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FRACP > Immunology > Flashcards

Immunology Flashcards

1
Q

Describe the 2 signal process of T-cell activation from an APC.

A

T-cell activation requires 2 signals between the T-cells and APC:

Signal 1: T-cell [TCR:peptide:MHC] APC – necessary but not sufficient

Signal 2: T-cell [CD28:B7] APC – activation of T-cell with IL-2 release and T-cell proliferation

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2
Q

What are CTLA-4 receptors?

A

CTLA-4 receptors are the doppelganger of CD28 in that they bind preferentially to B7 on APC cell and prevent the activation and proliferation of T-cells.

Normal function is to prevent autoimmunity.

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3
Q

Which interleukin is implicated in T-cell proliferation?

A

IL-2 is released upon activation of T-cell to promote T-cell proliferation

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4
Q

What is polyarteritis nodosa (PAN)? Which sex is it more likely to affect?

A

Medium vessel vasculitis that affects M > F.

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5
Q

Which organ systems are implicated in polyarteritis nodosa (PAN)? Which organ system that tends NOT to be implicated?

A

Systemic - fever, malaise, weight loss 80%

Neuropathy - mononeuritis multiplex, polyneuropathy 75%

Arthralgia/myalgia 60%

Skin - livedo reticularis, pupura, ulcers 50%

Renal disease 50%

GI - abdominal pain, rectal bleeding 40%

HTN - new onset 35%

Orchiditis - testicular pain 20%

Lungs tend NOT to be involved.

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6
Q

Which viral illness is polyarteritis nodosa (PAN) associated with?

A

Hep B

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7
Q

What are the investigations for polyarteritis nodosa (4)?

A
  1. Angiogram (mesenteric/renal) for vasculitis
  2. Hep B serology
  3. Complement C3/C4 - normal
  4. Biopsy affected tissue
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8
Q

True/False: complement C3/4 is elevated in polyarteritis nodosa (PAN).

A

False.

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9
Q

What is the treatment of polyarteritis nodosa (s)?

A
  1. Steroids
  2. Cytotoxics
  3. Treat Hep B is relevant.
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10
Q

What are 6 conditions are associated with pANCA (use mnemonic).

A

My Personal Computer Is Really Good! … So i Permanently ANCHORED it to my desk!

(MPCIRG = pANCA)

Microscopic polyangitis (MPA)

Polyarteritis nodosa (PAN)

Churg-Strauss (EGPA/Eosinophilic GPA)

IBD (esp. UC)

RPGN - Rapidly Progressive Glomerulonephritis (necrotising/cresentic GN)

Goodpasture’s Syndrome (anti-GBM)

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11
Q

What is the new name for Wegener’s Granulomatosis?

A

GPA (Granulomatosis with PolyAngiitis)

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12
Q

How is GPA (granulomatosis with polyangiitis) diagnosed (biochemistry/immunofluorescence/histopathology/urine)?

A

Biochem: c-ANCA, PR3

Immunofluorescence: Pauci-immune

Histopathology: necrotising medium vessels + granulomas

Urine: postive urinary sediment

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13
Q

Which organ systems are implicated in GPA (granulomatosis with polyangiitis)?

A

ELK:
ENT
Lung - PE (20x risk)
Kidney - haematuria/RPGN

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14
Q

What type of glomerular disease is GPA (granulomatosis with polyangiitis) associated with?

A

Rapidly-progressive GN (RPGN)

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15
Q

True/False: GPA (granulomatosis with polyangiitis) is more likely to relapse than Microscopic Polyangitis?

A

True.

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16
Q

What is the treatment of GPA (3)?

A
  1. Rituximab + prednisone (Rituximab as good as cytotoxic with less SEs)
  2. If RPGN then IVIG
  3. Maintenance = AZA or MTX (only if cytotoxics used)
  4. Relapse = cytotoxics then AZA afterwards
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17
Q

What is MPA (Microscopic Polyangiitis)?

A

Necrotising small vessel vasculitis

18
Q

What Ab-staining occurs in MPA (Microscopic Polyangiitis)?

A

Easy MPA (word contains MPo + P-anca + Pauci-immune):

  • MPO
  • p-ANCA
  • pauci-immune
19
Q

How is MPA (Microscopic Polyangiitis) diagnosed (biochemistry/immunofluorescence/histopathology/urine)?

A

Biochemistry: p-ANCA / MPO

Immunofluorescence: pauci-immune, small % with anti-GBM (Goodpastures)

Histopathology: necrotising small vessels

Urine: positive urinary sediment

20
Q

What are the points of differentiation between MPA and GPA (biochemistry/immunofluorescence/histopathology/urine)?

A

Biochem:
GPA = c-ANCA/PRS
MPA = p-ANCA/MPO

Histopathology:
Both are necrotising.
GPA = vasculitis of medium-sized vessels + granulomas
MPA = vasculitis of small-sized vessel with NO granulomas

Immunofluorescence and urine: Same - both pauci-immune and with positive urinary sediment.

Use:

  1. ‘WE CAn P-Pass this wRITten eXamination?’ (5)
  2. MPA (contains 3 things: MPO/p-ANCA/Pauci)
21
Q

Which is more severely affected in MPA; kidneys or lungs?

A

MPA: Kidneys > Lungs

‘Malaysia Pacific Airlines flies to Kuala Lumpur’

Glomerulonephritis +/- RPGN&raquo_space; alveolitis / haemoptysis

22
Q

What is the treatment for MPA (3)?

