium and enter tissues
leukocyte adhesion deficiency (LAD)
integrin defect
no diapedesis
recurrent soft tissue infections
LAD I
selectin ligand defect
WBC cannot bind to endothelials
LAD II
pts do not show normal signs of infection (no pus)
LAD
giant granules
abnormal function of plts, neuts, NK cells
neuro sx, skin hypopigmentation
Chediak-Higashi syndrome
defect in respiratory burst
granulomas form
chronic granulomatous disease
susceptible to S. aureus, Serratia, Aspergillus in first 1-2 years of life
chronic granulomatous disease
monos cannot secrete TNF-𝛼
susceptible to Mycobacteria
interferon-𝛾 receptor deficiency
associated with S. pneumo, S. pyogenes, H. influenzae, and SLE
C1, C4, C2 or C3 deficiency
C5-C9 deficiency interferes with ——–, the primary defense against…
MAC
GN organisms, especially N. meningiditis
lack C1 esterase inhibitor
too many anaphylatoxins
edema
hereditary angioedema
proteins that normally inactivate C’ cannot bind to membrane
PNH
3 common causes of secondary immunodeficiency
- malnutrition
- chemo
- deliberate immunosuppression
characteristics of tumor cells
- stop in particular developmental stage
- accumulate in large numbers
- originate from single clone
TdT+ in nucleus
B-ALL
endemic in Africa
highly vacuolated lymphs
Burkitt’s lymphoma
B-cells from lymph node follicles transform
follicular lymphoma
BCL1 and BCL2
1: mantle cell lymphoma
2: follicular lymphoma
lymphoma in MALT
associated with H. pylori, Sjogren’s syndrome, Hashimoto’s
marginal zone lymphoma
free light chain deposits in kidney
amyloids
overproduced IgM
hyperviscosity syndrome
Waldenstrom’s macroglobulinemia
CD4+ and CD8+, but little or no CD3+
T-ALL
T neoplasm of skin
Mycosis fungoides
leukemic phase: sezary syndrome
HTLV-1
adult t-cell leukemia
Hodgkin’s cells
Reed Sternberg
