Immunology Flashcards
1
Q
What type of virus is HIV
A
RNA retrovirus single stranded
Belongs to lentivirus family
2
Q
Which cells do HIV infect
A
CD4+
- t helper cells
- macrophages
3
Q
Pathogenesis of HIV
A
Attaches to CD4 via GP120 but uses co receptor either CCR5 or CXCR4
Replicates via a DNA intermediate
Integrates into host genome
HIV DNA transcribed to viral mRNA
Viral RNA translated to viral proteins
Packaging and release of mature virus
4
Q
What can predict HIV disease progression
A
Initial viral burden after primary infection settles
5
Q
What CD4 count defines AIDS
A
Less than 200
6
Q
Response when recognise PAMP
A
Th1 and h17
7
Q
How does immune system respond to toxins and helminthes
A
Detect a loss of function then get Th2 response
8
Q
What are inborn errors of immunity
A
Heterogenous group of genetic disorders resulting in immune dysfunction and ill health
485 single defects already identified
9
Q
What is the most common form of inborn errors of immunity
A
Antibody deficiency or B cell function
10
Q
What gene defects result in suceptibility to mycobacterial and BCG infection
A
Gene defects in generation of IL-12 adn response to IFN-gamma
Leads to reduced production of TNF to activate oxidative pathways
11
Q
What gives rise in critical influenza pneumonia susceptibility
A
Defects in TLR3 which is sensor of influenza A
12
Q
What is in mucous from membranes which protects against microorganisms
A
IgA prevents bacteria and viruses from binding to epithelial cells
Lysozyme which breaks down cell walls
Lactoferrin which starves bacteria of iron
13
Q
Which cells form part of innate immune response
A
Polymorphonuclear cells
Dendritic cells
Monocytes and macrophages
NK cells
14
Q
Where are granulocytes produced
A
Bone marrow then migrate to site of injury
15
Q
Other than cells what is included in the innate immune system
A
Complement
Acute phase proteins
Cytokins and chemokins
16
Q
What are examples of pattern recognition receptors
A
TLR
RIG-1
17
Q
What are monocytes and macrophages
A
Monocytes are produced by bone marrow and migrate to tissues where differentiate into macrophages
18
Q
Function of macrophages
A
Phagocytosis
Present processed antigens to T-cells
19
Q
What are mannose receptors
A
C-type lectin receptor found innate cells which detects pattern
20
Q
What type of receptors are those detecting PAMPs
A
Fc receptors
21
Q
What is opsonisation
A
Enables phagocytosis by marking the pathogen and making a bridge between it and phagocyte receptor
22
Q
What are examples opsonins
A
Antibodies
Complement components
Acute phase proteins
23
Q
What are 2 types of microbial killing
A
Non-oxidative- release bacteriocidal enzymes into phagolyosome
Oxidative- produce hydrochlorous acid
24
Q
What forms pus
A
Phagocytosis depletes neutrophil glycogen store which results in cell death
As cell dies enzymes are released causing liquefaction of adjacent tissue
25
What is function of dendritic cells prior to phagocytosis
Found in peripheral tissue
Express Fc receptors for Ig to detect immune complexes
26
What mediates migration of dendritic cells to lymph node
CCR7
27
What are the components of the adaptive immune system
Humoral immunity
Cellular immunity
Chemokines and cytokines
28
What makes up humoral immunity versus cellular
Humoral- B lymphocytes and antibodies
Cellular- T lymphocytes
29
What are the primary lymphoid organs
Organs where lymphocytes develop
Bone marrow- both T and B haemopatoetic stem cells and where B cells mature
Thymus- where T cells mature
30
What are the secondary lymphoid organs
Sites where naive lymphocytes and microorganisms interact
Spleen
Lymph nodes
MALT
31
What do all T cells express
CD3+
32
When is the thymus most active
Foetal and neonatal stages of life
Involutes after pregnancy
33
HLA class 1 proteins
A, B, C
34
HLA class 2 proteins
DR, DQ, DP
35
Most important HLA matches
In order
DR
B
A
When matching donors you want to minimise HLA differences
36
What does
- isograft
