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TORIC > Immunology > Flashcards

Immunology Flashcards

1
Q

2 mécanismes de défense du système immunitaire

A

Innate
Adaptive

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2
Q

Caractéristiques de l’immunité innée

A

« One size fits all » (no specificity)
Fast
No memory
Evolutionarily « old »

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3
Q

Components of Innate Immunity

A

Physical barriers : kin, corneal epithelium, orbital septum, etc.

Chemical : cytokines, lysozymes in tears, complement, fever

Non-specific effector cells
- Phagocytes = macrophages, dendritic cells
- Granulocytes (PMNs) = neutrophils, basophils, eosinophils, mast cells, NK cells

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4
Q

Innate Immunity Triggers

A

Bacterial-derived molecules
- Cell wall : lipopolysaccharide (LPS), lipotheichoic acid, HSP
- Exotoxins : collagenases

Non-specific molecules (recruitment) : complement, histamine, prostaglandins, ROS, cytokines…

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5
Q

Caractéristiques des prostaglandines

A

Vascular permeability
Capillary permeability → CME
Prostaglandin analogs involved in uveoscleral outflow
- First line agent for POAG
- Theoretical risk of increasing CME in uveitis patients = try to avoid in uveitis

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6
Q

Types of cytokines

A

Cytokines : broad term describing small proteins involved in cell signaling

Involved in BOTH innate and adaptive immune system

Types :
- Chemokine : involved in movement of cells (chemoattractant)
- Interleukins (IL) : promote development and differentiation of T + B cells
- Interferons (IFN) : produced in response to viral infected cells → upregulates NK cells and macrophages. Linked to « flu like symptoms » (= souvent les ES des Tx interferons)
- Tumor Necrosis Factor (TNF) : screwed by macrophages and CD4+ TH1. Prepares endothelium by vasodilatation and increasing permeability, adhesion

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7
Q

Caractéristiques de l’immunité adaptative

A

Highly specific
Slow (days)
Has memory
Evolutionarily « new » (only present in vertebrates)

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8
Q

Components of Adaptative Immunity

A

Humoral
- B cell mediated
- Mature cells secrete soluble Ig into extracellular fluid

Cellular
- T cell mediated
- Involves synthesis of cytokines + initiation of adaptive immune response

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9
Q

Caractéristiques de l’immunité humorale

A

Antibodies secreted by activated B cells
Target pathogens for opsonization
Neutralize receptors on bacterial or viral surfaces
Inactive circulating toxins

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10
Q

2 types de T cells dans l’immunité cellulaire

A

CD4 (helper T cells)
- Work with B cells to increase antibodies (Ab) production
- Always ask for this in HIV + patients
CD4 > 200 = systemically asx :)
CD4 < 200 = systemically symptomatic :(
CD4 < 50 = ocular manifestations

CD8 (cytotoxic T cells)
- Kills target or host cells infected by other pathogens

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11
Q

Types of CD4 cells

A

TH1
- Interacts with mononuclear phagocytes and helps destroy intracellular pathogens
- Secretes : IFNy, TNF-a, GM-CSF, IL-2

TH2
- Interact with B cells and helps them to divide, differentiate and make Ab
- Secretes : IL-4, IL-5, IL-10, IL-13, TGF-B

TH17
- Enhance neutrophil response to extracellular pathogens
- Secretes : IL-17, IL-21, IL-22, IL-26

T-Reg
- Maintains lymphocyte homeostasis (turn off active immune cells)
- Secretes : TGF-B, IL-10, IL-35

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12
Q

3 signals required for T-Cell activation

A
  1. T-Cell receptor binding with MHC (major histocompatibility complex)
  2. CD28 binding with B7 (CD80/86) on APC
  3. Cytokine activation e.g. IL-2, IL-12
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13
Q

Caractéristiques du Major Histocompatibility Complex (MHC)

A

MHC in humans is called HLA (human leukocyte antigen)
Prevents inbreeding (more HLA diversity → improved survival)
- Inbreeding = cosanguinité
- Lots of genetic diversity in form of subgroups (>25 A’s, 50 B’s, 10 C’s, 100 DR’s)
Located on chromosome 6, short arm
MHC molecules present glycoproteins to activate adaptative immune response

