immunomodulation Flashcards
what is immunomodulation
manipulating the immune system using immunomodulatory drugs to achieve a desired effect
name 2 ways that immune tolerance can be induced
immunomodulators used in allergy
adoptive immunotherapy
what is adoptive immunotherapy and when is it used
stem cell transplant BM transplant immunodeficiencies eg SCID AI diseases lymphoma and leukaemia inherited metabolic disorders
name 3 types of allergy immunomodulation
anti-IL5 monoclonal treatment
anti -IgE monoclonal treatment
allergen specific - SC/SL/ aero allergens
give an example of an anti-IL5 monoclonal treatment
mepolizumab prevents eosinophil recruitment and activation
limited for asthma
no clinical efficacy for hyper-eosinophilic syndrome
name an anti-IgE monoclonal therapy and describe its use
omalizumab asthma chronic urticarial angioedema may cause severe systemic anaphylaxis
how do aero-allergens help in allergy
promote Th2-Th1 switching Treg cells and tolerance use if anaphylaxis to insect venoms allergic rhinoconjuncitivitis -ve = localised and systemic allergic reactions
what are biologic immunomodulators
substances nearly identical to the body’s own signalling proteins
give an example of a monoclonal antibody
infliximab
give an example of a fusion protein
etanercept
what is the mode of action of corticosteroids in immunosuppression
decrease neutrophil margination decrease inflammatory cytokines inhibit phospholipase A2 lymphopenia decrease T cell proliferation decrease IgA production
what are the side effects of corticosteroids
CHO metabolism –> diabetes, hyperlipidaemia
decreased protein synthesis –> poor wound healing
osteoporosis
glaucoma, cataracts
psychiatric problems
what are the uses of corticosteroids
AI diseases e.g. CTD, vasculitis, RA
inflammatory disease eg crohns, sarcoid, GCA
malignancies e.g. lymphoma
allograft rejection
what are biologic DMARDs
disease modifying anti-rheumatic drugs
name 5 types of biologic DMARDs
anti-cytokines anti B cell anti T cell activation anti-adhesion molecules complement inhibitors
name 3 types of anti-cytokines
anti-IL6
anti-IL1
anti-TNF
name a type of anti B cell biologic DMARD
rituximab = chimeric monoclonal antibody
targets CD20 be cell surface
name 4 ways that lymphocytes may be targeted
IL-2 receptor MABS
M-TOR inhibitors
Calcineurin inhibitors
antimetabolites (inhibit purine nucleotide synthesis in T and B cells)
name 2 types of antimetabolites
AZA and MMF
how does AZA work
guanine antimetabolite
how does MMF work
non competitive inhibitor for IMPDH so prevents guanosine triphosphate synthesis
how do calcineurin inhibitors work
interfere with signals after TCR activation
prevent stimulate of cytokine production (c for c)
reversible inhibition of T cell activation, proliferation, clonal expansion
name 2 clacineurin inhibitors
CyA and Tacrolimus FK506
name an M-TORi and describe how it works
sacrolimus (rapamicin) is a macrolide antibiotic that binds to FKBP12 (and others) and inhibits mammalian target of rampamicin –> inhibits response to Il-2 so cell cycle arrect at G1-S phase
name 2 IL-2 receptor MABs
basilixumab
daclizumab
name 3 types of immunopotentiation
immunisation
immune stimulants
replacement therapies
describe a replacement therapy
pooled human immunoglobulin (IV or SC)for antibody deficient states
name some immune stimulants
G-CSF/ GM-CSF to stimulate BM to produce more neutrophils
IL2 T cell activation
a-interferon Hep C treatment
B-interferon MS
y-interferon certain intracellular infections + CGD + IL-12 deficiency
what is passive immunisation
giving specific high titre antibody for immediate but transient protection
animal sera and pooled human immunoglobulin
what are the uses of passive immunisation
VZV (pregnancy0 Hep B prohpylaxis and treatment snake bites botulism diptheria
what is active immunisation and what are the negatives
stimulate immune response and memory with antigenic material
problems are delay, allergy to vaccine component, limited use in immunocompromised
what is the target of methotrexate
folate synethesis (form of anti-metabolite)
what is the target of cyclophosphamide
cross links DNA (anti metabolite)
what is cyclophosphamide used for
vasculitis SLE
what is AZA used for
AI disease (IBD vasculitis SLE) allograft rejections
what is MTX used for
RA PSA polymyositis vasculitis
GvHD
what are the side effects of anti-metabolites
hepatitis
gastric upset
susceptibility to infections
BM suppression
what is a side effect of MTX
pneumonitis
what is a side effect of cyclophosphamide
cystitis
what are the side effects of calcineurin and MTORi
multiple drug interactions lymphomas hepato-toxicity hirsutism nephrotoxicity neurotoxicity hypertension opportunistic infections
what is the clinical uses of calcineruin and MTORi
transplantation and allograft rejection AI disease
what are biologic DMARDs mainly used for
inflammatory conditions
what is anti-TNF used for and what is a side effect
RA inflammatory conditions e.g crohns psoriasis ank. spond.
risk of TB
what is anti-IL6 used for
RA and AOSD
problem = control of serum lipids
what is anti-IL1 used for
AOSD and autoinflammatory conditions
