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Immunology & Inflammation > Exam 4-FINALLLL > Flashcards

Exam 4-FINALLLL Flashcards

1
Q

Methotrexate Mechanism of Action

A

inhibits the critical enzyme that cycles the cofactor that makes folate DHFR-dihydrofolate reductase
DHFR is involved in the synthesis of thymine from uracil

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2
Q

Methotrexate Side Effects and Interactions

A

ulcerative stomatitis, leukopenia, abdominal stress

Do not take NSAIDs before or during because they increase blood concentration of methotrexate

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3
Q

Leflunomide

A

Prodrug of antirheumatic metabolite A77 1726 which suppresses lymphocytes proliferation and inhibits cytokine synthesis
side effect: liver toxicity

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4
Q

Methotrexate

A

antimetabolite of folic acid

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5
Q

Leflunomide Mechanism of Action

A

A77 1726 inhibits dihydro-orotate dehydrogenase required for pyrimidine biosynthesis
Inhibits tyrosine kinase associated with cytokines possibly interfering with T and B cell production

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6
Q

Thalidomide indication

A

erythema nodosum leprosum (ENL)

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7
Q

Thalidomide Mechanism of Action

A

Unclear

May decrease circulating TNF-(a) in ENL but increase it in HIV

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8
Q

Echinacea

A

stimulates the innate immune system, increases phagocytosis and release from macrophages, Tcells of TNFs, interferons
possibly active polysaccharides
don’t use for more than 8 wks because can induce autoimmune process

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9
Q

Astragalus

A

Chinese medicine for hepatitis, cancer, colds, URIs, heart disease
generally safe

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10
Q

Levamisole

Immunostimulant

A

enhance 5-FU toxicity
mimics thymic hormone thymopoietin
inhibits most isoforms of alkaline phosphatase
restores depressed function of B/T cells, monocytes, macrophages

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11
Q

Imiquimod

A

treats actinic keratosis external, genital, and perianal warts from HPV
Toll Like Receptor agonist-7 agonists, stimulates immune system to produce interferon(a) and others. Activates macrophages, NK, TH1, Bcells.
Topical creams

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12
Q

active immunization involves stimulation with an antigen to develop immunological defenses against a future exposure

A

vaccine

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13
Q

passive immunization involves administering pre-formed antibodies from an external source

A

antibodies: immunoglobulins, monoclonal antibodies

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14
Q

Epoetin alfa, Darbepoetin alfa, granulocyte-colony stimulating factor, granulocyte macrophage colony stimulating factor

A

growth factors

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15
Q

Active immunization vaccine

A

protection not immediate because body responds and produces antibodies
excess of TH2 cells produced-imbalance leads to asthma, allergies

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16
Q

denaturing disinfectant kills pathogen, allows recovery of the surface antigens

A

killed pathogen vaccines

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17
Q

pass the pathogen through many generations of host animals to yield low virulent strain

A

live/attenuated pathogen vaccines

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18
Q

cowpox used in place of smallpox virus

A

live/ attenuated related strain vaccines

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19
Q

isolate the surface antigen from the pathogen, purify it and reconstitute into a vaccine preparation

A

cellular antigen from a pathogen vaccine

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20
Q

clone a piece of DNA encoding the surface antigen from the pathogen and over produce the antigen in E coli etc

A

genetically engineered pathogen vaccine

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21
Q

simple vaccine

A

contains only one kind of antigen or strain

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22
Q

multivalent vaccine

A

contains two or more kinds of antigens or strains that cause the same disease..full protection

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23
Q

polyvalent vaccine

A

contains two or more kinds of antigens or strains that cause different diseases–convenience

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24
Q

types of vaccine dosing

A

single dose, multiple dosing regimen, booster dose, co-administered vaccine

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25
Q

types of vaccines

A

viral, bacterial, toxoids, cancer/autoimmune

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26
Q

conjugate vaccines

A

covalently linked polysaccharide antigen and a carrier protein from the bacterium

