Immune Modulation Flashcards
1
Q
Types of Immune Modulation
A
Vaccination
Replacement
Suppression
Sensitisation
2
Q
Vaccination mechanism
A
Memory lymphocyte production → rapid polyclonal expansion of adaptive immune response
3
Q
Active vs Passive Vaccination
A
Active - your own body produces response - long-term protection
Passive - pre-formed antibodies given - around 3 weeks
4
Q
What are Dendritic cell vaccines
A
5
Q
Summarise Paediatric vaccination schedule
A
6
Q
Regular adult vaccinations
A
7
Q
Key travel vaccines
A
8
Q
2 non-travel vaccines that are given based on risk
A
9
Q
4 Types of Vaccine
A
Live attenuated
Inactivated/component/toxoid
Conjugate
DNA/RNA
10
Q
What is a live attenuated vaccine?
Give examples
A
Modified pathogen to limit pathogenesis
E.g. MMR-VBOY
11
Q
Inactivated vaccine examples
A
Influenza (quadrivalent),
Polio (Salk),
Cholera,
Bubonic plague,
Hep A,
Rabies, Pertussis
12
Q
Component vaccine examples
A
Hep B [HbS antigen],
HPV [Capsid],
Influenza recombinant quadrivalent) [haemagglutinin, neuraminidase]
13
Q
Toxoid vaccine examples
A
Diptheria
Tetanus
14
Q
Conjugate vaccine examples
A
NHS
Tetanus
15
Q
DNA/RNA vaccine examples
A
SARS-CoV-2
16
Q
What does an adjuvant do in vaccination?
A
Increases immune response without altering specificity
17
Q
2 Main types of adjuvant
A
Depot
Stimulatory
18
Q
How does a depot adjuvant work?
A
Slows antigen release → increased exposure to antigen → promotes immune response
19
Q
Depot adjuvant example
A
ALUM
20
Q
How does a stimulatory adjuvant work?
A
Mimics the action of PAMPs on TLR and PRRs → increased receptor activation → boosted immune response
21
Q
Stimulatory adjuvant example
A
CpG
22
Q
Types of Immune Replacement
A
Haematopoietic SCT
Ab replacement - specific/unspecific
Adoptive T cell transfer
23
Q
Types of adoptive T cell transfer
A
Virus specific T cells
TIL T cell therapy
TCR
CAR-T cell therapy
24
Q
Describe TIL T cell therapy
A
TILs from tumour → expanded with IL2 → infused into lymphoid depleted patient → destroys cancer cells
25
Describe CAR-T cell therapy
Chimeric receptor targets CD19 → greater immune response to tumour than TCR therapy
for ALL, NHL
26
1/2 life of normal human IVIG
18 days
27
Examples of recombinant cytokines
IL-2
IFN-alpha
IFN-beta
IFN-gamma
28
Recomobinant IL-2 uses
Renal cancer
(IL-2 2 kidneys)
29
IFN-alpha uses
Viruses - Hep B & C (ABC)
Cancer
30
IFN-beta uses
Relapsing remitting MS
31
IFN-gamma uses
C**G**D
32
Immune Checkpoint blockade drugs
Ipilimumab
Pembrolizumab
Nivolumab
33
Immune checkpoint blockade indications
Advanced melanoma
Metastatic renal cancer
34
Ipilimumab mechanism
Normally: CD80 and CD86 (APCs) interact with CTLA4 (inhibitory) and CD28 (stimulatory)
CTLA4 inhibitor → blocks CTLA4, all APC interactions now through CD28 → boosted T cell response
35
Pembrolizumab/nivolumab mechanism
PD-1 (prevent death-1) blocker monoclonal antibody
Normally, cancer cells bind PDL-1 to Treg PD-1 → prevents Treg cell killing of tumour cell
PD-1 blockade prevents binding of PDL-1 to PD-1 → enabling Treg cell killing of tumour cell
36
3 signals in naive T cell priming
Activation: MHC-TCR interaction
Survival: CD86/B7-CD28 interaction
Differentiation: cytokines
37
What are the adverse effects of immunosuppressive drugs?
Infusion reaction (IgE)
Injection reaction
Acute infection
Chronic infection
Malignancy
Autoimmunity
38
How do you manage acute infection due to immunosuppression?
Prevention: non-live vaccination
Mx: stop immunosuppression,
ABx - cover for atypicals
39
What chronic infections can be seen with immunosuppression?
TB
HIV
Hep B, C
JCV
40
TB during immunosuppression Mx
Ix: check exposure + CXR
Mx: prophylaxis/treat as needed
41
HIV and immunosuppression
Check for HIV before treatment
42
How to manage viral hep during immunosuppression?
HBcAb and HCAb before treatment
If positive → further Ix
43
What is John Cunningham virus?
