Lec 23 Flashcards
What is mech of chronic granulomatous disease?
defect of NADPH oxidase –> reduction in reactive oxygen species [ie superoxide] and absent respiratory burst in neutrophils –> increased susceptibility to catalase + organisms
What are the 7 catalase positive organisms?
- pseudomonas
- listeria
- aspergillus
- candida
- e coli
- staph aureus
- serratia
What is mech of DiGeorge syndrome?
22q11 deletion –> failure to develop 3rd and 4th pharyngeal pouches –> absent thymus and parathyroids –> no T cells –> recurrent viral/fungal infections
What is mech of X linked agammaglobulinemia?
defect in BTK a tyrosine kinase gene –> no B cell maturation –> no Ig all classes
What is mech of hyper-IgM syndrome?
usually due to defect in CD40L on Th cells --> no class switching have lots of IgM but no IgG/IgA/IgE --> have severe pyogenic infections early in life
What is idiopathic thrombocytopenic purpura?
have antiplatelet antibody –> IgG binds platelet antibody and coats Fc receptors
platelets phagocytozed in the spleen
What is mech of lupus?
B cell clones secreting autoantibodies
What is mech of type 1 diabetes?
T cell clones secreting anti-islet antibodies
What is immediate hypersensitivity?
antibody mediated; symptoms minutes to hrs after encounter antigen
What is delayed hypersensitivity?
cell mediated; response 2-3 days after exposure
What happens in type 1 hypersensitivity?
crosslinking of IgE on mast cells by antigen –> release of histamines, leukotrienes, eosinophil chemotactic factor
What are 3 examples of type 1 hypersensitivity?
- hay fever
- asthma
- urticaria [hives]
What are 2 treatments for hypersensitivity type 1?
- steroids decreased IgE production
- antihistamines block degranulation ofmast cells
What is mech of hypersensitivity type 2?
formation of antibody-antigen complexes –> IgM/IgG bind to fixed antigen on enemy cell and destroy cell
What is mech of hypersensitivity type 3?
antibody-antigen complexes cause tissue damage via complement activation
What are 3 examples of type 3 hypersensitivity?
- rash
- glomerulonephritis
- arthritis
What is mech of type 4 hypersensitivity?
- cell mediated
- occurs 2-3 days post expsoure
have local inflammation and tissue damage; non antigen-specific inflammatory cells [macrophages and neutrophils
Is immunosuppression antigen specific?
nope! its an induced state of immune non-responsiveness to all antigenic stimuli
What type of cells it the focus for most immunosuppressive drugs?
T cells
What is mech of action corticosteroids?
bind intracellular receptor which binds to severe genes in nucleus including IkB promotor –> which binds to NF-kB and prevents it from getting into nucleus and activating cytokine transcription
What is mech of action cyclosporine?
calcineurin inhibitor
binds cyclophilin and blcoks T cell activation by preventing IL-2 transcription
What is mech of action tacrolimus?
calcineurin inhibitor
binds FK506 binding protein [FKBP] and blocsk T cell activation by preventing IL-2 transcription
What are the 5 clinical uses for cyclosporine?
- transplant rejection prophylaxis
- psoriasis
- rheumatoid arthritis
- aplastic anemia
- immune mediated kidney disease
What are the clinical uses of tacrolimus?
- transplant rejection prophylaxis
- aplastic anemia
- immune mediated kidney disease
What are the 6 side effects of cyclosporine?
- nephrotoxicity
- htn
- hyperlipidemia
- hyperglycemia
- gingival hyperplasia
- hirsuitism
What are the e side effects of tacrolimus?
- nephrotoxicity
- htn
- diabetes
What is the mech of action sirolimus [rapamycin]?
mTor inhibitor
binds FKBP
blocks T cell activation and B cell differentiation by preventing IL-2 signal transduction = prevents T cells from moving G1 –> S
What are 2 clinical uses of sirolimus [rapamycin]?
kidney transplant rejection prophylaxis
graft vs host disease
What are the 5 side effects of sirolumis [rapamycin]?
- anemia, thrombocytopenia, leukopenia AKA BM suppression
- insulin residence
- hyperlipidemia
non-nephrotoxic
What is mech of action azathioprine?
purine analog and anti-proliferative
metabolized by liver to 6-mercaptopurine –> inhibits nucleotide synthesis/proliferation in T and B cells
What are 3 clinical uses of azathiaprine?
- transplant rejection prophylaxis
- autoimmune diseases –> RA, crohns, etc
- glomerulonephritis
What are 3 side effects of azathiaprine?
BM suppression with cytopenias [leukopenia, anemia, thrombocytopenia]
rash, fevere, N/V, diarrhea
secondary malignancies
What is mech of action of mycophenolate mofetil?
- selectively inhibits lymphocyte proliferation by inhibiting IMP dehydrogenase of the de novo purine synthesis path
thus relatively selective for lymphocytes b/c they are dependent on this path
What are 3 clinical uses of mycophenolate?
solid organ and BM transplant
lupus nephritis
RA
What are 2 side effects of mycophenolate mofetil?
GI toxicity
BM suppression
What is mech of action cyclophosphamide?
covalently X links DNA at guanine N-7
What are 3 clinical uses of cyclophosphamide?
- autoimmune diseases
- solid tumors, leukemia, lymphomas, and some brain cancers
- BM conditioning before transplant
What are 3 side effects of cyclophosphamide?
- myelosuppression
- hemorrhagic cystitis
- seoncdary leukemias
What can you give with cyclophosphamide to prevent hemorrhagic cystitis?
mesna
What is mech of action methotrexate?
Dihydrofolate reductase inhibitor → less dTMP → less DNA and protein synthesis
What are the 4 types of clinical uses of methotrexate?
- cancer: leukemias, lymphomas, choriocarcinoma, sarcoma
- abortion / ectopic pregnancy
- autoimmune: RA, psoriasis, IBD
- GVH treat + prevent
What is mech of action antithymocyte globulin?
- deplete circulating T cells through complement mediated lysis + trap in reticuloendothelial system
What is thymoglubin vs antithymocyte globulin?
antithymocyte globulin = made by immunizing horses w/ human thymocytes
thymoglobulin = from rabbits
What are 3 clinical uses of anti-thymocyte globulin?
- solid organ graft rejection
- acute GvHD
- aplastic anemia
What are 4 side effects of polyclonal antibodies?
- anaphylaxis
- serum sickness
- infection
- 2ndary lymphoma in solid organ recipients
What are 4 clinical uses of IVIG?
Agammaglobulinemia
ITP
Systemic inflammation
Kawasaki
What are 2 clinical uses of Rhogam
Maternal fetal Rh incompatibility
Immune mediated trhombocytopenia
What is mech of anti-CD25?
prevents IL-2 signaling on T cells
What is clinical use for anti-CD25?
solid organ transplantation
What drug is anti-CD52?
alemtuzumab
What are 2 clinical use of alemtuzumab?
CLL, MS
What is mech of action of rituximab?
anti-CD20
What is mech of action etanercept?
fusion protein produced by recombinant DNA = TNF decoy receptor –> inhibits TNF-a
What are 3 uses for etancercept?
RA
psoriasis
ankylosing spondylitis
What is type 1 drug allergy?
IgE mediated –> can lead to anaphylaxis
What is type 2 drug allergy?
induction of self antibodies; anti-drug antibodies directed at self cause hemolysis
if you withdraw drug reverses
What is type 3 drug allergy?
causes serum sickness
What is serum sickness?
type 3 hypersensitivity –> antibodies to foreign proteins produced –> immune complexes deposited in membrane and fix complement –> uritcaria, arhtralgias, rash, fever
