Immunology - Immune Modulation Flashcards
What 4 immune modulators boost the immune response?
- Vaccination
- Replacement of missing components
- Cytokine therapy
- Blocking immune checkpoints (for advanced melanoma)
What 6 immune modulators suppress the immune response?
- Steroids
- Anti-proliferative agents
- Plasmapharesis
- Inhibitors of cell signalling
- Agents directed at cell surface antigens
- Agents directed at cytokines
What is the mechanism of vaccination?
- APCs present peptide to T cells (CD4 + CD8)
- Clonal expansion: T cells with appropriate specificity proliferate + differentiate
- CD4 cells: release cytokines + activate other cells (B cells)
- CD8 cells: kill infected cells
- Effector T cells then die by apoptosis OR surive as memory cells
- B cells differentate to T cells independent (IgM) memory cells, OR undergo germinal centre reaction (T-cell dependent plasma cells ((IgA/IgG/IgE))
- End result = immune memory (infection remembered + individuals remain protected)
How is immune memory achieved in vaccination?
- Residual specific T + B cells with enhance capacity to respond to re-infection
- Pre-formed pool of high affinity Abs
What are the 3 ideal vaccine requirements?
- Generates immunological memory
- Practical - single injection, easy storage, inexpensive
- No adverse effects
What is passive vaccination and how long does it last for?
- Directly administering pre-formed antibodies/immunoglobulins
- ~3 wks
What are some examples of passive vaccination?
- HNIG (Human Normal Ig) = Hep A + Measles
- HBIG (Hep B Immunoglobulin) + Hep B
- HRIG (Human Rabies Immunoglobulin) = Rabies
- VZIG (Varicella Zoster Immunoglobulin) = Varicella
- Paviluzimab (monoclonal Ab to RSV) = RSV
What is herd immunity?
When enough people in the community are immunised against a disease, it makes it more difficult for the disease to get passed between those who aren’t immunised
Why is vaccination less effective in the elderly?
- Immune senescence
- Nutrition (insufficient energy due to poor nutrition; reduced availability of trace elements + minerals (reduced gut absorption))
What is immune senescence?
The process of remodelling lymphoid organs - happens in the elderly
1. Increased frequency of terminally differentiated effector memory T cells
2. Increased expression of senescence markers
3. Much reduced production of recent thymic emigrants which drive the naiive T-cell repertoire
What is the evidence and concept behind dendritic cell/cancer vaccines?
Evidence:
- Acquired defects in DC maturation/function seen in some malignancies allows cancer to evade immune recognition
Concept:
- Pt WBCs harvested + cultured with target “tumour” antigen
- WBCs re-infused back into pt to stimulate immune response
What is an example of a dendritic cell/cancer vaccine?
Provenge (Sipuleucel-T) = Prostate cancer
What vaccinations are received at 2 months of age?
- 6-in-1
- Men B
- Rotavirus
What vaccinations are received at 3 months of age?
- 6-in-1
- Rotavirus
- PCV (pneumococcal conjugate)
What vaccinations are received at 4 months of age?
- 6-in-1
- Men B
What vaccinations are received at 1 year?
- Hib/Men C
- Men B
- PCV (pneumococcal conjugate)
- MMR
What vaccination can be given between 2-10yrs?
Flu (annually) = Sept/Oct
What vaccinations are received at 3yrs 4 months of age?
- DTaP/IPV (4-in-1 booster)
- MMR
What vaccination is given at 12-13yrs of age?
- HPV (6, 11, 16 + 18)
What vaccination is given at 14yrs of age?
- Men ACWY
- T/D/aP (3-in-1 booster)
What conditions make up the 6-in-1 injection?
- Diptheria
- Tetanus
- acellular Pertussis (Whooping Cough)
- Inactivated Polio
- Haemophilus influenza type B
- Hepatitis B
What conditions make up the 4-in-1 booster vaccine?
- Diptheria
- Tetanus
- acellular Pertussis
- Inactivated Polio
What conditions make up the 3-in-1 booster vaccine?
