Immunopathology Buzzwords Flashcards
(430 cards)
1
Q
Autosomal recessive severe SCID with no production of lymphoid or myeloid cells
A
Reticular dysgenesis
2
Q
three examples of failure of neutrophil production
A
Reticular dysgenesis
Kostmann syndrome
Cyclic neutropaenia
3
Q
Autosomal recessive congenital neutropenia
A
Kostmann syndrome
4
Q
Autosomal dominant episodic neutropaenia
A
Cyclic neutropaenia
5
Q
Cyclic neutrophaenia occurs every ? days
A
21 days
6
Q
inheritance pattern Kostmann syndrome
A
AR
7
Q
Inheritance pattern cyclic neutropaenia
A
AD
8
Q
Inheritance pattern Reticular dysgenesis
A
AR
9
Q
phagocyte deficiency caused by failure of phagocyte migration
A
Leukocyte adhesion deficiency
10
Q
Leukocyte adhesion deficiency, deficiency of what?
A
Caused by deficiency of CD18 (β2 integrin)
11
Q
What does CD18 do?
A
CD18 normally combined with CD11a to produce LFA-1 (lymphocyte function associated antigen 1)
12
Q
Where do leukocytes bind to on endothelial cells?
A
CD18 normally combined with CD11a to produce LFA-1 (lymphocyte function associated antigen 1)
LFA-1 normally binds to ICAM-1 (intercellular adhesion molecule 1) on endothelial cells to mediate neutrophil adhesions and transmigration
13
Q
Diagnose:
- V high neutrophil count in blood
- Absence of pus formation
- Delayed umbilical cord separation
A
Leukocyte adhesion deficiency
14
Q
Nitroblue-tetrazolium neg (doesnt change from yellow to blue)
A
Chronic granulomatous disease
15
Q
Bacterial susceptibility in chronic granulomatous disease
A
Catalase positive - PLACESS
Pseudomonas, listeria, aspergillus, candida, E. coli, S. aureus, serratia
16
Q
Diagnose:
- lots of Granuloma formation
- Lymphadenopathy and hepatosplenomegaly
A
Chronic granulomatouus disease
17
Q
deficiency of NADPH oxidase
A
Chronic granulomatous disease
18
Q
Dihydrorhodamine flow cytometry test doest change to fluorescent rhodamine with H2O2
A
Chronic granulomatous disease
19
Q
Inability to form granulomas
A
IL-12, IL12-R, INFg, INFg-R deficiencies
20
Q
which cells produce IL-12
A
macrophagesWh
21
Q
which cell responds to IL-12
A
t cells and then produce IFNg
22
Q
Which cells produce TNF-alpha
A
macrophages
23
Q
IL-12, IL12-R, INFg, INFg-R deficiencies have a susceptibility to which infections
A
recurrent infections with encapsulated bacteria - NHS - neisseria, Haemophilus, streptococcus
24
Q
Failure to generate free radicals
A
chronic grnaulomatous disease
25
PLACESS - catalase positive
Pseudomonas
Listeria
Aspergillus
Candida
E. coli
S. aureus
Serratia
26
organism that infects macrophages
mycobacterium
27
Infections in phagocyte deficiency
Bacteria - Staphylococcus aureus, enteric bacteria
Fungi - Candida albicans, Aspergillus fumigatus
28
Infections in IL-12 deficiency
TB, atypical mycobacteria
29
Absent neutrophil count
Normal leucocyte adhesion markers
No neutrophils for NBT/DHR
No pus
Kostmann syndrome
30
High neutrophil count
Absent CD18
Normal NBT/DHR
No pus
Leucocyte adhesion deficiency
31
Normal neutrophil count
Normal leucocyte adhesion markers
Abnormal NBT/DHR
Pus present
Chronic granulomatous disease
32
Normal neutrophil count
Normal leucocyte adhesion markers
Normal NBT/DHR
Pus present
IL12/IFN-gamma deficiency
33
Treatment for Chronic granulomatous disease
IFN-g therapy
34
absence of NK cells in the peripheral blood
vs
NK cells are present but function is abnormal
Classical NK deficiency - absence of NK cells in the peripheral blood
Functional NK deficiency - NK cells are present but function is abnormal
35
Infections in NK cell deficiency
Increased risk of viral infections
(e.g. HSV, CMV, EBV, VZV)
36
Tx - NK cell deficiency
Prophylactic aciclovir
IFN-alpha - stimulate NK cytotoxic function
HSC transplant
37
Diagnosis: Recurrent infections with NO neutrophils on FBC
Kostmann syndrome
38
Diagnosis: Recurrent infections with HIGH neutrophils on FBC and no pus formation
Leucocyte adhesion deficiency
39
Diagnosis: Recurrent infections with hepatosplenomegaly and abnormal DHR
Chronic granulomatous disease
40
Diangosis: Infection with atypical mycobacteria
Normal FBC
IFN-gamma receptor deficiency
41
Diagnosis: Severe viral infections (e.g. chickenpox, disseminated CMV)
Classical NK cell deficiency
42
Factor H?
A regulatory protein in the alternative complment pathway
43
complement deficiency, common infections
Neisseria meningitidis
Haemophilius influenzae
Streptococcus pneumoniae
NOTE: susceptibility to N. meningitidis is particularly common in properidin and C5-9 deficiency
44
Mannose binding lectin deficiency
common but no immunodeficiency
45
Common terminal pathyway deficiency
Defect in C3, C5-C9
inability to make MAC, inability to lyse encapsulated bacteria
46
Severe meningococcal septicaemia - complement deficiency?
C7
47
Immunodeficiency in membranous glomerulonephritis
Secondary C3 deficiency
Nephritic factors stabilize C3 convertases -> C3 activation and consumption.
