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Immuno Path flashcards

1
Q

Different types of SCID

A

X-linked (unresponsive to cytokines - IL-2);
Low T, Low NK, High (non-functioning) B cell, Low Ig

ADA (presents 3 months);
Low T, Low B, Low NK, normal neutrophil

Reticular Dysgenesis (AK2);
Low ALL - presents very early
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2
Q

What is Bare Lymphocyte Syndrome 2

A

No CD4 cells –> cant class switch IgM to IgG/IgA

Normal CD8, absent/low CD4, HIGH IgM, Low IgG/IgA

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3
Q

CD40 mutation

A 
DEFECTIVE CD40 on T cell = no class switching
Normal CD9, Normal CD4, High IgM, Low IgG/IgA
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4
Q

Bruton

A

X linked, Tyrosine Kinase Gene
Stops Pre B cells maturing to B cells
Therefore No B cell or Igs, normal everything else

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5
Q

What ligand is commonly affected in LAD

A

CD18

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6
Q

Pathophysiology of CGD and treatment?

A

No oxidative killing, therefore NON-caseating granulomas form

NEGATIVE dihydrorhadanine and NBT

antibiotics, antifungals and interferon Gamma

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7
Q

What are primary innate immunodeficiencies susceptible to?

A

Staph Aureus
Enteric organisms
Candida Albicans
Aspergillus Flavus

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8
Q

What does NK cell deficiency predispose to

A

Viral infections and tumours

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9
Q

Primary innate immunodeficiency, recurrent atypical mycoplasma/ TB infections

A

IFN gamma receptor deficiency

Signalling failure; IL-12 and IFN gamma
(produced by macrophage and T cell) respectively
(receptor for T cell and macrophage) respectively

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10
Q

Inheritance for Kostmans vs Cyclical

A

AR vs AD

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11
Q

What is the most common complement immunodeficiency

A

C2, associated with SLE

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12
Q

Why are complement deficiencies associated with SLE

A

less removal of cellular debris gives NUCLEAR remnants causing ANA production –> SLE

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13
Q

Which organisms are complement deficiencies susceptible to>

A

NHS (encapsulated)

complement forms the attack complex which normally poked holes in the encapsulated organisms

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14
Q

CVID

A 
Common variable immunodeficiency
Presents later in life with IgG/IgA/IgE deficiency alongside;
another AI disease
Lung, liver, kidney problems
 \+ LYMPHOMA
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15
Q

What are the co-factors for HIV binding to T cells

A

CD20 (main), CCR5, CXCR4

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16
Q

What ligands does HIV use to bind?

A

gp120, gp41

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17
Q

What are the screening tests if you suspect someone has HIV

A

1) ELISA

2) rapid screening test (less sensitive)

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18
Q

What is diagnostic for HIV?

A

Western Blot (for HIV antibodies)

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19
Q

What are the most important HLAs for transplant matching

A

DR>B>A

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20
Q

How many HLA mismatches are too many?

A

> 6

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21
Q

what is the chance a sibling will have x amount of HLA matches

A 
25% = 6 MM
50% = 3 MM
25% = 0 MM
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22
Q

What are the types of graft rejection?

A

Hyperacute - preformed antibodies to ABO
Acute 1) T cell mediated; interstitial inflammation
2) Antibody mediated - vasculitis
Chronic - can be immune or non immune

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23
Q

Which drugs are used for prophylaxis of transplant rejection

A

1) antiproliferative - azathioprine (pro-drug which turns into 6-mercaptopurine) OR mycophenalate mofetil
2) Cell signalling inhibitor (calcineurin) such as tacrolimus or cyclosporin)
3) Steroids

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24
Q

C3 deficiency + lipodystrophy + glomerulonephritis?