- Tetanus
- Diptheria
- acellular Pertussis
What adult vaccines are given and at what age groups?
- Flu (annually) = 50yrs +
- Pneumococcal (PPV) = 60yrs
- Shingles = 70yrs
What vaccines are given during pregnancy?
- Flu (during appropriate season)
- DTaP/IPV from 16wks
= Diptheria, Tetanus, acellular Pertussis, Inactivated Polio
At what age can you received the first and second covid vaccinations?
5 years
When can you receive a covid booster dose?
- 16yrs +
- 12-15yrs at high risk/living with an immunocompromised person
When can you receive an additional primary dose of the covid vaccine?
Severely weakened immune system at time of initial vaccine
When can you receive an additional seasonal booster dose of the covid vaccine?
- 50yrs +
- High risk
- Pregnant
- Frontline HCP
Which vaccinations are given for travel purposes?
- Cholera
- Hep A
- Hep B
- Jap Enceph
- Tick-Bourne Enceph
- Typhoid
- Yellow Fever
How does the influenza vaccine work?
- CD8 T cells control viral load but response relied on anti-haemagglutinin antibody
- Protection begins within 7 days of immunisation
- Protection lasts 6 months
How does the TB/BCG vaccine work?
- BCG (Bacilli Calmette-Guerin) = attenuated strain of bovine TB
- Relies on T cell response
- Protects against primary infection (~20%) + progression to active TB (71%)
- Protection lasts ~10-15yrs
What are the different types of vaccines and their differences?
Live attenuated:
- Live pathogen
- Modified to limit pathogenesis
Inactivated/Component:
- Destroyed pathogen OR Isolated Antigenic proteins
Conjugate:
- Polysaccharide
- Antigenic protein carrier to enhance response
DNA/RNA Vaccines:
- Pathogen’s genetic material delivered to host cells via viral vector/lipid complex
- Host cells produce + express protein (leading to immune response)
What are some advantages + disadvantages of Live Attenuated vaccines and some examples?
Advantages:
- Lifelong immunity possible (no boosters)
- Protection against different strains likely
- Activates all phases of immune system
Disadvantages:
- Reversion to virulence e.g. VAPP (polio vaccine)
- Risk for immunosuppressed/deficient
- Storage issues (requires refridgeration)
E.g. (MMR-VBOY):
- MMR
- VZV
- BCG
- Oral (polio/typhoid)
- Yellow fever
- Influenza 2-17yo
What are some advantages + disadvantages of inactivated/component vaccines and some examples?
Advantages:
- No reversion
- Safe in immunodeficiency
- Easier storage
- Low cost
- Can eliminate wild-type virus from community
Disadvantages:
- Poor response “immunogenicity”
- Repeated boosters or modifications needed
- Does not follow natural route of infection (e.g SC injection for flu)
Inactivated e.g.
- Influenza
- Polio
- Cholera
- Bubonic plague
- Hep A
- Rabies
- Pertussis
Component/Subunit e.g:
- Hep B
- HPV
- Influenza
- Toxoids: Diptheria + tetanus
What are some advantages + disadvantages of conjugate vaccines and some examples?
Advantages:
- Effective against encapsulated bacteria
- Used for children
Disadvantages:
- Similar to inactivated/components
E.g (NHS):
- N. meningitidis
- H. influenzae
- S. pneumoniae
- Tetanus
What are some advantages + disadvantages of DNA/RNA vaccines and some examples?
Advantages:
- mRNA/lipid complex noninfectious + non-integrating
Disadvantages:
- Relatively new technology
- DNA may theoretically integrate to host’s DNA
- Possible autoimmunity responses (e.g. SLE)
- Need target that invokes good imune response
E.g:
- mRNA = SARS-COV-2
- Adenoviral vector: AstraZeneca + Sputnik
- Ongoing research into other uses
What vaccinations can’t HIV patients receive?
