Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Immunology Y5 > Immunology 7 - Immune-modulating therapies 1 & 2 > Flashcards

Immunology 7 - Immune-modulating therapies 1 & 2 Flashcards

1
Q

What mediates immunological memory?

WHat are the characteirstics of memory T cells and memory B cells?

A

T and B cells

T cells

  • different expression of cell surface markers - allows migration to non-lymphoid tissue where microbes may enter
  • longevity
  • rapid, robust response to subsequent antigen exposure

B cells

  • lonevity
  • pre-formed antibody - IgG, high affinity
  • rapid, robust response to subsequent antigen exposure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

By what mechanism can B cells provide immunological memory?

A

High affinity IgG remains circulating in blood

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

What antibody is used in influenza vaccine?

WHen does the vaccine start to work and how long is it effective for?

A

Antibody against haemagluttinin - this is the protein used by influenza to enter the cell

Starts working after 7 days; provides protection for up to 6 months

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

What is the best predictor of immunity to influenza following a vaccine?

A

IgG against haemaglutinnin (moreso than CD8 T cells)

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

Why is adjuvant used in some vaccines?

A

It stimulates an innate immune response

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

What are the indications for antibody replacement in a patient (general antibody replacement) and what is the process?

A
  1. Prepare from a pool of donors
  2. Infusion will contain IgG to a wide range of unspecified organisms
  3. Administer either IV or subcutaneously

Indications:

  • Primary antibody deficiency (3):
    • X-linked agammaglobulinaemia
    • X-linked hyper IgM syndrome
    • Common variable immune deficiency
  • Secondary antibody deficiency (3):Haematological malignancies:
    • CLL
    • Multiple myeloma
    • After bone marrow transplantation
  • Ohers
    • ITP
    • kawasaki’s disease
    • guillan barre syndrome
    • measles
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Give examples of specific immunoglobulins that can be given to patients

A

Hep B

tetanus

rabies

VZV

HIV - post exposure prophylaxis contains HIV immunoglobulin

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

explain the 4 main ways of adoptive cell transfer

A
  1. virus specific T cell expansion
    - used to prevent EBV associated post transplant lymphoproliferative disease
    - you take out T cells from Patient/another donor and inject virus (EBV) so the T cells are now able to mount an immune response against EBV
    - the active T cells can then be transferred back to the patient so after the transplant they can mount a response against EBV
  2. Tumour infiltrating lymphocyte (TIL) T cell therapy
    - take tumour out and culture with IL2
    - this stimulates T cell expansion within population
    - isolate the T cells and inject them back into the patient
  3. T cell receptor T cell therapy
    - take out T cells from patient with malignancy
    - insert gene that codes for specific TCR - targeting tumour surface antigen

eg CD19 to target ALL

  1. Chimeric antigen receptor T cell therapy
    - like T cell receptor T cell therapy but with chimeric antigen receptor (made of an antibody and TCR)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What monoclonal antibody can be used in melanoma treatment?

A

Ipilimumab (anti-CTLA4) or Nivolumab, an antibody specific for PD-1

These are immune checkpoint inhibitors - enhance the T cell response

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

In what disease can IFN gamma be given therapeutically?

A

Chronic granulomatous disease

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

In what disease can IL2 be given therapeutically?

A

Renal cell carcinoma
IL-2 expands NK and T cell responses via the IL-2 surface receptor

**think you have 2 kidneys; IL2**

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

In what diseases can INF alpha be given therapeutically?

what about interferon beta?

A
  1. Interferon alpha

ABC

Alpha for hepB

CML

+ multiple myeloma

+ hairy cell leukamiea

  1. interferon beta
    - relapsing MS (past)
  2. bechet’s (B FOR BECEHETS)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How do steroids inhibit the immune response?