- allograft
- xenograft
- split graft mean
Iso- from a twin
Allo- from same species
Xeno- from different species
Split- shared by 2 recipients (liver)
37
Complications of SCT
Graft failure
Infections
GVHD
Relapse
38
What is GVHD
Where donor cells recognise the patient as foreign
39
Acute GVHD presentation
Rash which can blister
GI- D&V with bloody diarrhoea
Liver- jaundice
Days to weeks
40
How is acute GVHD prevented
Methotrexate
Corticosteroids
Cyclosporin
41
Main prognostic factor for acute GVHD
Previous acute GVHD
42
What is pathology behind allergic reaction triggering
Normal epithelial function affected- breaking of epithelial barrier
43
Which route of transmission promtoes IgE sensitisation
Skin
Resp tract
If its oral it promotes IgG immune tolerance
44
What causes rapid onset symptoms in allergic reactions
Cross linking of IgE on the surface of mast cells and basophils
- release of histamine from granules
- release and synthesis of leukotrienes and prostaglandins
- pro-inflam cytokines which recruits inflam cells
- increases lymphatic flow to regional lymph nodes
- contraction of muscles in lungs and activation of sneezes and itches
45
What results in delayed symptoms of allergic reactions
Eosinophlic related tissue damage and cytokine release from Th2 T-cells (IL4, IL5, IL13)
46
What is most appropriate initial investigation for suspected peanut allergy giving urticaria and angioedema
Skin prick test
47
What allergic diseases will present in infancy and childhood
Dermatitis
Food allergy
48
Presentation of IgE allergic responses
Within 3-4 hours after exposure
Skin-angioedema, urticaria
Resp tract- cough, wheeze, nasal congestion
GI- D&V
Blood vessels- fainting, sense of impending doom
49
What is refractory anaphylaxis
No improvement in resp and cardio symptoms in response to 2 doses of IM adrenaline
50
What is the best lab test to diagnose anaphylaxis
Mast cell tryptase taken 30mins-2 hours after the initial symptoms start
51
What demotes a positive skin prick test
Wheal 3mm greater than negative control
52
What do sensitisation blood tests do
Detect IgE to whole allergen or a component of the allergen
53
What is function of compnoent resolved diagnostics
Test for IgE against the specific protein within a whole allergen
In essence identifies the exact protein to which someone is allergic to
54
How are allergic diseases diagnosed
Is made by a clinican based on epidemiology, history, exam, SPT etc NOT a blood sensitisation test
These are necessary but not sufficient
55
If have a raised mast cell tryptase which fails to return to baseline afer anaphylaxis what could be causes
Systemic mastocytosis
Hereditary alpha tryptassaemia
56
What is gold standard for diagnosing food and drug allergies
Double blind oral food challenge tests
57
Anaphylaxis guidelines
ABCDE
Call for HELP
Remove trigger
Lie patient flat
IM adrenaline in anterolateral aspect of thigh
Establish airway and give oxygen
If no response
-IM adrenaline
- fluid bolus
58
Difference between food allergy and food intolerance
Allergy- adverse health effect arising from a specific immune response
Food intolerance- non-immune reactions which include pharmacological, metabolic
59
Examples of food intolerances
Food poisoning
Enzyme deficiencies- lactase
Pharmacological- caffeine, tyramine
60
Allergy mechanism in atopic dermatitis
IgE
61
Allergy mechanism in contact dermatitis
T cell mediated
62
What can differentiate between IgE sensitisation and IgE mediated allergy
Component resolved diagnostics
63
What can give delayed food induced anaphylaxis
Occur 3-6 hours after eating red meat
IgE antibody to alpha-1-3-galactose
64
What mechanism is oral allergy syndrome
When have haye fever, get cross reaction to some homologous proteins in apples, pears, carrots and nuts but not cooked
65
Presentation of oral allergy syndrome
Swelling and itch of lips and mouth
66
What does a positive blood sensitisation/SPT suggest
Sensitisation not allergy!