- BCG
- Yellow fever
What are adjuvants?
Increase immune response without altering its specificity
What are three ways to ensure a good response + effective memory from a vaccine?
- Live vaccine
- More persistent antigen - depot adjuvant
- Assisted activation of immune response - stimulatory adjuvant
How does a depot adjuvant work?
- Slows release of antigen
- Injection of adjuvant + antigen mixture ensures steady stream of antigen leading to prolonged immune response
What are some features of the ALUM depot adjuvant and how does it work?
- Most common
- Primary adjuvant utilised in humans
- Generally safe + mild
MoA:
- Antigens absorbed to alum so acts as means of slowly releasing antigen
- Activates Gr1+ cells to produce IL4
- This helps prime naiive B cells (mainly antibody mediated response)
How do stimulatory adjuvants work?
- Mimic action of PAMPS on TLR/other PRRs
- Leads to boosted immune response
How does the CpG stimulatory adjuvant work?
- Immunostimulatory adjuvant activity linked to unmethylated DNA motif rish in CpG
- CpG = DNA where a cytosine nucleotide is situated next to a guanine nucleotide
- Activates TLRs on APCs stimulating expression of costimulatory molecules
What are some features of the Complete Freund’s (stimulatory) adjuvant?
- Water-in-oil emulsion containing mycobacterial cell wall components
- Mainly for animals
- Painful in humans
What are some features of the ISCOMS (immune stimulating complex) stimulatory adjuvant?
- Experimental
- Multimeric antigen with adjuvant built in
- Cell-mediated immune response + humoral response
- With saponin results in strong serum antibody response
What are some features of Interleukin-2 stimulatory adjuvant?
- Used to achieve seroconversionin Hep B sA+ individuals
What are some indications for a haematopoeitic SCT?
Life-threatening primary immunodeficiency:
- SCID
- Leukocyte defect
Haem malignancy
What are the two types of Ab replacement?
- Preformed IgG to wide range of unspecified organisms
- High titres of IgG to specific pathogens
What are some indications for Ab replacement (IgG to wide range)?
Primary Ab deficiency:
- Bruton’s X-linkde agammaglobulinaemia
- X-linked hyper IgM syndrome
- Common variable immune deficiency
Secondary acquired Ab deficiency:
- Haem malignancy
- Post BM transplant
Other:
- ITP, Kawasaki, GBS, Measles, Severe myasthenia gravis
- Toxic epidermal necrolysis
- CMV pneumonitis
- Dermatomyositis
- Chronic inflammatory demyelinating polyradiculopathy
What are some indications for Ab replacement (IgG to specific)?
Passive immunisation post-exposure:
- Hep B
- Rabies
- VZV (pregnancy <20wks or immunocompromised)
What are the different types of adoptive T cell transfer therapy and some indications of each?
Virus specific T cells:
- EBV-related B cell lymphoproliferative disease
- Severe viral infections in immunocompromised pts
Tumour infiltrating lymphocyte T cell therapy:
- Head + neck SCC
- Melanoma
- Lung + gynae Ca
TCR
CAR-T cell therapy:
- ALL
- Non-Hodgkin’s lymphoma
What is recombinant cytokine therapy, its aims and some examples?
Recombinant cytokines = pro-inflammatory cytokines
Aim:
- Boost immune response to cancer + some pathogens
E.g:
- IL2 (increases T cell response) = Renal cancer
- Interferon α = Antiviral effect (Hep B + C), Anti-cancer, Kaposi sarcoma, hairy cell leukaemia, CML, melanoma
ABC = Interferon Alpha for hep B + C + Cml
- Interferon β = relapsing remitting MS
- Interferon gamma (increases macrophage function) = chronic Granulomatous disease
What are some indications for immune checkpoint blockade?
- Advanced melanoma
- Metastatic renal cancer
- Other malignancies
What is the biggests risk for immune checkpoint blockade?
Autoimmunity
What are two examples of immune checkpoint blockade and how do they work?
Ipilimumab:
- Monoclonal Ab specific for CTLA4
- CTLA4 = inhibitory checkpoint found on T cells (competes with CD28 to bind CD86/B7 on APCS to block T cell activation)
- CTLA4 blockade leads to increased APC presentation to T cells, and increased T cell activation
Pembrolizumab/Vivolumab:
- Monoclonal Ab specific for PD-1
- PD-1 = programmed death receptor, found on regulatory T cells, binds PD-L1/2 on APCs/tumour cells leads to T cell inactivation + death
- PD-1 blockade leads to T cells remaining active and thus killing tumour cells
What are adverse effects of immunosuppressive therapies?
- Infusion reaction
- Injection site reactions
- Acute infection
- Chronic infection
- Malignancy
- Autoimmunity
How does an infusion reaction present as a result of immunosuppressive therapies?
- IgE mediated = Urticaria, hypotension, tachycardia, wheeze
- Not classical Type I hypersensitivity: headahce, fever, myalgia
- Cytokine storm
How does an injection site reaction present as a result of immunosuppressive therapies?
- Peak reaction at ~48rs
- ?Occurs at previous injection sites
- Mixed cellular infiltrates, often CD8 T cells
- Not generally IgE or immune-complex mediated
How can an acute infection as a result of immunosuppressive therapies be prevented and treated?
Prevention:
- Vaccination (not live)
- Avoid contact
Tx:
- Stop immunosuppression
- Abx (cover for atypicals)
How can a chronic infection as a result of immunosuppressive therapies be prevented + treated for patients with TB, HIV, Hepatitis + JCV infections?
TB:
- Check Hx/travel/contacts
- CXR/Elispot
- Give prophylaxis/Tx as needed
HIV:
- Check HIV status prior
- Consider risks vs benefits
Hep:
- B = check core Ab pre-treatment
- C = Check Ab pre-treatment
- Further Ix for active disease if positive serology
JCV (John Cunningham Virus):
- Polyoma virus that can reactivate
- Infects + destroys oligodendorcytes
- Causes progresive multifocal leucoencephalopathy (PML)
- Seen with +++ immunosuppressive agents
What are some examples of malignancies that can arise from conditions having immunosuppressive therapies, and how can this be prevented?
- EBV = lymphoma
- Non-melanoma skin cancer = HPV
- Melanoma = anti-TNF α
Prevention: Targeted immunosuppression lowers risk of cf. transplant regimes
How can autoimmunity arise as a result of using immunosuppressive therapies and some examples?
Dysregulation of the immune system:
- SLE + lupus-like syndromes
- APLS
- Vasculitis
- Interstitial lung disease
- Sarcoidosis
- Uveitis
- AI hepatitis
- Demyelination
What is the mode of action of steroids?
Prostaglandins:
- Inhibits phospholipase A2
- No breakdown of phospholipids to arachidonic acid
- Prostaglandin synthesis is blocked = reduced inflammation
Phagocytes:
- Inhibits phagocyte trafficking, phagocytosis + release of proteolytic enzymes
- Causes transient increases in neutrophil count
Lymphocytes:
- Lymphopenia (sequestered in lymphoid tissue)
- Blocks cytokine gene expression
- Decreased Ab production
- Promotes apoptosis
What are some indications for steroid use?
- Allergic disorders
- Autoimmune + autoinflammatory disease prevention + Tx
- Transplant rejection
- Malignancy
What are some side effects for steroid use?
Metabolic:
- Diabetes
- Central obesity
- Moon face
- Lipid abnormalities
- Osteoporosis
- Hirsutism
- Adrenal suppression
- HTN
- Immunosuppression = infection
Others:
- Cataracts
- Glaucoma
- Peptic ulceration
- Pancreatitis
- Avascular necrosis
What do anti-proliferative agents do and what are four examples?
- Inhibit DNA synthesis
- Cells with rapid turnover = most sensitive
E.g.:
- Cyclophosphamide
- Mycophenolate Mofetil
- Azathioprine
- Methotrexate
What is the mechanism of action of Cyclophosphamide?