Polyoma virus that can reactivate → infecting and destroying oligodendrocytes → Progressive Multifocal Leukoencephalopathy (PML)
44
Prednisolone mechanism of immunosuppression
1. Phospholipase A2 inhibition → reduced prostaglanding synthesis → reduced inflammation
2. Inhibits phagocyte tracking, phagocytosis and release of proteolytic enzymes → decreased phagocyte activity
3. Promotes lymphocyte apoptosis, splenic sequestration (CD4>8>B), ↓ antibody productions and blocks cytokine gene expression → lymphopenia
45
Corticosteroid SEs
Metabolic: Cushing's, diabetes, osteoporosis, adrenal suppression
Infection
Eyes: cataracts, glaucoma
GI: peptic ulcers, pancreatitis
Avascular necrosis
46
Antiproliferative agents
Cyclophosphamide
Mycophenylate mofetil
Azathioprine
Methotrexate
47
Antiproliferative agents SE
Bone marrow suppression
48
Cyclophosphamide mechanism of action
Alkylates guanine in DNA → DNA damage → no cell replication
B>T cells
49
Cyclophosphamide key SE
Haemorrhagic cystitis
50
Mycophenylate Mofetil mechanism
Anti-metabolite
Blocks I-5'-MPHDH → prevents de novo guanine synthesis → stops replication
T>B cell
51
Mycophenylate Mofetil key SE
Progressive Multifocal Leukoencephalopathy (JC virus)
52
Azathioprine mechanism of action
Anti-metabolite
Pro-drug
Metabolised in liver to 6-metacarptopurine → prevents de novo purine synthesis → prevents DNA replication
53
What to check for before giving azathioprine and why?
TPMT mutation - can lead to bone marrow suppression with azathioprine
54
Methotrexate Mechanism of action
Anti-folate
Inhibits DHFR → inhibits DNA synthesis
55
Methotrexate SEs
F2oL2ate
Foetus - teratogenic
Folate deficiency
Lung - pneumonitis, pulmonary fibrosis
Liver - hepatotoxic
56
Plasmapharesis what is it and indications
Removal of pathological antibody
Indicated in severe Type II HS disease e.g. Goodpasture's
57
Key SEs of plasma pharesis
Rebound antibody production
Anaphylaxis
58
Inhibitors of Cell Signalling
Calcineurin inhibitors - Tacrolimus, Cyclosporin
mTor (IL-2 pathway) inhibitors - Sirolimus, Rapamycin
Tofacitinib - JAK1/3 inhibitor
Apremilast - PDE4 inhibitor
59
Mechanism of Tacrolimus and Cyclosporin
Inhibit calcineurin → decreased IL-2 expression → reduced T-cell proliferation
60
Side effects of calcineurin inhibitors
Nephrotoxic, neurotoxic, hypertension
Tacrolimus - diabetogenic
Cyclosporin - Gingival hyperplasia
61
Sirolimus (Rapamycin) mechanism of action
mToR inhibition → T cell proliferation inhibition via IL-2 pathway
62
Sirolimus indication
Transplantation
63
Sirolimus SEs
Hypertension, less nephrotoxic than calcineurin inhibitors
64
Tofacitinib mechanism
Inhibits JAK-STAT signalling → inhibits production of inflammatory molecules by influencing gene transcription
65
Apremilast mechanism
PDE4 inhibitor → increases cAMP through protien kinase A pathway → modulates cytokine production
66
Apremilast indication
Psoriasis, psoriatic arthritis
67
Main agents against cell surface antigens
Rabbit anti-thymocyte globulin
Basiliximab
Abatacept
Rituximab
Vedolizumab
68
Anti-thymocyte globulin actions
Lymphocyte depletion
Inhibition of T cell migration and activation
69
Anti-thymocyte globulin uses
Allograft rejection
70
Anti-thymocyte globulin SEs
Infusion reactions, leukopenia
71
Basiliximab mechanism of action
Blocks IL-2 induced signalling and T cell proliferation
72
Basiliximab Indication
Allograft rejection (prophylaxis)
73
Abatacept mechanism of action
Blocks CD80 and CD86 → reduced co-stimulation of T cells by CD28
74
Abatacept indication
Rheumatoid arthritis
75
Abatacept main caution
Malignancy
76
Rituximab mechanism of action
anti-CD20 → depletes mature B cells
77
Rituximab indication
lymphoma, rheumatoid arthritis, SLE
78
Rituximab SEs
Infusion reactions, infections (PML), exacerbation CV disease
79
Vedolizumab mechanism of action
Anti-alpha-4-beta-7 integrin → inhibits binding to MadCAM1 → stops leukocyte binding to endothelium and extravasation to tissue
80
Natalizumab antibody and indication
anti-alph-4-beta-1 integrin
MS and Crohn's
81
Cytokines and receptor targets for immunomodulatory agents
82
Anti-TNF alpha drugs
CAIG
Certolizumab
Adalimumab
Infliximab
Golimumab
83
Anti-TNF-alpha indications
PAIR
Psoriasis/psoriatic arthritis
Ankylosing spondylitis
Inflammatory bowel disease
Rheumatoid arthritis
84
TNF-alpha antagonist mechanism and example
Inhibits TNF alpha and beta
Etanercept - PAR not PAIR
85
What conditions can IL-1 blockade be used for?
FMF
Gout
Adult Stills
86
What disorder does IL-6 play an important role in?
Rheumatoid arthritis
87
How do Tocilizumab and Sarilumab work?
Anti-IL-6 receptor
→ reduced macrophage, neutrophil, T cell, B cell activation
88
What disorders are IL-23 and IL-17 important for?
Axial spondyloarthropathies
Psoriasis/psoriatic arthritis
IBD (IL-23 only)
89
Give an example of an anti-IL-23 drug?
Guselkumab
anti-p19(alpha) subunit of IL23
90
91
What ILs can be targeted for Asthma and Eczema?
IL4, 5 and 13
92
How does Denosumab work?
It inhibits RANK-mediated osteoclast differentiation and function → decreased bone resorption
93
Allergic desensitisation procedure
Start small
Escalate dose every weeek until max dose reached
Maintenance dose given monthly for 3-5 years