67
Most commmon cause of secondary immunodeficiency worldwide
Malnutrition
68
Causes of secondary immunodeficiency
Malnutrition
Measles- get immune defects lasting months to years
TB
HIV
COvid
Haem cancers
Drugs
69
Drugs which cause immunodeficiency
Steroids
Cytotoxic agents- methotrexate, mycophenolate, cyclophosophamide, azathioprine
Calcineurin inhibitors- cyclosporine, tacrolimus
Anti-epileptics
DMARD
JAK inhibitors
Biologics
70
What is good s syndrome
Combined T and B cell defect with thymoma and antibody deficiency
71
What infections are those with Goods syndrome susceptible to
CMV
PJP
Mucocutaneous candida
72
Natural history of HIV
Acute phase where can have flu like illness
Asymptomatic but progressive
AIDS
73
Difference in transmission of HIV across disease course
Related to viral load in plasma
High in acute and aids but drops in asymptomatic
74
What is acute immune response to HIV
Induction of HIV-1 antibodies
CD8 T cell activation
75
How is HIV diagnosed if under 18 months
HIV RNA or DNA tests
76
What tests are done which can determine HIV treatment
Test for HLAB5701 to avoid prescribing abacavir as severe risk of SJS
Tropism test for CCR5 to determine if CCR5 antagonist therapy would work
77
What is first line for HIV in the UK
2 NRTI and 1 NNRTI
OR
2NRTI and INI
Mainly will change treatment due to drug toxicity rather than response
78
When likely to see PJP, toxoplasma and mycobacterium avium complex in HIV
PJP- CD4 less than 200
Toxoplasma- 100
MAC- 75
79
What is chronic benign neutropenia
Get a mild/moderate neutropenia common in african and middle eastern groups
Asymptomatic with no further investigation required
80
What is familial neutropenia
Adult onset severe neutropenia
Specific organ autoimmune disease
No increased infection risk
81
Which conditions give a severe congenital neutropenia
Kostmann syndrome
Cyclic neutropenia
82
What is genetic defect in cyclic neutropenia
Autosomal dominant- Neutrophil elastase
83
What is genetic defect of Kostmann syndrome
Autosomal recessive- HCLS-1 associated protein X-1 which prevents maturation of neutrophils
84
How do severe congenital neutropenias present
Present in first 3 months
Susceptible to oral, cutaneous and epithelial s. aureus infections, g-enteric bacteria and fungal infections
85
How are severe congenital neutropenias treated
G-CSF support
Stem cell transplantation
86
Pathophysiology of neutrophil leukocyte adhesion deficiency
Deficiency in CD18 which is used to remove neutrophils from circulation
87
What is result of luekocyte adhesion deficiency
delayed separation of umbilical cord
very high neutrophil counts in blood (20-100 x106/L)
Absence of pus formation
88
Pathophysiology of chronic granulomatous disease
Deficiency in NADPH oxidase which used to generate free radicals as such fail to kill certain bacteria
Get excessive inflammation from persistent recruitment of neutrophils and phagocytes causing granuloma formation
89
Presentation of chronic granulomatous disease
Granulomas
Hepatomegaly and lymphadenopathy
Recurrent infections from PLACESS often affecting skin
Pseudomonas
Listeria
Aspergillosis
Candida
Ecoli
S aureus
Serratia
90
Treatment of chronic granulomatous disease
Interferon gamma
91
Test for chronic granulomatous disease
Dihydrorhodamine (DHR) flow cytometry test. DHR is oxidized to rhodamine, which is strongly fluorescent, following interaction with hydrogen peroxide.
92
What are the 3 triggers for complement pathway
Immune complexes (antigen-antibody)
Bacterial endotoxin
Mannose binding lectin
93
How does classical complement system work
Immune complexes trigger C1 which begins cascade involving C1, C2 and C4. Ultimately activate C3
94
Pathophysiology of classical component deficiencies
These include deficiencies in C1q,2 and 4
This means that is failure to activate the complement system causing increased susceptibility to infections
95
What is link of classical complement deficiencies and SLE
If have deficiency of classical complement pathway then is accumulation of immune complexes which can deposit in the joints, skin and kidneys
96
Presentation of classical complement deficiencies
Susceptibility to infections namely Hib and strep pneumoniae
Severe skin disease
Co-existing SLE
97
Pathophysiology of alternative pathway deficiencies
Lack of factor B, D and P (properdin) mean less activation of terminal pathway from alternative pathway
98
Susceptibility of alternative pathway deficiencies
Encapsulated bacteria
99
Presentation of C3 deficiency
Increased suscpetibility to encapsulated bacteria infection
100
What are the types of C3 deficiency
