Hypersensitivity, Autoimmunity and Immunodeficiency Part 3 Flashcards
immunodeficiency disorders increase susceptibility to
infection due to failure of one or more divisions of the ummune system
primary immunodeficiencies are
inherited and may affect any part of the immune system
secondary (acquired) immunodeficiencies are a consequence of what
many pathogenic infections or other disease states which may directly attack the immune system or may subvert effective immune responses
primary immunodeficiencies are affected by what
-failure of lymphoctye development
-impaired granulocyte function
lack of macrophage receptors
-absence of particular complement complement components
when are primary immunodeficiencies apparent
-early in life as conferred maternal immunity wanes
what is X-linked agammaglobulinemia (XLA, Bruton’s Disease)
-patients have normal T cell function and cell-mediate immunity to viral infections but have very low immunoglobulin levels and cannot make Ab response
in XLA, Bruton’s Disease B cells fail to express what
a tyrosine kinase BTK, required for the maturation of pre-B cells to mature B cells
in XLA, Bruton’s DIsease when does B cell maturation stop
- after initial heavy chain gene rearrangement due to the mutation in BTK associated with the pre-B cell receptor and involved in pre B-cell signal transduction
- no Ig light chains are produced though heavy chains may be found in the cytoplasm
XLA, Bruton’s Disease is absent or markedly decreased numbers of what
- B cells in circulation with depressed levels of all classes of immunoglobulins
- Pre-B-cells in bone marrow are normal or reduced
in XLA, Bruton’s Disease what cells are underdeveloped
-underdeveloped, rudimentary germinal centers in lymph nodes, Peyer’s patches, appendix and tonsils
XLA, Bruton’s Disease has an absence of what cells
plasma cells
XLA, Bruton’s Disease has normal —– responses
T-cell mediated
when is XLA, Bruton’s Disease apparent
-at about 6 months of age with recurrent acute and chronic pharyngitis, sinusitis, ottitis media, bronchitis and pnaeumonia due to organisms typically cleared by antibody-mediated opsonization and phagocytosis
patients with XLA, Bruton’s Disease are susceptible to what
- H. influenza, S. pneumonia or S. aureus
- Giardia lamblia due to lack of IgA
how do you treat XLA, Bruton’s Disease
-treatment with transfusion of IV Ig from pooled serum
20% of XLA, Bruton’s Disease may develop what
autoimmune disease such as RA and dermatomyositis
what is common variable immunodeficiency (CVID)
-a variety of conditions with no clear pattern of inheritance, which affect B cell differentiation
how does CVID differ from XLA
-sexes affected equally and symptoms occur in the 2nd or 3rd decade of life
what cells are abnormal in CVID
-B cells are present, but do not develop into plasma cells bc of lack of T cell help, T-cell suppressor activity, or intrinsic B-cell defects
patients with CVID have a relative high incidence of what
autoimmune disorders and lymphoreticular neoplasias
what is the most common primary immunodeficiency disorder
isolated IgA Deficiency
what is the function of IgA
is a major Ig in mucosal secretions therefore patients with isolated IgA deficiency have airway and GI defense problems
isolated IgA deficiency is associated with what other disease
autoimmune diseases
what levels are normal in patients with isolated IgA deficinecy
-have normal or supranormal levels of IgM and IgG subclasses
what happens to IgA in patients with isolated IgA deficiency
-have a block in terminal differentiation of IgA secreting B cells to plasma cells
what is X-linked hyper- IgM (HIGM)
-an immunodeficiency due to mutation in CD40L, the T cell ligand which binds to CD40 on B cells- an interaction required for class switching in secondary responses
what is normal in HIGM
-have normal or supranormal levels of IgM, but lack the ability to produce IgG, IgA or IgE isotypes
the CD40L gene is located on what chromosome
x chromosome, 70% of HIGM clases are x-linked
what are other causes of HIGM
-defect in activation induced deaminase and enzyme involved in class switching
what is X-HIGM
-defect in cell mediate immunity as CD40-Cd40L interaction is critical for helper t cell mediated activation of macrophages in cell mediated immunity
male patients with X-HIGM present with what
recurrent pyogenic infections due to low levels of opsonizing IgG and have a variety of intracelular pathogens inducing Pneumocystis jirovenic (carinii)
DiGeorge Syndrome is a result from what
