Acquired Immunodeficiencies Flashcards
X-linked agammaglobulinemia (XLA)
defect in Bruton’s tyrosine kinase (req. for B cell development)
result: very few B cells
susceptibility: extracellular bacteria and some viruses (no neutralization)
symptom: underdeveloped tonsils
lambda5 deficiency
Pre-b cell receptor deficiency: lambda5 is a component of the surrogate light chain that pairs with the heavy chain during somatic recombination of light chain genes
result: apoptotic death of B cells: profound B cell deficiency
susceptibility: extracellular bacteria and some viruses (influenza needs to be neutralized)
X-linked hyper IgM syndrome: 2 causes
- Defect in T helper cell function: defect CD40 ligand expression; cells cannot receive secondary activation signal
- activation-induced cytidine deaminase (AID) deficiency; req. for isotope switching and somatic hypermutation
Selective IgA deficiency
Healthy unless exposed to parasite pathogens
Important parasite: Giardia lamblia (IgA prevents attachment needed for colonization in GI tract)
Risk: producing IgA specific hypersensitivity following a blood transfusions (because they do not make IgA)
Selective IgG deficiency
IgG1: susceptibility to many bacterial and viral pathogens
IgG2: susceptibility to encapsulated bacteria
Ab deficiency results in susceptibility to_______
extracellular bacteria and fungi, esp. encapsulated bugs that are resistant to phagocytes
What is the Tx for Ab deficiencies?
monthly injections of gamma globulin (passive immunization)
X-linked hyper IgM syndrome: CD40 ligand deficiency
TH1 cells cannot activate macrophages or B cells
susceptibility: mycobacterium in blood
NO granulomas
X-linked hyper IgM syndrome: AID defect
no class switching
CAN still activate effector T cells to supply second signals of activation to B and T cells
can have fully activated IgM B cells
IgM levels higher than in CD40 ligand deficiency
When would a person be unable to form germinal centers?
cannot activate B cells
When would a person be unable to form granulomas?
defect in macrophages
Common variable immunodeficiency (CVID)
group of immunodeficiense with common features (reduced Ab) but different etiologies
Dx doesn’t occur until 2nd or 3rd decade
Present: recurring bacterial and/or viral infections and hypogammaglobulinemia
Ataxia telangiectasia
Defect: ATM gene
Elevated: AFP (alpha-fetoprotein)
Result: B and T cell deficiencies (not SCID)
Present: cerebellar defects (ataxia), spider angiomas (telangiectasia), IgA (or IgE deficiency)
IL-12 signaling deficiency
Inability to generate TH1 response: decreased IFN-gamma- can’t activate macrophages
Result: normal B cells, T cells, and Ab isotope concentration
Present: disseminated mycobacterial infections
Job’s Syndrome
Hyper IgE syndrome
Defect: STAT-3 gene
Result: reduced production of IFN-gamma by TH1 cells and neutrophils that fail to respond to chemotactic signals
Highly polarized toward TH2 response
Present: high IgE; eczema, recurrent accesses with S. aureus, course facial features (broad nose, frontal bossing, deep-set eyes, doughy skin, retention of primary teeth)
FATED (facies, abscess, teeth, IgE, dermatologic)
chronic mucocutaneous candidiasis
group of disorders characterized by recurrent or persistent superficial infections of the skin, mucous membranes, and nails with Candida sp.
Caused by T cell dysfunction; undefined cytokine deficiency
TAP deficiency
very low MHC class I Result: CD8 T cell deficiency because very few are positively selected during thymic development susceptibility: intracellular pathogens
Bare lymphocyte syndrome (MHC class I)
TAP deficiency
alpha chain defect
CD8 alpha chain defect
Result: lack of CD8 expression
susceptibility: intracellular pathogens
Perforin deficiency
nonsense mutation
Result: dramatically reduced CTL and NK activity; normal number of CD8
SCID
CD4 T cell defects
B cells require effector T cell function
Bare lymphocyte syndrome (MHC class II)
No MHC class II
result: unable to mount CD4 T cell responses or B cell response
SCID
Wiskott-Aldrich syndrome
defect in cytoskeletal reorganization
result: T cells cannot activate B cells or macrophages; also effects CD8 T cells; normal levels of T and B cells, but affects Ab levels
SCID
Adenosine deaminase (ADA)
accumulation of toxic nucleotide catabolites that kills all lymphocytes during their development
NO B or T cells
SCID
Purine nucleotide phosphorylase
accumulation of toxic nucleotide catabolites that kills all lymphocytes during their development
NO B or T cells
SCID
common gamma chain deficiency
gamma chain is signaling component of a number of cytokine receptors (IL-2, IL-4, IL-7, IL-9, and IL-15)
Result: failure of T cells to proliferate; no effector T cells; still have T cells (no T cell activation), low B cells
SCID
NORMAL (relatively) NUMBER T CELLS
Janus Kinase (Jak3) deficiency
interacts with gamma chain
same phenotype as gamma chain
SCID
CD3 deficiency
No T cell function: lack of CD4 or CD8 T cells
SCID
DiGeorge Syndrome
Deletion chromosome 22: q11.2 i.e.
Present: congenital heart disease, palatal abnormalities, learning disabilities, hypocalcemia, facial abnormalities
Complete DiGeorge Syndrome
DiGeorge phenotype + absent or nonfunctional thymus
result: no T cells
Present: high susceptibility to bacterial, fungal, and viral infections
SCID
Tx: thymic transplant; can’t tx other DiGeorge symptoms
Hyper IgM
ZAP-70 deficiency
ZAP-70: TK that phosphorylates ITAMS via the T cell receptor complex; req. for T cell signaling
Result: absence of CD8 T cells and normal levels on non functioning CD4 T cells
SCID
Tx: bone marrow transplant
Omenn Syndrome
Defect: RAG
Result: no B cells and low number of oligoclonal auto reactive T cells
SCID: fungal bacterial and viral infections
Autoimmune: erythroderma, desquamation, alopecia, chronic diarrhea, failure to thrive, lymphadenopathy, and hepatosplenomegaly
Tx: bone marrow transplant
APECED
Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy
Defect: AIRE (transcription factor that regulates expression of self-proteins by epithelial cells in thymic medulla during T cell negative selection)
Symptoms: polyglandular autoimmunity (hypoparathyroidism, hypogonadism, adrenal insufficiency, T1DM, hypothyroidism) alopecia totalis, keratoconjunctivitis, tooth enamel hypoplasia, candidiasis, juvenile-onset pernicious anemia, GI problems
IPEX
Immune Dysregulation, Polyendocrinopaty, Enteropathy, X-linked syndrome
Defect: FoxP3 in CD4 T cells
Result: lack of Treg
Autoimmune (1st year of life): watery diarrhea, eczematous dermatitis, endocrinopathy (T1DM)
Also: Coombs-positive anemia, autoimmune thrombocytopenia, autoimmune neutropenia, and tubular nephropathy
Tx: immunosuppression or bone marrow transplant
ALPS
Autoimmune Lymphoproliferative Syndrome
Defect: no functional Fas, Fas-ligand, or caspase 10; immune cells fail to undergo apoptosis following an immune response
Result: large number of CD4-/CD8- T cells
Present: lymphadenopathy and splenomegaly; autoimmune hemolytic anemia and neutropenia, thrombocytopenia
Tx: immunosuppression and IVIg (passive immunity)
