Immune Mod Therapies Flashcards
What occurs to T cells during and after infection?
During infection there is massive T cell expansion
After infection, only some memory cells survive
What are the 3 APCs?
Denditic cells
Macrophages
B lymphocytes
What are the traits of memory T cells?
- Longevity
- Specific pattern of expression of cell surface proteins involved in chemotaxis cell adhesion (to allow cels to rapidly access non-lymphoid tissue)
- Rapid, robust response to subsequent antigen exposure (lower threshold of activation than naive cells)
What are the traits of memory B cells?
Longevity
Pre-formed antibody (high affinity IgG)
rapid robust response to subsequent antigen exposure
What are the aims of a vaccine?
MEMORY - generate long lasting response
PROTECTIVE response
no adverse reactions
Practical - one shot, easy storage
What antibody is required to fight off influenza?
Antibody against haemagglutiini
what is haemagglutinin?
The receptor-binding and membrane-fusion glycoprotein of the influenza virus
What are haemaglutinin antibodies detected with?
haemaglutinin antibodies are detected with an haemaglutinin inhibition assay
How does a haemaglutinin inhibition assay work?
Normally: red cells clump at the bottom forming a red spot
With virus: Sialic acid receptors on RBC bind to hemaglutinin on virus, causing RBC to haemagluttinate (haemaglutinin makes the cells stick together, causing diffuse coloration across the wall)
With Antibodies: antibodies bind to haemaglutinin prevent this haemagglutionation > RBC clump at bottom forming a red spot
What is BCG a strain of?
Of bovine TB
What kind of protection does BCG provide?
Some protection to primary infection (20%) > little protection against getting the infection
Protection against active progression to active TB (70%)
How will an individual with the BCG vaccine experience TB?
TB infection remains latent and well controlled
What is a Mantoux test?
Injection of small amount of liquid tuberculin intradermally
Examine area of infection 48-72 hours after tuberculin injection
Reaction is the area of swelling around the site
What are the types of vaccine you can have?
Live attenuated
Inactivated /component
Conjugate / adjuvant
What occurs in a live attenuated vaccine?
The live organism is modified to limit pathogenesis
What are examples of live attenuated vaccine
MMR BCG Yellow fever Typhoid Polio (sabin - oral) Vaccinia
What are advantages of the live attenuated vaccine?
Establishes infection (mild)
Raises broad immune response to multiple antigens (protection to MANY strains)
Activates ALL phases of immune system
Confers LIFELONG immunity
What are examples of inactivated vaccines?
Influenza Cholera Polio (Salk - injected) Hep A Pertussis Rabies
What are examples of toxoid vaccines?
Diptheria
Tetanus
What are examples of component vaccines?
Hep B
HPV
Influenza
What are disadvantages of the live attenuated vaccine?
Storage problems
Possible reversion to virulence > DO NOT give to immunocompromised
Spread to contacts of vaccine who have not consented to vaccine
Spread to immunocompromised/immunosuppressed
What are advantages of inactivated/component vaccines?
No mutation or reversion Can be used in immunodeficient patients Can lead to elimination of wild-type virus from the community Easier storage Lower cost
What are disadvantages of inactivated/component vaccines?
Do NOT follow normal route of infection
Have poor immunogenicity
May need multiple injections
Require conjugates / adjuvants to enhance effect
What is a conjugate vaccine made up of?
Polysaccharide + protein carrier
What does the polysaccharide cause?
A T cell independent B cell response
What are examples of conjugate vaccines?
haemophiliac influlenza B
Meningococcus
Pneumococcus
What is an adjuvant, and how does it work?
Increases the immune response without altering the specificity
Mimic actions of PAMPs on TLR and other PRR
What are examples of adjuvant’?
Aluminium salt
Lipid (monophosphoryl lipid A)
Freund’s anjuvant
What is the most commonly used adjuvant in humans?
Aluminium salt
What vaccines use aluminium salt as adjuvant?
Hep A
Hep B
What are theories for the function of aluminium salt?
Allow antigens to be slowly released over time, leading to prolonged antigenic stimulation
May induce a mild inflammatory r reaction that promoted development of adaptive immune response
May activate Gr1 IL4 oesinophils to prime naive B cells > antibody response
What is an adenovirus vector vaccine?
