Flashcards in Immuno: Acquired Immune Deficiencies Deck (52):
What is XLA (X-linked agammaglobulinemia)?
defect in Bruton's tyrosine kinase that prevents signal transduction in B cells; results in sparse B cell development and no humoral immune system
In a disease script or on wards, if you see/hear "underdeveloped tonsils" what disorder should you think?
X-linked agammaglobulinemia - deficiency of Bruton's tyrosine kinase and no B cells
A deficiency in B cell development would render a patient most susceptible to what type of pathogen?
extracellular bacterial pathogens (due to lack of humoral immune response) as well as many viruses (due to the inability to neutralize virions)
What is Pre-B cell receptor deficiency?
an inability to form the pre-B cell receptor due to a non-functional surrogate light chain; since the surrogate chain can't be formed, the pre-B cell and B cell receptors can't be formed, therefore apoptosis occurs leading to profound B cell deficiency
What is the genetic basis of Pre-B cell receptor deficiency?
mutation of the lambda-5 gene, which is a component of the surrogate light chain that pairs with the mu heavy chain during somatic recombination of light chain genes
(recall: lambda and kappa light chain genes)
What is X-linked hyper IgM syndrome?
Only Ab isotype produced is IgM because the B cells are deficient at class switching
What are the two causes of X-linked hyper IgM syndrome?
1. defect in CD40 ligand expression on T cell (needed for second signal of activation of B cells)
2. AID deficiency (needed for class switching)
If a person cannot activate macrophages, will there be germinal centers in their secondary lymphoid tissues?
Yes - if a person cannot activate B cells however there will be no germinal centers in the secondary lymphoid tissue
Selective IgA deficiency gives a patient the highest risk of what 2 things?
1. hypersensitivity to blood transfusion - because they will make an anti-IgA antibody
2. parasite pathogens
What is selective IgG deficiency?
deficiency of each or all of the IgG subtypes; IgG1 is very rare, while IgG2 is most common in kids and IgG3 most common in adults. IgG4 deficiency is of unknown significance.
What are the consequences of IgG1 and IgG2 deficiencies?
IgG1 - susceptibility to many bacterial and viral pathogens
IgG2 - susceptibility to encapsulated bacteria
What is CVID?
common variable immunodeficiency; group of about 150 disorders that feature reduced levels of antibodies, but different etiologies
What is the clinical presentation of CVID?
recurring infections mainly with bacterial and/or viral pathogens involving the ear, eyes, sinuses, nose, bronchi, lungs, skin, GI tract, joint, bones, CNS, parotid glands, etc.
CVID can be characterized by the presence of ____, but not as dramatic as that observed in XLA.
What is the genetic basis of Ataxia telangiectasia?
inherited defect in the ATM gene which encodes a DNA repair enzyme
What is the clinical presentation of Ataxia telangiectasia?
1. cerebellar defects (ataxia)
2. spider angiomas (telangiectasia)
3. IgA or IgE deficiency
Additionally: can also have elevated alpha-fetoprotein (AFP) levels in serum
What is the immune presentation of Ataxia telangiectasia?
B and T cell deficiencies, as well as very low levels of either IgA or IgE, but most typically IgA
What is the result of an IL-12 or IL-12 receptor deficiency?
inability to generate TH1 type responses; these patients make much less IFN-gamma
What is the clinical presentation of an IL-12 or IL-12 receptor deficiency?
most common susceptibility is to disseminated mycobacterial infections
What deficiency is caused by a genetic deficiency of STAT-3 function?
Job's syndrome, or hyper IgE syndrome;
What is the resulting deficiency in Job's syndrome?
result of deficient STAT-3 is the reduced production of IFN-gamma by TH1 cells (and strong bias toward differentiating TH2 cells), as well as neutrophils that fail to respond to chemotactic signals (undefined reason)
What are the clinical findings in Job's syndrome?
High IgE in blood.
2. recurrent abscesses with S. aureus
3. coarse facial features
Mnemonic: FATED - coarse/leonine Faces; cold staph Abscesses; retained primary Teeth; increased IgE; Dermatologic problems (eczema)
Chronic mucocutaneous candidiasis is a group of disorders characterized by what? What is the immune basis?
recurrent or persistent superficial infections of the skin, mucous membranes, and nails with Candida organisms, usually Candida albicans; immune basis is T cell dysfunction and undefined cytokine deficiency
TAP 1 or 2 deficiency affects what type of T cells?
