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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

25
HLA association avec la SEP
B7 DR2
26
HLA association avec Retinal Vasculitis
B44
27
Panuvéite versus Endophtalmie
Panuveitis : descriptive term and does NOT imply etiology Endophtalmitis : panvuveitis secondary to infection
28
Vrai ou Faux. Les stéroïdes inhibent les phospholipases, enzymes en amont de la cascade inflammatoire.
Vrai. S'il n'y a pas de réponse au Tx, requestionner le Dx pr r/o cause infectieuse ou néoplasique
29
Solutions : Acetates versus Phosphates
Acetates/Alchohols = Lipophilic + : augmentation [ ] intraoculaire - : shaking required Phosphates = Hydrophilic + : no shaking required - : diminution [ ] intraoculaire
30
2 principaux ES oculaires des corticostéroïdes
Cataractes IOP Plus la puissance est élevée, plus le risque est grand
31
Nommez différents corticostéroïdes topiques en ordre de puissance
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
General approch for non-infectious uveitis Tx
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
Algorithme sélection Tx IMT
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
What is the mediator of the anti-inflammatory effects of MTX?
Extracellular release of adenosine (/!\ PAS inhibition of folate metabolism)
35
Mécanisme d'action du MTX + posologie
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
Mécanisme d'action du MTX + posologie Mycophenolate Mofetil (CellCept)
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
Nom commercial du mycophenolate mofetil
CellCept
38
Mécanisme d'action du MTX + posologie de l'azathioprine
Converted to 6-MP → inhibit purine synthesis/DNA replication Posologie : - PO - 1-2 mg/kg (ocular dose) Therapeutic in environ 3 months
39
Nom commercial de l'azathioprine
Imuran
40
Monitoring des anti-metabolites
FSC Créatinine Bilan hépatique Test de grossesse Azathioprine : doser l'activité de l'enzyme TPMT avant début Tx (déficience possible et toxicité 2nd)
41
Médicaments inhibiteurs de la calcineurine
Cyclosporine Tracolimus
42
Mécanismes d'action et ES des calcineurin inhibitors
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
Nom générique de l'Humira
Adalimumab
44
Efficacité de l'Adalimumab
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
Classe biologique de l'Adalimumab (aka MA)
Anti-TNF
46
Contre-indications des anti-TNF
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
Mécanisme d'action et indications du Tocilizumab
Anti-IL6 Indications - JIA associated uveitis - Anterior uveitis - Intermediate uveitis - Post/Pan uveitis
48
Lequel des Rx est associé à un « mental health concerns » comme ES
IFN
49
Mécanisme d'action et indications du Rituximab
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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