DNA of relevant protein inserted to viral vector to produce a vaccine
This infects cells in vivo
What are ISCOMs?
mmune-stimulating complexes
These are cage like structures mixed with antigens to enhance cell-mediated immunity
What are DNA vaccines?
Plasmid containing gene of choice from the pathogen is inserted into a muscle cell
The plasmid does not replicate, but the gene encodes protein that is presented at the cell surface
This mimics the normal action of a virally infected cell and stimulates T cell response
What is a disadvantage of DNA vaccine?
Plasmid may integrate into host DNA and response to DNA could lead to autoimmune conditions eg SLE
What are dendritic cell vaccines used for?
FOr tumours where dendritic cell function is compromised
How do dendritic cell vaccines work?
Take patient’s dendritic cells and load them with a tumour antigen
Reintroduce them to the patient to boost immune response against tumour antigen
What is an example fo dendritic cell vaccine / personalised immunotherapY?=
PROVENGE - for prostatic cancer
How does PROVENGE work?
Remove WBC from patient’s bloods
Harvest and incubate APC with recombinant protein PAP-GMCSF
APC is infused back to patient
What is the technique for replacement of missing components of the immune system?
HAEMATOPOEIC stem cell transplantation
What are indications for hfaematopoeic stem cell transplant?
Life threatening immunodeficiency e.g. SCID
Haematological malignancy
Offers complete, permanent cure
What are antibody replacement therapies?
Immunoglobulins can be replaced bu giving human immunoglobulin from pool of >1000 donors
Contains pre-formed IgG to a variety of organisms
What are indications for antibody replacement=
Primary antibody deficiency (agammaglobulimae, hyper IgM syndrome, common variable immunodeficiency)
Secondary antibody deficiency (CL, multiple myeloma, after BM transplant=
When do you give specific immunoglobulin ?
Passive immunisation (for post exposure prophylaxis - TETANUS)
What are examples of specific immunoglobulin given for passive post exposure immunisation?
Hp B
Tetanus
Rabies
Varicella zoster
When is Adoptive Cell Transfer of virus specific T cells used?
Used for EBV in people who are immunosuppressed to prevent the development of B cell lymphoproliferative disease
How does Tumour Infiltrating Lymphocyte T cell therapy work?
You remove the tumour from the patient
You stimulate T cells within the tumour with cytokines so that they develop a response to the tumour
You the select and expand the tumour infiltrating lymphocyte and rein fuse into the patient
How does TCR therapy work?
Take T cells from patient
Insert gene that encodes a specific TCR (against tumour cell antigen)
Reinsert T cells
What type of receptors are used in CAR therapy?
insert CHIMERIC receptors (both B and T) into T cells
It usually recognises CD19 on B cells and harnesses T cells to kill it
What treatment can you use for advanced melanoma?
Ipilimumab (Antibody specific to CTLA4)
How does Ipilimumab work?
Ipilimumab binds to CTLA4, which would normally emit inhibitory signal
This means that CD80 and CD86 must act via CD28
CD28 transmits stimulatory signal
Thereby T cell response is enhanced
How do Pembrolizumab / Nivolumab work
Normally PD1 transmits an inhibitory signal to T cells
Its ligands PDL1 and PDL2 are present on APCs and tumour cells
If tumour cells express PD ligands they turn off T cells
NIVOLUMAB binds to PD1 > blocks this inhibitory effect > activates T cells
What is a risk of using Nivolumab?
As they invigorate the immune response, there is a risk of AI disease
What is interferon alpha used for?
Anjunct to Help B, Hep C, Kaposi, CML, MM
What is interferon beta used for?
Behcet’s disease, MS
What is interferon gamma used for?
Chronic Granulomatous disease
How does the influenza vaccine built?
INACTIVATED vaccine
The vaccine used is a trivalent vaccine. Each injected seasonal influenza vaccine contains three influenza viruses:
- one influenza type A subtype H3N2 virus strain
- one influenza type A subtype H1N1 (seasonal) virus strain
- one influenza type B virus strain
What is CAR T Therapy largely being used for
for targeting CD19
In ALL, NHL
