immuno Flashcards
1
Q
what is mutated in reticular dysgenesis (autosomal recessive severe SCID)
A
adenylate kinase 2 (AK2)
- a mitochondrial enzyme metabolism enzyme
2
Q
what is mutated in Kostmann syndrome
A
HAX-1 (HCLS1 associated protein X-1)
3
Q
severe congenital neutropenia with HAX1 mutation
A
Kostmann syndrome
4
Q
episodic neutropenia every 4-6 weeks, mutation in ELA2
A
cyclic neutropenia
5
Q
what is mutated in cyclic neutropenia
A
neutrophil elastase ELA-2
6
Q
what is the inheritance of cyclic neutropenia
A
autosomal dominant
7
Q
mutation in AK2 + low neutrophils, lymphocytes, macrophages, platelets, requiring bone marrow transplantation
A
reticular dysgenesis
8
Q
what is part of the adaptive immune response?
A
B lymphocytes - producing antibodies
T lymphocytes
cytokines and chemokines
9
Q
what is part of the innate immune response?
A
neutrophils, basophils, eosinophils
macrophages & monocytes
NK cells
Dendritic Cells
Acute phase proteins
complement
cytokines and chemokines
10
Q
recurrent infections, very high neutrophil counts in blood during infection, absence of pus formation, delayed umbilical cord separation.
A
leukocyte adhesion deficiency
11
Q
in leukocyte adhesion deficiency, what is the mutation/ deficiency?
A
CD18 deficiency.
CD11a/DC18 and CD11b/CD18 expressed on neutrophils regulate neutrophil adhesion and transmigration
12
Q
what receptors are involved in neutrophil adhesion and transmigration?
A
CD11a/ CD18
CD11b/CD18
13
Q
what complement proteins are involved in the classically pathway?
A
C1, C2, C4
14
Q
what is the main complement protein that is activated by the classical, alternative and lectin pathway?
A
C3
15
Q
Nitroblue Tetrazolium test abnormal/ negative
A
chronic granulomatous disease
16
Q
in chronic granulomatous disease, what is deficient?
A
NADPH oxidase
17
Q
Which complement proteins are involved in the lectin pathway?
A
C2 and C4
18
Q
which complement protein is involved in the alternative pathway?
A
C3
C3 binds directly to
techoic acid on Gram + bacteria and to LPS on gram - bacteria
+ involves factors B, I, P
19
Q
mx of chronic granulomatous disease
A
IFN gamma
20
Q
dihydrorhodamine flow cytometry test abnormal / negative
A
chronic granulomatous disease
21
Q
chronic granulomatous disease pathology
A
absent respiratory burst due to deficiency of one of the components of NADPH oxidase.
impaired killing if intracellular microorganisms and excessive inflammation with granuloma formation
22
Q
chronic granulomatous disease presentation
A
susceptibility to bacteria esp catalase + bacteria.
granuloma formation + lymphadenopathy + hepatosplenomegaly
23
Q
susceptibility to infection with mycobacteria (TB and atypical), BCG, Salmonella. What condition?
A
deficiency of IFNgamma/ IL12 and their receptors.
24
Q
what happens when one is deficient in early classical pathway? ie. C1/2/4
A
immune complexes fail to activate complement pathway -> increased susceptibility to infection
increased load of self-antigens
deposition of immune complexes which stimulated inflammation in skin, joints, kidneys e.g. SLE
25
SLE associated with which complement deficiencies?
most common C2
C1q, C1r, C1s, C2 and C4 deficiency all seen in SLE
26
complement deficient - susceptibility to?
encapsulated bacteria
e.g. neisseria meningitidis,
strep pneumoniae, h influenza
27
active lupus ix?
Complement levels
first low C4
then low C4 and low C3
28
increased infection in patients who have another cause of immune impairment e.g. premature infant, HIV infection, chemotherapy, antibody deficiency
MBL deficiency
29
low T cells and NK cells, normal B cells, but low Igs.
X linked SCID
30
4 month old, infections of all types, failure to thrive, persistent diarrhoea
SCID
31
what immune cells are vital for protection against viral infections and tumours?
NK cells and CD8 T cells
32
DiGeorge's syndrome
CATCH 22
Cardiac abnormalities (esp Tetralogy of Fallot)
Abnormal facies (low set ears, high forehead)
Thymic aplasia
Cleft palate
HypoCa/ HypoPTH
Chr22- deletion at 22q11.2
33
Thymic aplasia - reduced numbers of T cells. which condition?
DiGeorge's
34
Absent expression of MHC Class II molecules
Bare Lymphocyte Syndrome type II
35
absent expression of MHC Class I molecules
Bare lymphocyte syndrome type I
36
Bare lymphocyte Syndrome type II
```
absent MHC Class II
-> profound deficiency of CD4+ T cells
+ failure to produce IgA/ IgG because no class switching
```
infections of all types.
may be associated with sclerosing cholangitis
FTT after 3 months
37
Hyper IgM syndrome aka
CD40L deficiency
38
what gene is defective in Bruton's X linked hypogammaglobulinaemia
B cell tyrosine kinase gene
| BTK gene
39
absence of mature B cells and no circulating Ig. Recurrent infections. Family history where brother is affected.
X linked Bruton's hypogammaglobulinaemia
40
recurrent respiratory tract and GI tract infections
selective IgA deficiency
41
Selective IgA deficiency patients are at risk of what during blood transfusion?
anaphylaxis due to introduction of donor IgA
42
High IgM, undetectable Ig G, Ig A, Ig E. Normal number circulating B cells.
failure of class switching due to T cell defect.
recurrent infections- e.g. h influenza, strep pneumo, pseudomonas, pneumocystis jiroveci
Hyper IgM syndrome
aka CD40L defciency
43
what gene is mutated in Hyper IgM syndrome?
CD40 Ligand gene
| CD40L normally on T cell
44
Other than HIV, what other condition increases risk of pneumocystis jiroveci infection?
Hyper IgM syndrome
45
what are the likely pathogens in antibody/ B cell or CD4 T cell deficiency?
```
Strep pneumo
H influenzae
Strep pyogenes
pseudomonas
+ tetanus/ diphtheria + enterovirus
```
46
no germinal centre development within lymph nodes and spleen. No class switching occurring.
Hyper IgM syndrome
47
histology shows spongiosis + inflammatory infiltrate in the dermis + dilated dermal capillaries. if chronic: crusting, scaling, lichenification.
Atopic dermatitis/ contact dermatitis
48
defect in which protein predisposes patients with atopic dermatitis to staph aureus superinfection?