A

C3 nephritic factor (antibody to C3 convertase)

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25
Polygenic autoinflammatory condition?
Familial mediterranean fever (FMF)
26
What is FMF (symptoms, pathophysiology) + treatment
mutation in the MEFV gene causing failure to regulate cryopyrin regulation of neutrophils --->>> which means the inflammasome complex doesn't work fever + serositis (lung, mesenchyma) every 46-96 hours + AA deposits long term Treatment; colchicine (neutrophil inhibitor) + anti IL-1 and anti TNF alpha (anakinra and etanercept)
27
Name 3 monogenic autoimmune disease
APS-1/APECED - autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy IPEX - Immunodysregulation polyendocrinopathy enteropathy X-linked ALPS - autoimmune lymphoproliferative disorder
28
APS-1
Defect in the AIRE protein (means thymic central tolerance is defective so autoreactive T cells fly around causing loads of random AI disease) Autosomal recessive Hypoparathyroid + Addisons + candida infections (as also against IL17)
29
What do treg cells have on their surface
CD3 (all T cells), Foxp3 and CD25
30
What is IPEX
IPEX = immune dysregulationpolyendocrinopathy enteropathy. - treg malfunction because Foxp3 is mutated = lack of PERIPHERAL tolerance 3 Ds; polyendocrine and enteropathy; Dermatitis, Diabetes and Diarrhoea X-linked
31
ALPS
Autoimmune lymphoproliferative syndrome - failure to apoptose lymphocytes vis FAS pathway - CD4 negative and CD8 negative BOTH present - High lymphocyte count cytopaenia e.g. haemolytic anaemia and LYMPHOMA
32
Crohns disease gene
IBD1 - NOD2
33
HLA associations; seronegative arthropathies
PEAR; B27
34
HLA associations; goodpastures
DR2/DR15
35
HLA associations; Graves
DR 3
36
HLA associations; SLE
(DR )2,3, SLE
37
HLA associations; T1DM
DR3/4
38
HLA associations; Rheumatoid arthritis
DR4
39
Hypersensitivity disorders: atopic dermatitis
type 1
40
Investigations for allergy
acute; mast cell tryptase otherwise 1) RAST; can rule out allergy 2) Skin prick 3) Gold standard challenge test (in hospital)
41
Hypersensitivity disorders: serum sickness
type 3, reaction to proteins (penicillin) in antiserum
42
Hypersensitivity disorders: polyarteritis nodosa
type 3
43
Hypersensitivity disorders: SLE
type 3
44
Hypersensitivity disorders: T1DM
type 4
45
Hypersensitivity disorders: MS
type 4
46
Hypersensitivity disorders: Contact dermatitis
type 4
47
Hypersensitivity disorders: mantoux test
type 4
48
Autoantibodies: Antiphospholipid syndrome
cardiolipin, lupus anticoagulant, B2 glycopeptide
49
Autoantibodies: AI hepatitis
anti LKM-1 and anti smooth-muscle
50
Autoantibodies: congenital heart block in children when mothers have SLE
anti-Ro
51
Autoantibodies: Dermatitis herpertiformis
anti-endomysial
52
Autoantibodies: Diffuse cutaneous scleroderma
anti-topoisomerase (SCL-70) - nucleolar pattern
53
Autoantibodies: Sjogrens
anti ENAs; anti-Ro, anti-La (speckled pattern)
54
Autoantibodies: Myasthenia gravis
anti-Ach
55
Name live attenuated vaccines
MMR VBOY Measles Mumps Rubella VZV (no HIV) BCG Other; Sabin (polio) and typhoid Yellow fever (no HIV)
56
Name conjugate vaccines
NHS | pneumococcal is polysaccharide
57
Name toxoid vaccines
Diptheria, Tetanus
58
Name component vaccines:
HPV (capsid), HepB (HbS antigen), Influenza (HG/NA)
59
Name DNA/ RNA vaccines
COVID - target spike protein
60
Name vaccine adjuvants
aluminium salt (ALUM) - B cell maturation CpG IL2 - for Hep B (t cell)
61
T cell replacement therapies (3)
1) viral (leukaphoresis, sensitise, expand, return) 2) tumour (biopsy, isolate, expand, return) 3) CAR-T (leukaphoresis, prime against CD19, return to kill B cells - ALL and NHL)
62
General IVIG replacementt