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27
Q

toxoids

A

denatured toxin that has been inactivated

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28
Q

DNA vaccination advantage

A

expression of whole proteins, so HLA alleles do not matter

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29
Q

passive immunization-antibodies

A 
immediate protection administered to people who are already ill and lasts 1-3 months
1. Immunoglobulins
2. Monoclonal Antibodies
neutralize toxic molecules
eliminate target cells
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30
Q

How antibodies can eliminate target cells

A

cell growth control
macrophage clearance
complement-mediated cytotoxicity
antibody dependent cell mediated cytotoxicity

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31
Q

human immunoglobulins

A

rabies, tetanus, hep B, Rho

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32
Q

animal immunoglobulins

A

digoxin immune fab–sheep IgG used for digoxin overdose. binds TO digoxin

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33
Q

antiithymocyte globulin

A

gamma globulin from rabbit immunized with human thymocytes
polyclonal mix
directly kills T lymphocytes
binds to cell surface molecules that regulate cell function
indication: kidney rejection, aplastic anemia if not suitable for bone marrow transplant

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34
Q

monoclonal antibodies

A

synthesized from a single clone of B lymphocytes or plasma cells

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35
Q

-ximab

A

chimeric antibody (2/3rd human)

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36
Q

-umab

A

human antibody

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37
Q

-zumab

A

humanized antibody (90% human)

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38
Q

muromonab

attaches to T cell receptor

A

from mice that interacts with human CD3
instantly decreases T cells in blood, used 10-14 days and can’t be used again
side effect: cytokine release syndrome

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39
Q

-omab

A

mouse antibody

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40
Q

basiliximab

attaches to T cell receptor

A

chimeric maB that binds to IL2 receptor of activated Tcells
IL2 aka CD25
used with cyclosporine or tacrolimus+corticosteroids

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41
Q

belatacept

attaches to T cell receptor

A

prevent kidney rejection
soluble fusion protein CTLA4-Ig contains CTLA4 fused to Fc domain of human IgG antibody
produced by recombinant DNA tech
binds CD80 and CD86

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42
Q

Ways to treat malignancies with MAbs

A

enhance effector function
pre-target
indirect arming
direct arming

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43
Q

rituximab

for lymphomas

A

first MAb approved in USA for follicular lymphoma

chimeric IgG binds to CD20 which is on 90% of non-Hodgkin’s lymphomas

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44
Q

alemtuzumab

for lymphomas

A

humanized MAb directed against CD52 which is on mature lymphocytes
used for Bcell chronic lymphocytic leukemia

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45
Q

brentuximab vedotin

for lymphomas

A

chimeric IgG antibody specific for CD30+drug MMAE that disrupts microtubules+covalent linker
treatment of Hodgkin’s lymphoma and sALCL (non)
binding internalizes ADC-CD30 complex, MMAE released, microtubules network disrupts, apoptosis

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46
Q

tositumomab

for lymphomas

A

mouse IgG MAb linked to iodine131
antiCD20 for non-hodgkins
induces normal immune reactions and radioimmunoconjugates deliver cytotoxic ionization radiation
kills cells 1-2 mm away that are inaccessible to antibody

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47
Q

y-90-labeled ibritumomab tiuxetan

for lymphomas

A

mouse IgG anti CD20 radiolabeld

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48
Q

trastuzumab

anti-HER2

A

humanized IgG for breast cancer that overexpress HER2
inhibit HER2 signaling by blocking extracellular receptors. upregulates p27(kip1) to lead to cell cycle g1 arrest and growth inhibition

49
Q

cetuximab

A

chimeric MAb binds to EGFR

50
Q

panitumumab

A

human MAb binds to EGFR

51
Q

infliximab

for RA/Crohn’s/ankylosing spondylitis

A

chimeric IgG binds to free and bound TNF(a)

risk of infection esp Tb, severe hepatic rxns

52
Q

adalimumbab

for RA/Chron’s

A

human mAb that against TNF(a)

risk of infection

53
Q

tocilizumab

for RA

A

humanized mAb that inhibits IL6 receptor

for people who failed other therapies

54
Q

etanercept

for RA/psoriasis/ankylosing spodylitis

A 
dimeric fusion protein TNF receptor linked to Fc of IgG
binds TNF(a) to slow/stop joint damage, response 1-2 weeks
55
Q

omalizumab

for asthma

A

recombinant humanized mAb binds to circulating IgE to prevent its binding to mast cells and others. Cells can’t recognize the allergens