48
Cause of secondary C1, C2, C4 deficiency
Active lupus
49
C2 def
all have SLE, severe skin disease and high infections
50
Presents @ 3m with:
- Infections – all types
- FTT
- Persistent diarrhoea
- Unusual skin disease
- Colonisation of infant’s empty bone marrow by maternal lymphocytes à Graft vs host disease
SCID
51
X-linked SCID vs SCID (general)
X-Linked SCID has immature B cells, general SCID has no B cells
52
Mutation in X-linked SCID
Mutation of the common gamma chain of
the IL-2 receptor on Ch Xq13.1
53
adenylate kinase 2(AK2) mutation
Adenosine Deaminase def
54
presentation of Adenosine Deaminase def
low B, T and NK cells.
55
Deletion at Chr22q11.2
DiGeorge Syndrome
56
- Cardiac abnormalities à TOF
- Abnormal facies – high forehead, low
set ears
- Thymic aplasiaà T cell lymphopenia
- Cleft palate
- Hypocalcaemia/hypoparathyroidism
DiGeorge Syndrome
57
Absent expression of MHC class II molecules
Bare Lymphocyte Syndrome Type 2
CD4+ t helper cell deficiency - no class switching
58
Clinically:
- Unwell by 3 months & FTT
- Infection – all types
- May be associated w/ sclerosing
cholangitis
- FHx of sudden infant death.
Bare Lymphocyte
Syndrome Type 2
59
Failure to express CD40L on activated T cells
Hyper IgM syndrome
60
TPMP polymorphism , don't give
azathioprine -> susceptible to bone marrow failure
61
Cyclophosphamide SE
Haemorrhagic cystitis
62
Cyclophosphamide - MOA
Alkylates the guanine base of DNA -> damages DNA and prevents replication
63
Calcineurin inhibitors
Tacrolimus and Cyclosporin
64
mutation of MCH III
Common Variable
Immune Deficiency
65
JAK1and3 inhibitor
Tofacitinib
66
Defective B cell tyrosine kinase gene (BTK)
Bruton’s X-linked hypogammaglobulinemia
67
Mutation in ChXq26
Hyper IgM Syndrome
68
absence of mature B cells and no
circulating Ig after ~ 3 months
Bruton’s X-linked hypogammaglobulinemia
69
most common primary immunodeficiency
IgA deficiency
70
Renal cell cancer (most commonly used one)
IL-2
71
Chronic granulomatous disease à stimulates phagocytes
INF-g
72
Relapsing MS, Bechet’s
INFb
73
HCV, HBV, Kaposi
INFa
74
hairy cell leukaemia, CML, myeloma
INFa
75
Azathioprine - type of drug
Purine analogue
76
Azathioprine blocks?
blocks de novo synthesis of
adenine and guanine
77
Azathioprine - MOA
prevents DNA
replication
78
Azathioprine - metabolite
6-Mercaptopurine
79
Methotrexate - MOA
Inhibits dihydrofolate reductase (DHFR)
Decreases DNA synthesis
80
JAK 1 and 3 inhibitor indications ?
rheumatoid and psoriatic arthritis
81
Calcineurin inhibitors indications?
Rejection prophylaxis in transplantation
82
CH50 functional complement assay tests what?
test of classical pathway (C1, 2, 4, 3, 5-9)
83
Classical pathway has
1, 2, 4, 3, 5-9
84
AP50 functional complement assay tests what?
test of the alternative pathway (B, D, Properidin, C3, C5-9)
85
Alternative pathway has what?
B, D, Properidin, C3, C5-9
86
Severe childhood-onset SLE with normal levels of C3 and C4
C1q deficiency
87
Membranoproliferative nephritis with abnormal fat distribution (partial lipodystrophy)
C3 deficiency with nephritic factor
88
Meningococcus meningitis with a family history of a sibling dying aged 6
C7 deficiency
89
Recurrent infections when neutropaenic following chemotherapy, but previously well
MBL deficiency
90
Mutation in common gamma chain on Xq13.1
X-linked SCID
91
Main immuno problem in X-linked SCID
IL-2 Receptor deficient
This is a component of many cytokine receptors leading to an inability to respond to cytokines,
Causing arrest in T and NK cell development and the production of immature B cells
92
two mechanisms by which CD8+ T cells kill cells
Perforin and granzyme
Fas ligand
93
immunological consequences of an underdeveloped thymus gland
Normal B cell count
Low T cell count
Homeostatic proliferation with age
94
Normal CD8+
Very low CD4+
Normal B cell count
Low IgG
Unwell by 3 months of age
Infections of all types
Failure to thrive
Family history of early death
Bare Lymphocyte syndrome type 2
Deficiency of MHC Class II means that CD4+ T cells cannot be selected in the thymus leading to CD4+ T cell deficiency
95
CD4 low
CD8 low
B cells normal/low
IgM normal/low
IgG low
SCID
96
CD4 low
CD8 low
B cells normal
IgM normal
IgG normal/low
Di George
97
CD4 low
CD8 normal
B cells normal
IgM normal
IgG low
BLS Type 2
98
severe recurrent infections from 3 months of age, CD4 and CD8 are absent, B cells present, Ig low, normal facial features and echocardiogram
X-linked SCID:
99
young adult with chronic infection with Mycobacterium marinum
IFN-gamma receptor deficiency
100
recurrent infections in childhood, abnormal facial features, congenital heart disease, normal B cells, low T cells, low IgA and IgG
22q11.2 deletion syndrome
101
6-month old baby with two recent serious bacterial infections. T cell present but only CD8. IgM present but IgG is low.
Bare lymphocyte syndrome type 2
102
Class of Ig determined by?