Side effects of corticosteroids

A

Inhibit phospholipase A2 which is a key enzyme in prostaglandin formation
Also decrease phagocyte trafficking (hence there is a transient increase in neutrophil count)

Also cause lymphopenia - as lymphocytes get sequestered in lymphoid tissue

Side effects

Metabolic effects:

  • Cushingoid Sx
    • Diabetes
    • central obesity
    • moon face
    • lipid abnormalities
    • osteoporosis
    • hirsutism
    • adrenal suppression
  • Other effects:
    • Cataracts
    • glaucoma
    • peptic ulceration
    • pancreatitis
    • avascular necrosis of hip and knee
  • Immunosuppression

Can use the mnemonic BECLOMETHASONE

Buffalo hump

Easy bruising

Cataracts

Larger appetite

Obesity

Moonface

Euphoria

Thin arms & legs

Hypertension/ Hyperglycaemia

Avascular necrosis of femoral head

Skin thinning

Osteoporosis

Negative nitrogen balance

Emotional lability

*causes transient leukocytosis and neutrophilia

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

Recall 4 examples of anti-proliferative agents

A

Cyclophosphamide
Azothioprine
Mycophenalate

METHOTREXATE

CAMM

**not calcineurin inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the mechanism of action of cyclophosphamide?

A

Alkylating agent.

Alkylation of guanine –> inhibition of DNA synthesis (damages DNA)

*can’t use for too long due to toxicity

B cells > T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Side effects of cyclophosphamide

A
  • Toxic to proliferating cells:
    • Bone marrow suppression
    • Hair loss
    • Sterility (male >> female)
  • Haemorrhagic cystitis
  • Malignancy:
    • Bladder cancer
    • Haematological malignancies
    • Non-melanoma skin cancer
  • Infection:
    • Pneumocystis jirovei

MAIN ONES TO. BE AWARE OF: HAEMORRHAGIC CYSTITIS

(C AND C)

as it is excreted by the kidneys

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

What is the mechanism of action of azothioprine?

A

6-mercaptupurine : it’s a purine analogue

That interferes with normal purine synthesis

Affects T cells > B cells

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

What must always be checked before prescribing azothioprine?

A

TPMT activity

polymorphism means that they cannot metabolise azathioprine which leads to excess bone marrow toxicity

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

Explain how methotrexate works, main side effects to be aware of

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

How can plasma exchange be used to treat autoimmune diseases?

A

Removes problematic antibody (in exchange - you exchange it for albumin)
Need to give alongside an antiproliferative agent as it can cause a rebound increase in antibody production…
Only for severe disease

Indications: type II hypersensitivity reactions eg goodpasture’s, myasthenia gravis, vascular rejection, antibody mediated rejection

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

How do calcineurin inhibitors work?

A

Calcineurin causes an upregulation of IL2 - inhibition of this allows cell proliferation

**rmb il2 is a key cytokine that drives T cell proliferation**

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

Examples of inhibitors of cell signalling

A
  1. calcineurin inhibitors
  2. JAK inhibitors
  3. PDE4 inhibitors

(also mTor inhibitor - sirolimus- inhibits IL2 pathway)

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

Give examples of a calcineurin inhibitor?

Mechanism?

Tacrolimus vs ciclosporin

A

Ciclosporin and tacrolimus

*inhibit calcineurin production which inhibits IL2 production (T cell activation and proliferation is blocked)

Indications: rejection prophylaxis in transplantation

Side effects: Nephrotoxic, hypertension, neurotoxic (+ dysmorphic features + gingival hyperrophy with ciclosporin)

CICLOSPORIN HAS MORE SIDE EFFECTS THAN TACROLIMUS

**cycling is dangerous** **taxi is safe**

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

Give 2 diseases in which JAK2 inhibitors can be useful?

Example

A

Rheumatoid and psoriatic arthritis

Tofacitinib- Jak1/3 inhibitor

**none of the haematological malignancies!!

rmb PCV is treated with venesection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

By what mechanism do PDE4 inhibitors work, and in what disease are they useful?

