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Immunology Flashcards - Immune modulators

1
Q

What methods are avilable to boost the immune response (3)?

A

Vaccination
Replacement of missing components
Cytokine therapy

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2
Q

What methods are avilable to suppress the immune response (3)?

A

Non-specific immunosuppression
Ab removal
Targeted dampening of immune response

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3
Q

What methods are avilable to deviating the immune response (1)?

A

Desentisation

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4
Q

What are the indications for bone marrow transplantation (2)?

A

Life threatening primary immunodeficiencies (e.g. SCID, Leukocyte adhesion deficiency)
Haematological malignancy

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5
Q

Is BM replacement in SCID curative?

A

Yes, potentially

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6
Q

What is normal human immunoglobulin? How is it made?

A

Pooled from donors, contains preformed IgG to a range of unspecified organisms

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7
Q

What is the half life of normal human immunoglobulin?

A

18 days

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8
Q

What are the indications for Ab replacement with normal human immunoglobulin?

A

Ab deficiency (Primary or secondary)

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9
Q

Which primary Ab deficiencies benefit from Ab replacement with normal human immunoglobulin (3)?

A

X-linked agammaglobulinaemia
X-linked hyper-IgM syndrome
Common variable immune deficiency

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10
Q

Which secondary Ab deficiencies benefit from Ab replacement with normal human immunoglobulin?

A 
Haematological malignancies (e.g. CLL, multiple myeloma)
After bone marrow transplantation
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11
Q

What are specific immunoglobulins used for?

A

Post exposure prophylaxis

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12
Q

How are specific immunoglobulins derived?

A

From plasma donors with high titres of IgG antibodies to specific pathogens e.g. Hep B, tetanus, Rabies, Varicella zoster

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13
Q

What are recombinant cytokines used for?

A

Boost immune response to cancer and specific pathogens

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14
Q

What is interferon alpha used for (6)?

A 
Hep B
Hep C
Kaposi's sarcoma
hairy cell leukaemia
CML
malignant myeloma
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15
Q

What is interferon beta used for (1)?

A

Relapsing MS

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16
Q

What is interferon gamma used for (1)?

A

Chronic granulomatous disease

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17
Q

What are the three types of reconbinant cytokines used as treatment?

A

interferon alpha, beta and gamma

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18
Q

What type of molecule are corticosteroids?

A

synthetic glucocorticoids

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19
Q

Name a corticosteroid

A

Prednisolone

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20
Q

What is the bodies daily glucocorticoid output in terms of prednisolone?

A

5-7.5mg

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21
Q

What are the immune effects of corticosteroids (3)?

A

Reduced prostaglandin synthesis
Inhibits phagocyte migration and function
Inhibits lymphocyte function and promotes apoptosis

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22
Q

What are the metabolic effects of corticosteroids (7)?

A 
Diabetes
Obesity
Lipid abnormalities
Osteoporosis
Moon face
Hirsutism
Adrenal suppression
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23
Q

What are the other side effects of corticosteroids (6)?

A 
Immune suppression
Cataracts
Glaucoma
Peptic ulceration
Pancreatitis
Avascular necrosis
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24
Q

How do corticosteroids affect phagocytes?

A

Inhibit migration into tissue by decreasing adhesion molecule expression and blocking migration signals
Decrease proteolytic enzyme release