B defensin
49
exposure to birch pollen induces allergy to stony fruits (due to cross reactivity) e.g. melons, rosacea fruit. symptoms usually limited to mouth e.g. swollen tongue, lips
oral allergy syndrome
tx: avoid food. if ingested, wash mouth and take antihistamine.
2% get anaphylaxis and require adrenaline
50
latex allergy + allergy to banana/ papaya/ potato/ avocado/ kiwi/ mango/ melon
latex food syndrome
51
nasal itch and runny nose/ congestion, sneezing, anosmia. On examination: pale bluish swollen nasal mucosa
allergic rhinitis
52
ix of allergic rhinitis
skin prick test
| or RAST for specific IgE
53
mx of allergic rhinitis
oral antihistamine or
| steroid nasal spray
54
what differentiates acute from chronic urticaria?
acute: wheals which resolve completely within 6 weeks.
55
mx of acute urticaria
antihistamines
56
mx of anaphylaxis
1: IM 1:1000 adrenaline
ABC + seek help
Oxygen, elevate legs, inhaled bronchodilators, IV hydrocortisone (to prevent late phase response), chlorphenamine, IV fluids,
57
Gold standard test for food and drug allergy
double blind oral food challenge
- increasing volumes of offending food/ drug ingested under close supervision
but risk of severe reaction when testing
58
after an acute anaphylactic episode, how to confirm via ix?
measure serum mast cell tryptase (should return to baseline by 6h)
59
first line test for allergy
skin prick (more sensitive and specific than blood tests)
60
what is type II hypersensitivity?
Antibody mediated hypersensitivity.
antibody specific to cells/ organs
61
haemolytic disease of the newborn: what antibodies against what antigen? How to diagnose?
anti-D antibodies IgG -> rhesus antigens on neonatal erythrocytes.
diagnosis via positive direct antiglobulin Coombs test
62
autoimmune haemolytic anaemia
what antibodies against what antigen? How to diagnose?
autoantibodies against antigens on RBC surface. -> destruction of RBCs
low Hb, high reticulocytes, high Br, high LDH
Diagnosis by positive direct anti globulin Coombs Test
63
haemolytic disease of the newborn tx?
maternal plasma exchange, exchange transfusion of neonate
64
Autoimmune haemolytic anaemia treatment
steroids
65
autoimmune thrombocytopenic purpura
what antibodies to what antigens?
what type of hypersensitivity?
anti platelet antibody to gpIIb/IIIa on platelets
Type II hypersensitivity
66
autoimmune thrombocytopenic purpura features?
bruising/ bleeding/ purpura
low platelets
67
goodpastures syndrome
what type hypersensitivity? what antibody to what antigen?
Type II hypersensitivity
Anti-GBM ab to type IV collagen on basement membrane found in kidneys and lung
68
Diagnosis of Goodpastures?
anti GBM Ab
linear smooth IF staining of IgG deposits on BM
-> crescentic (rapid progressive glomerulonephritis on BM)
69
Goodpastures Syndrome Tx?
corticosteroids and immunosuppression
70
pemphigus vulgaris
what type of hypersensitivity?
what antibody against what antigen?
type II hypersensitivity
anti-desmoglein 3 antibody to epidermal cadherin
71
anti-desmoglein 3 antibody
to epidermal cadherin
pemphigus vulgaris
72
Graves Disease
what antibody to what antigen?
what type of hypersensitivity?
anti-TSHR antibody to TSH R
type II hypersensitivity
73
Graves Disease tx
carbimazole and propylthiouracil
74
Myasthenia gravis
what antibody to what antigen?
what type hypersensitivity?
anti-AchR ab to AchR
type II hypersensitivity
75
fatiguable muscle weakness, double vision, ptosis, tensilon test +ve, abnormal EMG
myasthenia gravis
76
myasthenia gravis tx
anticholinesterase (neostigmine, pyridostigmine)
if severe: e.g. affecting breathing. Plasmapheresis and IVIG
77
pernicious anaemia
what type hypersensitivity? what antibody to what antigen?
anti-IF and anti-parietal cells Ab to IF and parietal cells.
type II hypersensitivity
78
churg-Strauss syndrome (eosinophilic granulomatosis with polyangitis)
what antibodies to what antigen? what type hypersensitivity?
p-ANCA binds to medium and small vessels.
type II hypersensitivity
79
hypereosinophilia, asthma + vasculitis.
| p-ANCA +ve
Churg-Strauss
80
wegener's granulomatosis (granulomatosis with polyangitis)
what antibodies to what antigen?
what type hypersensitivity?
c-ANCA binds to medium and small vessels -> vasculitis
type II hypersensitivity
81
Wegeners, Churg-strauss, microscopic polyangitis tx?
cyclophosphamide
82
microscopic polyangiitis.
what antibody to what antigen? what type hypersensitivity?
p-ANCA to small vessels -> vasculitis
type II hypersensitivity
83
persistent itchy wheals lasting >6 wks + angiooedema in response to triggers e.g. medications, cold, exercise, food
chronic urticaria
84
urticarial eruption, often painful + bruising/ post inflammatory residual pigmentation at site of itching
urticarial vasculitis
inflammation of small blood vessels
85
chronic urticaria mx
avoid precipitants,
preventative antihistamine.
Im adrenaline for pharyngeal angioedema
86
what is type III hypersensitivity?
immune complex mediated - deposition of immune complexes in joints/ kidneys etc
87
SLE
| what type hypersensitivity?
type III hypersensitivity. immune complex deposition in joints, kidneys,
88
cryoglobulins causing joint pain, splenomegaly, skin, nerve and kidney involvement. sometimes associated with hep C infection.
Essential mixed cryoglobulinaemia
Type III hypersensitivity
89
serum sickness
what antibody to what antigen? what type hypersensitivity?
type III hypersensitivity
antibodies react to antiserum (e.g. antivenom / drugs like penicillin) forming Immune complexes that deposit.
gives rise to rashes, itching, arthralgia, lymphadenopathy.
90
what drugs may caused drug induced SLE?
hydralazine, procainamide, isoniazid
91
SLE Ix/ serum results?
reduced C4, may have reduced C3 if severe disease
antibodies to ds-DNA, ANA (Ro/La/ Smith), histones
ESR high, usually normal CRP
92
polyarteritis nodosa
what type of hypersensitivity?
type III
immune complex deposition in vessels -> aneurysm development
fever, arthralgia, skin, nerve, kidney involvement. pericarditis and MI.
93
what is type IV hypersensitivity?
T cell mediated hypersensitivity. delayed hypersensitivity.