Primary from genetic deficiency
Secondary- get autoantibodies against C3
101
What is associated with C3 deficiency
Membranoproliferative glomerulonephritis
102
What is significance of mannose binding lectin deficiency
Very common however does not affect susceptibility to infection unless coinciding factor causing immunodeficiency like chemo or premature infant
103
Pathophysiology of SCID
Encompassing term for various mechanistic pathways however all relate to defects in the generation of lymphoid precursors in the bone marrow
104
Presentation of SCID
Present by 3 months of age
Opportunistic infections
Live vaccine infected (BcG and rotavirus)
Persistent candida infection
Failure to thrive
Peristent diarrhoea
105
Which infections are SCID normally susceptible
Opportunistic- candida, PJP, CMV
Viral chest and GI infections- adenovirus, parainfluenza
RARELY BACTERIAL
106
Treatment for SCID
Stem cell transplant
107
Pathophysiology of DiGeorge syndrome
22q11 deletion
108
Congenital features of DiGeorge syndrome
CATCH
Cardiac abnormalities (TOF)
Atresia (oesophageal)
Thymic aplasia
Craniofacial defects (cleft palate)
Hypocalcaemia from hypoparathyroidism
109
Immune problems of DiGeorge syndrome
Thymic hypoplasia leading to reduced T cell counts
Increased incidence of autoimmune conditions and sino-pulmonary infections
110
How is IgA deficiency diagnosed
Serum IgA under 0.07g/L with normal Ig and B cell counts
111
Presentation of IgA deficiency
Most asymptomatic
Increased prevalence of allergic disorders and autoimmune diseases
Recurrent sino-pulmonary and GI infections
112
What is pathogenesis of common variable immune deficiency
Heterogenous conditions were is defect in B cell develpoment, maturation or function and fail to produce protective antibodies
113
Presentation of CVID
PRESENTS IN ADULTS
Recurrent sino-pulmonary infections with encapsulated bacteria
These can be so bad get bronchiectasis
Otitis media
Hib conjunctivitis
Enteric infections
Skin cellulitis, abscess HSV and VZV
Viral resp infections
Granulomatous infiltration
Autoimmune conditions common
Increased risk of B cell NHL and gastric cancers
114
Hallmarks of CVID
Increased infection susceptibility
Autoimmune conditions more prevalent
Granulomatous infiltration
Lymphoproliferative conditions common
115
Management of CVID
Normal human IVIG
116
Pathogenesis of X-linked agammaglobulinaemia
Mutation in bruton tyrosine kinase which is key in maturation of B cells
117
Presentation of x-linked agammaglobulinaemia
Presentation under 5
Recurrent bacterial infection of ENT, resp and GI
Encapsulated bacteria
118
Management of x linked agammaglobulinaemia
Normal human IVIg
119
Blood findings of x linked agammaglobulinaemia
Neutropenia
Reduction or absence of b cells
Absent of all Ig
120
MOst common cause of death in X linked agammaglobulinaemia
Acute or chronic lung disease
121
MOst common antibody deficiency
Selective IgA deficiency
122
What is immunopathology
Damage to the host caused by immune system
123
Difference between auto-inflammatory and auto-immune
Auto-inflammatory get activation of immate immune cells such as macrophages and neutrophils resulting in tissue damage
Auto-immune get activation of T and B cell responses in primary and secondary lymphoid organs
124
Genetic defect in familial mediterranean fever
Autosomal recessive loss of function mutation in MEFV which encodes pyrin-marenostrin
Leads to uncontrolled IL-1 production
125
Investigations for familial mediterranean fever
High CRP
High serum amyloid A
Send off to genetics lab for confirmation
126
Presentation of familial mediterranean fever
Periodic fevers lasting 48-96 hours associated with:
Abdominal pain due to peritonitis
Chest pain due to pleurisy and pericarditis
Arthritis
Rash
127
Treatment of familial mediterranean fever
Colchicine
IL-1 blocker
128
What does IPEX stand for
Immune dysregulation polyendocrinopathy enteropathy X-linked syndrome
129
Pathophysiology of IPEX
Mutations in Foxp3 which is needed for the development of CD25+ T reg cells. Menas is failure to negatively regulate T cell responses
130
How does IPEX present
Increased prevalence of autoimmune diseases
- DM
- Hypothyrodism
- enteropathy
- eczema
(Diarrhoea, DM, dermatitis)
131
What does ALPS stand for
Auto-immune lymphoproliferative syndrome
132
Pathophysiology of ALPS
Mutation in FAS pathway which is involved in apoptosis of lymphocytes
133
Presentations of ALPS
Very high lymphocytes
Splenomegaly and enlarged lymph nodes
Auto-immune diseases (typically cytopenias)
Lymphoma
134
Inheritance of ALPS
Autosomal dominant
135
What mutations is associated with Crohns disease