A

Inhibition of PDE4 –> inceased cAMP
cAMP modulates cytokine production
–> fewer cytokines
Useful in psoriasis and psoriatic arthritis

Example: Apremilast

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Recall 2 immune-modulating therapies that are useful in the prophylaxis of allograft rejection

A

Anti-thymocyte globulin - blocks T cell proliferation
Anti-CD25- daclizumab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Wha type of antibody is rituximab?

A

Anti-CD20

attacks mature B cells, but leaves plasma cells intact, so antibody production is not affected much

Uses:

  • lymphoma
  • rheumatoid arthritis
  • SLE
  • vasculitis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What monoclonal antibody can be used in IBD treatment?

A

Vedolizumab
Anti - alpha4beta7 integrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What is infliximab?

Indications

A

Anti-TNF alpha

Indications: \

Rheumatoid arthritis

Ankylosing spondylitis

IBD

Psoriasis and psoriatic arthritis

Familial Mediterranean feve

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What monoclonal therapy can be used in osteoporosis?

A

anti-RANK/RANK-ligand
Denosumab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is the mechanism of action of tofacitinib

A

JAK inhibition (jak 1 or jak 3)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is the mechanism of action of apremilast?

A

Anti-PDE4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is the mechanism of action of basilixumab?

A

Anti-CD25 (alpha chain of interleukin 2 receptor)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What is the mechanism of action of Abatacept?

when is it used?

A

CTLA4 infused immuonglobulin

it enhances the activity of CTLA4 (opposite of imilimumab)

used in rhuemtaoid arthritis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What is the mechanism of action of rituximab?

A

Anti-CD20

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What is the mechanism of action of natalizumab?

A

Anti-alpha4 integrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What is the mechanism of action of tocilizumab?

A

Anti-IL6-R

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What is the mechanism of action of muromonab

A

Mouse monoclonal against CD3

3 vowels in this

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What is the mechanism of action of dacilizumab?

A

Anti-CD25 (alpha chain of interleukin 2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What is the mechanism of action of alemtuzumab?

A

Anti-CD52

used in chronic lymphoid leukaemia and MS

side effect: CMV infection

alemtuzimab- ALL- targets all lymphocytes (cd52 is on all lymphocytes)

lymphocytes–>chronic lymphoid leukaemia and ms (which is type 4 hypersenstiivty)

ms

41
Q

What is the mechanism of action of adalizumab?

A

Anti-TNF alpha

42
Q

What is the mechanism of action of certolizumab?

A

Anti-TNF alpha

43
Q

What is the mechanism of action of golimumab?

A

anti-TNF alpha

44
Q

What is the mechanism of action of etanercept?

A

anti-TNF alpha/TNF beta fusion protein

45
Q

What is the mechanism of action of ustekinumab?

A

Anti-IL12/23

46
Q

What is the mechanism of action of Secukinumab?

A

Anti-IL17a

47
Q

What condition can be treated with apremilast?

A

Psoriasis

48
Q

What conditions can be treated with natalizumab?

A

MS
Crohn’s

49
Q

What conditions can be treated with abatacept?

A

Rheumatoid arthritis

50
Q

What type of vaccine is BcG vaccine? How do you test for response to BcG vaccine?

A

Live attenuated

Relies on T cell response

Protects against primary infection and prevents progression to secondary infection as well

protection lasts about 10-15 years

Mantoux test - tests development of immunity against TB.

must be interpreted with caution - can suggest active TB, latent TB or previous immunisation

51
Q

Examples of live attenuated vaccines

C/I

A
  • MMR-VBOY
  • MMR- HIV safe
  • VZV
  • BCG- not HIV safe
  • ORAL
    • Polio (Sabin oral)
    • Typhoid (oral)
  • Yellow fever- not HIV safe

C/I: immunosuppressed/pregnant

52
Q

Examples of inactivated vaccines

A
  • Influenza
  • Cholera
  • Bubonic plague
  • Polio (Salk)
  • Hepatitis A
  • Pertussis
  • Rabies

rich bpp

*rich ppl; high bp

53
Q

Examples of subunit vaccines

A
  • HepB
  • HPV
  • Influenza (HA, NA (Neuraminidase))

HHI

54
Q

Examples of toxoid vaccines

A

tetanus

diphtheria

55
Q

Conjugate vaccines

A
  • Neisseria meningitidis
  • Haemophilus influenza B
  • Streptococcus pneumoniae

Conjugate aids production of T cell response- allows germinal centre reaction to occur.