94
TIDM
what type hypersensitivity?
What antibodies to what antigens?
type IV hypersensitivity
anti glutamate decarboxylase antibodies (GAD converts Glutamate to GABA which stimulates insulin release)
anti- islet cell antibodies to pancreatic islet cells
anti insulin antibodies to insulin
anti-IA2 antibodies to tyrosine phosphotase
95
CSF shows oligoclonal bands of IgG on electrophoresis
Multiple sclerosis
96
multiple sclerosis
what type hypersensitivity?
what antibodies to what antigen?
type IV hypersensitivity (Th1 cells)
antibodies to myelin basic protein, proteolipid protein
97
rheumatoid arthritis
what type hypersensitivity
what antibodies to what antigens?
type IV hypersensitivity
anti-CCP
rheumatoid factor (anti-IgG igM)
to antigens in synovial membrane
also type III. due to immune complexes formed
98
most specific antibody for rheumatoid arthritis
anti-CCP ab
99
what are some environmental risk factors of rheumatoid arthritis?
smoking
| gum infection with porphyromonas gingivalis
100
mx of rheumatoid arthritis
analgesia e.g. NSAIDs
steroids
1. DMARDS e.g. methotrexate
2. TNFa e.g. infliximab, etanercept, adalimuimab
anti-IL6 e.g. tocilizumab
anti-CTLA4 Ig e.g. abatacept
JAK inhibitor e.g. tofacitinib
101
what are some complications of rheumatoid arthritis?
lung fibrosis, rheumatoid nodules, anaemia of chronic disease
102
mx of crohns disease
anti inflammatory drugs
e.g. mesalazine
TNFa antagonists e.g. infliximab
steroids
103
what HLA is associated with goodpastures syndrome?
HLA DR15/ DR2
104
HLA DR3 assoc with which diseases?
Graves disease
SLE
T1DM
105
HLA DR 4 assoc w?
rheumatoid arthritis
| T1DM
106
anti centromere antibodies
limited cutaneous scleroderma (CREST syndrome)
107
other than antitopoisomerase, what other antibodies are found in diffuse cutaneous scleroderma?
antibodies to RNA polymerase I, II, III
| fibrillarin antibodies
108
anti Ro and anti La antibodies
sjogrens syndrome
109
xerostermia, keratoconjunctivis sic. schirmers +ve. parotid/ salivary gland enlargement.
sjogrens syndrome
110
what is the most persistent autoantibody, even after tx? in coeliac disease?
anti-gliadin antibody
111
IPEX syndrome- what is it?
immune dysregulation, polyendocrinopathy, enteropathy and X-linked inheritance + autoimmune diseases
the only cure is bone marrow transplant.
eczematous dermatitis, nail dystrophy, autoimmune skin conditions such as alopecia universalis and bullous pemphigoid
112
immune dysregulation, polyendocrinopathy, enteropathy and X-linked inheritance + autoimmune diseases
what condition?
IPEX syndrome
113
anti cardiolipin and anti lupus anticoagulant antibodies
antiphospholipid syndrome
114
antiphospholipid syndrome antibodies?
anti cardiolipin
anti B2 glycoprotein
anti lupus anticoagulant
115
autoimmune hepatitis antibodies?
anti smooth muscle
anti LKM1 (liver-kidney-microsomal 1)
anti soluble liver antigen (SLA)
116
autoimmune hepatitis in paediatric population w poor response to steroid. which autoantibody?
anti LKM1 (liver kidney microsomal 1)
117
anti smooth muscle
anti LKM1 (liver-kidney-microsomal 1)
anti soluble liver antigen (SLA)
what condition
autoimmune hepatitis
118
churg-strauss syndrome antibody?
p-ANCA to myeloperoxidase
119
congenital heart block in infants of mothers w SLE. what antibody?
anti-Ro antibody
120
dermatitis herpetiformis. what antibody?
anti-endomysial IgA antibody
121
dermatomyositis what antibody?
anti-Jo 1 (to tRNA synthetase)
122
hashimotos thyroiditis what antibodies?
antibodies to thyroid peroxidase and thyroglobulin
123
mixed connective tissue disease
| antibody?
anti-U1RNP antibody (speckled pattern)
124
ANAs?
anti ro / la/ smith/ u1RNP
125
what is the most sensitive specific in pernicious anaemia?
anti parietal cells antibody
126
complications of pernicious anaemia?
peripheral neuropathy
| subacute combined degeneration of the cord
127
what proportion of sjogrens patients have +ve Rheumatoid factor?
60-70%
128
IFN gamma therapy for?
chronic granulomatous disease
129
IFN alpha therapy for?
Hep B, Hep C
Kaposis sarcome
hairy cell leukaemia, chronic myelogenous leukaemia, malignant myeloma
130
IFN beta therapy for?
relapsing Multiple sclerosis
131
pembrolizumab
anti-PD1 antibody
allows T cell activation. indications: advanced melanoma, lung cancer
132
ipilimumab
antibody for CTLA4 on T cell -
allows T cell activation
advanced melanoma
133
advanced melanoma immunological tx?
ipilimumab (anti CTLA4) and pembrolizumab (anti PD1) on T cells to activate T cells
134
BMT indications?
secondary to haem malignancy
| SCID/ leukocyte adhesion defect
135
what is the receptor binding and membrane fusion glycoprotein of influenza virus?
haemagglutinin
136
what are the anti proliferative agents? (cytotoxic agents that inhibit DNA synthesis)
Mycophenolate Mofetil
Azathioprine
Cyclophosphamide
Methotrexate
137
antiproliferative agent that inhibits de novo purine (e.g. adenine, guanine) synthesis and preferentially inhibits T cell activation and proliferation?
Azathioprine
138
antiproliferative agent that inhibits guanine synthesis and preferentially inhibits T over B cell proliferation?
mycophenolate mofetil
139
antiproliferative agent that inhibits dihydrofolate reductase therefore decreasing DNA synthesis (anti folate)
methotrexate
140
antiproliferative agent that alkylates guanine base of the DNA and affects B cells over T cells, but at high doses affects all cells w high turnover
cyclophosphamide
141
immunosuppressant that causes transient neutrophilia
prednisolone
142
immunosuppressant that increases risk of osteoporosis
prednisolone
143
immunosuppressant that works by reducing prostaglandin synthesis and may increase risk of cushings
prednisolone
144
antiproliferative agent against connective tissue disease e.g. SLE, vasculitis e.g. Wegener's,
+ SEs of increased risk of bladder ca, haemorrhage cystitis, infection/ bone marrow suppression
cyclophosphamide
145
antiproliferative agent used in transplantation, autoimmune diseases, vasculitis and has SEs of infection especially herpes virus reactivation and progressive multifocal leukoencephalopathy
Mycophenolate mofetil
146
Progressive multifocal leukoencephalopathy what virus?
