Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Kat's Pathology > Immune Modulating Therapies 2 > Flashcards

Immune Modulating Therapies 2 Flashcards

(100 cards)

Start Studying
1
Q

What is the purpose of immune modulation of the immune system?

A

To suppress the immune response in conditions where it is overactive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are some ways to suppress the immune system (6)

A 
Steroids. 
Anti-proliferative agents. 
Plasmapheresis. 
Inhibitors of cell signalling. 
Agents directed at cell surface antigens. 
Agents directed at cytokines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are corticosteroids

A

Synthetic glucocorticoids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are corticosteroids based on

A

Naturally occurring steroids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What do steroids not act on

A

Minderalocorticoid receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What disorders are corticosteroids used in (5)

A 
Allergic disorders 
Auto-immune disease 
Auto-inflammatory diseases 
Transplantation 
Malignant disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Give some examples of steroids (3)

A

Prednisolone
Dermovate
Hydrocortisone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What prostaglandin do steroids affects

A

Inhibit phospholipase A2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the normal action of phospholipase A2

A

Breaks down phospholipids to form arachidonic acid which is converted to eicosanoids (e.g. prostaglandins, leukotrines) by cyclo-oxygenase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What effect do corticosteroids have on phospholipase A2

A

Blocks arachidonic acid and prostaglandin formation and so reduces inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What effect do steroids have on phagocytes (3)

A

Decrease traffic of phagocytes to inflamed tissue (decreased expression of adhesion molecules on endothelium. Blocks the signals that tell immune cells to move from the bloodstream and into tissues - results in transient increase in neutrophil counts in blood).
Decreased phagocytosis.
Decreased release of proteolytic enzymes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What effect do steroids have on lymphocyte function (4)

A

Lymphopenia (sequestration of lymphocytes in lymphoid tissue - affects CD4+ T cells > CD8+ T cells > B cells)
Blocks cytokine gene expression
Decreased antibody production
Promotes apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What broad categories can the side effects of steroids be categorised into (3)

A

Metabolic effects.
Other effects.
Immunosuppression.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the metabolic effects of steroids (7)

A 
Diabetes. 
Central obesity. 
Moon face. 
Lipid abnormalities. 
Osteoporosis. 
Hirsuitism. 
Adrenal suppression.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the effects of steroids apart from metabolic ones (5)

A 
Cataracts. 
Glaucoma. 
Peptic ulceration. 
Pancreatitis. 
Avascular necrosis.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What systems do steroids act on to suppress the immune system (3)

A

Prostaglandins.
Phagocytes.
Lymphocytes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are some anti-proliferative immunosuppressants (4)

A

Cyclophosphamide.
Mycophenolate.
Azathioprine.
Methotrexate.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the MOA of anti-proliferative immunosuppressants.

A

Inhibit DNA synthesis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What cells are most sensitive to the effects of anti-proliferative immunosuppressants

A

Cells with rapid turnover.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the toxic effects of anti-proliferative immunosuppressants (4)

A

Bone marrow suppression
Infection
Malignancy
Taratogenic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the MOA of cyclophosphamide

A

Alkylates guanine base of DNA - damages DNA and prevents cell replication.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What cells does cyclophosphoamide most affect

A

B cells > T cells, but at high doses affects all cells with high turnover.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the major indications for cyclophosphoamide (2)

A

Multisystem connective tissue disease or vasculitis with severe end organ involvement (e.g. GPA (Wegener’s granulomatosis), SLE)
Anti-cancer agent.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the side effects of cyclophosphoamide (4)

