2-Immunodeficiency Flashcards
immunodeficiencies
definition
lack of an immune system or failure of components that inc susceptibility to infection
-primary/congenital OR secondary/acquired
acquired/secondary immunodef
from AIDS, drugs for transplantation or cancer, malnutrition
affected components
- defect humoral imm = infection extracelluar bacteria
- CMI impaired = infection virus and intracell
- if both then infections with all classes microorganisms
cancers of viral etiology
EBV > lymphomas
HPV > skin cancers
T cell deficiencies = inc risk bc less immunosurveillance
B cell deficiency characteristics
- dec serum Ig levels
- normal skin test rxn
- lymphoid tissue germinal centers dec or absent
- extracellular bacteria susceptible
T cell deficiency characteristics
-normal or dec Ig levels
-dec skin test rxn
-normal follicles + dec paracortical region of lymphoid tissue
-virus, intracell bact, fungi susceptible
X linked agammaglobulinemia
aka bruton’s agammaglobulinemia
-no mature B cells so little Ig
-block in B cell maturation bc normal pre-B levels in marrow
-B cell tyrosine kinase mutation
-males only, female carriers don’t manifest disease bc other X is normal
-onset 6 mo to 1 yr, mean dx 3 yr olds
-pyogenic bacteria suscept
X linked agammaglobulinemia
diagnosing
absence of circulating B lymphs via flow cytometry but after 6-9 mo bc maternal antibodies
controlled by monthly injections of pooled gamma globulin + antibiotic therapy but NOT vaccines bc no antibody resp
common variable immunodeficiency
mature B cells not diff into plasma cells so dec antibodies
-males and females suscept to recurrent bacterial infection
-progressive pulmonary insufficiency
selective IgA deficiency
most common immunodef
-asymptomatic but maybe inc infections of mucosal sites
-IgM can compensate
-IgE anti-IgA so severe/fatal anaphylatic rxn if given plasma with IgA
selective IgA deficiency
diagnosis
severely dec IgA levels, others are normal
-B cells with surface IgA but no diff into plasma cells
-T cells still intact
-maybe inc allergy, GI tract disease, autoimmune
only treat with antibiotics NO antibodies/gamma globulin
hyper IgM syndrome
overabundance of IgM+ lack other isotypes
either x linked or type 2
x linked hyper IgM syndrome
inherit def of CD40L on T cells so CD40 on B cells not engaged and no isotype switching
hyper IgM type 2 syndrome
inherit mutation in gene activation induced cytidine deaminase so prevents isoype switching
-reasons unknown
DiGeorge Syndrome
aka congenital thymic hypoplasia
-def of T cells bc small or no thymus
-poor CMI vs virus and fungi
-maternal alcoholism and chromosome 22q11 deletion
-treat with age bc of extrathymic maturation
DiGeorge symptoms
-facial features distinct
-parathyroid glands
-heart vessles
bc from third and fourth pharyngeal pouches during embryogenesis
-immunoglobulin levels near normal but T cells severly dec
SCID
fail of B and T cells to dev from bone marrow stem cells so little/no humoral OR CMI = death from overwhellming infection
-live viral vaccines can be fatal
also called swiss type agammaglobulinemia
causes of SCID
- autosomal recessive - ADA adenosine deaminase def so toxic metabolites destroy lymphs
- RAG1/2 def- failure of VDJ rearrange, no recombinase in immunoglobulins and TCR genes
- x linked SCID- mutation in gene for y chain for cytokine receptors for IL2,4,7,9,15 so lymphs not dev properly
SCID treatment
bone marrow transplant but gene therapy used to transfect autologous bone marrow stem cells with ADA
chronic granulomatous disease
recurrent bacterial infections from early childhood
-NADPH def so neutros not make superoxide for respir burst
bone transplant or gene therapy treat or antibiotic therapy but still fatal
myeloperoxidase deficiency
dec or absent myeloperoxidase so no hypochlorous acid for antibacterial and antifungal
compensatory mechanisms so no inc suscept but still fungal
chediak higashi syndrome
low yield
leukocyte adhesion deficiency
defect in beta chain of LFA-1 and Mac-1 adhesion moles so neutros not adhere to endo cells for extravasation
-recurrent bact/fungal infections
-wound healing problems
-extremely high WBC levels/leukocytosis
leukocyte adhesion deficiency
treatment
neutropenia
low yield
either
wiskott-aldrich syndrome
- immunodef
- eczema
- thrombocytopenia, lack platelets
no WASP protein so cells not traffic to sites of inflamm and B/T cells not interact
ataxia telangiectasia
-loss ability to coord muscles
-vascular lesions
-inc incidence tumors
defect in ATM