A
  1. Rituximab + Prednisone
  2. Plasmaphoresis improved renal outcomes
  3. Maintenance: AZA / MTX (only if cytotoxic used).
23
Q

What is another name for Churg-Strauss?

A

EGPA (eosinophilic granulomatosis with polyaniitis)

24
Q

Which HLA is Churg-Strauss/EGPA associated with?

A

HLA-DRB4

25
Q

What are the clinical features of Churg-Strauss/EGPA?

A

Mnemonic: ‘Strauss was an A-PLUS Nazi composer’
(Churg-Strauss is an Asthma ‘PLUS’ syndrome / Neuropathy)

Typically:

Asthma / Eosinophilic pneumonia ‘plus’ neuropathy (peripheral neuropathy, mononeuritis multiplex)

Other ‘plus’ syndromes:

Glomerulonephritis
Cardiac (myocarditis, coronary arteritis)
Dermatological (purpura)

26
Q

How often is p-ANCA positive in Churg-Strauss/EGPA?

A

50% of EGPA is p-ANCA PA is 50% of EGPA letters…

27
Q

What are the histopathological findings of Churg-Strauss/EGPA?

A

Granuloma + Eosinophils in small/medium vessels

28
Q

What single agent is used in Churg-Strauss/EGPA?

A

Prednisone only.

29
Q

Compare:

  1. GPA
  2. MPA
  3. EGPA

in terms of vessel size, histopath, biochem/immunofluorescence (if relevant)

A
  1. GPA
    Medium vessels
    Necrotising vessels + Granulomas
    c-ANCA / PR3 / pauci-immune
  2. MPA
    Small vessels
    Necrotising vessels only
    p-ANCA / MPO / pauci-immune
  3. EGPA
    Small/Medium vessels
    Granulomas + Eosinophils (extravascular)
    p-ANCA (50%)
30
Q

Patient with fever, haemoptysis and positive urinary sediment and p-ANCA positive.

What are the DDx?

How might the DDx be differentiated?

A

DDx for positive p-ANCA = MPA, PAN, Churg-Strauss, IBD, RPGN, Goodpastures.

‘My Personal Computer Is Really Good, so i Permanently ANCHORED it onto my desk’

NOT PAN - tends not to involve lungs.
NOT Churg-Strauss (EGPA) - no asthma/eosinophilia
NOT IBD/RPGN - not consistent with presentation

Therefore DDx: MPA vs. Goodpastures (Anti-GBM)

Need Biopsy:
Anti-GBM = Anti- GBM (obviously)
Necrotising pauci-immune small vessel = MPA

31
Q

What might cryoglobulinaemia be associated with?

Which types?

A

Many things.

Type I = lymphoproliferative disorders
Type II = acute Hep C
Type III = autoimmune disorders (SLE/Sjogrens/PAN/RA)

Other: infections, renal transplants, idiopathic.

32
Q

Which cells types are IL-7 receptors found in?

What is it’s normal function?

A

B-cells T-cells Lymphoid progenitor cells

Interaction with IL-7 permits development of maturation, proliferation and survival of B-cells and T-cells

33
Q

Mutation of the IL7-R genes is associated with which 2 conditions?

A
  1. Multiple sclerosis

2. SCID (severe combined immune deficiency) state - no T-cells, normal B-cells and NK-cells

34
Q

With SCID, what cell line is deficient and which are preserved?

A

No T-cells
Normal B-cells and NK-cells.

NB: SCID aka T-B+NK+SCID

35
Q

Which cell from the innate immune system is important in the control of viral infections?

A

NK-cells

36
Q

IL-5 is produced by which 2 cell types?

What is the function of IL-5 (2)?

A

Th-2 cells (helper T-cells) and mast cells

Functions:

  1. Stimulates B-cell growth and increases Ig production.
  2. Eosinophil activation
37
Q

IL-3 is produced by which 2 cell types? What is the function of IL-3 (2)?

A

T-cells and basophils.

Functions:

  1. Differentiation of multipotent haematopoetic stems into myeloid progenitor cells or lymphoid progenitor cells (requires addition of IL-7)
  2. Stimulates the proliferation of myeloid lineage cells in conjunction with other chemokines: EPO, GM-CSF and IL-6.
38
Q

What are the cytokines that encourage a Th1 vs. Th2 response (i.e. helper T-cells)?

What is the utility of a Th1 response vs. Th2 response?

A

Naive helper T-cells (CD4) attach to APC via MHC II.

Thn = naiive T-cells 
Th0 = undifferentiated Th cell

Th1 response:

Normal fn: intracellular microbes.
Abnormal fn: autoimmunity
Cytokines: IL-12/IFN-alpha > Thn or Th0 > Th1 > IFN-gamma/IL-2

NB: alpha then gamma (in order)

Th2 response:

Normal fn: humoral immunity
Abnormal fn: allergies
Cytokines: IL4 > Thn or Th0 > Th2 > IL-4/IL-5/IL-10/IL-13

NB: Th2 have no ‘2’ in any of the cytokines.

39
Q

Which helper T-cell is implicated in autoimmune disease and intra cellular infections?

A

Th1

40
Q

Which helper T-cell is implicated allergies and humoral immunity?

A

Th2

41
Q

Which 4 cytokines are involved in Th1 response?

A

IL2, IL12, IFN-alpha, IFN-gamma

42
Q

Which 4 cytokines are involved in Th2 response?

A

IL 4, 5, 10, 13

FRACP (20 decks)

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