CD8+ T cells; functional TAP-1/-2 is needed for successful positive selection of CD8+ T cells in the thymus
TAP deficiency results in what?
very low levels of MHC class I molecules and defective responses to IC pathogens (due to CD8+ T cell deficiency)
What is CD8 alpha chain defect?
lack of CD8 expression, which gives the same phenotype as TAP transporter deficiency
What is the result of a nonsense mutation in perforin?
dramatically or totally reduced CTL activity; normal numbers of CD8 T cells but they are unable to induce PCD of target cells; this means high susceptibility to viral and IC bacterial infections
____ T cell defects can result in SCID.
Lack of MHC molecules (class I or class II, makes for different types) is also known as ___ ___ ___.
Bare lymphocyte syndrome
Wiskott-Aldrich syndrome is a defect in what?
cytoskeletal reorganization that is needed for T cells to deliver cytokines and other signals to B cells and macrophages (cell cross-talk deficiency)
Deficiency of what results in accumulation of TOXIC nucleotide catabolites that MURDERS developing B and T cells?
deficiency of adenosine deaminase (ADA) or purine nucleotide phosphorylase
Common gamma chain deficiency is a deficiency of _____________. This is important because _____________.
its namesake, which is a component of many cytokine receptors.
Important because these receptors act through Jak3 pathway to induce T cell proliferation, and without the chain in the receptor there will be no effector T cells. AT ALL.
What is the phenotype of Janus Kinase 3 (Jak3) deficiency?
basically the same as common gamma chain deficiency: no T cell signaling or proliferation, no effector T cells
What is CD3 deficiency good for?
Absolutely nothing. In fact, it results in the lack of CD4+ or CD8+ T cells. Hmm. That's funny. Sounds like A TOTAL LACK OF T CELL FUNCTION. Hence, SCID.
Thymic aplasia means no development of what?
T cells. If you got this wrong you should just go home now. We can't help you.
What is a congenital condition that would result in a person not having a thymus?
complete DiGeorge syndrome (22q.11 deletion)
What infections are typical of SCID?
fungal, bacterial, and viral infections.
ZAP-70 deficiency prevents expression of functional ZAP-70. What is ZAP-70 and what does this disease look like?
ZAP-70 is a tyrosine kinase that associated with phosphorylated ITAMs during signaling via TCR complex; the disorder phenotype is absence of CD8+ T cells, normal number of NON-functional CD4+ T cells, results in SCID
What is the treatment for ZAP-70 deficiency?
bone marrow transplant
Omenn syndrome is caused by partial active ____ genes. What kind of B and T cells numbers/activity is there?
RAG genes - due to a mis-sense mutation; there is an absence of B cells and low numbers of oligoclonal auto-reactive T cells (yes, this syndrome results in an autoimmune disorder too)
What are the phenotype and symptoms of Omenn syndrome?
phenotype is SCID (pt develops bacterial/fungal/viral infections) and looks essentially the same as common gamma chain deficiency; symptoms include erythoderma, desquammation, alopecia, chronic diarrhea, failure to thrive, lymphadenopathy, hepatosplenomegaly
What is the treatment for Omenn syndrome?
bone marrow transplant
APECED stands for what, and is caused by what?
- "Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy"
- results from genetic deficiency of gene that encodes AIRE (a TF)
What are the characteristics of APECED?
polyglandular problems, including:
hypoparathyroidism, hypogonadism, adrenal insufficiency, type-1 diabetes, latent hypothyroidism, alopecia totalis, keratoconjunctivitis, tooth enamel hypoplasia, candidiasis, juvenile-onset pernicious anemia, GI problems
IPEX results from genetic deficiency of _____ expression in _____.
FoxP3 expression in CD4 Treg cells
What does IPEX stand for?
Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked Syndrome (IPEX)
What does IPEX result in, and what is the clinical presentation?
Results in autoimmunity to variety of host tissues in first year of life due to lack of Treg function; common clinical triad of:
1. watery diarrhea
2. eczematous dermatitis
3. endocrinopathy (type I diabetes)
*Additionally: most kids display Coombs-positive anemia, AI thrombocytopenia, AI neutropenia, and tubular nephropathy
What is the treatment for IPEX?
aggressive immunosuppression and/or bone marrow transplant
Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disease characterized by ____ and ____. This results from what?
lymphadenopathy and splenomegaly; results from immune cells that fail to undergo apoptosis following immune response, which is itself a result of deficient expression of either Fas, FasL, or casp-10
What are the 3 cell surface molecules of which a deficiency could cause ALPS?
What is the clinical presentation of ALPS?
AI hemolytic anemia, neutropenia, thrombocytopenia, splenomegaly, lymphadenopathy, often also have a large number of CD4- and CD8- T cells