IBD1 gene of chr 16- NOD2 (most common)
CARD15
136
What are mixed pattern diseases
Involve mutations in both the innate and adaptive immune system
137
Main genetic allele associated with ank spond
HLA B27
138
Presentation of ank spond
Back pain worse in morning with stiffnesss
Large joint arthritis
Enthesitis- pain where ligaments/tendons insert
139
Management of ank spond
NSAIDS
Anti-TNF alpha
Anti- IL17
140
What are the types of immunological diseases
Monogenic auto-inflammatory
Polygenic auto-inflammatory
Mixed pattern diseases
Polygenic auto-immune diseases
Monogenic auto-immune diseases
141
What is the genetic association of goodpasture syndrome
HLA-DR15
142
What are 2 examples of genetic polymorphisms seen in polygenic autoimmune disease
Protein tyrosine phosphatase non-receptor 22
Cytotoxic t lymphocyte associated protein 4
143
What is Protein tyrosine phosphatase non-receptor 22 polymorphism associated with
SLE
RA
T1DM
144
What is Cytotoxic t lymphocyte associated protein 4 polymorphism associated with
Hashimotos
SLE
T1DM
145
What are the 4 hypersensitivity reactions
Type 1- IgE
Type 2- antibody reacts with cellular antigen
Type 3- antibody reacts with soluble antigen to form immune complex
Type 4- T-cell mediated
146
What is autoantigen in goodpastures
Noncollagenous domain of basement membrane collagen type IV
Anti glomerular basement membrane
147
What is the autoantigen in pemphigus vulgaris
Epidermal cadherin
Anti-desmoglein
148
Antibody in hashimotos
Anti thyroid peroxidase antibodies
Can get antithyroglobulin
NOTE IS VERY COMMON FOR PEOPLE IN GENERAL POPULATION TO HAVE
149
What type of immunological reaction is T1DM
Type IV
Get T cell infiltration of the pancreas
150
What are some of the antibodies in T1DM
Anti-islet cell antibodies
Anti-glutamic acid decarboxylase antibodies
Often predate the development of DM and do not play a role in diagnosis
151
Antibodies in pernicious anaemia
Anti gastric parietal cells
Anti intrinsic factor- most specific
152
Presentation of B12 deficiency
Macrocytic anaemia
Degeneration of spinal chord subacute
Peripheral neuropathy
OPtic neuropathy
153
Antibodies in coeliac
Anti tissue transglutaminase
Anti endomysial
154
Which antibody can be seen in IBD
P-ANCA
MORE UC THAN CROHNS
155
What are antibodies in primary biliary cholangitis
Anti mitochondrial antibody
ANA
156
Antibodies in Myasthenia gravis
Anti acetylcholine receptor
Anti-striational (if with myositis)
157
What antibody is seen in myasthenia gravis if concurrent myositis
Anti-striational
158
What antibody is seen in neuromyelitis optica spectrum
Anti aquaporin 4
159
What antibody is seen in optic neuritis
Anti myelin oligodendrocyte glycoprotein
160
What antibodies can be seen in encephalitis
Anti NMDA receptor
161
What antibodies can be seen if seizures
Anti GABA receptor
Normally underlying malignancy too
162
What are genetic predispositions to RA
HLA DR4
Peptidyl arginine deaminase as increases citrullination of proteins
163
Environmental predispositions to RA
Smoking
Gum infection with porphyromonas gingivalis as expresses peptidyl arginine deaminase which promotes citrullination
164
Which antibodies are present in RA
Anti cyclic citrullinated proteins- most sensitive
Rheumatoid factor- antibody against Fc portion of IgG
165
What are the antibodies present in SLE
- ANA
- Anti DsDNA
- anti Ro
-anti La
- anti Sm
- anti U1RNP
166
What are the investigations done if psoitive ANA
Will do dsDNA
And extractable nuclear antigens
- anti Ro
-anti La
- anti Sm
- anti U1RNP
- scl70
- centromere
167
What are Ro, La, Sm and U1RNP all
Ribonucleoproteins- extractable nuclear antigens
168
What are the complement profiles of C3 and C4 in SLE
C4 reduced in active disease and severe disease
C3 only reduced in severe disease
169
What is seen in antiphospholipid syndrome
Recurrent thromosis
Recurrent miscarriage
Can get valvular disease
170
What antibodies test for in antiphospholipid syndrome
Anti-cardiolipin
Lupus anticoagulant
Anti beta 2 glycoprotein 1
171
Presentation of sjogrens
Dry eyes
Dry mouth
Arthralgia
Fatigue
172
Lip biopsy finding in sjogrens
B cell and T cell infiltration
CD4+ most prominent
173
What antibodies seen in sjogrens
Anti-Ro
Anti La
Speckled staining
174
What is risk of sjogrens or SLE with anti Ro antibodies during pregnancy
Can cross react with foetal cardiac tissue causing neonatal heart block
175
What antibody seen in polymyositis and dermatomyositis
Anti Jo-1 (anti t-RNA synthetase)
Speckled pattern
176
What are second line immune deficiencies tests
Measure concentration of vaccine antibodies