56
Q

What is a heteortypic pathogen?

A

Pathogen that infects other animals but does not cause disease or causes mild disease in humans

57
Q

Indications for stem cell transplant

A
  • Life-threatening primary immunodeficiencies
    • SCID
    • Leukocyte adhesion defect
  • Haematopoietic malignancy
58
Q

Types of antibody replacement

A
  1. normal human immunoglobulin - used for antibody deficiency (primary or secondary)
  2. specific
    - eg VZ Ig, HBV Ig etc.

used for post exposure prophylaxis when person has not been exposed to the organism before

59
Q

which cytokine is responsible for T cell clonal expansion?

A

IL-2

60
Q
A
61
Q

Indications for CAR-T cell therapy

Main side effect

A
  • not effective for solid malignancies
  • B cell lymphoma
  • ALL in kids
  • non - hodgkin’s lymphoma

**think cars are moving/mobile–>not useful for solid malignancies, only for haematologicla malignancies**

Cytokine release syndrome

62
Q

Side effects of azathioprine

A

BM suppression

hepatotoxicity

Infection

63
Q

MOA of mycophenolate mofetanil

What is the main risk associated with this?

A

A purine anti-metabolite

It blocks de novo guanosine nucleotide synthesis

→ ****prevents DNA replication

Also affects T cells>B cells

Main risk: bone marrow suppression, infection - HERPES VIRUS REACTIVATION, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY, malignancy, teratogenic

mycoPhenolate- Pml

64
Q

Antibodies against IL-6 receptor

A

Tocilizumab, Sarlimumab

Inhibits action of macrophages, neutrophils, B cells and T cells

Used in rheumatoid arthritis, castleman’s disease (IL6 producing tumour)

65
Q

Example of TNF alpha antagonist

A

Etanercept

Blocks action of TNF alpha by blocking the receptor

Used in:

  • Rheumatoid arthritis
  • Ankylosing spondylitis
  • Psoriasis/ Resistant Psoriasis and psoriatic arthritis

RAP (rapping has INTERCEPTED the music industry)

rheumatoid arthritis

ankylosing spondilitis

psoriasis

66
Q

Importance of IL12 and IL23

A

IL12: promotes Th1 differentiation

IL23: promotes Th17 cell production

67
Q

Example of drug against IL12 and IL23

A

Ustekinumab

Psoriasis and psoriatic arthritis

Crohn’s disease

u-stick- –> needlestick injjury to SKIN–>psoriasis/psoriatic arthritis

68
Q

Example of drug against IL-12

A

Guselkumab

69
Q

Drug against IL-17 alpha

A

Psoriasis and psoriatic arthritis

Ankylosing spondylitis

70
Q

Which vaccines must be given to people on immunosuppressive treatment?

A

Pneumococcal and influenza

71
Q

Which organism are you more susceptible to if on TNF blockers?

A

Tuberculosis

72
Q

Which monoclonal antibody is associtaed with HepB reactivation?

A

Rituximab

cd20- is on B cells

hepB

73
Q

Which virus leads to progressive multifocal leukoencephalopathy?

A

JC virus

*commonly reactivates following treatment with natalizumab for multiple sclerosis

74
Q

Summarise the ways in which the immune system can. be boosted

A
75
Q

Summary of ways in whcih the immune system can be suppressed

A
76
Q

Live attenuated vaccines: advantages and disadvanatgaes and examples

A
77
Q

which is the only live attnuated vaccine that is safe to give in HIV?

