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Heme > Lec 23 > Flashcards

Lec 23 Flashcards

1
Q

What is mech of chronic granulomatous disease?

A

defect of NADPH oxidase –> reduction in reactive oxygen species [ie superoxide] and absent respiratory burst in neutrophils –> increased susceptibility to catalase + organisms

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2
Q

What are the 7 catalase positive organisms?

A
  • pseudomonas
  • listeria
  • aspergillus
  • candida
  • e coli
  • staph aureus
  • serratia
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3
Q

What is mech of DiGeorge syndrome?

A

22q11 deletion –> failure to develop 3rd and 4th pharyngeal pouches –> absent thymus and parathyroids –> no T cells –> recurrent viral/fungal infections

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4
Q

What is mech of X linked agammaglobulinemia?

A

defect in BTK a tyrosine kinase gene –> no B cell maturation –> no Ig all classes

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5
Q

What is mech of hyper-IgM syndrome?

A 
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
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6
Q

What is idiopathic thrombocytopenic purpura?

A

have antiplatelet antibody –> IgG binds platelet antibody and coats Fc receptors
platelets phagocytozed in the spleen

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7
Q

What is mech of lupus?

A

B cell clones secreting autoantibodies

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8
Q

What is mech of type 1 diabetes?

A

T cell clones secreting anti-islet antibodies

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9
Q

What is immediate hypersensitivity?

A

antibody mediated; symptoms minutes to hrs after encounter antigen

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10
Q

What is delayed hypersensitivity?

A

cell mediated; response 2-3 days after exposure

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11
Q

What happens in type 1 hypersensitivity?

A

crosslinking of IgE on mast cells by antigen –> release of histamines, leukotrienes, eosinophil chemotactic factor

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12
Q

What are 3 examples of type 1 hypersensitivity?

A
  • hay fever
  • asthma
  • urticaria [hives]
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13
Q

What are 2 treatments for hypersensitivity type 1?

A
  • steroids decreased IgE production

- antihistamines block degranulation ofmast cells

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14
Q

What is mech of hypersensitivity type 2?

A

formation of antibody-antigen complexes –> IgM/IgG bind to fixed antigen on enemy cell and destroy cell

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15
Q

What is mech of hypersensitivity type 3?

A

antibody-antigen complexes cause tissue damage via complement activation

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16
Q

What are 3 examples of type 3 hypersensitivity?

A
  • rash
  • glomerulonephritis
  • arthritis
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17
Q

What is mech of type 4 hypersensitivity?

A
  • cell mediated
  • occurs 2-3 days post expsoure
    have local inflammation and tissue damage; non antigen-specific inflammatory cells [macrophages and neutrophils
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18
Q

Is immunosuppression antigen specific?

A

nope! its an induced state of immune non-responsiveness to all antigenic stimuli

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19
Q

What type of cells it the focus for most immunosuppressive drugs?

A

T cells

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20
Q

What is mech of action corticosteroids?

A

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

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21
Q

What is mech of action cyclosporine?

A

calcineurin inhibitor

binds cyclophilin and blcoks T cell activation by preventing IL-2 transcription

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22
Q

What is mech of action tacrolimus?

A

calcineurin inhibitor

binds FK506 binding protein [FKBP] and blocsk T cell activation by preventing IL-2 transcription

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23
Q

What are the 5 clinical uses for cyclosporine?

A
  • transplant rejection prophylaxis
  • psoriasis
  • rheumatoid arthritis
  • aplastic anemia
  • immune mediated kidney disease
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24
Q

What are the clinical uses of tacrolimus?

A
  • transplant rejection prophylaxis
  • aplastic anemia
  • immune mediated kidney disease
25
Q

What are the 6 side effects of cyclosporine?

A
  • nephrotoxicity
  • htn
  • hyperlipidemia
  • hyperglycemia
  • gingival hyperplasia
  • hirsuitism
26
Q

What are the e side effects of tacrolimus?

A
  • nephrotoxicity
  • htn
  • diabetes
27
Q

What is the mech of action sirolimus [rapamycin]?

A

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

28
Q

What are 2 clinical uses of sirolimus [rapamycin]?