56
Q

mepolizumab

for asthma/allergic rhinitis

A

humanized IL-5 antagonist mAb produced by recombinant DNA tech

57
Q

efalizumb

for psoriasis

A

recombinant humanized IgG that binds CD11a which is important in Tcel mediated steps in psoriasis pathogenesis.
inhibits CD11a interaction with ICAM mlcls…inhibits the APC T cell interaction and adhesion

58
Q

Interferon (a)-2b

cytokine

A

produced by recombinant DNA in E coli. to treat cancers and hep B

59
Q

Interferon (b)-1a/b

cytokine

A

produced by rDNA for neurological exaberations in relapsing MS

60
Q

Interleukin-2

cytokine

A

aka T-Cell growth factor
produced by rDNA, not glycosylated, no terminal alanine, serine substituted for Cys125 that normal IL2 has
cancers, induces a cytolytic response

61
Q

Interleukin-11

cytokine

A

aka platelet growth factor
produced by rDNA and one A.A. shorter than normal IL11
used after myelosuppressive chemotherapy

62
Q

anakinra

interleukin receptor agonist, cytokine

A

recombinant human IL1 receptor antagonist for RA.
slows degradation of joint, well tolerated
don’t give with anti-TNF agents
risk of infection ex. Tb

63
Q

G-CSF M-CSF GM-CSF Multi-CSF EPO TPO

A

growth factors that control expansion, proliferation, differentiation of myeloid cells

64
Q

Granulocyte-Colony Stimulating Factor Analogs

G-CSF

A

Fligastrim Pegfilgastrim
produced by rDNA to stimulate bone marrow to produce more WBCs
for neutropenia or after bone marrow transplant

65
Q

Granulocyte-Macrophage-Colony Stimulating Factor
GM-CSF
Sargramostim

A

produced by rDNA in yeast, for bone marrow transplant

hastens myeloid reconstitution

66
Q

Granulocyte-Macrophage-Colony Stimulating Factor
GM-CSF
Erythropoietin

A

Epoetin for dialysis and chemotherapy. increases RBC

Darbepoetin Alfa-has 2 extra carb chains=more stable=longer half life. For anemia from renal failure and chemotherapy

67
Q

induction immunosupression

A

meds given right after transplant to prevent acute rejection for up to 30 days.
ex. methylprednisolone, atgam, thymoglobulin, OKT3, basiliximab

68
Q

maintenance immunosuppression

A

meds given before, during, or after transplant with the intention to maintain them long term.
ex. prednisone, cyclosporing, rapamycin

69
Q

anti-rejection immunosuppression

A

treat acute rejection up to 30 days after rejection

ex. methylprednisolone, atgam, etc

70
Q

RA pathophysiology

A

activated T cells stimulate macrophages and fibroblast-like synoviovytes
proinflammatory mediators (TNF(a) and ILs)/proteases generated
synovial inflammatory response
destroy cartilage and bone

71
Q

biologics that treat RA

A

infliximab, adalimumab, anakinra, rituximad, tocilizumab, etanercept

72
Q

DMARDs vs Biologics

A 
DMARDs: oral-daily or weekly
target entire immune system
know if working w/in months
risk of infections
range of side effects 
biologic: injection daily-monthly
target certain steps in inflame process
know if working w/in 4-6 wks
risk of serious infections
much more expensive
73
Q

Skin anatomy

A

4 mm thick, largest organ in body

74
Q

Epidermis

A

outer stratified layer, keratinocytes, hair follicle
4 layers:
stratum corneum, granular layer, spinous layer, basal layer

