Immuno 9: Immune Modulation Therapies 1 Flashcards
Describe Clonal expansion in T cells?
If an antigen is presented to a T cell receptor which has high specificity for it, the T cell proliferates and differentiates into T helper, Cytotoxic and memory cells
List 3 vaccines given to the elderly aged over 65?
Pneumococcal vaccine (Pneum PPV)
Flu vaccine
Shingles
Describe clonal expansion in B cells ?
If the B cell receptor has high specificity for the antigen presented, the B cell will become activated and undergo proliferation and differentiation into IgM secreting plasma cells and B memory cells
Where do B cells undergo Isotype switching ?
Germinal centres
Where do plasma cells reside ?
Bone marrow
which bacteria is in the BCG vaccine ?
Bovine tuberculosis
Give 3 examples of live attenuated vaccines ?
MMR
Yellow fever
Typhoid
Give 2 examples of Toxoid vaccines (Inactive toxins) ?
Diphtheria
Tetanus
Give 3 examples of subunit vaccines ?
Hep B (HBsAG)
HPV (capsid)
Influenza (HA)
Give one advantage of a life vaccine compared to a component/inactivated vaccine ?
Longer lasting immunity (life long)
Immunity is broader (protects against more strains)
Give an advantage of a component/inactivated vaccine compared to a live vaccine ?
Can be given to immunocompromised patients
Give 3 examples of conjugate vaccines ?
HiB (haemophilus influenza B)
Meningococcus
Pneumococcus
List 2 indications for Haematopoeitic stem cell transplantation ?
SCID
Haematological malignancy
List 3 primary immunodeficiency diseases in which Antibody replacement (pool of antibodies to variety of organisms) is indicated ?
Bruton’s X-linked agammaglobulinaemia
X-linked hyper IgM syndrome
Common variable immunodeficiency
In which 2 Haematological malignancies is Antibody replacement indicated ?
CLL
Multiple myeloma
List 3 diseases in which IgG immunoglobulin therapy can be used ?
Shingles infection (varicella zoster)
Rabies (post exposure)
Hepatitis B
Give one example of an infection in which adoptive cell transfer (ACT) can be used to infuse a donor’s T cells ?
EBV infection in immunocompromised patients.
T cells from a donor are isolated and exposed to EBV antigen to stimulate Clonal expansion of specific T cells. These T cells are infused into the immunocompromised recipient to treat EBV infection.
How does Ipilimumab work in treatment of advanced melanoma ?
Ipilimumab blocks CTLA4 which is an inhibitory receptor on T cells
This causes increased T cell activation and boosts the immune response
T cells have CD28 (activator receptor) and CTLA4 (inhibitory receptor).
CD80 and CD86 on APCs can bind to either to activate/inhibit T cells
How does Pembrolizumab and nivolumab work in the treatment of advanced melanoma ?
They inhibit PD-1 receptors on T cells.
This causes increased T cell activation because PD-1 is an inhibitory pathway.
PD-1 receptors on T cells cause an inhibition of T cells when activated by PD-ligand 1 or 2 on APC or tumour cells
What side effects are more common in patients receiving monoclonal antibodies for advanced melanoma ?
Auto-immune diseases (arthritis, thyroid disease, Diabetes)
Because the T cell response is over stimulated
Match up the recombinant cytokine treatment with the disease that they are used in ?
IFN alpha Chronic granulomatous disease
IFN beta Hepatitis B
IFN gamma Behçet’s disease
IFN alpha Hepatitis B
IFN beta Behcet’s disease
IFN gamma Chronic granulomatous disease
what happens when B cells with appropriate specificity get selected
proliferate
differentiate into T cell independent IgM plasma cells
undergo germinal centre reaction and differentiate into T cell dependent IgG producing memory and plasma cells
list 3 types of APC
dendritic cells
macrophages
B lymphoctes
features of memory B and T cells
memory T - different pattern of expression of cell surface proteins involved in chemotaxis and cell adhesion, allowing rapid access to non-lymphoid tissues
memory B - circulating pre-formed high-affinity IgG antibodies present
name the membrane fusion glycoprotein of influenza virus
haemagglutinin (HA)
target for antibodies
describe a use for virus specific T cell adaptive cell transfer
for EBV in the immunocompromised
to prevent development of B cell lymphoproliferative disease
functional EBV specific T cells
blood taken from pt/ matched donor - mononuclear cells isolated and stimulated with EBV peptides - expansion of EBV specific T cells
what is tumour infiltration T cell therapy
remove tumour
stimulate T cells within the tumour with cytokines in the presence of the tumour so they develop resistance to it
select and expand tumour infiltrating lymphocytes and reinfuse into the patient
what is TCR and CAR T cell therapy
T cells taken from patient
viral/non-viral vectors are used to insert fragments of genes into these T cells
these gene fragments encode receptors
for TCR therapy - insert a gene that encodes a specific TCR against a tumour cell antige
for CAR therapy (chimeric antigen receptor) - receptors contain both B and T cell components
used in ALL and NHL
how can we block immune checkpoints
Iplimumab - antibody specific to CTLA4 - advanced melanoma
Pembrolizumab and Nivolumab - antibodies specific to PD1 - activates T cells - advanced melanoma
list clinical uses of recombinant cytokines
interferon alpha - adjunt in treatment of hep B, C, kaposi sarcoma, CML, multiple myeloma
interferon beta - behcets disease, relapsing MS
interferon gamma - chronic granulomatous disease
