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Immunology Flashcards

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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)?

Study These Flashcards
A

Necrotising small vessel vasculitis

18
Q

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

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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)?

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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)?

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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?

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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)?

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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?

Study These Flashcards
A

EGPA (eosinophilic granulomatosis with polyaniitis)

24
Q

Which HLA is Churg-Strauss/EGPA associated with?

25
What are the clinical features of Churg-Strauss/EGPA?
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
How often is p-ANCA positive in Churg-Strauss/EGPA?
50% of EGPA is p-ANCA PA is 50% of EGPA letters...
27
What are the histopathological findings of Churg-Strauss/EGPA?
Granuloma + Eosinophils in small/medium vessels
28
What single agent is used in Churg-Strauss/EGPA?
Prednisone only.
29
Compare: 1. GPA 2. MPA 3. EGPA in terms of vessel size, histopath, biochem/immunofluorescence (if relevant)
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
Patient with fever, haemoptysis and positive urinary sediment and p-ANCA positive. What are the DDx? How might the DDx be differentiated?
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
What might cryoglobulinaemia be associated with? Which types?
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
Which cells types are IL-7 receptors found in? What is it's normal function?
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
Mutation of the IL7-R genes is associated with which 2 conditions?
1. Multiple sclerosis | 2. SCID (severe combined immune deficiency) state - no T-cells, normal B-cells and NK-cells
34
With SCID, what cell line is deficient and which are preserved?
No T-cells Normal B-cells and NK-cells. NB: SCID aka T-B+NK+SCID
35
Which cell from the innate immune system is important in the control of viral infections?
NK-cells
36
IL-5 is produced by which 2 cell types? What is the function of IL-5 (2)?
Th-2 cells (helper T-cells) and mast cells Functions: 1. Stimulates B-cell growth and increases Ig production. 2. Eosinophil activation
37
IL-3 is produced by which 2 cell types? What is the function of IL-3 (2)?
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
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?
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
Which helper T-cell is implicated in autoimmune disease and intra cellular infections?
Th1
40
Which helper T-cell is implicated allergies and humoral immunity?
Th2
41
Which 4 cytokines are involved in Th1 response?
IL2, IL12, IFN-alpha, IFN-gamma
42
Which 4 cytokines are involved in Th2 response?
IL 4, 5, 10, 13

FRACP (20 decks)

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