A

MMR

78
Q

Inactivated vaccines: advantages and disadvantages and examples

A

inactivated: SHIA

Salk

Hep A

Influenza

Anthrax

79
Q

Conjugate vaccines

A
80
Q

DNA/RNA vaccines

A
81
Q

What are the ky adjuvants used in vaccines?

A

**key one to remember is aluminium

82
Q
A
83
Q

What are the key passive vaccines to know about?

how long do they usually last?

A

HNIG- human noromal immunoglobulin - given for hep A and measles

HBIG

HRIG- rabies

varicella zoster

pavilizumab- against RSV

regeneron- experimental for covid 19

**usuallyy last about 3 weeks so don’t give longterm protection

84
Q

Which vaccines do at risk groups need to get?

A

influenza

pcv

bcg

85
Q

which vaccine sneed to be given to epopel who travel?

A

cholera

hep A

hep B

ja encephalphilitis

tick bourne encephalitis

typhoid

yellow fever

86
Q

which vaccines do pregnant women need to get?

A

pertusssis

87
Q

which vaccine is important in people aged 70-79

A

shingles vaccine

88
Q
A
89
Q

what is the full form of bcg?

A

bacilli calmette guerin

90
Q

Describe how dendritic vaccines against tumours work (nB these are still being trialeld and have not been rolled out)

A
  • Acquired defects in DC maturation and function is associated with some malignancies
  • This suggests a rationale for using *ex vivo-*generated DC pulsed with tumour antigens as vaccines
  • You can take the dendritic cells out of a patient and load them with the appropriate antigen in vitro
  • Then insert them back into the patient so there is an immune response towards it
  • It focuses on tumour associated antigens or mutational antigens

Process:

  • Blood draw
  • Leukapheresis- remove WBCs from patient’s blood
  • Incubate APCs with prostatic acid phosphatase (present in prostate cancer)
  • AND GM-CSF (promoted dendritic cell proliferation)
  • APCs are infused back into patient
  • Loaded dendritic cells stimulate the patient’s immune response against prostatic acid phosphatase → killing the prostate cancer cells
91
Q

Why doesn’t vaccination work effectively in the elderly?

A

Immune senescence: Increased frequency of terminally differentiated effector memory T cells in the elderly; Increased expression of senescence markers; Much reduced production of recent thymic emigrants which drive the naïve T-cell repertoire.

Nutrition: insufficient energy because of poor nutrition; Reduced availability of trace elements and minerals (reduced gut absorption)

92
Q

What are some indications of CAR-T cell therapy?

what is a key risk?

A
  1. B cell lympoma
    - can engineer chimeric antigen receptor to express CD19 receptor
    - binds to CD19 on malignant B cells and kills them
  2. ALL in kids
  3. some forms of NHL

key risk: cytokine release syndrome

93
Q

what is the normal physiological function of CTLA4 and how is it used for therapeutic purposes?

what about PD1?

A

CTLA4

  • normally it is expressed on T cells (eg CD8 positive T cells)
  • it competes with CD28 for binding to B7 on antigen presenting cells
  • i.e. it inhibits the activation of T cells by Antigen presenting cells
  • if you block it, there will be more antigen presentation to T cells

–>ipilimumab - antibody specific for CTLA4

–>used in advanced melanoma

PD1/PDL1

  • PD Ligand 1 and 2 found on APCs/tumour cells
  • they bind to PDL1 on T cells to inactivate them
  • if you block PD1 then T cells can be activated –> kill tumour cells

Side effects - risk of autoimmune disease

94
Q

What is rabbit anti thymocyte globulin?

A

Blocks T cell proliferation

(Thymus- T cells)

used in allograft rejection

95
Q

What is daclizumab?

A

IL-2 receptor antibody, targets CD25
Organ transplant rejection

96
Q

What are all the anti TNF alpha antibodies?

A
97
Q

Injection site reactions vs infusion reactions

A

infusions are deeper into the body

IgE is a worse reaction - more systemic

98
Q

ankylosing spondilitis: you have tried NSAIDS and have tried anti TNFalpha, what else can you give?

A

anti IL17

Immunology Y5 (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions