misssense mutation in fibrillin structural protein
connective tissue defect, death by aortic rupture
Duchenenne/Becker Muscular dystrophy
deletion with reduced synthesis of dystrophin
x linked recessive
spectrin, ankryn, or protein 4.1
heteogeneous molecular lesion
-hemolytic anemia, splenomegaly
X linked recessive
deletions, insertions, nonsense mutations, and others; reduced synthesis or abnormal factor VIII
inability to form clots
deletion of Rb protein
neurofibramatosis type 1
heterogeneous molecular lesion..
-multiple neurofibromas, gliomas of optic nerve, cafe a ulait skin lesions, iris lesions.
splice site mutation or frameshift mutation with stop codon; reduced amount
-hexosaminidase A deficiency. improper metablolism of gangliosides in nerves cells; early death. progressive deterioration of mental and physical abilities that
commences around six months of age and usually results in death by the age of four. The disease occurs when harmful quantities of cell membrane components known as gangliosides accumulate in the brain's nerve cells, eventually leading to the premature death of the cells. A ganglioside is a form of sphingolipid, which makes Tay–Sachs disease a member of the sphingolipidoses. There is no known cure or treatment.
SCID- what defect(s) cause this?
Defect: most common is x linked mutation with gamma subunit of cytokine receptors neneded to signal transduction related to binding of several cytokines (esp il-7) receptor. Common AR form is adenosine deanimase deficiency-> defects in both cell and humoral immunity. t cell defect leads to secondary defect in humoral immunity.
SCID- clinical presentation
presentation: opportunistic infections of infants; Graft vs host dz, post vaccination infections.
-candadiasis and FTT in early infancy. suceptoble to infections due to a wide range of bacteria, fungi
-small thymus, hypoplasia of other lymphoid tissues.
-marked depletion of the T cell areas and in some cases, also b cell areas.
missense mutations; impaired secretion from liver to serum. a1 antitrypsin deficiency.
lesion: deletions, point mutations, reduction of synthesis, transport to cell surface, or binding to LDL lipoprotein.
-elevated levels of cholesterol predisposes person to plaque formation
vitamin D resistant rickets
point mutations, failure of normal signaling
-X linked dominant
deletions: reduced amount
defective mRNA processing--> reduced amount
sickle cell anemia
point mutation. missense mutation of glutamic acid to valine.
deletions and other mutation of cystic fibrosis transmembrane conductive regulator.
-mucous production that blocks ducts of certain glands, lung passaes; often fatal by early adulthood
x linked dominant...skin abnormalities that evolve throughout childhood and young adulthood.Many affected infants have a blistering rash at birth and in early infancy, which heals and is followed by the development of wart-like skin growths. In early childhood, the skin develops grey or brown
patches (hyperpigmentation) that occur in a swirled pattern. These patches fade with time, and adults with incontinentia pigmenti usually have lines of unusually light-colored skin (hypopigmentation) on their arms and legs.
hereditary optic neuropathy
-rapid vision looss due to optic nerve death.
-dwarfism associated with defects in growth receptors of long bones.
ehlers danlos syndrome
adult polycystic kidney disease
formation of cysts in the kidney; leads to hypertension, kidney failure.
progressive degeneration of nervous system; dementia; early death.
asence of pigment in skin, eyes, hair
slow growth, heart defects; high rate of leukemia
accumulation of galactose in liver; mental retardation
lack of DNA repair enzymes, sensitivity to UV light; skin cancer; eary death
color blindness: green
x linked recessive; insensitivity ot green light; 60 to 75% of color blindness cases.
color blindness: red
x linked recessive
insensitivity ot red light; 20 to 40% of color blindnes cases
x linked recesssive
metabolic defect caused by a lack of enzyme alpha galactosidase A; progressive cardiac and renal problems; early death
glucose 6 phosphate DH deficiency
X linked recessive
benign condition that can produce severe, even fatal anemia in the presence of certain foods, drugs
X linked recessive
"Christmas disease" clotting defect caused by a lack of factor XI
X linked recessive
metabolic defect caused by lack of enzyme hypoanthine-guanine phosphoribosyl transferase (HGPRT) causes mental retadation, self-mutilation, early death,
x linked agammablobulinemia (Brutons)
pre B cell--> B cell due to tyrosine kinase mutation on x chromosome.
presentation: pyogenic infections in males @ approx six months. Inc risk of entroviral infections, giardiasis, absemnt plasma cells; CMI intact.