JC virus
147
antiproliferative agent used in transplantation, autoimmune diseases and auto inflammatory disease such as crohns and Ulcerative colitis
+ if ppl have TPMT polymorphism, are unable to metabolise the drug
Azathioprine
148
antiproliferative agent that is used in RA, psoriasis, Crohns, and in chemo. + SEs such as folate deficiency causing megaloblastic macrocytic anaemia + pneumonitis/ pulm fibrosis and hepatotoxicity
methotrexate
149
calcineurin inhibitors?
tacrolimus and cyclosporin
calcineurin normally activates IL-2. -> calcineurin inhibitors reduce T cell activation and proliferation
150
calcineurin inhibitor with side effects of nephrotoxicity, neurotoxicity, HTN, dysmorphic features and gum hypertrophy
cyclosporin
151
calcineurin inhibitor with side effects of nephrotoxicity, neurotoxicity, HTN and is diabetogenic
tacrolimus
152
anti CD25 / anti IL2R (alpha chain)
Basiliximab
153
what are calcineurin inhibitors indicated in?
transplant rejection prophylaxis by reducing T cell activation and proliferation
154
what is Sirolimus? and some side effects?
Sirolimus blocks clonal proliferation of T cells, is used for transplant rejection prophylaxis and has fewer side effects than tacrolimus. SEs are hypertension and a little nephrotoxicity
155
what is tofacitinib?
a JAK inhibitor used in rheumatoid arthritis
156
What is apremilast?
a PDE4 inhibitor used in psoriasis and psoriatic arthritis
157
anti CD25 antibody, inhibits T cell proliferation, used pre and post surgery to prevent allograft rejection
Basilixumab
158
anti CTLA4-Ig, reduces T cell activation, may be used in Rheumatoid arthritis
Abatacept
159
anti-CD20, depletes mature B cells
Rituximab
160
Rituximab indicated for?
anti-CD20, depletes mature B cells.
| lymphoma, rheumatoid arthritis, SLE
161
anti-alpha4 integrin (binds to VCAM1 to mediate rolling/arrest of leukocytes)
Natalizumab
162
Natalizumab - what is is used for
an anti-alpha4 integrin antibody used inhibit T cell migration
-> relapsing and remitting MS, crohns disease
163
anti-IL6 R antibody
Tocilizumab
164
Tocilizumab indicated for?
anti-IL6 R antibody
reduces macrophage, T cell, B Cell, neutrophil activation
used in Rheumatoid arthritis, castleman's disease
165
mouse monoclonal antibody against OKT3, blocks CD3 on T cells
muromonab-CD3
166
muromonab used for?
blocks CD3 on t cells
| indicated in active allograft transplant rejection (as T cells are the main mediator of acute organ rejection)
167
anti RANK Ligand antibody
denosumab
168
indications for denosumab?
osteoporosis, multiple myeloma, bone mets
anti-RANK ligand antibody -> reduces osteoclast differentiation and function
169
anti-IL12/23
ustekinumab.
170
ustekinumab indicated for?
psoriasis/ psoriatic arthritis
171
anti-IL17A
secukinumab
172
secukinumab indicated for?
psoriasis, psoriatic arthritis, ankylosing spondylitis
173
anti-TNFa antibodies
infliximab, adalimumab (fully human monoclonal ab), certolizumab, golimumab
for rheumatic arthritis, ankylosing spondylitis, psoriasis, psoriasis arthritis, inflammatory bowel disease
174
TNF alpha antagonist
etanercept
175
anti-thymocyte globulin indicated for?
lymphocyte depletion. for allograft rejection (renal/ heart)
176
monoclonal antibody that binds to CD52 found on lymphocytes resulting in depletion
alemtuzumab
for CLL, MS
177
IL2 receptor antibody, targets CD25, for organ transplant rejection prophylaxis (not Basiliximab)
Daclizumab
178
3 stages of transplant rejection
recognition of foreign antigen
activation of antigen specific lymphocytes
effector function (T cells etc)
179
where are HLA A / B / C molecules expressed
MHC class I expressed on all cells
180
where are HLA DR/DQ/DP molecules expressed
MHC Class II expressed on antigen presenting cells but can also be unregulated on other cells under stress.
181
what antigens are important in allograft transplant?
HLA- MHC on chr6
ABO blood antigens
Minor HLA
182
Acute transplant rejection is usually due to what sort of recognition?
direct presentation
whereby DONOR APC present antigen and/ MHC to recipient T cells
183
chronic transplant rejection is usually due to what sort of recognition?
indirect presentation
whereby Recipient APC presents donor antigen to recipient T cells.
184
what are the different effectors in the effector phase of graft rejection?
1. graft infiltration by alloreactive CD4 cells
2. Cytotoxic cell death - release of toxins to kill target, punch holes in target cells, apoptotic cell death
3. macrophages- phagocytosis
4. antibodies bind to graft endothelium
185
hyper acute transplant rejection
time frame?
mechanism?
min- hours
preformed antibodies in recipient activate complement
186
hyper acute transplant rejection
time frame?
mechanism?
pathology?
treatment?
time frame: min- hours
mechanism: preformed antibdoies which activate complement
prevention via cross match (ABO) and HLA matching
pathology shows thrombosis and necrosis
187
actue (cellular) transplant rejection
time frame?
mechanism?
pathology?
treatment?
time frame: weeks to months
mechanism: CD4 activating a type IV reaction
pathology: cellular infiltrate, interstitial inflammation and tubulitis
treatment: T cell immunosuppression (e.g. calcinuerin inhibitors)
188
acute (antibody mediated) transplant rejection
time frame?
mechanism?
pathology?
treatment?
time frame: weeks- months
mechanism: B cells producing antibodies that attack vessels in donor organ/tissue
pathology: vasculitis, C4d
treatment: antibody removal and B cell immunosuppression
189
chronic transplant rejection
time frame?
mechanism?
pathology?
treatment?
time frame: months to years
mechanism: immune and non-immune mechanism. multiple acute rejections, hypertension, hyperlipidaemia, multiple infections
pathology: fibrosis, glomerulopathy (kidneys), vasculopathy (ischaemia), bronchiolitis obliterans (lungs)
treatment: minimise organ damage
190
Graft vs Host Disease
time frame?
mechanism?
pathology?
treatment?
time frame: days to weeks
mechanism: donor lymphocytes attacking host tissue
pathology: skin (rash), gut (diarrhoea, vomiting, bloody stool), and liver (jaundice) involvement
Treatment: prevention/ immunosuppression- corticosteroids
191
Acute vascular rejection
when does this occur?
after xenograft
| similar to hyperacute but 4-6 days after transplant
192
before a transplant what should you always check in donor and recipient?
determine donor and recipient blood group and HLA type and maximise similarity
Check recipients pre formed antibodies against ABO and HLA
Cross match between donor and recipient. (tests if serum from recipient is able to bind/ kill donor lymphocytes)
193
after transplant, what should you do to check if patient will or will not reject graft?
