Immunodeficiency Disorders Flashcards
What causes X-linked agammaglobulinemia
Defect in BTK, a tyrosine kinase gene that results in no B cell maturation (X-linked recessive; think more in boys)
How might X-linked agammaglobulinemia present?
recurrent bacterial and enteroviral infections after 6 months (decreased maternal IgG)
What are the findings of X-linked agammaglobulinemia?
Absen B cells in peripheral blood
decreased Ig of ALL classes
Absent lymph nodes and tonsil
What causes Selective IgA deficiency?
Unknown but most common primary immunodeficiency
How might Selective IgA deficiency present?
Majority are ASYMPTOMATIC but can see upper respiratory and GI illness, autoimmune disease, atopy, and anaphylaxis to IgA containing blood products
Common variable inmmunodeficiency is a defect in B cell DIFFERENTIATION that can be caused by a no. of things. How might it present?
Can be acquired in 20s-30s and shows an increased risk of autoimmune disease, bronchiectasis, lymphoma, and sinopulmonary infections
What are the main findings of Common variable inmmunodeficiency?
Decreased plasma cells and immunoglobulins
What causes DiGeorge Syndrome?
22q11 deletion causing failure of the 3rd and 4th pharyngeal pouches to develop (absent thymus and parathyroids)
How does DiGeorge Syndrome present?
tetany (hypocalcemia)
recurrent viral/fungal infections
conotruncl abnormalities (e.g. tetralogy of Fallot or truncus arteriosus)
What are the main findings of Digeorge Syndrome?
decreased T cells, PTH, and calicum
Absent thymic shadow on CXR (present below)
How might IL-12 receptor deficiency present?
AR disease of decreased Th1 response and increased risk of disseminated mycobacterial and fungal infections (may present after BCG vaccine administration)
Decreased levels of IFN-y
What is Job syndrome?
Defeciency of TH17 cells due to STAT3 mutation causing impaired recrutiment of neutrophils to infection sites
How might Job syndrome present?
FATED
Facies
Cold (nonnflammaed) staph abscesses
retained primary teeth
elevated IgE (and decreased IFN-y)
Derm problems such as eczema
Describe chronic mucocutanoeus candidiasis
Disease of noninvascice candida albicans infections of skin and mucous membranes due to T-cell dysfunction
What causes SCID?
Several types including defective Il-2R gamma chain (most common, X-linked) and adenosine deaminase deficiency (AR)
How does SCID present?
Failure to thrive, chronic diarrhea, and trush
Reucrrent infections of all sources (e.g. bacterial, viral, fungal, and protozoal)
How is SCID tx?
Bone marrow transplant (no rejection concerns!)
What are some classic findings of SCID?
Decreased T cell receptor excision cricles (TRECS)
Absense of thymic shadow on CXR, germinal centera on lymph node biopsy, and T cells via flow cytometry
What causes ataxia-telangiectasia?
Defect in ATM gene leading to failure to repair DNA breaks and subsequent cell cycle arrest
How does ataxia-telangiectasia present (classic triad)?
Cerebellar defects, spider angiomas, and IgA deficiency
What are the findings of Ataxia-telangiectasia?
Elevated AFP
Decreased IgA, IgG, and IgE
Lymphopenia and cerebellar atrophy
What causes hyper-IgM syndrome?
Most commonly due to defective CD40L on Th cells causes a class switching defect (X-linked recessive)
What are the classic symptoms of hyper-IgM syndrome?
Severe pyogenic infections early in life
opportunistic infections with Pneumocytsis, CMV, and Cryptosporidium
What are the lab findings of hyper-IgM syndrome?
Elevated IgM and vastly decreased IgG, IgA, and IgE
What causes Wiskott-Aldrich Syndrome?
Mutation in WAS gene (X-linked recessive; think in boys) causing T cells to be unable to reorganize actin cytoskeleton
How might Wiskott-Aldrich Syndrome present?