If antibodies are low then can offer vaccination wit pneumovax II and tetanus and measure response
This is a criteria for IgG in replacement some conditions
177
Which vaccines are used to investigate immune deficiency
Pneumovax II
Tetanus
178
How is HIV diagnosed (options available)
4th gen ELISA then to confirm use western blot
Rapid point of care tests available which provide answer in 20 minutes however less sensitive than 4th gen test
179
If in acute HIV have suspicion of HIV but serological tests negative what use
HIV RNA tests
180
How is HIV monitored
Viral load
CD4 count
181
What is viral load set point
3-6 months after initial infection a steady state HIV-1 viral concentration is observed in blood
Used to predict long term outcomes
182
When is ART offered to prevent infection
Prevent transmission to seronegative partners
Pregnancy
Following inadvertant exposure follwoing occupational exposure or high risk sex
183
What are the phases of T cell mediated transplant rejection
Phase 1- presentation of donor HLA by an APC
Phase 2- T cell activation and inflammatory cell recruitment
Phase 3- effector phase with organ damage
184
What are phases of antibody mediated rejection
Phase 1- B cells recognise foreign HLA
Phase 2- proliferation and maturation of B cells with anti HLA antibodies
Phase 3- effector phase where antibodies bind to graft endothelium
185
Graft biopsy of t cell mediated rejection
Inerstitial inflammation and tubulitis
Arteritis
186
Graft biopsy of antibody mediated rejection
Antibody deposition
Complement deposition
All in endothelium
187
Which antibodies can exist in antibody mediated rejection
Anti-HLA
Anti-A or anti-B
188
Where can anti-HLA antibodies seen in organ rejection arise from
Anti-HLA are not naturally occuring
- pre formed- prev transplant, pregnancy, transfusion
- post formed- arise from transplant
189
How can rejection be prevented by tissue typing
ABO and HLA tissue-matching
Screen for anti-HLA antibodies
190
What induction agents are given for baseline suppression in prevention of graft rejection
Anti CD52- alemtuzumab
OKT3- muronomab-CD3
Anti-CD25 (IL2-R)- daclizumab
191
As well as induction agents which baseline immunosuppression agents are given to prevent SOT rejection
Calcineurin inhibitor
Mycophenolate or azathioprine
+/- steroids
192
How can organ rejection be detected
Monitor organ function ie creatinine
Screen for antibodies (anti-HLA)
193
How is T cell mediated organ rejection treated
IV steroids
OKT3- muronomab-CD3
194
How is antibody mediated rejection treated
IVIG
PLasma exchange
Rituximab
195
How is drug toxicity treated of immunosuppressive agents treated
Reduce dose
196
If are immunocompromised and then contract a viral infection how is it treated
Reduce dose
197
What is moa of tacrolimus and cyclosporin
Calcineurin inhibitor- needed for T cell proliferation
198
What is MOA of azathioprine
Prevents purine (adenine and guanine) synthesis
199
What is moa of mycophenolate motefil
Prevents guanine synthesis by inhibiting inosine-5'-monophosphate dehydrogenase (5-IMD)
Anti-proliferative affecting T>B cells
200
What is MOA of methotrexate
Inhibits dihydrofolate reductase which so is anti folate
201
What is MOA of daclizumab
IL-2 receptor antibody, targets CD25
202
What is MOA of rituximab
Anti-CD20 which depletes mature B cells but not plasma cells
203
What is MOA of muromonab-CD3
Blocks CD3 on T cells
204
What is MOA of alemtuzumab
Binds to CD52- blocks all T cell production
205
Which immunosuppressive agent is strongly linked with JC virus
Mycophenolate motefil
206
What is main side effect of calcineurin inhibitors
Gingival hypertrophy
207
What is main side effect of cyclophsophamide
Haemorrhagic cystitis due to excretion product acrolein
208
What is MOA of cyclophoshamide
Alkylates guanine which inhibits DNA synthesis
209
What is MOA of corticosteroids
Inhibits phospholipase A2
210
What is MOA of infliximab
TNF-alpha inhibitor
211
What is MOA of denusomab and what used in
Anti-RANK ligand
Osteoporosis
212
How is contact dermatitis diagnosed
Patch testing
213
What is immunopathology of an allergic reaction
if an allergen is taken up by a macrophage, it is processed
intracellularly and peptides are presented via major histocompatibility
complex on the cell surface to T cells of the TH2-cell (E) subclass. TH2-
cell secrete IL-4, which stimulates B cell (B) proliferation. TH1-cells (D)
do not play a role in the pathogenesis of type I hypersensitivity but do
contribute to type IV hypersensitivity reactions. B cells in turn produce
allergen-specific antibodies of the IgE variety. IgE binds to mast cells
(A) via the Fc receptor.