- Alkylates guanine base of DNA
- Damages DNA + prevents cell replication
- Affects B cells > T Cells, but at high doses affects all cells with high turnover
What are some indications for cyclophosphamide use and some side effects?
Indications:
- Connective tissue disease
- Vasculitis
- Anti-cancer agent
SEs:
- Bone marrow suppression
- Hair loss
- Sterility (M>F)
- Haemorrhagic cystitis
- Malignancy: bladder, haem, non-melanoma skin
- Infection: PCP
What is the mechanism of action of Mycophenolate Mofetil?
- Anti-metabolite
- Inhibits IM PDH, prevents guanine synthesis
- Blocks de novo nucleotide synthesis - prevents replication of DNA
- Prevents T>B cell proliferation
What are some indications for Mycophenolate Mofetil use and some side effects?
Indicators:
- Transplantation
- Auto-immune diseases
- Vasculitis
SEs:
- Bone marrow suppression
- Infection: HSV reactivation, progressive multifocal leukoencephalopathy (JC virus)
What is the mechanism of action of azathioprine?
- Anti-metabolite
- Metabolised by liver to 6 mercaptopurine
- Blocks de novo purine (e.g. adenine, guanine) synthesis
- Prevents replication of DNA, preferentially inhibits T cell activation + proliferation > B cell
What are the indications for azathioprine use and some side effects?
Indicators:
- Transplantation
- Auto-immune disease
- Auto-inflammatory diseases
SEs:
- Bone marrow suppression - TPMT polymorphism
- Infection
- Hepatotoxicity
What is the mechanism of action of methotrexate?
- Anti-folate
- Inhibits dihydrofolate reductase (DHFR)
- Decreases SNA synthesis
What are the indications for methotrexate use and some side effects?
Indicators:
- RA
- Psoriasis
- Crohn’s
- Chemotherapy
SEs:
- Bone marrow suppression
- Infection
- Malignancy
- Teratogenic
- Pneumonitis
- Pulmonary fibrosis
- Hepatotoxicity
- Folate deficiency (macrocytic megaloblastic anaemia)
What is the mechanism of action of plasmapharesis?
- Removal of pathogenic antibody
- Patient blood passes via separator
- Plasma treated to remove immunoglobulins + reinfused (or replaced with albumin in plasma exchange)
What are the indications for plasmapharesis and some side effects?
Indicators:
- Severe Ab-mediated Type II disease (Goodpasture syndrome, myasthenia gravis, Ab mediated transplant rejection/ABO incompatibility)
SEs:
- Rebound Ab production limits efficacy
- Given with anti-proliferative agent to reduce risk
- Anaphylaxis
What are some examples of drugs that are inhibitors of cell signalling?
- Tacrolimus
- Cyclosporin
- Sirolimus / Rapamycin
Tofacitinib - Apremilast
What is the mechanism of action of tacrolimus and cyclosporin?
- Inhibits Calcineurin
- Prevents T cell proliferation/function via reduced IL-2 expression
What are some indications for Tacrolimus/Cyclosporin use and their side effects?
Indicators:
- Rejection prophylaxis (transplantation)
- SLE
- Psoriatic arthritis
- Can be used in pregnancy
Tacrolimus SEs:
- Nephrotoxic
- HTN
- Neurotoxic
- Diabetogenic
Cyclosporin SEs:
- Nephrotoxic
- HTN
- Neurotoxic
- Dysmorphism
- GINGIVAL (GUM) HYPERTROPHY
What is the mechanism of action of Sirolimus + Rapamycin and their indications and side effects?
MoA:
- mTor inhibitor
- Inhibits T cell proliferation via IL-2 pathway
Indicators:
- Transplantation
SEs:
- HTN
- Less nephrotoxic
What is the mechanism of action of Tofacitinib and its indications?