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14
Q

Caractéristiques du MHC Class I

A

MHC I region = HLA A, B, C
Present on all cells (except mature RBC)
Purpose is to present endogenous Ag (often virus) to CD8+
CD*+ kills cells that display foreign Ag in MHC class I
Increase in transcription by IFN-alph, beta or gamma

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15
Q

Caractéristiques du MHC Class II

A

MHC II region = HLA DR, DQ, DW
Present only on APC (macrophages, dendritic cells and some B cells)
Present exogenous Ag (phagocytosed) to CD4+ cells
CD4 activate other effectors of immune system
Increase transcription of IFN-gamma

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16
Q

MHC heritability

A

HLA heritability is transferred as one set of 6 major HLA subtypes (A, B, C, DR, DQ and DW)

1/4 siblings have identical HLA (important for organ transplant)

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17
Q

HLA association : DRB1

A

DRB1 = Tubulointerstitial Nephritis and Uveitis Syndrome (TINU)

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18
Q

HLA association : A29

A

A29 = Birdshot Chorioretinopathy
- > 90% positivity
- Env. 8% de la population caucasienne

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19
Q

HLA association : B27

A

B27 = AAU, AS, IDB, PsA, Reactive Arthritis
- Env. 8% de la population caucasienne

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20
Q

HLA association : B51

A

B51 = Behcets Diasease

21
Q

HLA association : DR4

A

DR4 = SO, VKH

22
Q

HLA association avec l’AJI

A

A2
DR5
DR8
DR11

23
Q

HLA association avec intermediate uveititis

A

B8
B51
DR2
DR15

24
Q

HLA association avec la sarcoïdose

A

B8
B13

25
Q

HLA association avec la SEP

A

B7
DR2

26
Q

HLA association avec Retinal Vasculitis

A

B44

27
Q

Panuvéite versus Endophtalmie

A

Panuveitis : descriptive term and does NOT imply etiology

Endophtalmitis : panvuveitis secondary to infection

28
Q

Vrai ou Faux. Les stéroïdes inhibent les phospholipases, enzymes en amont de la cascade inflammatoire.

A

Vrai.
S’il n’y a pas de réponse au Tx, requestionner le Dx pr r/o cause infectieuse ou néoplasique

29
Q

Solutions : Acetates versus Phosphates

A

Acetates/Alchohols = Lipophilic
+ : augmentation [ ] intraoculaire
- : shaking required

Phosphates = Hydrophilic
+ : no shaking required
- : diminution [ ] intraoculaire

30
Q

2 principaux ES oculaires des corticostéroïdes

A

Cataractes
IOP

Plus la puissance est élevée, plus le risque est grand

31
Q

Nommez différents corticostéroïdes topiques en ordre de puissance

A

Puissance faible à élevée :
Loteprednol etabonate 0,2% (Alrex)
Fluorometholone 0,1% (FML) = Loteprednol etabonate 0,5% (Lotemax)
Prednisolone Phosphate 1% (not commonly seen)
Prednisolone Acetate 1% (PF) = Dexamethasone Phosphate 0,1% (Maxidex)
Difluprednate 0,05% (Durezol)

32
Q

General approch for non-infectious uveitis Tx

A

Anterior (w/o CME)
- Topical steroids (typically Prednisolone 1%) +/- cycloplegia if PS
- Systemic IMT if severe anterior uveitis not maintained on ≤ 2 drops of PF

Anterior (+ CME)
- Topical steroids (durizol aka difluprednate 0,05%)
- Local steroids versus systemic IMT if bilateral or recalcitrant

Intermediate/Posterior/Panuveitis
- Local steroid versus systemic IMT (drops alone won’t cut it)

33
Q

Algorithme sélection Tx IMT

A
  1. Rule out systemic + local infx
  2. Prednisolone 60 mg (steroid sparing IMT if > 10 mg/d or < 3 mois)
  3. Antimetabolites (MTX, MMF, CsA, AZA)
  4. Anti-TNF : Adalimumab → Infliximab

3rd line :
- CsA
- Daclizumab (anti-IL2)
- Toxilizumab (anti-IL6)
- IFN

4th line : Bring out the Big Guns
- Alkylating agents (CP, chlorambucil)
- Rituximab

Special situations
- Local Tx (PSTK, IVK, Ozurdex, Retisert)
- IV steroids

MMF : mycophenolate
CsA : cyclosporine-A

34
Q

What is the mediator of the anti-inflammatory effects of MTX?