Heavy chain
103
Effector function of Immunoglobulin
Fc portion of heavy chain
104
abnormal B cell tyrosine kinase (BTK) gene
Bruton’s X-linked hypogammaglobulinaemia
Prevents the maturation of B cells at that point at which they emerge from the bone marrow
105
Boys present in the first few years of life
Recurrent bacterial infections (e.g. otitis media, pneumonia)
Viral, fungal and parasitic infections
Failure to thrive
Bruton’s X-linked hypogammaglobulinaemia
106
mutation in the CD40 ligand gene
Hyper IgM syndrome
107
adenylate kinase 2
Reticular dysgenesis
108
Blockage of maturation of IgM cells through germinal centres into B cells that produce other classes of Immunoglobi
X-linked Hyper IgM syndrome
109
Normal B cells
Normal T cells
No germinal centre reactions
High IgM
Absent IgG, IgA and IgE (failure of isotype switching)
X-linked Hyper IgM syndrome
110
Boys present in the first few years of life
Recurrent infections (mainly bacterial)
Subtle abnormality in T cell function (predisposes to PCP, autoimmunity and malignancy)
Failure to thrive
X-linked Hyper IgM syndrome
111
Marked reduction in IgG, IgA and IgE
Poor/absent response to immunisation
CVID
112
Failure of differentiation of B lymphocytes
CVID
113
May present in adults or children
Recurrent bacterial infection (often severe)
Pulmonary disease (e.g. interstitial lung disease)
GI disease (e.g. IBD-like disease)
Autoimmune disease (e.g. AIHA)
Malignancy (e.g. NHL)
CVID
114
most common immunodeficiency
IgA deficiency
115
CD4 low
CD8 low
B cell low
IgM low
IgG low
IgA low
SCID
116
CD4 normal
CD8 normal
B cell low
IgM low
IgG low
IgA low
Bruton’s X-linked Hypogammaglobulinaemia
117
CD4 normal
CD8 normal
B cell normal
IgM high
IgG low
IgA low
X-linked Hyper IgM syndrome
118
CD4 normal
CD8 normal
B cell normal
IgM normal
IgG normal
IgA low
Selective IgA deficiency
119
CD4 normal
CD8 normal
B cell normal
IgM normal
IgG low
IgA low
Combined variable immunodeficiency
120
adult with bronchiectasis, recurrent sinusitis and development of atypical SLE
CVID
121
1-year old boy. Recurrent bacterial infections, CD4 and CD8 cells present, B cells absent, absent IgG, IgA and IgM
Bruton’s X-linked hypogammaglobulinaemia
122
recurrent bacterial infections as a child, episode of PCP, high IgM, absent IgA and IgG
X-linked hyper IgM syndrome
123
recurrent respiratory tract infections, absent IgA, normal IgM and IgG
IgA deficiency
124
driven by components of the innate immune system - disease type?
Autoinflammatory = driven by components of the innate immune system
125
driven by components of the adaptive immune system - disease type?
Autoimmune = driven by components of the adaptive immune system
126
Does autoinflamm or autoimmune have HLA associations?
Autoimmune
127
Does autoinflamm or autoimmune have autoantibodies?
Autoimmune
128
Monogenic autoinflammatory?
Familial mediterranean Fever
129
List examples of polygenic autoinflammatory diseases
Crohn’s
UC
Osteoarthritis
Giant cell arteritis
Takayasu’s
130
monogenic autoimmune diseases
IPEX
ALPS
131
List examples of polygenic autoimmune diseases
Rheumatoid arthritis
Myasthenia
Pernicious anaemia
Graves disease
132
List examples of mixed pattern diseases
Ankylosing spondylitis
Psoriatic arthritis
Behcet’s
133
Monogenic autoinflammatory disease - which cytokine signalling pathways are affected?
TNF-alpha or IL-1
134
Which protein is upregulated in autoinflammatory diseases caused by gain-of-function mutation in NLRP3?
Cryopyrin (aka NLRP3)
135
Mutation of NLRP3 diseases?
- Muckle Wells syndrome
- Familial cold autoinflammatory syndrome
- Chronic infantile neurological cutaneous articular syndrome/Neonatal Onset Multisystem inflammatory disorder (NOMID)
136
Mutation of NLRP3 inheritance pattern
AD
137
Gene mutation in FMF
MEFV gene
138
What does the MEFV gene encode
Pyrin-marenostrin:
ordinarily a negative regulator of the inflammatory pathway → mutation leads to increased inflammation
139
Describe the inflammasome complex function
The pathway is activated by toxins, pathogens and urate crystals
These act via cyropyrin and ASC (apoptosis-associated speck-like protein) to activate procaspin 1
Activation of procaspin 1 results in the production of NFkB, IL-1 and apoptosis
140
Does loss or gain of function of pyrin-marenostrin lead to hyperactivity of the inflammasome complex?
loss of function
141
Does loss or gain of function of cryopyrin lead to hyperactivity of the inflammasome complex?
Gain of function
142
inheritance pattern of Familial Mediterranean Fever
AR
143
Cells that contain Pyrin-marenostrin
Neutrophils
144
Periodic fevers lasting 2-4 days associated with:
Abdominal pain (peritonitis)
Chest pain (pleurisy, pericarditis)
Arthritis
Rash
FMF
145
Complications of FMF
AA Amyloidosis -> renal failure
146
treatment of FMF
Colchicine 500 micrograms
- it bind to tubulin and disrupts neutrophil migration and chemokine secretion
Anakinra - IL-1 receptor blocker
Etanercept - TNF-alpha blocker
147
APECED stands for?
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy
148
Mechanism of defects in AIRE
AIRE = transcription factor - regulates expression of self-antigens
Defect = failure of central tolerance and release of auto-reactive T cells
149
Autoimmune conditions in APECED
Hypoparathyroidism (COMMON)
Addison’s disease (COMMON)
150
Patients with APECED more prone to what infection and why?
Candida - they produce antibodies against IL-17 and IL-22
151
What does IPEX stand for?
Immune dysregulation polyendocrinopathy enteropathy X-linked syndrome
152
mutation in IPEX
FoxP3 - required for dvlpt of Treg cells
153
“Diabetes, dermatitis, Diarrhoea”
IPEX
154
What does ALPS stand for?