-inc risk for AI disease
selective IgA deficiency
terminal differentian of IgA cells does not occur.
-recurrent respiratory, GU, and GI tract infections; increase in allergic and AI disease.
common, variable immunodeficiency
terminal differentiation from B cells to plasma cells. cause unknown; some have identified decreased t cll regulation of B cell; others have shown B cell defects
-antibody of all classes deficiency but sometimes only IgG
-male and female @ inc risk of bacterial infection in adolescents and young adults; hyperplastic lymphoid follicles; increase risk for AI dz esp RA. lymphoma is a late complication.
Di George's syndrome
failed abnormal development of 3rd and 4th pharyngeal pouch (incudes thymus, parathyroid gland, great vessels) 22q deletion.
-tetany, facial dysmorphism, congential heart defects, opportunistic fungal/viral infections; paracortical areas of lymph nodes depleted of T cells; Ig may e none or decreased ased on severity of T cell defect
Wiskott Aldrich syndrome
x linked recessive. mutation in gene involved in signal transduction and cytoskeletal integrity; causes premature destructionso f platelets leading to thrombocytopenia.
-thymus is normal early in life--> progressive T cell deficiency--> decrease in CMI.
-IgM normal. IgG Iga IgE may be increased.; increased risk for lymphoma.
what neoplasms are AIDS patients @ increased risk for?
kaposi sarcoma, B cell lymphomas, invasive cell carcinoma.
primary brain lymphoma
AIDS defining fungal infections (3)
1.candidiasis of bronchi, trachea, lungs, or esophagus
2. cocciomycosis; extrapulmonary or systemic
3. histoplasmosis; extrapulmonary or systemic
AIDS defining parasitic infections (3)
1. chronic cryptosporidiosis
2. pneumocystis pneumonia
AIDS defining viral infections (3)
1.CMV other than liver, spleen or LN
2. chronic herpes simplex ulcer or systemic
3. varicella zoster.
AIDS defining bacterial infections (3)
1. typical or atypical disseminated or extrapulmonary mycobacterial inection.
3. salmonella septicemia
AIDS defining conditions/stipulations
CD4 count less than 200 or development of opportunistic infection.
also can be dx with AIDS by: hiv encephalopathy, progressive multifocal leukoencephalopathy, or HIV wasting syndrome.
what drug is recommended for prevention of HIV via occupational exposure?
How does HIV enter the cell?
GP 120 binds with CD4 leading to confirmational change that allows CCR5 chemokine binding. it leads to confirmational change allowing GP41 to penetrate membrane. fusion of HIV with cell and genome enters host cell.
what methods are T cells lost during HIV infection?
1. lysis 2. apoptosis of uninfected cells due to binding of gp120 on cd4 molecule, aberrant signaling and activation of death pathways.
3. cd8 killing of infected cells
4. formation of sycytial giant cells through fusion of infected and uninfected cells.
B and T cell mitogen
T cell mitogen
B cel mitogen
in vitro immune functions in AIDS
-decreased response to mitogens, alloantigens, and soluble antigens.
-decreased specific cytotoxicity
-decreased helper function of pokeweed mitogen induced B cell Ig production
-dec Il-2 and TnF-gamma production
in vivo immune dysfunction in AIDS
-lymphopenia (reversal of cd4:cd8 ratio_
-preferential loss of activated and memory T cells
-suceptibility to opportunistic infections and neoplasms.