1) primary immunodeficiencies | 2) secondary immunodeficiencies (CLL, MM, BM transplant)
63
Interferon therapies
IFN alpha; hep B and C + CML IFN Beta; Behcets IFN gamma: CGD
64
Melanoma treatments
checkpoint blockers; - anti PDL1 = PEMBROLIZUMAB/ nivolumab - anti CTLA4 = IPILIMUMAB
65
name anti proliferative agents (4)
azathioprine, mycofenalate mofetil, cyclophosphamide, methotrexate
66
MOA and considerations: azathioprine
used for transplant prophylaxis prodrug --> 6 mercaptopurine (BM suppression) T>B cells antimetabolite (purine) need to measure TPMT levels -- allopurinol
67
MOA and considerations: mycofenalate mofetil
used for transplant prophylaxis T>B cells antimetabolite (guanine) complication; progressive multifocal leukoencephalopathy (reactivating the JC virus)
68
MOA and considerations: cyclophosphamide
B > T cells connective tissue, vasculitis, cancer Haemorrhagic cystitis
69
MOA and considerations: Methotrexate
folate Rheumatoid arthritis, psoriasis, crohns + abortions BM suppression
70
Name cell signalling inhibitors:
Tacrolimus, Cyclosporin, Sirolimus (MTOR), Tofacetinib (JAK-STAT), Apremilst
71
MOA and considerations: Tacrolimus/ Cyclosporin
Rejection prophylaxis in transplants calcineurin inhibitor nephrotoxic and ototoxic cyclosporin --> gingival gum hypertrophy
72
Name agents directed at cell surface antigens BAM No Receptor Today!
Basilixumab (anti CD25) - allograft rejection Anti-thymocyte (allograft rejection) Muromonab (mouse, anti-CD3) - active allograft rejection Natalizumab (for relapsing remitting MS) Tocilizumab (anti IL6) - RA, doesnt work in PA Abatacept (anti-CTLA4) - RA and melanoma Rituximab (anti CD20) - depletes mature B cells for LYMPHOMA
73
Name agents against cytokines
anti TNF alphas (infliximab, adalimumab, Certolizumab, Golimumab) - RA + PEAR Etanercept (TNFa and TNFb) - RA + PEAR Secukinumab (anti IL17) - 3rd line Ank,Spon + psoriasis Ustekinumab (anti-IL12 and IL23) - psoriasis Denosumab (anti-RANKL) - osteoporosis
74
Autoantibodies: dermato/polymyositis
Anti-Jo-1 (tRNA synthetase)
75
HLA association: Coeliac
DQ 2 and 8 | 'I ate too much at Dairy Queen'
76
What can be used as a marker of SLE severity?
C3, C4 (C4 depletes first, if severe C3 depletes)
77
Treatment for Ankylosing Spondylitis
NSAIDs --> Etanercept (anti TNFa/b) --> Secukinumab (anti IL17)
78
What causes a post transplant lymphoproliferative disease?
EBV
79
What does rituximab do?
Cell surface antigen blocking of CD20 Used in LYMPHOMA ( and ALL) Rheumatoid arthritis and SLE
80
What is the Gag protein (HIV)
intrastructural support
81
C1 inhibitor deficiency
hereditary angioedema
82
Which drug commonly can cause anaphylaxis (drug reaction)
ACEi (think hypertension)
83
Mutation for HIV resistance
CCR5-delta 32
84
Which immune cell produced in the bone marrow, migrates to perform oxidate and non oxidative killing methods?
neutrophil
85
A teenage girl who gets an erythematous rash when cross-country running
Cold urticaria
86
A 60 year old lady with recurrent chest infections, reduced total serum protein and ITP. What is the diagnosis
CVID
87
What immunodeficiency is susceptible to mycobacteria?
IFN gamma deficiency
88
What does common gamma chain mean and thus what is the related immunodeficiency
IL2 and X-linked SCID
89
What cell type do antibodies bind to in antibody mediated solid organ transplant rejection?
Endothelial | the other is T cell mediated
90
ALUM effect of vaccine
helps B cell maturation
91
CpG effect on vaccine
Activates Toll-like receptors on APCs to increase costimulation
92
What adjuvant can you give to people receiving the HepB vaccine
IL 2

Year 5 (7 decks)

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