75
Q

epithelial stem cells

A

in basal layer
slow cycling, potential to proliferate and regenerate
epidermal stem cells: quiescent stem sells, committed progenitors, wound repair
hair follicle stem cells: HF cycling, epidermal repair post injury

76
Q

wound healing order

A

Hemostasis, inflammation, proliferation, remodeling

77
Q

haemostasis: vasoconstriction, platelet aggregation, blood coagulation

A

NEURAL vasoconstriction: blood vessel constriction (epineph, prostaglandins, serotonin)
platelet aggregation: PDGF, TGF, IGF, thrombin
CONTACT/TISSUE FACTOR coagulation of blood: cascade, fibrinolytic cascade

78
Q

Inflammation

A

vasodilation, increase vasc permeability, inflam cells, chemotaxis, cell response
neutrophils=main, macrophages
heat, redness, pain/swelling, raised temp

79
Q

proliferation

A

stimulated by inflame response, replace lost epidermal/dermal tissue with scar tissue, scaffolding to laid for repair of wound, collagen ECM and granulation tissue formed

reepithelialization: epithelial cells,
angiogenesis: endothelial cells, new vessels
fibroplasia: fibroblast/myo-fibroblast differentiation, new ECM components

80
Q

keratinocyte proliferation

A

keratinocytes detach, mirgrate, proliferate, differentiate, and stratify to neo-epidermis

81
Q

fibroblast proliferation

A

keratinocyte (IL1 and TGF(b))>fibroblast>myofibroblast (tissue contraction during remodeling)

82
Q

Angiogenesis

A

generates new vessel formation, brings in oxygen and nutrients
creates granulation tissue to fill in/heal wound
sprout UPWARDS

83
Q

Remodeling

A

regression of blood vessels and granulation tissue
wound contraction and collagen remodeling
wound strength is 80% of original
no hair follicles or sweat glands

84
Q

primary intention of healing

A

all tissue closed with suture material

ex. surgery, clean cuts

85
Q

secondary intention of healing

A

wound left open and close naturally

ex. bed sores, burns

86
Q

tertiary intention of healing

A

wound left open for number of days then closed if found to be clean

87
Q

hypertrophic scar

A

rapid growth, (a)SMA+ myofibroblasts, collagen parallel to skin surface, vertically oriented vessels
surgery, burn wounds, rupture of wound common

88
Q

keloid scars

A

constant growth, extend beyond margins of tissue damage, genetic, thick collagen bundles, more in pigmented skin

89
Q

Negative pressure wound therapy

A

for lower extremity, chronic, diabetic wounds, ulcers

vacuum pump, drainage tubing and a dressing set

90
Q 
TH1 phenotype
(psoriasis?)
A

older siblings, exposure at day care , Tb/measles/HepA infection, rural env, endotoxin
TNF(a) IFN(y) IL17

91
Q 
TH2 phenotype
(atopic dermatitis?)
A

use of antibiotic, western life/hygiene, urban, diet, sensitization to house mites/dust mites/cockroaches
IL4 IL5 IL13

92
Q

psoriasis

A

chronic, lifelong disease. common in adults, hereditary, thick silvery scales
more in US and western countries
peaks at 16-22 and 57-60
9 susceptible regions. PSOR1 chromosome 6 (50%)

93
Q

atopic dermatitis

A

comes and gos, children , environmental, red/inflamed skin

94
Q

Koebner phenomenon

A

scratching causes areas next to plaque to be spread to

95
Q

Environmental factors of psoriasis

A

physical trauma, infections, stress, drugs, alcohol, smoking, obesity

96
Q

IL18

A

important part of psoriasis pathogenesis

determines severity

97
Q

psoriasis Th1

A

secrete INF(y) and TNF (a) leading to angiogenesis, epidermal neutrophiles and lymphocytes infiltration

98
Q

psoriasis Th17

A

secretes IL17 IL22 and TNF(a) leading to activation of keratinocytes and endothelial cells

