Immuno conditions

Question 1

ANCA vasculitides - Rx

Answer 1

GC - EPG likely respond

MPA need IS, consider if overlaps eg antiTNF etc

GPA induction w/ GC + IS

Drug induced: stop & monitor v short course steroids

Question 2

ANCA - large vessel vasculitides

Answer 2

GCA
Takayasu
(think Aorta & into visceral eg abdominal etc)

Question 3

ANCA - med vessel vasculitides

Answer 3

PAN
Kawasaki
(think visceral abdo, subclav, axillary)

Question 4

ANCA - sml vessel vasculitides

Answer 4

think sml arteries through arterioles, capillaries & venules etc - ANCA + non ANCA (other IC mediated)

Arterioles = HSP, IgA, Crygoglob
Capillaries = antiGBM
?T3 hypersens
AAV:
- EPG (c/s)
- GPA (weg)
- MPA

Question 5

A/E after CAR-T

Answer 5

1) CRS (fever WITH hypoxia, hypoTN) - can happen from any immunoRx (fever might not present if Tocilizumab tho)
2) ICANS (CNS involvement; ie. CRS + encephalopathy) - headache in wk post CAR-T
3) TLS
4) Decreased Ig
5) OI

Question 6

Rx CAR-T A/E

Answer 6

1) CRS: IL6 blocker (Tocilizumab) + supportive
2) ICANS: Tocilizumab if concurrent CRS, STEROIDS, Levetirecatam, Benzos, ICU
Consider antifungal,
EEG; MRI & LP if severe

Question 7

Rx - VITS (& timeframe of presentation)

Answer 7

4-42days (Plts <150 & unusual thrombosis or DVT/PE, arterial)

Give non heparin AC
Urgent IviG

Question 8

Type 1 hypersensitivity - immune rxn, examples, Rx

Answer 8

• Antigen
• IgE
• (mediated by IL4, mast cells, (cAMP), histmaine - IL5 & eisinophils 2nd)
  Initial <6hr, delayed 6-16hrs

Types: ANAPHYLAXIS
- Atophic - Urticaria, angiooedema, asthma, eczema, llergic rhinitis/conjunctivitis,

Rx: Antihistamines, Adrenaline, Theophylline (late phase - steroids, indomethacin, cerrizine, cyclosporin)

Anaphylotoxins C3a & C5a (generated w/ C’ activation) can degranulate mast cells w/ same outcome but NOT t1 as IgE not involved
Likewise CUI is AI as AutoAbs stimluate mast cell degranulation rather than IgE

Question 9

CUI - Rx

Answer 9

H1 antihis QID (50% refractory)

Omalizumab (anti-IgE)

Traditional IS - Cyclosporine, HCQ, dapsone

?IL5r - benralizumab

Question 10

Bullous pemphigoid - Fx, Cause, Rx

Answer 10

T2 hypersensitivity (Ab mediated → cytotoxic cellular destruction)

Med induced: (vals fat abdo covered by pemphigoid)
Vildagliptin (DPP4) frusemide, ACE, cipro, B-lactams, PD1

Rx - Doxy (or Pred), topical steroids, (2nd line IS, Omalizu)

Screen for malignancy as it is associated! also neuro disorders

Question 11

Type 2 hypersensitivity - MoA, examples

Answer 11

IgG mediated 2*

• antigen (cell/matrix) w/ C’ & innate cell cytotoxicity
• cell surface receptor - Ab alters signalling - cellular dysfxn

Eg. Drug allergies

Blood issues - ABO, haemolysis, HITS

Organ specific - thyrotoxicosis, graft rejection, MG, antiGBM

Skin - bullous pemphigoid (Ab mediated) IgG & activated T cells attack collagen in BM of epidermis (Vals fab abdo covered by pemphigoid)

Question 12

Type 3 hypersensitivity - MoA, Examples, Skin

Answer 12

Immune complex (IgG + antigen) depositing into tissue

• Serum sickness (mAb) - 1wk after w/ fever, arthrtitis, nephritis, rash
• Vasculitis, drug induced SLE
• Local deposits (farmers lung, RA)
• GN (post strep GN, SLE nephritis)
• Arthrus reaction

Skin - sml vessel vasculitis - bx for IgA

Question 13

Type 4 Hypersensitivity - MoA, cells, examples

Answer 13

Delayed - T cell - Th1 (macrophages IFNy, cytokines), Th2 (eisinophils, IgE) or Tc

• Contact dermatitis - maculopapula exanthema
• Granulomatous eg Tb, sarcoid, CD
• Intracell infections (myco, fungi, hlemiths, schisto)
• Chronic graft rejection
• Chronic asthma, allergic rhinitis, delayed urticaria??
• DRESS/SJS/DHIS/TENS

Question 14

C1 esterase inhibitor def - C’ levels

Answer 14

• C4 + C2 LOW
• Not C3 - unclear why
• Increased anaphylatoxin production C2a C4a

Question 15

Eculizumab - Pathophysiology

Answer 15

• mAb: C5
• Blocks C5 to C5 convertase (C5b)
• C5b goes on to make MAC
• Also C5a which is opsonin (& anaphylotoxin)
• Use in atypical HUS & PNH
• Vulnerable to encapsulated organisms