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25
How do corticosteroids affect lymphocytes?
Sequestration in lymphoid tissue CD4>CD8>B Induction of apoptosis at high doses Inhibition of cytokine gene expression Decrease Ab production
26
How do corticosteroids decrease prostaglandin synthesis?
Inhibition of phospholipase A2
27
Name 4 anti-proliferative agents
Cyclophosphamide Mycophenylate Azathioprine Methotrexate
28
How do cytotoxics work?
Inihibition of DNA synthesis
29
What is cyclophosphamide?
Anti-proliferative immunosuppressant / cytotoxic
30
What is the MoA of cyclophosphamide?
Alkylation of the guanine base of DNA, causing damage and preventing replication.
31
Which cells does cyclophosphamide affect most?
B cells > T cells, but all cells with high turnover at high doses
32
What are the major indications for cyclophosphamide?
Auto-immune diseases such as multisystem connective tissue disease or vasculitis with severe end organ involvement (e.g. wegeners granulomatosis, SLE) Cancer
33
What are the side effects of cyclophosphamide (3)?
Toxicity to proliferating cells (BM depression, hair loss, sterility M>>F) Haemorrhagic cystitis Complications of long term immunosuppression
34
What is azathioprine?
Anti-proliferative immunosuppressant / cytotoxic
35
What is the MoA of Azathioprine?
Metabolised to 6-mercaptopurine | This blocks de novo purine synthesis, preventing DNA replication
36
What cells does azathioprine affect?
T cells - activation and proliferation
37
What are the indications for Azathioprine (3)?
Transplantation Auto-immune disease Auto-inflammatory diseases (e.g. crohn's, UC)
38
What are the side effects of azathioprine (3)?
Bone marrow suppression (esp leukocytes and platelets, and individuals who have TPMT polymorophisms) Hepatotoxicity (uncommon) Complications of long term immunosuppression
39
What is mycophenylate?
Anti-proliferative immunosuppressant / cytotoxic
40
What is the mechanism of action of mycophenylate?
Blocks de novo nucleotide synthesis, preventing DNA replication
41
Which cells does mycophenolate affect most?
T>B
42
What are the indications for mycophenylate (2)?
Used in transplantation as an alternative to azathioprine | Used in auto-immune disease and vasculitis as an alternative to cyclophosphamide
43
What are the side effects of mycophenylate (2)?
Bone marrow suppression (esp leukocytes and platelets) Hepatotoxicity (uncommon) Complications of long term immunosuppression (esp risk of herpes virus reactivation and progressive multifocal leukoencephalopathy)
44
What is the purpose of plasmapharesis?
Remove pathogenic Abs
45
What is the main limitation of plasmapharesis?
Rebound antibody production limits efficacy so need to give anti-proliferative too
46
What are the indications for plasmapharesis?
Severe Ab mediated disease: Goodpastures, severe acute myasthenia gravis, severe vascular rejection
47
Name 3 cell signalling inhibitors
Cyclosporin Tacrolimus Sirolimus
48
What is the MoA of cyclosporin?
Inhibits calcineurin, interrupting T cell signalling pathways and preventing IL2 release, therefore stopping T cell activation and proliferation
49
What is the MoA of tacrolimus?
Inhibits calcineurin, interrupting T cell signalling pathways and preventing IL2 release, therefore stopping T cell activation and proliferation
50
What are the side effects of cyclosporin?
``` Dysmorphism +++ Nephrotoxic ++ HTN ++ Neurotoxic ++ Diabetogenic + ```
51
What are the side effects of tacrolimus?
Diabetogenic +++ Nephrotoxic ++ HTN ++ Neurotoxic ++
52
How do recombinant Abs work?
Target cell surface antigens
53
What is the target of anti-thymocyte globulin?
T-cell surface molecules
54
How does anti-thymocyte globulin work?
Depletes and modulates T cell function
55
What are the indications for anti-thymocyte globulin?
Allogract rejection
56
What are the side effects of anti-thymocyte globulin (4)?
Infusion reaction Leukopenia Infection Malignancy
57
What is the target of Basiliximab?
CD25, IL-2 receptor on T cells
58
What is the MoA of basiliximab?
Binds to IL-2 receptor, stops T cell proliferation
59
What are the indications for Basiliximab?
Prophylaxis of allograft rejection
60
What are the s/e of basiliximab (2)?
Infusion reaction Infection ?long term malignancy
61
What is abatacept?
CTLA4-IG fusion protein
62
What is the target for abatacept?
CD80 and CD86 receptors on antigen presenting cells
63
What is the MoA of abatacept?
Prevents CD28 and CTLA4 proteins on T cells binding to APCs, preventing T cell activation
64
What are the indications for abatacept?
Rheumatoid arthritis
65
What are the s/e of abatacept?
Infusion reaction Infection (TB, Hep B, Hep C) ?long term malignancy
66
What is a cytokine storm?
Potentially fatal immune reaction - positive feedback loop of cytokines activating lymphocytes and macrophages causing cytokine release.
67
What are the clinical features of a cytokine storm?
Vascular leak causing pulmonary oedema, cerebral oedema, cardiovascular collapse, poor peripheral perfusion and shock
68
What is the target of rituximab?
CD20
69
What is the MoA of rituximab?
Binds to CD20 on B cells, depleting mature B cells
70
What are the indications for Rituximab?
Lymphoma Rheumatoid arthritis SLE
71
What are the s/e of rituximab?
Infusion reaction Infection (Progressive multifocal leukoencephalopathy) Exacerbates CV disease
72
What is the target of natalizumab?
alpha4 integrin on T cells
73
What is the MoA of natalizumab?
Binds to alpha4 integrin, stopping VCAM1 and MadCAM1 binding and preventing T cell migration
74
What are the indications of natalizumab?
Highly-active relapsing-remitting MS | Crohn's
75
What are the s/e of natalizumab?
Infusion reactions Infection (progressive multifocal leukoencephalopathy Hepatotoxicity ?long term malignancy
76
What is the target for tocilizumab?
IL-6 receptor - membrane bound and soluble
77
What is the MoA of tocilizumab?
Inhibits IL6 driven activation of neutrophils, macrophages, T and B cells.
78
What are the indications of tocilizumab?
Castleman's disease | Rheumatoid arthritis
79
What are the s/e of tocilizumab?
``` Infusion reactions Infection Hepatotoxic Elevated lipids ?long term malignancy ```
80
What is the action of anti-thymocyte globulin?
Bind cell surface antigens
81
What is the action of basiliximab?
Bind cell surface antigens
82
What is the action of abatacept?
Bind cell surface antigens
83
What is the action of rituximab?
Bind cell surface antigens
84
What is the action of natalizumab?
Bind cell surface antigens
85
What is the action of tocilizumab?
Bind cell surface antigens
86
Name 4 drugs that target TNFalpha
Infliximab Adalimumab Certolizumab Golimumab
87
What are the indications of anti-TNFalpha?
Rheumatoid arthritis Ankylosing spondylitis Psoriasis and psoriatic arthritis Inflammatory bowel disease
88
What are the s/e of anti-TNFalpha drugs (5)?
``` Infusion / injection reactions Infection (TB, Hep B, Hep C) Lupus-like conditions Demyelination Malignancy ```
89
What is etanercept?
Decoy TNF receptor
90
What is the MoA of etanercept?
Binds TNFalpha and beta, preventing their physiological action
91
What are the indications for etanercept?
Rheumatoid arthritis Ankylosing spondylitis Psoriasis and psoriatic arthritis
92
What are the s/e of etanercept?
``` Injection site reactions Infection (TB, Hep B, Hep C) Lupus-like conditions Demyelination Malignancy ```
93
What is the target of ustekinumab?
p40 subunit of IL12 and IL23
94
What is the MoA of ustekinumab?
Binds IL12 and IL23, preventing T cell and NK cell activation
95
What are the indications for ustekinumab?
Psoriasis
96
What are the s/e of ustekinumab?
Injection site reaction Infection (TB) ?malignancy
97
What is the action of ustekinumab?
Cytokine blockade
98
What is the action of infliximab?
Cytokine blockade
99
What is the action of adalimumab?
Cytokine blockade
100
What is the action of certolizumab?
Cytokine blockade
101
What is the action of golimumab?
Cytokine blockade
102
What is the action of etanercept?
Cytokine blockade
103
What is the action of denosumab?
Cytokine blockade
104
What is the target of denosumab?
RankL
105
What is the MoA of denosumab?
Prevents RANK activation on osteoclasts, stopping differentiation and function
106
What are the indications of denosumab?
Osteoporosis
107
What are the s/e of denosumab?
Injection site reactions Infection Avascular necrosis of the jaw
108
What are the main side effects of immunosuppression?
Injection site reactions Infusion reactions Infection
109
What are injection site reactions?
Mixed cellular infiltrates peaking at 48h. Often with CD8 cells.
110
What are infusion reactions?
IgE mediated effects - urticaria, hypotension, tachycardia, wheeze Also: headaches, fevers, myalgias Cytokine storm
111
How do you protect immunosuppressed PTs against infection?
Avoidance Low threshold for treatment Vaccination
112
Which vaccines can you not use in an immunosuppressed PT?
BCG Measles Yellow fever Polio (some)
113
What causes progressive multifocal leukoencephalopathy?
John cunningham virus (JC virus)
114
How does the JC virus cause PML?
infects and destroys oligodendrocytes
115
Which cancers present in immunosuppressed PTs?
Lymphoma (EBV) | Non-melanoma skin cancers (HPV)
116
What are the auto-immune s/e of immunosuppression (8)?
``` SLE / lupus like syndromes Anti-phospholipid syndromes Vasculitis Interstitial lung disease Sarcoidosis Uveitis Autoimmune hepatitis Demyelination ```
117
How can we deviate normal immune responses?
Allergen desensitisation
118
When is allergen desensitisation indicated?
Monoallergic disorders - bee, wasp venom, grass pollen, house mite dust

Y5 - Immunology (1 decks)

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