214
Which C proteins involved in membrane attack complex
C5b through to 9
215
What is presentation when defect in terminal pathway forming membrane attack complex
Defects in C5b through to 9 lead to recurrent infection with encapsulated bacteria
216
What is difference between a mature and immature dendritic cell
Immature- phagocyte
Mature- antigen presenting cell
217
Which cells derive from monocytes
Macrophages
218
When on what drug do you get repeated mouth and lip swelling after procedures
ACEi
219
Which vaccines are given to the elderly
Pneumococcal PPV
Shingles
Flu
220
Which cells are involved in adaptive immune response to vaccines
APC presents to specific receptor effector T-cell
which then proliferate
Specific antigen binds toIgm b-cells which undergo proliferation to memory b-cells and plasma cells with high affinity antibodies
221
Which antigen confers immunity to Influenza vaccine
Haemoagglutinin
222
How does tuberculin test work
Inject tuberculin into arm and measure induration width 48 hours later
223
How do conjugate vaccines work
Contain a weak antigen alongside a stronger antigen to trick immune system into generating stronger response to weaiker antigen
224
When is interferon alpha given to boost immune response
Hep B and C
225
When is IL-2 given to stimulate T cell response
Renal cell cancer
226
When are haematopoietic stem cells given
SCID
Leukocyte adhesion defect
Haem malignany
227
Which organisms are bloods for IVIG screened for
HIV
Hep B and C
228
Indications for antibody replacement
Primary AB deficiency
- X linked agammaglobulinaemia
- X linked hyper IgM syndrome
- CVID
Secondary deficiency
- CML
- myeloma
229
When are specific abs given
Hep B exposure from sex/needlestick etc HBSag
Rabies exposure from a bite
VZV in pregnant women
Suspected tetanus exposure
230
What is adoptive cell transfer
Can give specific T cells to a recipient
231
Types pf adoptive cell transfer
Virus specific T cells
Tumour infiltrating T cells
Tcell receptor T cells
Chimeric antigen T cells
232
What is virus specific t cell therapy
Take allogenic or autologous T cells
Expose to antigen
Grow them and give back to recipient
233
When is virus specific T cell therapy used
EBV related B cell lymphoproliferative disease
Persistent viral infection in immunocompromised
234
How does tumour infiltrating lymphocyte therapy work
Excise a tumour
Identify lymphocytes which have infiltrated tumour and expand them
235
Blood features of coeliac
IDA
- hypochromic and microcytic
Megaloblastic
- hypersegmented
- macrocytosis
Hyposplenism
- howell-jolly bodies
236
Hyposplenism causes
Coeliac
SLE
SCD
IBD
237
What exact antigen does anti-tissue transglutaminase respond to
Gliadin
238
What type of antibodies are anti-TTG and endomysial
IgA
239
Where take biopsy in coeliac
Deeper duodenum as presence of brunners gland distorts biopsy
240
Define atopy and anaphylaxis
Atopy- tendancy to produce IgE
Anaphylaxis- allergic reaction with an A,B or C definition
241
Person had anaphylaxis then a few hours later has same symptoms, what cause
Anaphylaxis is biphasic
242
What is used to measure complement
C3 and C4
CH50
AP50
243
What is livedo reticularis seen in
Antiphospholipid- net like discolouration of legs
244
Non serological blood findings of APL
Thrombocytopenia
Prolonged APTT
245
How is renal disease monitored in SLE
Urine dip
246
Why get recurrent infections in myeloma
Suppression of BM expansion by IgG
247
Why get anaemia in myeloma
Plasma cells crowd out the BM
248
What are T-cell receptor T cells and chimeric antigen receptor cell therapy
Involves the insertion of genes into T-cells which provokes development of T cell receptors on their surface which can bind to ligands on tumour cells
249
Difference between chimeric antigen receptor cell therapy and t-cell receptor T cell therapy
In chimeric the genes inserted are made up of recombinant genes
250
Use of chimeric antigen receptor T cells
Can get T cells to express receptors which bind to CD19 of some non-hodgkin lymphomas and b lymphocytes in ALL
251
Which cell is most affected by steroids
CD4+
252
Side effects of antiproliferative immunosuppressants
BM suppression
Infection
Malignancy
253
What is MOA of rapamycin/sirolimus
mTOR inhibitor which prevents T cell proliferation via IL-2
