Inflammation + male repro Flashcards
What type of immunity is defective with SCID? What are the major causes of SCID?
Humoral AND cell-mediated
- Cytokine receptor defects – IL-2 Receptor gamma chain deficiency – X-linked recessive!!
- Adenosine deaminase deficiency - autosomal recessive disorder, without deamination there is toxic accumulation within the lymphocytes
- MHC class II deficiency – recognized by CD4+ T cells which then helps T and B cells, so if it is missing, then you get defective function of T and B cells
What 3 types of infections are you predisposed to when you lack immunoglobulins (ex. in Brutons agammaglobulinemia)?
- recurrent bacterial infections [b/c lack of opsonization]
- enterovirus infections
- Giardia infections [IgA protects mucosa of GI tract and giardia binds mucosa of GI tract]
What are findings with common variable immunodeficiency and what do these pts have an increased risk of?
- low immunoglobulins and plasma cells
- increased risk for autoimmune diseases and lymphoma
**acquired disease!
Pts with which GI disease has a high propensity for IgA deficiency?
Celiac disease
Pts with hyper-IgM syndrome have increased risk of which infections?
pyogenic infections (b/c lack of IgG and IgG is an opsonin)
mucosal infections (lack of IgA)
What is autoimmune polyendocrine syndrome?
mutation in AIRE gene within the medullar epithelial cell – therefore some subset of self-antigens cannot be presented to developing T cells during negative selection and therefore those cells that do not get exposed to the subset are released in to the periphery and there are self-reactive lymphocytes within the periphery
Presents with..
- hypoparathyroidism
- Adrenal failure
- chronic candida infections of skin and mucosa
What two cells present self-antigens to developing T cells in the medulla of the thymus?
- dendritic cell
2. medullary epithelial cell
What is Peripheral tolerance? What happens if there is a defect in the apoptotic pathway?
Antigen recognized in peripheral tissue without co-stim receptor cell immune cell undergoes apoptosis/anergy – 2nd signal is required for T cell to become active
autoimmune lymphoproliferative syndrome (ALPS) – mutation of the Fas apoptosis pathway (Fas-L, Fas (CD95) [most common] or caspase def) allowing for survival or self-reactive lymphocytes leading to IgG production in the blood, proliferation of lymphocytes that are self-reacting, and hepatosplenomegaly – these patients may progress to lymphoma
What receptors are found on regulatory T cells?
CD4+ CD25+ FoxP3+
CD25+ = IL-2R, so regulatory T-cells are dependent on T cells for growth and survival
FoxP3+ = transcription factor required for development and maintenance of regulatory T cells
**there may be autoimmunity due to CD25 polymorphism and FOXP3 mutation (IPEX syndrome)
What two genes are association with autoimmunity?
- HLA subtypes
- PTPN22 = tyrosine phosphatase and mutations/polymorphisms result in gain of function which decreases signaling necessary for functioning
**there also needs to be an environmental trigger on top of mutations/polymorphisms
What are the symptoms of SLE?
RASH OR PAIN
Rash Arthritis ( non-erosive) Serositis Hematologic disorders (decreased complement (esp Cw), cytopenia) [esp due to TYPE II HSN REACTION] Oral/nasopharyngeal ulcers Renal disease Photosensitivity Antinuclear antibodies Immunologic disorder Neurologic disorders
Which antibodies are sensitive and specific for lupus?
SENSITIVE = Anti-ANA SPECIFIC = Anti-dsDNA and anti-Sm
Anti-dsDNA – can be used to follow disease activity and prognosis
What is anti-phospholipid antibody?
Anti-phospholipid antibody + hypercoagulable state
increases risk of DVT, hepatic vein thrombosis, placental thrombosis and cerebral thrombosis
**these pts require lifelong anticoagulation
Although anti-phospholipid antibody interferes with PTT test and shows an elevated PTT (thinking that the pt can’t coagulate their blood), these pts actually present with a hypercoagulable state.
**this may be associated with lupus, but is more commonly its own entity
What is the effect of an Anti-SSA positive mother on her fetus?
Neonatal lupus and congenital heart block – Anti-SSA can cross the placenta
Which two molecules are responsible for a majority of fibrosis formation?
TGF-B and PDGF