After transplant: check again for new antibodies vs the graft (via cytotoxicity assay/ flow cytometry/ solid phase assay)
194
before a transplant, what medication would you give to induce the patient?
suppress T cell response
| e.g. anti-CD25 Basiliximub or anti-CD52 Alemtuzumab or OKT3 (muromonab)/ Anti-thymocyte globulin
195
after a transplant, what medication would you give to the patient to reduce rejection?
immunosuppressants
e.g. calcineurin inhibitors + mycophenolate mofetil/ azathioprine +/- steroids
196
how to treat episodes of acute rejection. medications against cellular rejection?
steroids. OKT3/ anti-thymocyte globulin
197
how to treat episodes of acute rejection. medications against antibody-mediated rejection?
IVIG, plasma exchange, anti-CD20 (e.g. rituximab), anti-C5
198
what happens in a haematopoietic stem cell transplant
eliminate host immune system via total body irradiation/ cyclophosphamide/ etc
replace with own (autologous) or HLA matched donor (allogeneic) bone marrow
199
what is graft vs host disease?
occurs in allogeneic haemotopoietic stem cell transplan where donor lymphocytes react against host tissues.
related to level of HLA incompatibility
200
GvHD prophylaxis?
methotrexate
| cyclosporine
201
symptoms of GVHD?
skin (rash)
GI (diarrhoea, vomiting, abdo pain, nausea, bloody stools)
liver (jaundice)
202
GvHD - treatment?
corticosteroids
203
complications post transplantation?
increased risk of infections (bacterial, viral, fungal)
+ opportunistic infections due to immunosuppression (e.g. BK virus, CMV, pneumocystis carinii)
+ malignancy risk
- viral associated (x100) e.g. Kaposi's sarcoma, lymphoproliferative disease (EBV)
- skin cancer (x20)
- other cancers e.g. lung, colon (x2-3)
+ atherosclerosis
- Hypertension, hyperlipidaemia (x20) increase risk of death from MI
204
HIV virus targets?
CD4+ T helper cells
also CD4+ monocytes and dendritic cells
205
What viral proteins are used in HIV infection?
reverse transcriptase to convert HIV RNA into DNA
integrase which integrates HIV DNA into host cells genes
Protease that allows for cleavage of proteins into final virus after viral transcription and protein synthesis
206
how does HIV virus bind to host cell?
binds via gp120 on CD4+ T cells
then conformational change via gp41 for entry into cell
207
HIV co-receptors?
CXCR4 / CCR5 on macrophages
208
what are the neutralising antibodies of the HIV virus?
anti-gp120
| anti-gp41
209
what are the non-neutralising antibodies of the HIV virus?
anti-p24 gag IgG
the gag protein is an intrastructural support for HIV
210
what are the naturally produced chemokines that prevent HIV entry?
MIP-1a, MIP-1b and RANTES
produced by CD8 T cells
-these block co-receptors.
211
what is the median time from infection with HIV to development of AIDS in typical progressors?
8-10 years
212
what is the median time from infection with HIV to development of AIDS in rapid progressors?
2-3 years
213
what is the median time from infection with HIV to development of AIDS in long term non progressors?
stable CD4 counts and no symptoms even after 10 years
214
what factor predicts disease progression?
initial viral burden
215
what is the screening test for HIV?
antibody test for anti-HIV ab via ELISA
usually done from 1 month onwards and if v high risk, again at 2 months
216
what is the confirmation test for HIV?
usually done when the screening test is positive.
detect Ab via western blot
or
PCR for HIV RNA
217
what has happened in the patient for HIV screening test to be +ve
Patient must have seroconverted.
seroconversion is the period of time during which HIV antibodies develop and become detectable.
Seroconversion occurs usually 1-3 wks after infection, but could take up to 6 months.
often not always accompanied by flu like symptoms including fever, rash, swollen lymph nodes and muscle aches.
218
After diagnosis of HIV, what do you want to monitor in the patient?
```
Viral Load (via PCR)
CD4 Count (via FACS)
```
AIDS = <200 cells/ microL
219
HIV patient Tx?
commence combination antiretroviral therapy immediately once diagnosis of HIV is confirmed
usually 2NRTIs + Protease inhibitor/ NNRTI or 2nd line: integrase inhibitor
this allows substantial control of viral replication, increase in cd4 t cell counts, and improvement in their host defences
220
if HIV+ mother has viral load <50, would you recommend breastfeeding her child?
still recommend formula feeding the child
221
in Pregnancy, what can you do reduce HIV transmission from mother to child?
1. take antiretroviral therapy and aim Viral load <50
2. avoid breastfeeding after birth and choose formula feeding
3. have a C-section if VL>50 and recommended by specialist team
222
what treatment should babies born to HIV+ mothers get after birth?
baby should be given antiretrovirals (3 drug combination) within 4 h and continued until 4-6 wks of age if VL> 50
zidovudine monotherapy if VL<50
223
what tests will baby born to HIV+ mother need after birth?
tested for HIV during first 2 days of life, on discharge from hospital, at 6 wks and at 12 wks. A further test at 18 months old.
224
If baby is tested positive for HIV, what important treatment?
PCP prophylaxis with co-trimoxazole
225
if untreated HIV+ve woman presents in labour , what tx?
stat dose of nevirapine, and commence fixed dose zidovudine with lamivudine and raltegravir.
IV zidovudine infused for the duration of labour and delivery
226
if untreated HIV+ve woman is pregnant, what tx to start?
combivir (zidovudine + lamivudine)
truvada (tenofovir + emtricitabine)
kivexa (abacavir + lamivudine)
227
what is maraviroc?
an HIV drug. CCR5 antagonist, attachment inhibitor
228
what is enfuvirtide?
a HIV fusion inhibitor
229
some e.g.s of nukes (nucleoside RTIs) used in HIV
zidovudine, abacavir, emtricitabine, lamivudine
230
tenofovir
a nucleotide RTI
231
efavirenz?
a non nucleoside RTI
| SEs include CNS effects
232
dolutegravir, raltegravir?
integrase inhibitors.