254
What is MOA of jakinibs
Inhibit JAK-STAT signalling which prevents production of cytokines
255
What are JAKinibs used in
Psoriasis
RA
Ank spond
256
What are PDE4 inhibitors used in
Psoriasis
257
What is MOA of PDE4 inhibitors
Modulates cytokine release
258
MOA of basilixumab and daclizumab
Binds to IL2R/CD25 reducing T cell proliferation
259
MOA of abatecept
Reduces costimulation of T cells via CD28
260
MOA of vedolizumab
Binds to alpha 4 beta 7 integrin which inhibits leukocyte adhesion
261
MOA of tocilizumab
IL-6 receptor antibody
262
What is tocilizumab (IL-6 antibody) used for
RA
263
MOA of secukinumab
Anti-IL17
264
MOA of guselkumab
Anti-IL23
265
MOA of mepolizumab
Anti-IL5
266
Use of mepolizumab
Eosinophilic asthma
267
What is most common classical pathway deficiency
C2
268
What are the most common SCIDs
X-linked SCID most common
Adenosine deaminase deficiency 2nd most common
269
Pathophysiology of X-linked SCID
Defective gamma chain on IL-2 leading to no t-cells and NK cells but immature B-cell production
270
Blood findings of x-linked SCID
Low T-cells and NK cells
Normal B cells
271
Pathophysiology of ada deficiency
Adenosine deaminase deficiency which is enzyme involved in leukocyte deficiencies
Low all b and t cells
272
Blood findings of ADA deficiency
Low T and NK cells
Low B cells
273
Inheritance of hyper IgM syndrome
x-linked recessive
274
Presentation of hyper IgM
Failure to thrive
Recurrent bacterial infections
PJP infection
275
What are the polygenic auto-inflammatory disease
IBD
Osteoarthritis
GCA
Takayasus arteritis
276
What are the mixed pattern disease
Ank spond
Psoriatic arthritis
Behcets disease
277
What does speckled mean when it comes to antibodies
Under immunofluorescence it means the nucleus is speckled with antibodies
278
What ENA have speckled appearance
Ro
La
U1RNP
279
What gel and coombs in RA
4
3 if RF positive
280
Difference between direct and indirect antigen detection in transplant rejection
Direct- donor APC presents foreign antigen to host T cells (acute)
Indirect- host APC presents foreign antigen to T cells like in infection
281
How to remember which cells antiproliferative agents affect the most
B cells
- cyclophosphamide
T cells- ones which have T in
- azathioprine
- mycophenolate motefil
Can include tacrolimus here too
282
MOA of ustekinumab
Anti-IL12 and IL-23
283
Name for beef tapeworm
Taenia saginata
284
What is the target of the antibody P-ANCA?
Myeloperoxidase
285
What is the target of the antibody C-ANCA?
Proteinase 3
286
What hematological cells create a "respiratory burst" in order to kill phagocytosed pathogens?
Neutrophils- done by NADPH oxidase
287
What is the worst SCID
Reticular dysgenesis
288
What is the minimum number of Fc receptors on the surface of mast cells that must bind to an antigen to cause mast cell degranulation
2
289
Which cell surface receptor allows cells of the innate immune system to bind to immunoglobulins?
Fc
290
What test can be used to identify the allergens in allergic rhinitis?
Skin prick
291
Antibodies in diffuse systmeic sclerosis
Topoisomerase (Scl70)
Fibrillarin
292
What is the maximum number of viral capsids that a molecule of IgM, IgA and IgG may bind to?
IgM- 10
IgA- 4
IgG- 2
293
What is use of natalizumab
Relapsing remitting MS
294
MOA of natalizumab
Targets alpha4integrin
295
T helper cells involved in bacterial versus allergies
Bacterial infections- T helper 1 cells
Allergies- T helper 2 cells
296
Monoclonal vs polyclonal antibodies
Monoclonal antibody = a solution of identical antibodies Polyclonal antibody = a solution of mutliple antibodies with different affinities for the same antigen (or target molecule)
297
What is example of integrase inhibitor
Dolutegravir
298
What chemical is responsible for urticaria and swelling in allergy
Histamine
299
What is latex food syndrome
Latex food syndrome is an IgE mediated type 1 hypersensitivity reaction to fruits and seeds, that is caused by cross-reactivity to latex antigens.
300
HLA association of DM
DR3 and DR4
301
HLA association of goodpastures
DR15
302
Presentation of hereditary angioedema
Recurrent bouts of swelling around mouth and neck
303
Pathophysiology of herditary angioedema
Acquired C1-inhibitor deficiency
