immuno test 3 Flashcards
multiple sclerosis
T cell mediated auto immunity-> demylinated CNS tissue
cd4 and cd8 cells and many MHC-II cells
relapse remitting- myelin destroyed then Na channel increase to compensate
others are chronic
previous EBV, Hep B, Adenovirus 2, HLA -DR2 linked`
DM1
T cell mediated autoimmunity
CD8 t cell destroy B cells
HLA-A2 presented to CD8 will destroy B cells
may be some Ab function too
RA
both Ab and T cell mediated
auto immune disease- chronic inflammation of
onset of fever, fatigue, anorexia, joint pain and swelling
initiated by deposition of IC and chronic inflammation response-> infiltrate of Macrophage, T cell, and plasma cells
ACPA’s and RF( an IgM against IgG) for IC in joint and activate compliment
Hashimotos thyroditis
most likely a T cell mediated( type 4 hyper sensitivity)
but there are auto antibodies to thyroid peroxidase and thyroglobulin
dry skin, puffy ace, brittle hair and nails, and constantly cold
HLA_ DR5, DR3, and B8 associated
bone marrow transplant and ablation
treatment of scleroderma and SLE
MS treatment
IFN-B
humanized antibody against integrin a4 ( natalizumab)
immuno deficiency
characterized by increased, persistent, and /or recurrent infections with unusual organisms- opportunistic infections
phagocytic deficiencies
infections characterized by opportunistic extracellular pathogens( S. aureus, Strep. pneumo, E COli, pseudomonas) and fungi ( canidida and aspergillis)
normal range of PMN in blood
2000 to 6000
congenital graulocytosis (kostmanns syndrome)
primary neutrophil deficiency
almost complete absence of peripheral Neutrophils maturation arrest at amyloid progenitor stage
manifest with severe bacteria and fungal infections
G-CSF and bone marrow transplant indicated
new congenital neutrophil defect charcteristics
mutation in VPS45 gene, in 7 patients
neutropenia
neutrophil disfunction
nephromegaly
secondary neutropenia
radiation or chemo induced neutropenia
quicker recovery
qualative deficiency in neutrophils
defect in any point in the process of phagocytosis
- adherence defect
- chemotactic defect
- killing defect
Myasthenia Gravis
organ specific auto immunity
Ab produced to the ACh receptors at neuromuscular junction
-drooping eyelids, difficult chew, swallowing and breathing and eventually respiratory failure
some neonates have transient symptoms if mother has dx
HLA-DR3
Autoimmune hemolytic anemia (AIHA)
Ab produced to the Rh antigen or I antigen and target RBC for destruction
RBC destroyed by compliment or Mphage phagocytosis
presence of anemia, hemolysis with reticulocytosis, low haptoglobin, ^ LDH, ^IBIL, + direct antiglobin test
warm Hemoglutinnins- IgG class to the Rh antigen at 37C
cold hemaglutinnins- IgM class to the I antigen below 37C
SLE pathology
Systemic multi organ autoimmune disease w/Ab to DS DNA
ANA Abs for IC with DSDNA and other nuclear proteins then trapped in BM of Kidney, artery wall, synovium to induce inflammation
compliment deficiency->lack of C3B-> less phag of IC
HLA-DR3 and DR2
SLE clinical presentation
fever, joint pain, malar rash, CNS damage, damage to heart and Kidney
women 15-45 10x more than men
diag test ANA indirect fluorescence on HEP-2
Scleroderma
systemic autoimmune characterized by fibrosis, arthritis, hair loss, and arteritis
ANA are present, not to DNA or RNA but to DNA and RNA synthesis enzymes-topoisomerase 1 and RNApolymerase1 and sometimes centromeres
more common in women 30-50
diag test ANA indirect fluorescence on HEP-2 with different staining that SLE
Sjorgren syndrome
systemic autoimmune disease of the exocrine glands especially salivary and lacrimal
present with dry eyes and dry mouth, 50% OF PTS HAVE ANOTHER AUTOIMMUNE DISEASE
dial-presence of Ab to cytoplasmic agent SS-a(RO) and SS-B(LA) (both are cytoplasmic protein- RNA complexes
detected on elisa/western blot,new research on anti M3Rab
Graves disease
Antibody mediated autoimmunity, manifest as hyperthyroid
TSI_ thyroid stimulating immunoglobulin activates the TSH receptor
women 4:1 and presents with low TSH and high T3 and T4
HLA-DR3
can cross the placenta leading to transient hyperthyroid in neonate
Goodpastures syndrome
Type 2 hypersensitivity
Abs are produced against the a3chain of the basement membrane collagen(IV collagen)
Ab bind to Renal BM and alveolar BM-> rapid fatal if untreat
Fc portion also ligates Fcgama receptors on monocytes, PMN, tissue basophil, and mast cells ->activation of these cells
also Ab lead to compliment activation to exacerbate injury
Congenital Agranulocytosis (Kostmann’s syndrome)
1o phagocytic immunodeficiency, neutrophils
50% B/C OF ELANE(19) gene and 15% B/C HAX1 gene(1)
-Maturation arrest at myeloid progenitor stage
-Manifest with severe bacterial and fungal infections within the first month of life
-Recombinant G-CSF or bone marrow transplant
induced Neutropenia
2o phagocytic immunodeficiency
LAD
qualitative deficiency
autosomal recessive primary, defect in selectin/integrin binding
LAD1 - defective B chain of integrin CD18(ch1)
LAD2- defective selectin cd11a or cd11b
PMN cannot extravasate to extravascular tissue
recurrent bacterial infection with abnormal inflammation and no pus - soft tissue and periodontitis
ALLOgenic stem cell transplant is only treatment