233
what is contraindicated in individuals with confirmed anaphylactic hypersensitivity to egg products?
influenza
234
e.g.s of live attenuated vaccines
a Yellow Chicken TOMB
```
Yellow Fever
Chicken Pox
Typhoid
Oral Polio
MMR
BCG
```
235
e.g.s of component/ subunit vaccines
Hep B (HbS Ag)
HPV (Capsid)
Influenza (haemagluttinin, neuraminadase)
236
e.g. of inactivated toxoid vaccine
diphtheria
| tetanus
237
e.g. of conjugate vaccines
PMH
pneumococcus
meningococcus
Hib
238
e.g. of inactivated vaccines
HIP CRAB
Hep A
Inactivated Polio
Pertussis
Cholera
Rabies
Anthrax
Bubonic Plague
239
what do adjuvants do?
increase the immune response without altering its specificity
240
what adjuvant is a water-in-oil emulsion containing mycobacterial cell wall components? not used clinically in humans
complete Freund's adjuvants
241
what adjuvant is an unmethylated DNA motif, which activates TLR-9 on APCs, thus stimulating expression of costimulatory molecules?
CpG
242
what adjuvant helps adsorb antigens and then releases the antigens slowly and also induces mild inflammatory reaction, thus increasing the development of the adaptive immune response?
aluminium salts
e.g. in Hep A, B, Hib vaccines
243
what adjuvant is a multimeric antigen with adjuvant built in?
ISCOMs
| immune stimulating complex
244
what is pavilizumab?
a monoclonal antibody for RSV
245
a monogenic anti-inflammatory disease where patient gets periodic fevers lasting 48-96h assoc w abdo pain (peritonitis), chest pain (pleurisy and pericarditis), arthritis. Defect in Pyrin-marenostrin, coded in MEFV gene.
familial Mediterranean fever
an auto recessive condition
lack of pyrin-marenostrin means excessive TNFa, IL1 (inflammatory cytokines) production
246
what sites are not normally exposed to the immune system?
eyes
testes
CNS
247
a monogenic autoimmune disease, with mutation in AIRE (an autoimmune regulator)
- antibodies against parathyroid and adrenal glands -> Addison's and hypoPTH
and antibodies agains IL17 & IL22 (predisposing to candidiasis)
Autoimmune polyendocrine syndrome type 1 (APS-1)
aka
APECED syndrome
248
a monogenic autoimmune disease with a mutation in the FAS pathway -> failure of apoptosis of lymphocytes. features of increased lymphocytes + Lymphadenopathy and splenomegaly and is assoc w lymphoma.
ALPS
autoimmune lymphoproliferative syndrome
249
a monogenic autoimmune disease with mutation in Foxp3 (required for development of Treg cells) -> endocrinopathy (T1DM, thyroid), diarrhoea, eczematous dermatitis.
IPEX syndrome
250
contraindications to skin prick testing.
extensive eczema, dermatographism, previous anaphylactic reaction, antihistamines should be discontinued 48h before testing.
251
lung cancer due to heavy smoking habit. what mutation is associated with the subtype of lung cancer pt is most likely to develop.
p53 and RB1 - small cell carcinoma
p53, c-myc, kras- squamous cell carcinoma
p53
252
put the viruses susceptible to acyclovir in order of susceptibility
herpes simplex 1 > herpes simplex 2 > varicella zoster
253
fever, conjunctivitis, maculopapular rash starting on face + spreading to whole body. + cervical and occipital lymphadenopathy
Rubella
- sub occipital and post auricular lymphadenopathy
254
infiltrative heart diseases like amyloidosis, haemochromatosis and sarcoidosis.
what type of cardiomyopathy are pts with these conditions likely to develop?
restrictive cardiomyopathy.
there is impaired ventricular compliance, and patient have big atria albeit a normal heart size.
255
what is the earliest visible gross lesion in atherosclerosis?
fatty streak
256
asbestos exposure -> greatest risk of which kind of lung cancer?
bronchial carcinoma.
although the strongest risk factor for mesothelioma is asbestos exposure.
257
v low leucocyte alkaline phosphate + neutrophilia
chronic myeloid leukaemia.
the low leukocyte alkaline phosphatase is a result of low activity in malignant neutrophils.
if accompanied by immature erythrocytes, then it will be termed a leukoerythroblastic reaction, caused by fibrosis or infiltration of the BM.
258
used in treatment of highly active relapsing-remitting multiple sclerosis and crohns disease
natalizumab.
binds to a4-integrin found on VCAM1 to arrest leucocyte migration.
259
what immune therapies increase risk of progressive multifocal leucoencephalopathy due to activation of the JC virus?
mycophenolate mofetil, rituximab, natalizumab.
any neuropsychiatric changes in patients on treatment should prompt further investigation.
260
triad of neurological abnormality, respiratory compromise after recent hx of total hip replacement surgery.
fat embolism
261
swollen gums, brusiing, petechiae, anaemia, poor wound healing, peifollicular and subperiosteal haemorrhages, corkscrew hair, haemarthrosis
vitamin C deficiency.
| Scurvy.
262
what protein in synthesised more by the liver in response to inflammatory cytokines in anaemia of chronic disease?
hepcidin.
the liver produces more hepcidin in response to IL-6. Hepcidin reduces iron absorption by the small intestines and causes iron accumulation in macrophages. together, these processes cause anaemia.
263
histology of someone after a myocardial infarction shows normal histology, CK-MB is also normal. how long has it been since the coronary event happened?
under 6 hours.
264
histology of someone after a myocardial infarction shows granulation tissue, new blood vessels, myofibroblasts, collagen synthesis. how long has it been since the coronary event happened?
1-2 wks
265
histology of someone after a myocardial infarction shows a strengthening, decellularising scar. how long has it been since the coronary event happened?
wks - months
266
histology of someone after a myocardial infarction shows infiltration of polymorphs but debris still present. how long has it been since the coronary event happened?
1-4 days
267
histology of someone after a myocardial infarction shows removal of debris. how long has it been since the coronary event happened?
5-10 days
268
histology of someone after a myocardial infarction shows loss of nuclei, homogenous cytoplasm, necrotic cell death. how long has it been since the coronary event happened?