A

Extracellular release of adenosine (/!\ PAS inhibition of folate metabolism)

35
Q

Mécanisme d’action du MTX + posologie

A

Folic acid analogue + inhibitor of dihydrofolate reductase → inhibits DNA replication
Anti-inflammatory effect = realize of extracellular adenosine

Posologie :
- PO ou s/c
- 20 mg (minimal ocular dose)
- q1sem
- AF 1mg PO die

Therapeutic in environ 3 mois

36
Q

Mécanisme d’action du MTX + posologie Mycophenolate Mofetil (CellCept)

A

Inhibitor of IMPDH enzyme involved in purine synthesis/DNA replication

Posologie :
- PO
- 1000 mg BID (minimal ocular dose)

Therapeutic in environ 3-4 weeks
(work faster, lower s/e profile)

37
Q

Nom commercial du mycophenolate mofetil

A

CellCept

38
Q

Mécanisme d’action du MTX + posologie de l’azathioprine

A

Converted to 6-MP → inhibit purine synthesis/DNA replication

Posologie :
- PO
- 1-2 mg/kg (ocular dose)

Therapeutic in environ 3 months

39
Q

Nom commercial de l’azathioprine

A

Imuran

40
Q

Monitoring des anti-metabolites

A

FSC
Créatinine
Bilan hépatique
Test de grossesse
Azathioprine : doser l’activité de l’enzyme TPMT avant début Tx (déficience possible et toxicité 2nd)

41
Q

Médicaments inhibiteurs de la calcineurine

A

Cyclosporine
Tracolimus

42
Q

Mécanismes d’action et ES des calcineurin inhibitors

A

Inhibit NF-AT (nuclear factor of activated T lymphocytes) reducing T cell transduction and IL-2 production (needed for T-cell activation)

Both CsA and Tracrolimus requires trough levels

Both equally effective, tacrolimus better tolerated

ES :
- CsA : systemic HTN, nephrotoxicity (avoid Rx in elderly)
- Tacromlimus = nephrotoxicity

43
Q

Nom générique de l’Humira

A

Adalimumab

44
Q

Efficacité de l’Adalimumab

A

Even though the initial success rates are high…
With a conservative measure about ONE THIRD will eventually need another strategy

L’Adalimumab (Humira) is the first and only FDA approved biologic drug for the Tx of post/pan uveitis

45
Q

Classe biologique de l’Adalimumab (aka MA)

A

Anti-TNF

46
Q

Contre-indications des anti-TNF

A

Untreated latent TB (risk of reactivation)
Demyelinating disease (peut exacerber la maladie, penser à faire un screening chez les jeunes F)
Moderate to severe CHF
Recent LIVE vaccination (MMR, yellow fever, BCG, etc.)
Chronic or active hepatitis
Active severe infection
Active malignancy

47
Q

Mécanisme d’action et indications du Tocilizumab

A

Anti-IL6

Indications
- JIA associated uveitis
- Anterior uveitis
- Intermediate uveitis
- Post/Pan uveitis

48
Q

Lequel des Rx est associé à un « mental health concerns » comme ES

A

IFN

49
Q

Mécanisme d’action et indications du Rituximab

A

Humanized monoclonal anti-CD20 antibody (B-cells)
Goal : remove B-cell clones responsible for the production of pathogenic autoantibodies
Longer term effect > 6-9 months

Indications :
- Behçet’s disease
- OCP
- Ophtalmie GPA
- Orbital inflammation
- Scleritis dans rheumatoid arthritis (RA)
- VKH
- Birdshot chorioretinopathy (BCR)
- Autoimmune retinopathy (AIR)
- Peripheral ulcerative keratitis (PUK)
- JIA

TORIC (17 decks)

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