A

kidney transplant rejection prophylaxis

graft vs host disease

29
Q

What are the 5 side effects of sirolumis [rapamycin]?

A
  • anemia, thrombocytopenia, leukopenia AKA BM suppression
  • insulin residence
  • hyperlipidemia

non-nephrotoxic

30
Q

What is mech of action azathioprine?

A

purine analog and anti-proliferative

metabolized by liver to 6-mercaptopurine –> inhibits nucleotide synthesis/proliferation in T and B cells

31
Q

What are 3 clinical uses of azathiaprine?

A
  • transplant rejection prophylaxis
  • autoimmune diseases –> RA, crohns, etc
  • glomerulonephritis
32
Q

What are 3 side effects of azathiaprine?

A

BM suppression with cytopenias [leukopenia, anemia, thrombocytopenia]
rash, fevere, N/V, diarrhea
secondary malignancies

33
Q

What is mech of action of mycophenolate mofetil?

A
  • 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

34
Q

What are 3 clinical uses of mycophenolate?

A

solid organ and BM transplant
lupus nephritis
RA

35
Q

What are 2 side effects of mycophenolate mofetil?

A

GI toxicity

BM suppression

36
Q

What is mech of action cyclophosphamide?

A

covalently X links DNA at guanine N-7

37
Q

What are 3 clinical uses of cyclophosphamide?

A
  • autoimmune diseases
  • solid tumors, leukemia, lymphomas, and some brain cancers
  • BM conditioning before transplant
38
Q

What are 3 side effects of cyclophosphamide?

A
  • myelosuppression
  • hemorrhagic cystitis
  • seoncdary leukemias
39
Q

What can you give with cyclophosphamide to prevent hemorrhagic cystitis?

A

mesna

40
Q

What is mech of action methotrexate?

A

Dihydrofolate reductase inhibitor → less dTMP → less DNA and protein synthesis

41
Q

What are the 4 types of clinical uses of methotrexate?

A
  • cancer: leukemias, lymphomas, choriocarcinoma, sarcoma
  • abortion / ectopic pregnancy
  • autoimmune: RA, psoriasis, IBD
  • GVH treat + prevent
42
Q

What is mech of action antithymocyte globulin?

A
  • deplete circulating T cells through complement mediated lysis + trap in reticuloendothelial system
43
Q

What is thymoglubin vs antithymocyte globulin?

A

antithymocyte globulin = made by immunizing horses w/ human thymocytes

thymoglobulin = from rabbits

44
Q

What are 3 clinical uses of anti-thymocyte globulin?

A
  • solid organ graft rejection
  • acute GvHD
  • aplastic anemia
45
Q

What are 4 side effects of polyclonal antibodies?

A
  • anaphylaxis
  • serum sickness
  • infection
  • 2ndary lymphoma in solid organ recipients
46
Q

What are 4 clinical uses of IVIG?

A

Agammaglobulinemia
ITP
Systemic inflammation
Kawasaki

47
Q

What are 2 clinical uses of Rhogam

A

Maternal fetal Rh incompatibility

Immune mediated trhombocytopenia

48
Q

What is mech of anti-CD25?

A

prevents IL-2 signaling on T cells

49
Q

What is clinical use for anti-CD25?

A

solid organ transplantation

50
Q

What drug is anti-CD52?

A

alemtuzumab

51
Q

What are 2 clinical use of alemtuzumab?

A

CLL, MS

52
Q

What is mech of action of rituximab?

A

anti-CD20

53
Q

What is mech of action etanercept?

A

fusion protein produced by recombinant DNA = TNF decoy receptor –> inhibits TNF-a

54
Q

What are 3 uses for etancercept?

A

RA
psoriasis
ankylosing spondylitis

55
Q

What is type 1 drug allergy?

A

IgE mediated –> can lead to anaphylaxis

56
Q

What is type 2 drug allergy?

A

induction of self antibodies; anti-drug antibodies directed at self cause hemolysis

if you withdraw drug reverses

57
Q

What is type 3 drug allergy?

A

causes serum sickness

58
Q

What is serum sickness?

A

type 3 hypersensitivity –> antibodies to foreign proteins produced –> immune complexes deposited in membrane and fix complement –> uritcaria, arhtralgias, rash, fever

Heme (20 decks)

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