6- 24 hours
269
what do you see in MEN1?
parathyroid hyperplasia/ adneoma, pituitary adenoma, pancreatic endocrine tumour (often pheochromocytoma)
270
what do you see in MEN2A?
parathyroid, medullary thyroid cancer, phaeochromocytoma.
271
what do you see in MEN 2B?
medullary thyroid cancer, phaeochoromocytoma, neuroma, marfanoid phenotype.
272
what organism responsible for infective endocarditis in a patient undergoing colonoscopy?
streptococcus bovis
273
mTOR inhibitor?
sirolimus
274
magnesium deficiency can lead to hypo....?
hypoCa, hypoK, hypoPTH
275
Histology of pt w acute rheumatic fever
beady fibrous vegetations (verrucae), Aschoff bodies (granulomas) and Anitschkow cells (enlarged macrophages in granulomas)
276
beady fibrous vegetation in acute rheumatic fever histology
verrucae
277
enlarged cells within granulomas in acute rheumatic fever histology
anitschkov myocytes
278
granulomas in acute rheumatic fever histology
Aschoff bodies
279
what are signs of immunological phenomenon in infective endocarditis
glomerulonephritis, osler's nodes, Roth spots, splenomegaly
280
what are signs of emboli formation in infective endocarditis?
janeway lesions, splenic infarcts
281
what is the gene mutation most assoc with adenocarcinoma of the lung?
EGFR mutation
282
what are the immune therapies that bind to PD-1 to allow T cell activation?
Pembrolizumab and Nivolumab.
283
what immune therapy binds to CTLA-4 to allow T cell activation? used to treat advanced metastatic melanoma
Ipilimumab
284
what immune therapy binds to IgE and Is used in treating severe asthma?
omalizumab
285
what antiviral is a pyrophosphate analogue that acts as a non competitive inhibitor of DNA polymerase and can be used to treat CMV infection?
foscarnet
286
what cluster of differentiation is typically present on surface of a T cell to act as a costimulatory signal for activation of the T cell?
CD28
once CD80/86 binds to it.
287
adenocarcinoma. pt treated w tyrosine kinase inhibitor which he did not respond to. what mutation is commonly assoc w this?
k-ras
288
ejection fraction of a pt with long standing coronary heart disease falls after stent is inserted. why?
reperfusion injury.
due to oxidative stress, calcium overload, inflammation.
commonly, this leads to arrhythmias + biochemical abnormalities.
HF, indicated by a reduced ejection fraction, may last a few days but will normalise with sufficient treatment.
289
hepcidin causes iron to accumulate in which cell?
macrophages
290
what molecule is affected in TTP?
ADAMTS13 enzyme
a metalloprotease responsible for cleaving large multimers of vWF into smaller units.
-> inhibition of ADAMTS13 occurs in TTP
291
defect in a5-chain of type IV collagen, resulting in eye and hearing abnormalities?
alports syndrome
| x-linked
292
IPEX syndrome- what gene involved?
foxp3.
- this gene is required for the development of T regulatory cells. this condition is characterised by immunodeficiency, resulting in diarrhoea and eczema and endocrinopathies including T1DM and thyroid disease.
293
what three sites are classically affected in hereditary angio-oedema?
upper airway, subcutaneous tissues and abdo organs (diarrhoea/ abdo pain).
294
what antibodies are characteristically produced against a patient with primary membranous glomerulonephritis?
antibodies to phospholipase A2 receptor, a protein found on podocytes.
-> IC deposition on glomeruli and thus, nephrotic syndrome
295
what does anti-cyclic citrullinated protein antibody bind to?
filaggrin - the filament aggregating protein
296
type 2 autoimmune hepatitis- what autoantibody?
anti-LKM-1.
| anti liver/ kidney microsomal-1 antibody
297
anti centromere antibodies in the presence of Primary biliary cirrhosis indicates?
portal HTN
298
high risk related to oculocutaneous albinism?
- metabolic condition affecting the production of skin pigment melanin.
higher risk of skin malignancy e.g. malignant melanoma.
299
features of primary biliary cirrhosis
pruritus (increased bile salts in circulation).
| reduced absorption of fat soluble vitamins e.g. A, D, E, K -> bruising/ night blindness/ osteomalacia.
300
anti-CD11a antibody against CD11a on T cells, inhibits the migration of T cells. indicated in the tx of psoriasis
efalizumab
301
rheumatoid arthritis
| how does it affect the complement pathway?
high CH50.
| complement factors are acute phase proteins and a high CH50 indicates acute or chronic inflammation.
302
recurrent infections + addisons, hypothyroidism + hypoPTH
autoimmune polyendocrine syndrome Type 1. APECED syndrome: mutations in the AIRE gene.
dysfunctional parathyroid/ adrenal gland, hypothyroidism, gonadal failure, alopecia and vitiligo.
303
common causes of non-igE mediated systemic histamine release
opioids, NSAIDs, contrast agents, exercise
304
antibodies related to pemphigus vulgaris
anti-desmoglein 1 and anti-desmoglein 3
305
initial encounter with antigen, mediated by which cell type?
antigen presenting cells such as macrophages engulf the allergen and presets peptides on the cell surface via MHC.
306
initial encounter with antigen, what cytokine is released first?
CD4+ T cells recognize the peptide and bind to the macrophage acting as APC.
The macrophage then releases IL-12 which leads to production of memory CD4+ T cells.
307
transplant from identical twin is called?
isograft
308
brutons agammaglobulinaemia mx?
IVIG
309
main cytokine responsible for fibrosis seen in CREST syndrome?
TGF-beta.
stimulates collagen production by fibroblasts.
310
T1DM: autoantibodies to tyrosine phosphatase
anti-IA-2 and anti-phogrin abs.
311
autoimmune polyendocrine syndrome. ptosis and difficulty w eye movement. diffuse pigmentation of the retina. hypoPTH and hypoCa.
Kearns-Sayre syndrome.
312
epidermolysis bullosa caused by autoantibodies to?
type VII collagen.
| bullae usually induced by trauma.
313
axial rigidity/ stiffness assoc w hx of autoimmune disease and circulating anti-glutamic acid decarboxylase antibodies
stiff man syndrome.
314
Guillain barre syndrome: what is the target for autoantibodies?
ganglioside LM1.
symmetrical inflammatory polyneuropathy that begins in the legs and ascends to involve motor neurone of the arms, face and muscles of respiration. pathogenesis involves cross reactivity between antibodies to the pathogen and components of peripheral n myelin components such as ganglioside LM1.