MoA:
- JAK1/3 inhibitor
- Influences gene transcription via JAK-STAT signalling pathway
- Inhibits production of inflammatory molecules
Indicators:
- RA
- Psoriatic arthritis
- Axial spondyloarthritis
What is the mechanism of action of apremilast and its indications?
MoA:
- PDE4 inhibitor
- Increases cAMP
- Influences gene transcription via protein kinase A pathway
Indicators:
- Psoriasis
- Psoriatic arthritis
What are some drug agents that are directed against cell surface antigens, block signalling + cell depletion?
- Basiliximab
- Abatacept
- Rituximab
- Vedolizumab
- Natalizumab
- Tocilizumab
- Muromonab-CD3
- Anti-thymocyte globulin (ATG)
- Dacilizumab
- Efalizumab
- Alemtuzumab
What is the mechanism of action of, indications for and side effects of basiliximab?
MoA:
- Anti-CD25 (α chain of IL-2 receptor)
- Inhibits T cell proliferation
Indicators:
- Allograft rejection (prophylaxis)
SEs:
- Infusion reactions
- Infection
- Malignancy
- GI disturbance
What is the mechanism of action of, indications for and side effects of Abatacept?
MoA:
- Anti-CTLA4-Ig fusion protein
- Reduces co-stimulation of T cells via CD28
Indicators:
- RA
SEs:
- Infusion reactions
- Infections: TB, HBV, HCV
- Malignancy
- Cough
What is the mechanism of action of, indications for and side effects of Rituximab?
MoA:
- Anti-CD20
- Depletes mature B cells (not plasma cells)
Indicators:
- Lymphoma
- RA
- SLE
SEs:
- Infusion reactions
- Infection: PML
- Exacerbation CV disease
What is the mechanism of action of, indications for and side effects of Vedolizumab?
MoA:
- Anti-α-4-β-7integrin
- Inhibits cell migration (blocks integrin binding to MadCAM1)
Indicators:
- IBD
SEs:
- Infusion reactions
- Hepatotoxicity
- Infection
- Malignancy
What is the mechanism of action of, indications for and side effects of Natalizumab?
MoA:
- Anti-α-4-β-1 integrin (binds to VCAM1 + MadCAM1 to mediate rolling/arrest of leukocytes)
- Inhibits T cell migration
Indicators:
- Relapsing-remitting MS
- Crohn’s disease
SEs:
- Infusion reactions
- Infection: PML
- Malignancy
- Hepatotoxicity
What is the mechanism of action of, indications for and side effects of Tocilizumab?
MoA:
- Anti-IL6-receptor
- Reduces macrophage, T cell, B cell, neutrophil activation
Indicators:
- Castleman’s disease
- RA
SEs:
- Infusion reactions
- Infection
- Hepatotoxic
- Hyperlipidaemia
- Malignancy
What is the mechanism of action of, indications for and side effects of Muromonab-CD3?
MoA:
- Blocks CD3 on T cells
- Mouse monoclonal antibody (OKT3)
Indicators:
- Active allograft transplant rejection
SEs:
- Fever
- Leucopenia
What is the mechanism of action of, indications for and side effects of Anti-thymocyte globulin (ATG)?
MoA:
- Lymphocyte depletion
- Modulation of T cell activation + migration
Indicators:
- Allograft rejection (renal, heart)
SEs:
- Infusion reactions
- Leucopenia
- Infection
- Malignancy
What is the mechanism of action of and indications for Dacilizumab?
MoA:
- IL-2 receptor antibody
- Targets CD25
Indicators:
- Organ transplant rejection prophylaxis
What is the mechanism of action of Efalizumab?
- Anti-CDIIa
- Inhibits migration of T cells
What is the mechanism of action of, indications for and side effects of Alemtuzumab?
MoA:
- Monoclonal Ab that binids to CD52 found on lymphocytes resulting in depletion
Indicators:
- CLL
- MS
- T cell rejection (transplant)
SEs:
- CMV infection
What are some agents that are directed at cytokines/receptors?