A

Toxic to proliferating cells (bone marrow suppression, hair loss, sterility M>F)
Haemorrhagic cystitis (toxic metabolite acrolein excreted via urine).
Malignancy (bladder, haematological, non-melanoma skin cancer)
Infection (pneumocystis juroveci)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What is the MOA of azathioprine
Metabolised by liver to 6 mercaptopurine Blocks de novo purine (e.g. adenine, guanine) synthesis - prevents replication of DNA
26
What cells does azathioprine preferentially affect
Inhibits T cells activation and proliferation
27
What are the indications for the use of azathioprine (3)
Transplantation Auto-immune disease Auto-inflammatory diseases (e.g. Crohn's, UC)
28
What are the side effects of azathioprine (3)
Bone marrow suppression (cells with rapid turnover (leucocytes and platelets) are particularly sensitive). Hepatotoxicity (idiosyncratic and uncommon) Infection (serious infection less common than with cyclophosphoamide)
29
How many people are particularly susceptible to the bone marrow suppression effects of azathioprine
1/300
30
What must be checked before starting a patient on azathioprine treatment
Thiopurine methyltransferase (TPMT) activity. Check TPMT activity or gene variats before treatment if possible - always check FBC after starting therapy.
31
What is the MOA of mycophenolate mofetil
Blocks de novo nucleotide synthesis - prevents replication of DNA
32
What cells are affected by mycophenolate mofetil
Prevents T>B cell proliferation
33
What are the indications to use mycophenolate mofetil (2)
Widely used in transplantation as an alternative to azathioprine Also used in auto-immune diseases and vasculitis as an alternative to cyclophosphoamide.
34
What are the side effects of mycophenolate mofetil (2)
Bone marrow suppression (cells with rapid turnover (leucocytes and platelets) are particularly sensitive). Infection (particular risk of herpes virus reactivation, and PML)
35
What is plasmapheresis
Patient's own blood passes through cell separator with the aim of removal of pathogenic antibodies Own cellular constituents reinfused. The plasma is treated to remove immunoglobulins and then reinfused (or replaced with albumin in 'plasma exchange')
36
What are the problems with plasmapheresis
Rebound antibody production limits efficacy, therefore usually given with anti-proliferative agent
37
What are the indications for plasmapheresis (3)
Severe antibody mediate diseases (type 2 hypersensitivity reactions) ``` Goodpastures syndrome (anti-glomerular basement membrane antibodies) Severe acute myasthenia gravis (anti-acetyl choline receptor antibodies) Severe vascular rejection (antibodies directed at donor HLA molecules) ```
38
How do calceineurin inhibitors suppress the immune system
Calcineurin is part of the cascade for the upregulation of IL-2 (cytokine transcription - blockages prevents lymphocyte proliferationa and effector functions) Part of the T cell signalling pathway
39
What two drugs inhibit calcineurin
Ciclosporin | Tacrolimus
40
What are the side effects of ciclosporin (5)
``` Dysmorphic features. Nephrotoxicity. Hypertension. Neurotoxic. Diabetogenic. ```
41
What are the side effects of tacrolimus (4)
Nephrotoxicity. Hypertension. Neurotoxic. Diabetogenic.
42
Give an example of a JAK inhibitor
Tofacitinib (JAK 1 and JAK 3 inhibitor)
43
What is the MOA of tofacitinib (3)
JAK1 and JAK3 inhibitor. Interferes with JAK-STAT signalling. Influences gene transcription. Inhibits production of inflammatory molecules.
44
What condition is tofacitinib effective in
Rheumatoid arthritis
45
What is the MOA of apermilast
PDE4 inhibitor Leads to increase cAMP. Influences gene transcription. Modulates cytokine production.
46
What conditions is apermilast effective in (2)
Psoriasis. | Psoriatic arthritis.
47
What are some drugs directed at cell surface antigens (immunosuppressive actions) (6)
``` Rabbit anti-thymocyte globulin Basiliximab - anti-CD25 Abatacept - CTLA4-Ig Rituximab - anti-CD20 Natalizumab - anti-alpha4 integrin Tocilizumab - anti IL-6 receptor ```
48
What is the MOA of agents directed at cell surface antigens (2)
Blocks signalling pathways. | Cell depletion occurs.
49
What are the indications for anti-thymocyte globulin
Allograft rejection (renal, heart)
50
What is the dosing of anti-thymocyte globulin
Daily IV infusion
51
What is the MOA of anti-thymocyte globulin (3)
Lymphocyte depletion Modulation of T cell activation Modulation of T cell migration
52
What are the side effects of anti-thymocyte globulin (4)
Infusion reactions Leukepenia Infection Malignancy
53
What is the MOA of basiliximab
Inhibits T cell proliferation | Antibody directed at CD25.
54
What are the side effects of basiliximab (3)
Infusion reaction Infection Concern RE long term risk of malignancy
55
What are the indications for basiliximab