also can happen in NKand CTL and the interacting with B cells
Lazy leukocyte syndrome
primary defect
defect in the PMN ability to respond to cheekiness or an inability to produce C3a, C5a
Can’t recognize chemotactic signals to leave the vasculature and thus they don’t leave the circ NO PUS
ALLOgenic stem cell transplant is only treatment
killing defects
Chronic granulomatous disease
Chediak higashi syndrome
Chronic granulomatous disease
most prevalent primary defect of iintracell killing
X linked recessive, first 2 years of life
defect in cytochrome B and NADPH oxidase, also in myeloperoxidase and G6PD
Can’t kill phagocytosed pathogens decrease H2O2- allows for the survival of catalase- producing bacteria (e.g. Staph aureus)
Actimmune® (r IFN- gamma) but ultimately require allogeneic bone marrow stem cell transplant
myeloperoxidase deficiecy
manifest same way as chronic granulomatous disease
Chediak higashi syndrome
autosomal recessive primary defect
mutatein LYST gene(Ch1)->codes micritubule polymerization
defect in producing lysosomes and killing
present cells with large granules in cytoplasm
resurrent pyogenic infections(staph and strep) (silver hair and eyes
BMT required
Bruton’s X-linked agammaglobulinemia
primary defect of B cell development, defect BTK gene
Block in B cell development at the pre-B cell stage due to inability of mu heavy chain to signal with surrogate light chain, thus severely decreased mature B cell numbers and decreased Ig levels
Severe recurrent bacterial infections with Streptococcus pneumonia, Staphylococcus aureus, Haemophilus influenza, and other bacteria that form capsules
HISG monthly
X-linked hyper-
IgM syndrome
-primary defect, little to no isotope switch
-no functional CD40 L to bind to CD40 to induce isotope switch of B cells, so ^^^levels of IgM
-also have high levels of auto antibodies to PMN, platelet and RBCs( careful in transfusing)
-get Streptococcus, otitis media, septicemia and pneumonia
need BMT
IgA deficiency
- most common isotope deficiency, little or no IgA in serum
- Repeated respiratory and GI infections; tend to have sever allergies and antibodies against IgA (risk of reaction against transfused plasma), also autoimmune dx-SLE and CD
- Treat infections as arise (in chronic situations, treat prophylactically); also treat allergies
Common variable 1o immunodeficiency (hypogammaglob ulinemia)
-primary deficiency
-Significantly low levels of Ig and no plasma cells, but normal B cell numbers
defect in cytokine receptor expression and TJ2 cytokines
HISG treatment
20-40 w/ recurrent infections of Uand LRT
also otitis media, diarrhea, pneumonia, and sinusitis
digeorge syndrome
primary defeciency, defect in 3 and4th pharyngeal pouch
deletion on the 22 chromosome, facial, hypo parathyroid, and cardiovascular defects
decreased CD3 cells
Repeated viral, fungal, and protozoan infections; no DTH reaction
complete athymia need transplant or die by age 2
zap 70 defect
primary defect, autosomal recessive
-a tyrosine kinase vital to cell signaling thru TCR
-Loss of CD8+ Tcells with non-functional CD4+
T cells
BMT is only cure
Chronic Mucutaneous Candidiasis
no t cells response to Candida infection autosomal dominant STAT1 mutation autosomal recessive AIRE mutation -Present with severe and repetitive candida infections of skin, nails, and mucous membranes without propensity for disseminated disease anti fungal treatment and boost CMI
Job syndrome
Autosomal dominant STAT3 (ch17) mutation, so that T cells default to Th2’s.
Manifest with High IgE, eczema, eosinophilia and recurrent infections Staph aureus and Candida, staph accesses, retained primary teeth
BMT treatment
bare lymphocyte syndrome
Loss of all CD8+ T cells (types I and II) and/or CD4+ T cells (Type II only) because they cannot be positively selected in the thymus
Recurrent opportunistic viral, bacterial, and fungal infections.
no antigen specifice t cell response but the is mitten response
need BMT
SCID
Loss of T cells and B cells. 40% of SCID is caused by mutations in IL2RG and 20% are due to mutations in ADA
-Constant diarrhea, failure to thrive, thrush and recurrent viral, bacterial, fungal, and/or protozoan infections
BMT
OMENN syndrome
autosomal recessive mutation in RAG1 or RAG2( both ch11)
no b cells and few t cells that can be auto reactive
inability to generate heavy/light chains (B cells) or T cell receptors
manifest with lymphadenopathy, eosinophilia, and hepatosplenomegaly
need BMT
Wiskott-Aldrich syndrome
B cells, T cells,macrophages, X linked
- Mutations in WASP protein & results in normal B and T cell numbers, but defective Ab production and killing activity
- Eczema, defective Ab production, decreased cytotoxic killing ability. thrombocytopenia and unusually small platelets; increased risk of AI dx and lymphomas
- HISG to replace missing Ab, but ultimately a bone marrow transplant
Ataxia Telangiectasia
autosomal recessive mutation in inATM gene on ch11
Atm encodes for DNA repair of dsDNA breaks
low b and t cell numbers with no class switching, especially IgA
Increased susceptibility to pneumonia, and increased risk of leukemia and lymphoma
also possible neurologic and other organ system damage
BMT needed
symptoms of GVH disease
rash, hepato-splenomegaly,lymphadenopathy, anemia, weight loss and wasting, diarrhea