- Infliximab
- Adalimumab
- Certolizumab
- Golimuab
- Etanercept
- Ustekinumab
- Guselkumab
- Secukinumab
- Denosumab
- Tocilizumab
- Sarilumab
- IL-1 blockade
- IL-4/5/13 blockade
What is the mechanism of action of, indications for and side effects of infliximab, adalimumab, certolizumab + golimumab?
MoA:
- Anti-TNFa
Indicators:
- RA
- Ankylosing spondylitis
- Psoriasis
- Psoriatic arthritis
- IBD
- Familial Mediterranean Fever
SEs:
- Infusion/injection site reactions
- Infection: TB, HCV, HBV
- Lupus-like conditions
- Demyelination
- Malignancy (Lymphoma)
What is the mechanism of action of, indications for and side effects of Etanercept?
MoA:
- TNFalpha/TNFbeta receptor p75-IgG fusion protein
- Inhibits both cytokines
Indicators:
- RA
- Ankylosing spondylitis
- Psoriasis
- Psoriatic arthritis
- JIA
SEs:
- Infusion/injection site reactions
- Infection: TB, HCV, HBV
- Lupus-like conditions
- Demyelination
- Malignancy (Lymphoma)
What is the mechanism of action of, indications for and side effects of Ustekinumab?
Moa:
- Anti-IL-12 + IL-23
- Binds to p40 subunit
Indicators:
- Psoriasis
- Psoriatic arthritis
SEs:
- Injection site reactions
- Infection: TB
- Malignancy
- Cough
What is the mechanism of action of, indications for and side effects of Guselkumab?
MoA:
- Anti-IL-23
- p19 alpha subunit
Indicators:
- Psoriasis
- Psoriatic arthritis
SEs:
- Injection site reactions
- Infection: TB
- Malignancy
What is the mechanism of action of, indications for and side effects of Secukinumab?
MoA:
- Anti-IL-17A
Indicators:
- Psoriasis
- Psoriatic arthritis
- Ankylosing spondylitis
SEs:
- Infection: TB
What is the mechanism of action of, indications for and side effects of Denosumab?
MoA:
- Anti-RANK ligand
- Inhibits RANK mediated osteoclast differentiation + function
Indicators:
- OSTEOPOROSIS
- Multiple myeloma
- Bone mets
SEs:
- Injection site reactions
- Infection
- Avascular necrosis of jaw
What is the mechanism of action of, indications for and side effects of Tocilizumb + Sarilumab?
MoA:
- Anti-IL-6
- Reduce macrophage, T + B cell, + neutrophil activation
Indicators:
- RA
- Castleman’s disease
SEs:
- Infusion reactions
- Infection
- Hepatotoxicity
- Liid abnormalities
- Malignancy
What is the mechanism of action of and indications for IL-1 blockade?
MoA:
- Anti-IL-1
Indicators:
- Familial Mediterranean Fever
- Gout
- Adult-onset Still’s disease
What is the mechanism of action of and indications for IL-4/5/13 blockade?
MoA:
- IL-4R α subunit antibody
- Anti-IL13 Ab
- Anti-IL5 Ab
Indicators:
- Eczema
- Asthma
- Eosinophilic asthma
What is an allergic disorder?
An immunological process resulting in immediate + reproducible symptoms after allergen exposure
- Usually IgE mediated Type 1
- Allergen normally an otherwise harmless substance
What is allergen sensitisation?
Detection of specific IgE (skin prick/blood test) to allergen
What is the process of allergen desensitisation?
Supervised administration of allergen
1. Start with tiny dose every week until maximal dose reached
2. Maintenance dose given monthly for 3-5yrs
What are some features of allergen desensitisation?
- Reduces clinical Sx of monoallergic disorders
- Good for: bee/wasp venom, grass pollen, house dust mite
- Not good for: food, latex
- Costly, laborious + risk of severe adverse reaction
- Only Tx that alters natural course of disease