Prophylasis of allograft rejection
56
What is the dosing of basiliximab
IV given before and after transplant surgery
57
What is abatacept indicated for
Rheumatoid arthritis
58
How is abatacept given (2)
IV 4 weekly or subcutaneously weekly.
59
What is the MOA of abatacept
Reduces T cell activation
60
What are the side effects of abatacept (3)
Infusion reaction Infection (TB, HBV, HCB) Caution RE malignancy
61
What are the indications for rituximab (3)
Lymphoma Rheumatoid arthritis SLE
62
What is the dosing for rituximab
2 doses IV every 6-12 months (RA)
63
What is the MOA of rituximab
Depletes mature B cells - antibody specific for CD20
64
What are the side effects of rituximab (3)
Infusion reactions Infection (PML) Exacerbation of CV disease.
65
What is the MOA of natalizumab
Inhibits T cell migration (alpha4 integrin specific)
66
What is the role of alpha4 integrin
Alpha4 expressed with beta1 or beta7. Bind to VCAM1 and MadCAM1 to mediate rolling/arrest of leukocytes. Bind to non-endothelial VCAM1 in lymphoid tissue.
67
What are the indications for natalizumab (2)
Highly active relapsing-remitting MS | Crohns' disease.
68
How is natalizumab given
IV every 4 weeks.
69
What are the side effects of natalizumab (4)
Infusion reactions Infection (PML) Hepatotoxic Concern RE malignancy
70
What is the MOA of tocilizumab
Reduces macrophage, T cell, B cell, neutrophil activation.
71
What are the side effects of tocilizumab (5)
``` Infusion reactions. Infection. Hepatotoxic Elevated lipids Caution RE malignancy ```
72
What are the indications for tocilizumab (2)
Castleman's disease. | Rheumatoid arthritis.
73
How is tocilizumab given
IV every 4 weeks
74
What are some drugs directed at blocking the action of cytokines (8)
``` Infliximab - anti-TNFalpha Adalimumab - anti-TNFalpha Certolizumab - anti-TNFalpha Golimumab - anti-TNFalpha Etanercept - TNF receptor p75-IgG fusion protein Ustekinumab - anti IL-12 and IL-23 Denosuman - anti-RANK ligant Secukinumab - anti IL-17 ```
75
What are the side effects of anti-TNFalpha immunosuppressive drugs (5)
``` Infusion or injection site reactions. Infections (TB, HBV, HCV). Lupus-like conditions Demyelination. Malignancy ```
76
What are the indications for anti-TNFalpha drugs (4)
Rheumatoid arthritis Ankylosing spondylitis Psoriasis and psoriatic arthritis Inflammatory bowel disease
77
How are anti-TNFalpha drugs administered
Subcutaneous or IV
78
What is the MOA of ustekinumab
Inhibits IL-12 and IL-23
79
What are the indications for ustekinumab (2)
Psoriasis, psoriatic arthritis | Crohns disease.
80
What comprises IL-12
p40+p35
81
What comprises IL-23
p40+p19
82
How is ustekinumab administered
Subcutaneously every 12 weeks
83
What are the side effects of ustekinumab (3)
Injection site reactions Infection (TB) Concerns RE malignancy
84
What is the MOA of secukinumab
Inhibits IL-17A
85
What are the side effects of secukinumab
Infection (TB)
86
What are the indications of secukinumab (2)
Psoriasis and psoriatic arthritis. | Ankylosing spondylitis
87
How is secukinumab administered
SC load and then monthly
88
What is the MOA of denosumab
Inhibits RANK mediated osteoclast differentiation and function
89
What is denosumab used for
Osteoporosis
90
How is denosumab administered
SC every 6 months
91
What are the side effects of denosumab (3)
Injection site reactions Infection - mildly immunosuppressive Avascular necrosis of jaw
92
What are the main types of reactions with biologic agents
Infusions reactions | Injection site reactions
93
What are some infusion reactions (3)
Urticaria, hypotension, tachycardia, wheeze - IgE mediated. Headaches, fevers, myalgias - not classical type 1 hypersensitivity Cytokien storm
94
What are injection site reactions
Peak reaction at ~48 hours May also occur at previous injection sites (recall reactions) Mixed cellular infiltrates, often with CD8 T cells Not generally IgE or immune complexes
95
What are the risks of acute infection if on immunosuppressive agents
Risk often > 2 x background
96
What are the best ways to prevent infection in people on immunosuppressive agents (2)
Avoidance | Vaccination
97
How are people on immunosuppressive treatment managed if they have an acute infection
Temporarily stop immunosuppression Consider atypical organisms Appropriate antibiotics
98
What kind of vaccines cannt be used on immunosuppressed patients
Live attenuated
99
What malignancies are associated more with immunosuppression (3)
Lymphoma (EBV) Non-melanoma skin cancers (HPV) Melanoma (increased risk in patients treated with anti-TNFalpha)
100
What auto-immune disorders are more common in immunosuppressed patients (8)
``` SLE and lupus-like syndromes ANti-phospholipid syndromes Vasculitis Intestitial lung disease Sarcoidosis Uveitis Autoimmune hepatitis Demyelination ```

Kat's Pathology (105 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions