Immu 3: 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
Then undergo
list 3 types of APC
dendritic cells
macrophages
B lymphoctes
3 aims of vaccines
- MEMORY: generate protective, long-lasting immune response
- No adverse reactions
- Practical considerations e.g. one vaccine, easy storage, inexpensive
Immunological memory is mediated by
B and T lymphocytes
Where do B cells undergo Isotype switching ?
Germinal centres
Where do plasma cells reside ?
Bone marrow
which bacteria is in the BCG vaccine ?
What does this vaccine protect against?
Bovine tuberculosis
Progression to active tuberculosis
Give 5 examples of live attenuated vaccines ?
Does pt get Sx?
- MMR
- BCG
- Yellow fever
- Typhoid (oral)
- Polio (oral)
Pt gets mild Sx
6 examples of inactivated vaccines
- Influenza
- Cholera
- Bubonic plague
- Polio (Salk)
- Hepatitis A
- Pertussis, Rabies
Give 2 examples of Toxoid vaccines (Inactive toxins) ?
Diphtheria
Tetanus
Give 3 examples of subunit vaccines ?
Which sort of infections is this usually for?
- Hep B (HBsAG)
- HPV (capsid)
- Influenza (HA)
Usually for vaccines (vaccine contains a component/subunit of the vaccine)
Give 3 advantages of a live vaccine compared to a component/inactivated vaccine ?
- Longer lasting immunity (life long)
- Immunity is broader (protects against more strains)
- activate ALL phases of the immune system: T cells, B cells, with local IgA, humoral IgG
Give 3 advantages of a component/inactivated vaccine compared to a live vaccine ?
- Can be given to immunocompromised patients
- Storage easier
- Lower cost
Why might conjugate vaccines be better than inactivated/component vaccines?
- To help avoid the problems of inactivated/ component vaccines, you can put on a protein carrier with a polysaccharide
- So conjugate vaccine has a protein carrier on top of a polysaccharide (NB inactivated ONLY has polysaccharide), which promotes T cell immunity which enhances the B cell/ antibody response
- Polysaccharide ALONE induces a transient T cell independent B cell response (particularly in children) and does NOT stimulate a good T cell response (this is in inactivated/component vaccines)
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 ?
What is MoA?
Shingles infection (varicella zoster)
Rabies (post exposure)
Hepatitis B
MoA: post-exposure prophylaxis (passive immunisation)
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.
what is TCR and CAR T cell therapy
- T cell receptor T cells (TCR-T cell therapy)
- Chimeric antigen receptor T cells (CAR-T cell therapy)
TCR (T cell receptor T cells 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 antigen
CAR-T therapy (Chimeric antigen receptor T cells)
- for CAR therapy, stead of putting a vector with a TCR in, a chimeric antigen receptor (which is a mix of an antibody and T cell receptor) is inserted
used in ALL and NHL
In CAR-T therapy, against CD is it effective against?
- most common use of this method is for a TCR expressing CD19 variable antibody fragment (so the antibody recognises CD19) which is put onto the end of CD28 and CD3z (which is the signalling domain)
Which conditions are CAR-T therapy useful against? (2)
- Used for Acute Lymphoblastic Leukaemia in kids
- Used for some form of non-Hodgkin lymphoma
Ipilimumab targets which 2 immune checkpoints?
- CTLA4 (INHIBITORY signal)
- CD28 (STIMULATORY signal)
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
Pembrolizumab and Nivolumab are used for which 2 conditions?
- Advanced melanoma
- Metastatic renal cell cancer
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 (Pembrolizumab and Nivolumab)?
Auto-immune diseases (arthritis, thyroid disease, Diabetes)
Because the T cell response is over stimulated
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
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
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
how can we block immune checkpoints (2)
- Iplimumab - antibody specific to CTLA4 - advanced melanoma
- Pembrolizumab and Nivolumab - antibodies specific to PD1 - activates T cells - advanced melanoma
Which IL is CD8 T cell response dependent on?
IL-2
What is a common adjuvant that can be added to vaccines to increase immune response without altering its specificity?
Aluminium salts
Use of IFN alpha cytokine therapy (4)
- Hairy cell leukaemia
- CML
- Multiple myeloma
- Used as an adjunct for: HBV, HCV, Kaposi sarcoma
Use of IFN beta cytokine therapy (2)
- Behcet’s
- relapsing MS
Use of IFN gamma cytokine therapy (1)
Stimulates phagocytes in patients with Chronic granulomatous disease