99
Q

psoriasis pathogensis

A
  1. epidermal keratinocyte proliferation
    shortening of cell cycle, migration of neutrophils to cornified layer, silvery plaques
  2. vascular alterations
    hyperproliferation, dilation increased permeability, bright erythema
  3. inflammation
    T lymphocyte activation, IFK(y) TNF(a) IL17
    RETE PEGS
100
Q

4 types of psoriasis

A
  1. plaque-most common, red/salmon color, covered by silvery patches, knees elbows, scalp chest lower back, limbs
  2. guttate-dew drop like red spots on trunk region in young adults, erupt suddenly with infections and resolve naturally
  3. pustular-localized eruption of sterile pustules, redness but no scales, trunk extremitires, palm soles and nails
  4. erythrodermic-shed skin, appear suddenly whole body, scaly and itchy, alters thermoregulation
101
Q

Atopic dermatitis

A

chronic or recurrent, kids (early)
50% develop other allergic symptoms w/in first year and can also develop asthma
dry skin, itching, redness, swelling, scaling, oozing

102
Q

dermatitis distribution

A

infants: faces then hands and feet
older kids: skin folds esp elbow and knees
adults: face and hands

103
Q

genes involved in skin barrier function

A

chromosome 1q21:Human EDC=epidermal diff complex
FLG mutations that encodes filaggrin
SCCE-degrades corneodesmosomes
SPINK5: increases protease activated Th2 responses

104
Q

genes involved in immune system

A

CD14 monocyte differentiation
IL4, IL18 SNP associated with asthma and allergy
TLR2: children of farmers
TSLP: thymic stromal lymphopoietin

105
Q

Atopic dermatitis immune responses

A

dry skin disrupts epidermal barrier, increased water loss=reduced lipids, entry of allergens, Th2 response (IL4 IL5 IL13)
=IgE

106
Q

Types of dermatitis

A

contact: after being exposed
seborrheic: recurrent rash in scalp/brow/forehead/ears
nummular:coin shaped rashes itch and burn
neurodermatitis: thickened area cuased by itching and rubbing
stasis: lower legs, damage to vales in large veins
dyshidrotic eczema: small itchy blisters fingers/toes/hands feet

107
Q

soap free cleansers

A

reduce irritation and dryness to increase absorption of topicals

108
Q

emollient

A

moisturize and soften skin to reduce itching, trap moisture

apply after bathing

109
Q

topical corticosteroids

A

hydrocortisone, fluticasone, flucinonide, clobetasol propionate
many side effects

110
Q

calcineurin inhibitor

A

block Tcell transduction AND IL2 transcription to suppress itching/inflammation
facial areas

111
Q

cyclosporine

A

short term trtmnt works well but comes back. improves quality of life

112
Q

UV light therapy

A

direct sunlight can help

113
Q

antihistamines

A

reduce itch

114
Q

biologics for atopic dermatitis

A

dupilumab: blocks IL4 and IL13

xolair/omalizumab: asthma, IgE blocker

115
Q

VitD3 analog

A

calcipotriene, calcitriol

equivalent to medium-potent corticosteroid

116
Q

VitA Retinoid

A

teratogenic, burn, sting

117
Q

anthralin/dithranol

A

naturally occurs in bark of araroba tree, stains clothes brown/red

118
Q

oral, systemic therapies

A

if cover 5-10% of body
methotrexate
cyclosporine-cyclophilin and NF-AT.
acitretin-oral retinoid, 8 wks. multiple prescreenings
otezla-inhibits phosphodiesterase 4 which degrades cAMP

119
Q

biologics

A

target either Tcells or block inflame action of TNF(a)
Enbrel (etanercept) tumor necrosis factor receptor fusion protein
humira (adalimumab) antibody to TNF(a), blocks action with p55 and p75 surface receptors
remicade (infliximab) one mlcl drug binds to two TNF(a)s and can bind to soluble and membrane bound TNF
Amieve (alefacept) fusion protein of CD2 of LFA3, reduces # of T cells, CD4 CD8 cells
Ustekinumab: against IL12 and IL23
secukinumab (cosentyx) IL17A agonist

Immunology & Inflammation (3 decks)

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