Immune modulation Flashcards

1
Q

how do corticosteroids work

A

inhibit phospholipase A2

- Blocks arachidonic acid and prostaglandin formation and so reduces inflammation

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2
Q

what is the effect of steroids on phagocutes

A

decreases expression of adhesion molecules on endothelium leading to a transient increase in neutrophil counts as they cant enter the issue - decreased phagocytosis, decreased proteolytic enzymes

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3
Q

what is the action of steroids on lymphocytes

A

lymphopenia - sequestration of lymphocytes in lymphoid tissue mainly affecting CD4 >cd8> b cells promotes apoptosis

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4
Q

what are the side effects of steroids

A

diabetes, central obesity, moon face, lipid abnormalities, osteoporosis, hirsuitism, adrenal suppresion , cataracts, peptic ulcers, pancreatitis, avascular necrosis, infection

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5
Q

how do antiproliferative immunosuppresants/cytotoxic agents work

A

kill faster dividing cells first

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6
Q

side effects of cyclophasphamide

A
Toxic to proliferating cells
Bone marrow depression
Hair loss
Sterility (male>>female)
Haemorrhagic cystitis
Toxic metabolite acrolein excreted via urine
Malignancy
Bladder cancer
Haematological malignancies
Non-melanoma skin cancer
Infection
Pneumocystis jiroveci
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7
Q

side effects of azathioprine

A

Side effects
Bone marrow suppression
Cells with rapid turnover (leucocytes and platelets) are particularly sensitive
1:300 individuals are extremely susceptible to bone marrow suppression
Thiopurine methyltransferase (TPMT) polymorphisms
Unable to metabolise azathioprine
Check TPMT activity or gene variants before treatment if possible; always check full blood count after starting therapy
Hepatotoxicity
Idiosyncratic and uncommon
Infection
Serious infection less common than with cyclophosphamide

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8
Q

side effects of mycophenolate mofetil

A

effects
Bone marrow suppression Infection
Cells with rapid turnover (leucocytes and platelets) are
particularly sensitive
Infection
Particular risk of herpes virus reactivation
Progressive multifocal leukoencephalopathy (JC virus

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9
Q

what is the aim of plasmapheresis

A

removal of pathogenic antibody
Patient’s blood passed through cell separator
Own cellular constituents reinfused
Plasma treated to remove immunoglobulins and then reinfused (or replaced with albumin in ‘plasma exchange’)

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10
Q

what are the indications for plasmaphoresis

A

Severe antibody-mediated disease
Goodpasture syndrome
Anti-glomerular basement membrane antibodies
Severe acute myasthenia gravis
Anti-acetyl choline receptor antibodies
Antibody mediated transplant rejection/ABO incompatible
Antibodies directed at donor HLA/AB molecules

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11
Q

describe how IL2 is expressed

A

t cell receptor engagement - increased cytoplasmic calcium, binds to calmodulin, activates calcineurin, activates NFATc, upregulates IL2

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12
Q

when are calcineurin inhibitors used

A

Inhibit T cell proliferation/function

Used in:
Transplantation
SLE
Psoriatic arthritis

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13
Q

how do ciclosporin and tacrolimus work

A

inactivates calcineurin

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14
Q

how do jak inhibitors work and what are they effective in treating

A

Inhibit JAK-STAT signalling (associated with cytokine receptors)

Influences gene transcription
Inhibits production of inflammatory molecules

Effective in Rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis

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15
Q

how do PDE4 inhibitors work

A

modulates cytokine production effective in psoriasis

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16
Q

what is rituximab

A

anticd20 (b cells) antibody

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17
Q

basiliximab

A

anti cd25 (t cells), blocks IL2 indicued signallinh

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18
Q

anti thymocyte globulin indications

A

allograft rejection, needs daily IV infusions, modulates t cell activity

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19
Q

abatacept

A

reduces costimulation of t cells via cs28 used for rheumatoid

20
Q

anti IL1 use

A

gout, familial mediterranean fever, stills

21
Q

anti il6

A

rheumatoid

22
Q

anti il17/23

A

axial spondyloarthritis, psoriasis,

23
Q

ant il4/5/13

A

eczema, asthma

24
Q

anti rank

A

osteoporosis

25
anti tnf alpha
rhematoid, psoriasis, IBD, ank spond,
26
immunosuppression side effects
Infusion reactions Urticaria, hypotension, tachycardia, wheeze – IgE mediated Headaches, fevers, myalgias – not classical type I hypersensitivity. acute infection, TB, HBV, HCV, HIV jcv, malignancy, autoimmunity
27
john cunningham virus
John Cunningham Virus (JCV) Common polyomavirus that can reactivate - Infects and destroys oligodendrocytes Progressive multifocal leukoencephalopathy Associated with use of multiple immunosuppressive agents
28
APCs include
dendritic cell, macrophage, b lymphocyte
29
describe the adaptive immune response
Clonal expansion following exposure to antigen T cells with appropriate specificity will proliferate and differentiate into effector cells (cytokine secreting, cytotoxic) B cells with appropriate specificity will proliferate and differentiate to T cell independent (IgM) (memory and) plasma cells undergo germinal centre reaction and differentiate to T cell dependent IgG/A/E(M) memory and plasma cells Plasma cells secrete high affinity specific antibodies Immunological memory Pre-formed pool of high affinity specific antibodies Residual pool of specific T and B cells with enhanced capacity to respond if re-infection occurs
30
how does the influenza vaccine work
targets hemagglutinin and neutralizes - haemagluttinates
31
how does the mantoux test work
Inject 0.1 ml of 5 tuberculin units of liquid tuberculin intradermally. The tuberculin used in the Mantoux skin test is also known as purified protein derivative, or PPD. The patient's arm is examined 48 to 72 hours after the tuberculin is injected. The reaction is an area of induration (swelling that can be felt) around the site of the injection.
32
what are the types of vaccines (5)
1. Live vaccines 2. Inactivated/Component vaccines Conjugates+ Adjuvants increase immunogenicity 3. RNA vaccines 4. Adenoviral vector vaccines 5. Dendritic cell vaccines
33
give examples of live attenuated vaccines
MMR BCG Yellow fever Typhoid (oral) Polio (Sabin oral) Influenza (Fluenz tetra for children 2-17 years)
34
what are the advantages of live vaccines
Establishes infection – ideally mild symptoms Raises broad immune response to multiple antigens – more likely to protect against different strains Activates all phases of immune system. T cells, B cells – with local IgA, humoral IgG May confer lifelong immunity, sometimes just after one dose
35
what are the problems of live vaccines
Possible reversion to virulence (recombination, mutation). Vaccine associated paralytic poliomyelitis (VAPP, ca. 1: 750,000 recipients) Spread to contacts Spread to immunosuppressed/immunodeficient patients Storage problems
36
what are some inactivated vaccines
Inactivated Vaccines Influenza (inactivated quadrivalent), Cholera, Bubonic plague, Polio (Salk), Hepatitis A, Pertussis, Rabies. ``` Component/subunit vaccines Hepatitis B (HbS antigen), HPV (capsid), Influenza (recombinant quadrivalent - less commonly used) ``` Toxoids (inactivated toxins) Diphtheria, Tetanus.
37
what are conjugate vaccines and name some
polysaccharide plus protein carrier to promote b cell response Haemophilus Influenzae B Meningococcus Pneumococcus (Prevenar)
38
how do adjuvants work
mimic PAMPS Aluminium salts (humans) Lipids – monophosphoryl lipid A (humans HPV) Oils -Freund’s adjuvant (animals)
39
Dendritic cell vaccines
Acquired defects in DC maturation and function associated with some malignancy suggests a rationale for using ex vivo–generated DC pulsed with tumour antigens as vaccines Focus on tumour associated antigens or mutational antigens
40
how does dendritic cell vaccine work for prostatic cancer
Personalised immunotherapy for prostatic cancer Remove white cells from patient’s blood (leukaphoresis) APCs are harvested and incubated with recombinant protein PAP-GMCSF Prostatic acid phosphatase-granulocyte macrophage colony stimulating factor APCs infused back to patient Stimulates patient’s immune response
41
what are the indications for antibody replacement therapy
Primary antibody deficiency X linked agammaglobulinaemia X linked hyper IgM syndrome Common variable immune deficiency ``` Secondary antibody deficiency Haematological malignancies Chronic lymphocytic leukaemia Multiple myeloma After bone marrow transplantation ```
42
when are specific Igs used
Hepatitis B immunoglobulin – needle stick/bite/sexual contact – from HepBSag+ve individual Rabies immunoglobulin – to bite site following potential rabies exposure Varicella Zoster immunoglobulin – women <20 weeks pregnancy or immunosuppressed where aciclovir or valaciclovir is contraindicated Tetanus immunoglobulin – no specific preparation available in UK – use IVIG for suspected tetanus
43
what are the types of adoptive cell transfer of t cells
Virus specific T cells Tumour infiltrating T cells (TIL – T cell therapy) T cell receptor T cells (TCR - T cell therapy) Chimeric antigen receptor T cells (CAR – T cell therapy
44
what is CAR -T therapy
T cells with chimeric receptors targeting CD19 Patient’s own T cells Genetically engineered to express receptor Expanded in vitro Used for acute lymphoblastic leukaemia in children Used for some forms of non-Hodgkin lymphoma
45
what is ipilimumab antibody against CTLA 4 and pembrolizumab/nivolumab antibody against PD1 used for?
Action Antibody binds to CTLA4 Blocks immune checkpoint Allows T cell activation Indications - Advanced melanoma Complications - Autoimmunity