Autoimmune lymphoproliferative syndrome
155
mutation in FAS pathway
ALPS
156
Immune consequence of FAS pathway mutation
Mutations in the FAS pathway leading to defects in apoptosis of lymphocytes
157
High lymphocyte count
Large spleen and lymph nodes
Autoimmune disease (usually cytopaenias)
Lymphoma - over time
ALPS
158
mutation in Crohn's disease
NOD2 - aka CARD-15 on chromosome 16
159
What is NOD2 - where? what does it recognise?
found in cytoplasm of myeloid cells - acts as microbial sensor - recognises MURAMYL DIPEPTIDE
160
Crohn's treatment?
Corticosteroids
Azathioprine
Anti-TNF-alpha antibodies
Anti-IL 12/23 antibodies
161
HLA-B27
Ank spon
162
Ank spon heritability
90%
163
Immunosuppressive Tx for ank spon
Anti-TNF-alpha
Anti-IL17
164
HLADR3
Graves and SLE
165
HLADR3/4
T1DM
166
HLADR4
Rheumatoid Arthritis
167
HLADR15
GOodpasture's
168
frequent mutation in polygenic autoimmune
PTPN22
CTLA4
169
What does PTPN22 do?
suppresses T cell activation
170
What does CTLA4 do?
regulates T cell function (expressed by T cells)
171
Anaphylactic hypersensitivity - immediate hypersensitivity which is IgE-mediated
Type I Hypersensitivity
172
Immune complex hypersensitivity - antibody reacts with soluble antigen to form an immune complex
Type III Hypersensitivity
173
Delayed-type hypersensitivity - T cell mediated response
Type IV Hypersensitivity
174
Cytotoxic hypersensitivity - antibody reacts with cellular antigen
Type II Hypersensitivity
175
Type I inflammatory pre-formed mediates
HIstamine
Serotonin
Proteases
176
Type I inflammatory synthesised mediates
Leukotrienes
Prostaglandins
Bradykinin
Cytokines
177
IgE mediated type I response
IgE binds to a foreign antigen (e.g. pollen)
The Fc portion binds to mast cells and basophils leading to degranulation
178
Antibodies binding to cellular antigens lead to cell death how?
antibodies can activate complement (by binding to C1) or bind to NK cells and macrophages resulting in phagocytosis
179
Autoantigen in Goodpasture's
non-collagenous domain of basement membrane collagen IV
180
Autoantigen in Pemphigus vulgaris
Epidermal cadherin
181
Autoantigen in Grave's disease
TSH receptor
182
Autoantigen in Myasthenia gravis
Nicotinic acetylcholine receptor
183
Tpye IV hypersensitivity mediated diseases
Insulin-dependent DM - pancreatic beta-cell antigen
MS - myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein
184
Graves’ disease antibody
Anti TSH receptor
185
Hashimoto's antibodies
Anti-thyroid peroxidase (TPO) antibodies
Anti-thyroglobulin antibodies
186
Gel and Coombs class for T1DM
Type IV Hypersensitivity
CD8 T cell mediated destruction of pancreatic islet cells
187
Autoantibodies in T1DM
Anti-glutamic acid dehydrogenase (GAD)
Anti-islet antigen (IA2)
Anti-islet cell
Anti-insulin
188
Major complication of B12 def
Subacute degeneration of the spinal cord (involving the posterior and lateral columns)
Megaloblastic anaemia
189
myasthenia gravis antibody
nicotinic acetylcholine receptors
190
Progessive muscle weakness following repetitive activity
Drooping eyelids, double vision
Dysarthria, dysphasia
Proximal muscle weakness
Symptoms worse at the end of the day
Myasthenia gravis
191
Tensilon test
Myasthenia gravis
administer very short-acting acetylcholinesterase inhibitor which causes a rapid improvement in symptoms (rarely used)
192
Goodpasture’s syndrome - antibody
Anti-GBM
193
What does Anti-GBM bind to?
Collagen type IV
194
Lungs - SoB, haemotypsis, widespread crackes
Kidneys - haematuria, oedema, reduced urine output, hypertension
Goodpasture's syndrome
195
RA polymorphisms
HLA DR1
HLA DR4
PTPN22
PAD 2 and PAD 4 polymorphisms
196
peptidylarginine deiminases (PAD) (enzyme involved in what?)
RA
197
Porphyromonas gingivalis gum infection causes?
RA
198
What is a pannus
inflamed synovium in RA
199
What diesease are ANA found in
Connective tissue autoimmune disease
200
SLE hypersensitivity type?
III - antibodies bind to antigens -> immune complexes form and deposit in tissues
201
Two types of ANA are?
Anti-dsDNA - specific for SLE
Anti-ENA - extractable nuclear antigens - Scl-70, centromere
202
Complement titres to measure in SLE
C3 and C4 will be low
203
immunofluorescence patterns between dsDNA and ENA antigens
anti-dsDNA = homogenous
anti-ENA = speckled pattern
204
Livedo reticularis on skin
Anti-phospholipid syndrome
205
antibodies in antiphospholipid syndrome
Anti-cardiolipin
Anti-beta2 glycoprotein-1
Lupus anticoagulant
206
pathophysiology of Sjorgren’s syndrome?
Autoimmune destruction of exocrine glands
207
Sjogren's antibodies
Anti-Ro and Anti-La
208
Sjogren's malignancy risk of?
MALT lymphoma
209
main features of limited cutaneous systemic sclerosis
Calcinosis
Raynaud’s phenomenon
Esophageal dysmotility
Sclerodactyly
Telangiectasia
NOTE: also pulmonary hypertension
210
Cytokines involved in Systemic sclerosis
Th2 and Th17
Type I collagen alpha 2 chains
FIbrillin 1
TGF-beta
211
antibody seen in limited cutaneous systemic sclerosis
anti-centromere
212
antibody seen in diffuse cutaneous systemic sclerosis
anti-topoisomerase (aka anti-Scl70)
213
perivascular CD4+ T cell and B cells are seen, this can cause an immune complex-mediated vasculitis (type III response)
Dermatomyositis
214
CD8+ T cells surround HLA Class I expressing myofibres, CD8+ T cells kill these myofibres via granzyme/perforin (type IV response)
Polymyositis
215
Heliotrope rash
Gottron papules
Photosensitivity
Dermatomyositis
216
Gold standard for inflamm myopathies
Muscle biopsy
217
anti-aminoacyl tRNA synthetase (e.g. Jo-1), anti-Mi2
Dermatomyositis
218
anti-aminoacyl tRNA synthetase antibody is cytoplasmic
Polymyositis
219
dsDNA+ve
SLE
220
ENA +ve
SLE
Sjogren's
Diffuse Cutaneous Systemic Sclerosis
Limited Cutaneous Systemic Sclerosis
221
Cytoplasmic ANA +ve
Myositis
222
Classification system for systemic Vasculitides
Chapel Hill
223
Small vessel vasculitides
Microscopic polyangiitis (pANCA)
Eosinophililc Granulomatosis with polyangiitis (pANCA)
aka Churg-Strauss syndrome
Granulomatosis with polyangiitis (cANCA)
224
cANCA antiboy
Proteinase-3
225
pANCA antibody
myeloperoxidase
226
cANCA fluorescence
Cytoplasmic fluorescence
227
pANCA staining pattern
Perinuclear staining pattern
228
How B cells undergo clonal expansion
1. differntiate into T-cell independent IgM plasma cells
2. Germinal centre reaction and becoem IgG/A/E memory and plasma cells
229
Does CD8 or CD4 undergo more pronounced proliferation following activation
CD8
230
Antigen-presenting cells
Dendritic
Macrophages
B lymphocytes
231
Cell surface receptor in influenza vaccine
Haemagglutinin (HA)
232
Which receptors on RBCs bind to Haemagglutinin A on influenza virus
Sialic acid receptors
233
Influenza protection lasts?
6 months
234
Type of BCG vaccine
attenuated
235
Mantoux test?
Liquid tuberculin (PDD) is injected intradermally
after 48-72 hrs, a reaction would appear as a wheel around the injection site (this is suggestive of latent TB, active TB or previous BCG)
236
What is a live attenuated vaccine? List some examples.
MMR,
Varicella zoster,
BCG,
Oral polio (Sabin)
Yellow fever,
nasal influenza, typhoid,
237
adv of live attenuated vaccines
- lifelong immunity
- activates all phases of immune system
- broad immune response to multiple antigens
238
disadv of live attenuated vaccines
Reversion to virulence:
- Spread to contacts (immunosuppressed patients)
- paralytic poliomyelitis
- storage problems
239
Inactivated vaccines
Inlfuenza (quadrivalent)
Cholera
Polio (Salk)
Hep A
Pertussis
Rabies
240
Toxoid vaccines
Diphtheria
Tetanus
241
Component/Subunit vaccines
Hep B (HBsAg)
HPV (capsid)
Influenza (HA)
242
adv of inactivated/component vaccines
no risk of reversion to virulent form
immunodeficient patients can use
storage eaiser
lower cost
243
disadv of inactivated/component vaccines
multiple injections
poor immunogenicity
244
conjugate vaccines mechanism?
Polysaccharide and protein carrier
245
List some examples of conjugate vaccines.
encapsulated bacteria
Haemophilus influenzae type B
Meningococcus
Pneumococcus
246
adjuvants - how they work
They mimic the action of PAMPs on TLR and other PRRs
247
examples of adjuvants
aluminiumm salts
lipids - monophosphoryl lipid A
248
what is the most common adjuvant
aluminium salts
249
protein in SAR-CoV-2
spike protein
250
What are dendritic cell vaccines?
Used against cancer
DCs collected from patient and exposed to tumour antigen to boost immune response
251
Immunoglobulin prepared from thousands of pooled donors
Covers wide range of unspecified antigens
Contains pre-formed IgG
Administered IV or SC
Human normal immunoglobin
252
IL-2 cytokine therapy mechanism
stimulates T cells in renal cancer
253
IFN-gamma cytokine therapy mechanism
enhance macrophage function in CGD
254
IFN-alpha cytokine therapy mechanism
enhance macrophage function in CGD
255
When might specific immunoglobulin be given?
post-exposure prophylaxis for:
Varicella Zoster
Tetanus
Hepatitis B
Rabies
256
Boosting immune response, types of adoptive T cell transfer? [4]
Virus-specific T cells
Tumour infiltrating T cells (TIL)
T cell receptor T cells (TCR)
Chimeric antigen receptor T cells
257
How does Virus-specific t-cell therapy work?
Take WBCs from patient or someone matched -> stimulate in vitro with EBV antigens -> expansion of EBV specific T cells -> put back in patient
258
TCR and CAR T cell therapy
Take T cell from patient with malignancy -> insert genes to express [T cell receptor / antibody and T cell receptor] -> expand and put back into pt.
259
Tisagenlecleucel
CAR T cell therapy for CD19
260
Tisagenlecleucel targets what?
CD19
261
Tisagenlecleucel treats what?
NHL and ALL
262
What is the difference between TCR and CAR T cell transfer?
TCR is specific for HLA/MHC molecules on tumour cell
CAR T is specific for antigens on the tumour surface
263
Ipilimumab is what?
monoclonal antibody
264
Ipilimumab blocks what?
CTLA4 on T cells -> blocks inhibition and allows more T cell proliferation
265
Ipilimumab is used when?
Advanced melanoma
266
Pembrolizumab and nivolumab are what?
monoclonal antibodies
267
Pembrolizumab and nivolumab block what?
PD-1 that is expressed on T cells
268
Pebrolizumab and nivolumab MOA
Inhibit negative signal from ligands on tumour cells -> by binding PD-1 -> increased T cell activation and proliferation
269
When are Pembrolizumab and nivolumab used?
advanced melanoma, NSCLC, metastatic renal cell carcinoma
270
How much prednisolone = endogenous steroid?
3-4 mg pred
271
Effect of steroids on prostaglandins?
Corticosteroids inhibit phospholipase A2
272
What does phospholipase A2 do?
converts phospholipids into arachidonic acid which is subsequently converted into prostaglandins and leukotrienes by cyclo-oxygenases
273
Steroids on macrophages?
Decreases macrocyte trafficking to site of inflammation
Decreased endothelial adhesion molecule expression (results in transient neutrophilia)
Decreases phagocytosis
Decreases release of proteolytic enzymes
274
Steroids on lymphocytes?
Lymphopenia
Blocks cytokine gene expression
Decreases antibody production
Promotes apoptosis
275
Anti-proliferative agent
Cyclophosphamide
Mycophenolate
Azathioprine
Methotrexate
276
Alkylates the guanine base of DNA which inhibits replication
Cyclophosphamide
277
Cyclophosphamide used for?
SLE
Vasculitis
NHL
278
Cyclophosphamide Side effects?
Haemorrhagic cystitis
Bladder cancer
Bonde marrow suppression
Sterility in males
279
What is the most toxic anti-proliferative?
cyclophosphamide
280
Blocks de novo purine synthesis by inhibiting HGPRT
azathioprine
281
Azathioprine metabolised to?
6-mercaptopurine in the liver
282
HGPRT stands for
Hypoxanthine-guanine phosphoribosyltransferase
283
Indications for azathioprine
Bone marrow suppression
Hepatotoxicity
284
Precaution (polymorphism) with Azathioprine
TPMT activity needs checking
TPMT required for azathioprine inactivation and metabolism
- 1 in 300 individuals have TPMT polymorphism which means that they are unable to metabolise azathioprine leading to severe bone marrow suppression
285
TPMT stands for?
Thiopurine methyltransferase
286
Dangerous CI with azathioprine
Allopurinol
287
Allopurinol inhibits what?
Xanthine oxidase
288
Blocking de novo purine nucleotide synthesis by inhibiting IMPDH thus preventing DNA replication
Mycophenolate mofetil
289
Indications for mycophenolate mofetil
transplant immunosuppression
290
Adverse effects of mycophenolate mefetil
BM suppression
Herpes reactivation
Progressive leukoencephalopathy (JC virus)
291
indications for plasmapheresis
Goodpasture's
Severe acute myasthenia gravis
Antibody mediated transplant rejection
292
How do calcineurin inhibitors work?
calcineurin blocks IL-2 production
293
Describe the calcineurin pathway
Normally, TCR engagement leads to increased cytoplasmic calcium which binds to calmodulin leading to the activation of calcineurin
Calcineurin then activates NFATc resulting in the upregulation of IL-2
IL-2 acts back on T cells to stimulate activation and proliferation
294
Calcineurin inhibitors?
Ciclosporin
Tacrolimus
295
INdications for calcineurin inhibitors
Transplant
RA
Eczema severe
Psoriasis
Psoriatic arthritis
IBD (UC)
296
JC virus
progressive multifocal leukocencephalopathy
297
JC virus associated with use of what?
Mycophenolate mofetil
298
Plasmapheresis
cell separator removes autoreactive Igs from patient blood
299
rebound antibody production?
After plasmapheresis, plasma cells that remain still start producing antibodies, despite antibodies being removed initiallyWh
300
What is often given with plasmapheresis
Anti-proliferative agents
301
Ciclosporin risks
Nephrotoxic
HTN
Neurotoxic
Dysmorphic features !!
302
Tacrolimus risks
Nephrotoxic
HTN
NEurotoxic
Diabetogenic !!
303
What do mTOR inhibitors do?
Inhibit T cell activation and proliferation
304
Example of mTOR inhibitor
Sirolimus
305
What is Tumour infiltrating T cell transfer?
Remove pt tumour -> culture with IL-2 -> expansion of tumour-specific T cells -> put back into patient
306
Advanced melanoma is treated with what immune checkpoint blocking agent?
Ipilimumab
OR
Pembrolizumab + Nivolumab
307
What treats relapsing MS?
INF-beta
308
What treats CGD?
IFN-gamma
309
What treats HCV?
IFN-alpha
310
What treats hairy cell leukaemia?
IFN-alpha
311
What treats Renal cell carcinoma (Cytokine therapy)
IL-2
312
What treats Behcet's?
IFN-beta
313
What treats Kaposi, CML, Myeloma and HBV
IFN-alpha
314
Which anti-proliferative agent affects B cells more than T cells?
Cyclophosphamide
315
Which anti-proliferative agent affects T cells more than B cells?
Mycophenolate mofetil
Azathioprine
316
metabolite of azathioprine
6-Mercaptopurine
317
Mechanism of Anti-proliferative / cytotoxic agents
- Damages DNA (cyclophosphamide)
- Prevents or decreases DNA replication (Mycophenolate mofetil, Azathioprine, Methotrexate)
318
Inhibits dihydropholate reductase
Methotrexate
319
Purine analogue that blocks de novo adenine and guanine synthesis
Azathioprine
320
Purine anti-metabolite that blocks de novo guanine synthesis
Mycophenolate mofetil
321
Inhibitors of cell signalling
Tacrolimus
Cyclosporin
Tofacitinib
Apremilast
322
MOA of these inhibitors of cell signalling:
TACROLIMUS
Cyclosporin
Tofacitinib
Apremilast
Tacrolimus - Inhibit T cell prolif; blocks IL-2 production
323
MOA of these inhibitors of cell signalling:
Tacrolimus
CYCLOSPORIN
Tofacitinib
Apremilast
Cyclosporin - Inhibit T cell prolif; blocks IL-2 production
324
MOA of these inhibitors of cell signalling:
Tacrolimus
Cyclosporin
TOFACTINIB
Apremilast
Tofacitinib - reduces JAK STAT singalling
325
MOA of these inhibitors of cell signalling:
Tacrolimus
Cyclosporin
Tofacitinib
APREMILAST
Apremilast - Increased cAMP -> increased PKA -> reduced cytokine production
326
JAK 1 & 3 inhibitor example
Tofactinib
327
Calcineurin inhibitors examples
Tacrolimus
Cyclosporin
328
PDE4 inhibitor?
Apremilast
329
Rejection prophylaxis in transplantation?
Cyclosporin or Tacrolimus
330
Indication for JAK inhibitor
Rheumatoid arthritis
Ulcerative colitis
Psoriatic arthritis
Axial spondyloarthritis
331
Indication for PDE4 inhibitor
Psoriasis
Psoriatic Arthritis
332
Basic mechanism:
1. BASILIXIMAB
2. Abatacept
3. Rituximab
4. Vedolizumab
5. Natalizumab
anti-CD25 (alpha chain of IL-2 receptor)
333
Basic mechanism:
1. Basiliximab
2. ABATACEPT
3. Rituximab
4. Vedolizumab
5. Natalizumab
CLTA4-Ig
334
Basic mechanism:
1. Basiliximab
2. Abatacept
3. RITUXIMAB
4. Vedolizumab
5. Natalizumab
anti-CD20
335
Basic mechanism:
1. Basiliximab
2. Abatacept
3. Rituximab
4. VEDOLIZUMAB
5. Natalizumab
anti-alpha4beta7 integrin
336
Basic mechanism:
1. Basiliximab
2. Abatacept
3. Rituximab
4. Vedolizumab
5. NATALIZUMAB
anti-alpha4beta1 integrin
337
-cept means?
Receptor + Immunoglobulin
338
adverse-effects of anti-thymocyte globulin
Infusion reactions
Leukopaenia
Infection
Malignancy
339
Basiliximab and Daclizumab MOA
anti-CD25 (alpha chain of IL-2 receptor)
340
What interleukin can't be produced with Basilixima and Daclizumab
IL-2
341
Abatercept MOA
bind to CTLA4 T cell via CD80 and CD86 receptors
Inhibits CD28 engagement on T cell -> no activation
342
Rituximab MOA
Anti-CD20 -> depletion of mature B cells
343
Indications for rituximab
B cell Lymphoma
RA
SLE
344
How often Rituximab given?
IV 2 doses every 6-12 months
345
Adverse effects of rituximab
Progressive multifocal leukoencephalopathy (PML)
CVD exacerb
Infusion Rx
346
Vedolizumab MOA
Blocks alpha-4-beta-7-integrin -> inhibits leukocyte migration
347
Vedolizumab use?
IBD
348
Vedolizumab adverse effects?
Infusion Rx
Hepatotoxic
PML
Malignancy
349
Tocilizumab / Sarlimumab MOA
Antibody against IL-6
350
Indication for Tocilizumab / sarlimumab
RA
Giant Cell Arteritis
Castleman's disease - IL6 producing tumour from HHV8
351
Anti-TNF-alpha antibodies
Infliximab
Adalimumab
Certolizumab
Golimumab
352
How are Anti-TNF-alpha Ab given?
Subcut
Infliximab can also be IV
353
Anti- TNF-alpha indications?
IBD
Ank Spon
RA
Psoriasis and Psoriatic arthritis
FMF
354
side-effects of anti-TNFα antibodies
Infusion reactions
Infection (TB reactivation, HBV, HCV)
Lupus-like conditions
Demyelination
Malignancy
!!! screen for latent TB before starting
355
etanercept MOA
TNFalpha/TNFbeta receptor p75-IgG fusion protein -> receptor goes round binding to TNF
356
Ustekinumab MOA
Anti IL-12 and anti IL-23
357
Secukinumab MOA
Anti-IL-17a
358
Guselkumab MOA
Anti-IL23 -> ab against p19 subunit
359
Denosumab MOA
Anti-RANK ligand -> inhibits RANK mediated osteoclast differentiation
360
Osteoporosis Immune med
Denosumab
361
IBD Immune meds
Infliximab (/adalimumab / certolizumab / golimumab)
Ustekinuma
362
Throat swelling wihtouth decreased BP?
C1 esterase inhibitor deficiency
363
What conditions is the IL-23 and IL-17 pathway important for?
Ankylosing spondylitis, psoriasis and psoriatic arthritis, IBD (not IL-17)
364
Which antibodies inhibit IL-17 and IL-23?
Secukinumab - IL-17
Guselkumab - IL-23
365
Interleukins in Asthma and Eczema
IL4
IL5
IL13
Th2 and eosinophil response
366
Antibodies treating asthma and Eczema?
Dupilumab - IL-4
Mepolizumab - IL-5
Tralokinumab - IL-13
367
Types of infusion reaction
IgE mediated (T1 hypersensitivity)
Non-T1 Hypersensitivity
368
Urticaria
Hypotension
Tachycardia
Wheeze
After infusion
IgE-mediated infusion reaction
369
Headache
Fever
Myalgia
After infusion
Non-T1 hypersensitivity infusion reaction
370
injection site reactions peak when?
48 hrs
371
Injection site reaction -> clinical sign?
Cutaneous necrosis
372
Diseases to screen for before immunosuppression
TB, HBV, HCV, HIV
373
JC virus important in immunosuppression why?
John Cunningham Virus
Common polyomavirus - majority of population has been exposed to it
Usually kept well under control by immune system
In the case of severe immunosuppression, the virus can reactivate and destory oligodendrocytes, leading to PML
374
immunosuppression agents leading to PML (JC virus activation)?
Vedolizumab
Rituximab
375
Reaction type in allergic disorder
IgE mediated Type I hypersensitivity
376
Th2 response?
1. Damaged epithelium releases signalling molecules
2. cytokines act on Th2, Th9 and ILC2 cells
3. They then produce IL4, IL5 and IL13
4. These act on basophils and eosinophils
5. IL4 stimulates B cells to produce IgE and IgG4
377
Allergens can cross-link IgE leading to mast cell degranulation and the release of histamines, prostaglandins and leukotrienes
Allergic response initiated by parasites and allergens
Not mediated by Th2 cells
378
Peptide presentation via MHC to TCR or Th2 cells
Induces production of what IL?
IL-4
379
How does oral route promote tolerance to allergense?
Treg in GI mucosa inhibits IgE synthesis -> promotes tolerance
380
Theories behind increasing Allergies
1. Hygiene hypothesis - reduced childhood infection increases allergy susceptability
2. Lack of vitamin D and fatty acids in diet
3. Loss of symbosis with gut and respiratory bacteria due to altered composition and biodiversity
4. Increase in epithelium-damaging agents due to industrialisation
381
Functional allergen tests?
Mast cell tryptase
Basophil activation test
Allergen challenge
382
Allergen specific IgE (sensitisation) tests?
Skin Prick
Serum IgE (RAST)
383
Ix collected in acute episode
Serial Mast cell tryptase
Blood/urine histamine
384
Pos skin prick/specific IgE Test = ?
Sensitisation not allergy
385
Specific IgE Test prognostic markers?
Concentration - higher levels means more symptoms
Affinity to the target - higher affinity means increased risk
Capacity of IgE antibody to induce mast cell degranulation
386
Biomarker for anaphylaxis
Mast cell tryptase
387
How is mast cell released during anaphylaxis
Tryptase is pre-formed protein found in mast cell granules
Systemic degranulation during anaphylaxis results in increased serum tryptase
388
Mast cell tryptase peaks?
1-2 hours peak
6-12 hrs baseline
389
MMast cell tryptase doesnt return to baseline?
Systemic mastocytosis
390
Gold standard for food/drug allergy?
Challenge test
391
Basophils increase which markers when activated
CD64
CD203
CD300
392
emergency management of anaphylaxis in adults
0.5mL of 1:1000 (>12 years old)
give 2 doses if no improvement after first
If still no improvement -> refractory anaphylaxis
393
common drug cause of angioedema
ACEi
394
Cytokine key for dvlpt of eosinophils
IL-5
395
most common organ transplant
Kidney then liver
396
Half life of transplanted kidney
12 yrs
397
HLA encoded on which chromosome?
Chromosome 6
398
Alleles of HLA class I
A, B, C
399
Alleles of HLA Class 2 (2 letters for class 2)
Class II - DR, DQ, DP
400
Basic structure of HLA Class I
Domains:
3 alpha
1 beta-2 microglobulin
1 transmembrane
401
Basic structure of HLA Class II
2 alpha
2 beta
2 transmembrane
402
HLA Class I where?
All cells
403
HLA Class II where?
APC
404
HLA alleles most immunogenic
A, B, DR
405
HLA mismatch code e.g. 1:1:0 are for?
A, B, DR Alleles
406
Gold-standard diangosis of graft rejection
biopsy
407
Types of rejection
1. T-cell mediated
2. Antibody-mediated
408
T-cell mediated rejection MOA
1) presentation of donor HLA by APC in context of recipient HLA
2) T cell activation, inflamm cell recruitment
3) Organ damage - effector phase
409
Features of T-cell mediated rejection
Lymphocytic interstitial infiltration
Tubulitis - WBCs in tubular epithelium
Arteritis - WBCs within vascular wall
410
3 signals of T cell activation
Antigen/MHC interaction with TCR
Co-stim molecular expression - CD80/96 interaction with CD28
IL-2
411
AB antigens present where?
Endothelial cells
Erythrocytes
412
Antibody mediated rejection phases?
1) B cells recognise foreign HLA
2) Prolif of B cells and anti-HLA antibody production
3) Effector phase - Ab bind to graft endothelium -> intravascular disease
413
Anti-AB vs Anti-HLA antibodies?
Anti-AB antibodies are naturally occuring (pre-formed)
Anti-HLA antibodies are not naturally occuring but can be pre-formed due to previous exposure to epitopes
414
Presence of inflammatory cells within the capillaries of the graft - hallmark for?
Antibody-mediated transplant rejection
415
Assays for anti-HLA antibodies
Cytotoxic assays
Flow cytometry
Solid phase assays
416
Targets for T-cell pathway immunosuppression in transplants
Calcineurin inhibitors
IL-2 inhibitors - e.g. Anti-CD25 antibody = Basiliximab
417
Drugs that target TCR
Muromonab - anti-CD3 antibody
Anti-thymocyte globulin
418
Anti-CD52 antibody
Alemtuzumab
419
Anti-CD20 antibody
Rituximab - depletes B-cells
420
BAFF inhibitor - BAFF required for B cell survival
Belimumab
421
Proteosome inhibitor
Bortezomib - inhibits degradation of pro-apoptosis proteins
422
Complement inhibitor example?
Eculizumab - Targets C5
423
Graft-vs-Host-Disease Pathophys?
During SCT, the host immune system is eradicated and replaced by autologous or allogeneic bone marrow
In allogeneic stem cell transplant, donor lymphocytes can attack host tissues
424
Preventing GvHD
Methotrexate + ciclosporin
425
Opportunistic infections in Transplant recipients
CMV
BK virus
PCP
426
Malignancies in transplant recipients
Kaposi sarcoma
EBV
Skin cancer
427
Define positive tryptase test
>1.2 baseline + 2
428
Milky fluid produced by rubber trees (Hevea brasiliensis)
Latex
429
Complement deficiency investigations
CH50
AP50
C3 and C4
430
Main interferon in SLE
Type 1 INF