failed development of the 3rd and 4th pharyngeal pouches which leads to thymic hypoplasia with low #’s of functionally active T cells
-T cell number may rise to normal within 1-2 yrs of life thymus tissue transplant is effective
DiGeorge Syndrome has a lack of what
T cells in lymph nodes, spleen and peripheral blood
infants with DiGeorge Syndrome are extremely vulnerable to what
viral, fungal, and protozoal infections and intracellular bacteria
are B cells affected in DiGeorge Syndrome
B cells and serum immunoglobulins are unaffected
patients with DiGeorge syndrome may have parathyroid hypoplasia leading to
hypocalcemic tetany and other midline development abnormalities including the face and aortic arch
90% of DiGeorge Syndrome cases have a deletion in what chromosome
22q11
what is severe combined immunodeficiency (SCID)
-a group of conditions with leukocytopena, impaired cell-mediated immunity, low or absent antibody levels and undeveloped secondary lymphoid tissues
patients with SCID have an autosomal recessive
adenosine deaminase deficiency or purine nucleoside phosphorylase deficiency
what type of disease is SCID
X-linked or autosomal recessive traits where enzymes are not affected but due to an inability to recombine antigen receptor molecules
different forms os SCID may be correlated to points of what pathway
lymphomyeloid differentiation pathway
what type of disease is Wiskott-Aldrish Syndrome
X-linked
what are the symptoms of Wiskott-Aldrich Syndrome
-thrombocytopenia, eczema and susceptibility to recurrent infections leading to early death
how do you treat Wiskott-Aldrich Syndrome
-bone marrow transplantation
what is the mechanism of Wiskott-Aldrich Syndrome
- normal thymus with progressive age-related depletion of T cells and loss of cellular immunity
- cannot synthesize Abs to polysaccharide antigens even though B cell response to these antigens do not require T cell help
patients with Wiskott-Aldich Syndrome are prone to developing
malignant lymphomas
genetically, how does Wiskott-Aldrich Syndrome occur
-the gene maps to the X chromosome and encodes the Wiskott-Aldrich protein that links several membrane receptors to the cytoskeleton leading to abnormal cell-cell adhesion and leukocyte migration
what are genetic deficiencies of components of innate immunity
-hereditary deficiencies in complement components (C3 classical and alternative pathways) result in increased susceptibility to infection with pyogenic bacteria
deficiencies in –, – and – increase the risk of immune complex-mediated disease (SLE)
C1q
C2
C4
deficiencies in C1q, C2, C4 impair the clearance of what
apoptotic cells or antigen-Ab complexes
deficiencies of C5-C8 of the classical pathway result in recurrent infections by
Neisseria gonococci and meningococci only
lack of regulatory protein C1 inhibitor allows increased
C1 activation increased vasoactive complement mediators and results in hereditary angioedema
there are congenital defects if phagocytes including defects of pahgocyte oxidase enzyme leading to
chronic granulomatous disease and defects in integrins and selectin ligands with resultant leukocyte adhesion deficiencies
primary immune deficiency disease are caused by what
mutations in genes involved in lymphocyte maturation or function in innate immunity leading to increased susceptibility to infections in early life
XLA failure of B-cell maturation
lack of antibodies; mutations in BTK gene
CVI
defects in Ab production, unknown cause
IgA deficiency
failure of IgA production, cause unknown
X-SCID failure
T and B cell maturation mutation of the common V chain of cytokine receptor leading to failure of IL-7 signaling and defective lymphopoiesis
autosomal SCID
- failure of T-cell development, secondary defect in antibody responses
- approx 50% of cases due to mutation of gene encoding ADA leading to accumulation of toxic metabolites
X-linked hyper IgM syndrome
failure to produce isotype-switched high affinity antibodies (IgG, IgA, IgE; mutation in gene encoding CD40L)
secondary immune deficiencies are —- that primary immune disorder
more common
where are secondary immune deficiencies found
in malnutrition, infection, cancer, renal disease or sarcoidosis
what is the most common cause of secondary immune deficiencies
-therapy induced suppression of the bone marrow and of lymphocyte function
AIDs is a retroviral disease caused by
HIV
AIDs is characterized by what
infection and depletion of CD4+
T cells are profound immunosuppression with opportunistic infections, secondary neoplasms, and neurologic manifestations