Thrombocytopenic purpura
Eczema
Recurrent Infections
Increased risk of cancers
What are the lab findings of Wisckott-Aldrich syndrome?
Decreased to normal IgG, IgM
Elevated IgE and IgA
Fewer and smaller platelets
What causes leukocyte adhesion deficiency (type I)?
Defect in LFA-1 integrin (CD18) protein on phagocytes causing impaired migration and chemotaxis (AR)
How might leukocyte adhesion deficiency (type I) present?
Recurrrent bacterial skin and MUCOSAL infections with absent pus formation
delayed seperation of the umbilical cord (30+ days)
and impaired wound healing
NOTE: A pseudo-neutrocytosis will be seen
What causes Chediak-Higashi syndrome (AR)?
Defect in lyosomal trafficking regulator gene (LYST) causes microtubule dysfunction in phagosome-lysosome fusion (AR)
How might Chediak-Higashi syndrome present?
Recurrent pyogenic infections by staph and strep spp.
infiltrative lymphohistiocytosis
partial albinism
peripheral neuropathy
progressive neurodegeneration
What are the lab findings of Chediak syndrome?
pancytopenia and mild coag defects
What causes CGD?
Defect in NAPDH oxidase causing impaired formation of ROS and respiratory burst in neutrophils (X-linked recessive)
CGD places one at an increased risk of infection with which bugs?
Catalase + including:
Need PLACESS
Nocardia, Pseudomonas, Listeria, Aspergillus, Candida, E. Coli, S aureus, and Serratia
Other findings of CGD?
Abnormal dihydrorhodamine test
Negative nitroblue tetrazolium blue reduction test
Note about Bacterial infections and immunodeficiency
Decreased T cells typically leads to risk of SEPSIS
Decreased B cells leads to risk of encapsulated bacteria (SHiNE SKiS)
Decreased granulocytes leads to increased risk of infection with which bacteria?
Stapylococcus
Burkholderia cepacia
Pseudomonas aeruginosa
Serratia
Nocardia
T cell immunodeficiency mainly increases the risk of infection with which viruses?
CMV, EBV, JCV, VZV
B cell immunodeficiency mainly increases the risk of infection with which viruses?
Enteroviral encaphalitis and poliovirus
T cell immunodeficiency mainly increases the risk of infection with which fungi?
Candida and PCP
B cell immunodeficiency mainly increases the risk of infection with which fungi?
Giardiasis (no IgA)
Granulomatous immunodeficiency mainly increases the risk of infection with which fungi?
Systemic candida and Aspergillus
Basic definitions of grafts:
Autograft- from self
Syngereic graft (isograft)-f rom identical twin/clone
Allograft- from nonidentical individual of same species
Xenograft- from diff. species
Describe a hyperacute transplant rejection
Onset within MINUTES nd occurs due to pre-exisiting recipient Abs reacting to donor antigens (type II rxn) and activating complement causing widespread thrombosis of graft vessels (necrosis)
The graft must be removed
Describe an acute transplant rejection
Onset with weeks to months and can be caused by a CD8 T cell rxn against donor MHCs or via Abs that develop after the transplant and induce complement
marked by vasculitis of graft vessels with dense lymphocytic infiltrate
Prevent with immunosuppressants
Describe a chronic transplant rejection
Onset within MONTHS to YEARS and caused by a CD4+ T cell response to recipient APCs presenting donor peptides (both cellular and humoral components)
Marked by proliferation or vascular smooth muscle and parenchymal fibrosis (dominated by ateriosclerosis) due to T cell response
What causes graft-vs.-host disease?
Grafted immunocompetent T cells proliefrate in the immunocompromised host and reject host cells with foreign proteins leading to SEVERE organ failure
Timeline varies
How might GVD present?
Maculopapular rash, jaundice, diarrhea, and HTN
Usually in bone marrow and livert transplants (rich in lymphocytes)
Potential beneficial for BM transplant in leukemia pt.