315
pt presents w floaters and loss of accommodation in R eye, several weeks after experiencing trauma to L eye.
sympathetic ophthalmia, a granulomatous CD4+ T cell mediated disease.
trigger for the disease is trauma to damaged eye. the eye is an immunoprivileged site and is therefore, under normal circumstances, protected from possible autoimmune attack. Trauma to the eye breaks the tolerance -> increased photoreceptor antigen presentation to immune cells.
316
how does skin act as an immune barrier.
tightly packed keratinized cells -> limits colonisation.
Low pH, low oxygen tension of skin. Sebaceous glands: hydrophobic oils repel water + microorganisms, lysozyme destroys structural integrity of bacterial cell wall, ammonia and defensins.
317
how does secreted mucus act as an immune barrier?
Physical barrier.
Secretory IgA. Lysozyme and antimicrobial peptides. Lactoferrin act to starve invading bacteria of iron. Cilia- directly trap pathogens + contribute to removal of mucous, aided by physical manoeuvres such as coughing and sneezing.
318
how does commensal bacteria act as an immune barrier?
Compete with pathogenic microorganisms for scarce resources. Produce fatty acids and bactericidins that inhibit the growth of many pathogens
319
what do pattern recognition receptors recognize? e.g. Toll like receptors.
PAMPs - pathogen associated molecular patterns. e.g. bacterial sugars, DNA, RNA
320
NADPH oxidase complex converts oxygen into what reactive oxygen species?
superoxide and hydrogen peroxide
321
what does myeloperoxidase form from hydrogen peroxide and chloride?
HCl - highly oxidant and antimicrobial. part of oxidative killing.
322
APC that resides in peripheral tissues
dendritic cells.
323
characteristics of the adaptive immune system?
wide repertoire of antigen receptors, exquisite specificity, clonal expansion of cells w appropriate specificity, immunological memory.
324
site of B cell maturation?
Bone marrow
325
site of T cell maturation?
Thymus.
326
secondary lymphoid organs?
Spleen, LNs, MALT
327
what subset of T cells helps CD8 T cells and macrophages?
Th1 cells
328
what subset of T cells express CD25+ and Foxp3+ and releases IL10 / TGFb
Treg cells
329
B cell differentiation involves which ligands?
CD40-CD40L interaction
330
what region of the immunoglobulin is associated with antigen recognition and binding?
Fab region
331
What region of the immunoglobulin assoc w effector function?
Fc region
332
how does the IL12-IFNy network usually work?
Infected macrophages produce IL12 -> IL12 induces T cells to produce IFNy -> IFNy stimulates macrophages to produce TNF and activates NADPH oxidase.
333
Where is the mutation in X linked SCID?
Mutation of gamma chain of IL2 receptor on chromosome Xq13.1
334
Very low or absent T and NK cell numbers, Normal or increased B cell numbers but low Igs
X linked SCID
335
what is deficient in auto recessive SCID?
```
Adenosine deaminase (ADA) deficiency
-> accumulation of precursors are toxic to lymphocytes.
```
336
Auto recessive SCID immune cell numbers?
Very low or absent T, B and NK cell numbers
337
what are the dysmorphic features of child with Digeorges syndrome?
High forehead, cleft palate, small mouth and jaw.
Low set, abnormally folded ears
338
mx of auto recessive SCID?
PEG-ADA enzyme replacement therapy
339
why does the oral route promote immune tolerance whereas the skin induces IgE sensitisation?
Ingestion of peanuts by mouth tends only to produce IgA or IgG response which are generally quite harmless. Food digested by the gut produces peptides of lower allergenity.
When skin barrier is disrupted (eg atopic dermatitis), allergen can access the dermis, where the dendritic cells can detect the allergen, causing release of cytokines and IgE antibodies
340
what is the most common allergic disease in adults?
allergic rhinitis (20%)
341
indications for specific IgE blood tests?
Patients who can’t stop anti-histamines
* Patients with dermatographism
* Patients with extensive eczema
* History of anaphylaxis
* Borderline/equivocal skin prick test results
342
what is in an emergency community anaphylaxis kit?
epipen: preloaded adrenaline, prednisolone 20mg, and antihistamine tablet-cetrizine 10mg.
must call for ambulance and attend A+E after using emergency kit
343
what is food associated exercised induced anaphylaxis?
Food induces anaphylaxis if individual exercises within 4-6 hours of ingestion. Common triggers = wheat, shellfish, celery.
344
some indications for plasmapheresis?
when Ab itself is directly pathogenic. e.g. severe acute myasthenia gravis, severe vascular rejection of donor organ, goodpastures syndrome.
345
what do calcineurin inhibitors do?
blocks IL-2 -> inhibit T cell activation and proliferation
346
What is apremilast used for? mode of action?
effective in psoriasis, psoriatic arthritis.
| PDE4 inhibitor.
347
what is Tofacitinib used for?
| mode of action?
Effective in rheumatoid arthritis.
| Interferes with JAK-STAT signalling (JAK1 and JAK3 inhibitor)
348
what does JC virus destroy?
infects and destroys oligodendrocytes
349
Periodic fevers lasting 48-96 hours associated with: abdominal pain due to peritonitis, chest pain due to pleurisy and pericarditis, arthritis, skin
familial mediterranean fever.
| mutation in MEFV gene - encoding pyrin-marenostrin.
350
Mx of familial mediterranean fever?
Colchicine - binds to tubulin in neutrophils and disrupts function. Anakinra (IL-1R antagonist). Etanercept (TNFa inhibitor)
351
long term risk of familial mediterranean fever?
amyloidosis.
| due to extra deposition of AA protein (increased SAA- acute phase protein)
352
APECED/ Autoimmune polyendocrine syndrome type 1 defect?
AIRE - autoimmune regulator
353
What organs are affected in APECED- autoimmunity wise? and what infection most susceptible to?
parathyroid and adrenal glands - HypopTH and addisons.
| + candida infections.
354
IPEX syndrome - mutation in?
Foxp3 - required for Treg cell development
355
IPEX presentation?
endocrinopathy - T1DM, thyroid disease. diarrhoea, eczematous dermatitis
356
ALPS (autoimmune lymphoproliferative syndrome) mutation in??
FAS pathway - failure of death of T lymphocytes
357
ALPS (autoimmune lymphoproliferative syndrome) presentation
assoc w lymphoma.
| high lymphocyte numbers w large spleen and LNs.
358
what gene mutation is assoc w 30% of crohns disease?
NOD2 gene
359
Tx of Crohns Disease
corticosteroid, azathioprine, anti-TNFa, anti-IL12/23
360
Tx of Ankylosing Spondylitis
NSAIDs. Anti-TNFa, anti-IL17, antil-IL12/23.
