I15 Flashcards
In general, antibody deficiencies result in an increased susceptibility to what kinds of infections?
extracellular bacterial and fungal, especially encapsulated bugs that are resistant to phagocytosis
What are some examples of inherited antibodies deficiencies?
X-linked agammaglobulinemiapre-B cell receptor deficiencyX-linked hyper IgM syndromeselective IgA deficiencyselective IgG deficiency
What is the preferred treatment for inherited antibody deficiency?
Monthly passive immunization (IVIg) as a replacement therapy.
What is X-linked agammaglobulinemia caused by?
is a condition that results from a mutation that renders Bruton’s tyrosine kinase non-functional. Btk is required for B cell development, and a defect in this gene results in an inability of B cells to survive bone marrow development.This results in a patient having very low B cell counts, leaving them without a humoral immune system
Patients with X-linked agammaglobulinemia are susceptible to which kinds of infections?
extracellular bacterial pathogens as well as many viruses because they lack the ability to neutralize virions
X-linked agammaglobulinemia is associated with what main clinical presentation?
underdeveloped tonsils in young children
What is Pre-B cell receptor deficiency caused by?
A genetic defect in the surrogate light chain (lambda 5 gene) that results in apoptotic death of B cells during the early stages of B cell development.lambda 5 is a component of the surrogate light chain that pairs with the mu heavy chain during somatic recombination of light chain genes Patients are susceptible to both extracellular bacteria and many viruses.
What are the possible causes of X-linked hyper IgM syndrome?
1) A defect in CD40 ligand (or CD40) production results in an inability of helper T cells to activate B cells and macrophages. Almost all of the antibodies that will be produced by a person with this condition will be IgM, and the patient’s IgM levels will probably be higher than in an immunocompetent person.2) In contrast, a person with AID deficiency would be unable to class-switch, but these patients are able to have fully activated B cells. The IgM levels in these patients will be higher that those with a CD40 ligand deficiency.Better to have the AID deficiency because effector T cells would still be able to supply the second signals of activation to B cells.
A person that can activate B cells will have germinal centers in their secondary lymphoid tissues.Those that cannot activate B cells, for whatever reason, will not have any germinal centers in their secondary lymph nodes.
A person that can activate B cells will have germinal centers in their secondary lymphoid tissues.Those that cannot activate B cells, for whatever reason, will not have any germinal centers in their secondary lymph nodes.
What is Selective IgA deficiency caused by?
one of (if not the) most common genetic immunodeficiency. The genetic mutation(s) are unknown, and most people with this problem never are diagnose unless they are exposed to PARASITE pathogens
What are some major problems with those who have selective IgA deficiency?
these patients are at risk for developing anaphylactic reactions following blood transfusions. Because they do not make any IgA, there are not tolerant to the IgA that is transplanted in during a transfusion.It is also important for you to know that patients with selective IgA deficiency have an increased chance of developing immediate type hypersensitivities, such as asthma, as well as autoimmune diseases that include systemic lupus erythematosus and rheumatoid arthritis.
In adults, what are the relative percentages of IgG subtypes in circulation?
IgG1- 60-70%IgG2- 20-30%IgG3- 5-8%IgG4- 1-3%
Notes on Selective IgG deficiency.
genetic cause is unknown; likely heterogeneousdeficiency of each IgG subtype is possible:IgG1 deficiency (most important) is very rare; susceptibility to many bacterial and viral pathogens IgG2 deficiency is most common in kids; susceptibility to encapsulated bacteria IgG3 deficiency s most common in adultsIgG4 deficiency is of unknown significance
What is common variable immunodeficiency?
a group of around 150 primary immunodeficiencies that have common features that typically include reduced levels of antibodies, but different etiologies (many of which remain undefined). Causes are genetic, but diagnosis typically does not occur until 2nd or 3rd decade of patient’s life
What are the clinical manifestations of common variable immunodeficiency?
recurring infections mainly with bacterial and/or viral pathogens involving the ears, eye, sinuses, nose, bronchi, lungs, skin, GI tract, joints, bones, CNS, parotid glands
What other symptom is common with common variable immunodeficiency?
hypogammaglobulinemia is typical, but not as dramatic as observed in X-linked agammaglobulinemia
What is Ataxia telangiectasia caused by?
caused by an inherited defect in the ATM gene (encodes a DNA repair enzyme).Causes B and T cell deficiency in some patients (but not as bad as SCID) and patients have low lymphocyte numbers (especially T cells) in the blood and very low levels of either IgA or IgE (most typically IgA)
Patients with Ataxia telangiectasia typically have the following clinical triad:
(1) Ataxia (cerebellar defects)(2) Spider angiomas(3) Either IgA (most commonly) or IgE deficiency•• elevated alpha-fetoprotein levels are also common
What are some of the consequences of genetic IL-12 deficiency?
Any deficiency that results in defective IL-12 signaling leaves a patient with the ability to make only small amounts of IFN-gamma. This in turn results in very diminished ability to produce TH1-type CD4 effector cells and the inability to fully activate macrophages. Mutation in either chain of the IL-12 heterodimer or the IL-12 receptor can cause this condition.
The most common susceptibility observed in patients with IL-12 deficiency is to ____.
disseminated mycobacterial infections.
What is Job’s syndrome?
a genetic deficiency of STAT-3 function that results in reduced production of IFN-gamma by TH1 T cells and neutrophils that fail to respond to chemotactic signals (for some undefined reason)These patients make immune responses that are highly polarized toward a TH2 phenotype. One of the end results of this is high concentrations of IgE in the blood.
What are the main clinical manifestation of Job’s syndrome?
Patients suffer from eczema and recurrent abscesses with Staph aureus (primarily). These patients also have characteristic facial features that include a broad nose, frontal bossing (which is an unusually prominent forehead with a very prominent brow ridge), deep set eyes, and retention of primary teeth.Common mnemonic: FATED- coarse of leonine Facies, cold staph Abscesses, retained primary Teeth, increased IgE, and Dermatologic problems (eczema)
What is Chronic Mucocutaneous Candidiasis?
a condition (or panel of conditions) that results from undefined T cell dysfunction leaves patients susceptible to recurrent or persistent superficial infections of the skin, mucous membranes, and nails with Candida organisms, usually Candida albicans (yeast only)
What does TAP-1 or TAP-2 deficiency (aka bare lymphocyte syndrome (MHC class I)) result in?
results in very low numbers of CD8+ T cells in the repertoire because MHC class I is unstable if peptides are not loaded into their binding groove. The end result is that very few CD8+ T cells receive positive selection in the thymus, so there are very few CD8+ T cells in the repertoire, and really no ability to generate an effector CD8+ T cell response.A CD8 alpha chain defect results in essentially the same phenotype as a TAP transporter deficiency for the same reasons. Patients with these conditions are highly susceptible to viral and some intracellular bacterial infections.
