boosting the immune system Flashcards
4 ways to boost the immune system
Vaccination
Cytokine therapy
Replacement of missing components
Blocking immune checkpoints
what cells does the adaptive immune response use
B
T
how do you get the repetoire of antigen receptors in the adaptive immune response
genes for segments of receptors are rearranged
nucleic acids deleted/added at sites of rearrangement randomly
create trillions of receptors
can get autoreactive cells - need to delete/tolerise autoreactive cells
they can differentiate between very small molecular differences
summarise clonal expansion
T cell with right specificity - proliferate and differentiate into effector cells (cytokine secreting, cytotoxic)
B cell with right specificity prolif and either:
* diff into T cell independent plasma and memory cells (IgM)
* do germinal centre reaction with T cell help via CD40L-> T cell dependent IgG/A/E(M) mempry and plasma
plasma secrete high affinity specific Ab
summarise T cell immunological memory
residual pool of specific T and B cells with enhanced capacity to respond
- memory T cells stay long time w/o ag - becayuse have low level proliferation in response to cytokines = longevity
- different pattern of expression of cell surface protein involved in chemotaxis/cell adhesion -> memory cells access non-lymphoid tissues - where see infection
- more rapid response to ag than naive cells
pre-fromed pool of high affinity specific Ab
what happens to number of CD8 T cells in and after infection
get massive number of specific CD8 cells through clonal expansion
then after primary infection - number drops
-> left with memory cells
same with CD4 cells - just less clonal expansion
summarise germinal centre reaction
when B cell see ag
go to germinal centre
T cell help via CD40L:
- -> isotope switching
-> T cell dependent IgG/A/E(M) memory and plasma - and stim maturation of receptors - receptors mutate and highest affinity are selected
->
- diff into plasma cells - receptors secreted as Ab
- or stay as T cell dependent memory cells
Summarise B cell memory
Pre-formed antibody
Circulating high affinity IgG antibodies
Longevity
Long lived memory B cells and plasma cells
Memory B cells are more easily and rapidly activated than naïve cells
3 key features we want from a vaccine
- MEMORY – preformed antibodies, memory T cells, memory B cells, to provide protective immunity
- No adverse reactions
- Practical considerations – one shot, easy storage, inexpensive…
theory behind influenza vaccine
Haemagglutinin is the receptor vinding and membrane fusion glycoprotein of the influenza virus
and is what neutralising Ab target - need vaccine to target this
summarise influenza haemagglutination inhibition assay
**Red cell in well – sink -> red spot**
Sialic acid receptors on RBC bind to haemagluttinin of influenza virus to ‘haemagluttinate’
If **virus receptors bind to haemagluttanin -> haemaglutinate – haemaglutination across cell**
**If Ab – block this reaction – go back to red cells **
theory of the TB vaccine (BCG)
T cells protect against primary TB and progression of TB to active - T cell mediated type 4 response
Injected with tuberculin (mantoux test) intradermally
Look at arm 48-72hrs later
If immunity get T cell infiltration around the tuberculin -> induration (swelling that can be felt)
+ve after infection/vaccination
Now do IGRA or ?spot
What are the types of vaccine
- Live vaccines
- Inactivated/Component vaccines
Conjugates+ Adjuvants increase immunogenicity - RNA vaccines
- Adenoviral vector vaccines
- Dendritic cell vaccines
summarise live attenuated vaccines
live organism -> immune response
modified (attenuated) to limit pathogenesis (less virulent)
egs of live vaccines
MMR
BCG
Yellow fever
Zostavax
Typhoid (oral)
Polio (Sabin oral)
Influenza (Fluenz tetra nasal spray
for children 2-17 years)
advantages of live vaccines
Establishes infection – ideally mild symptoms
Raises broad immune response to multiple antigens – more likely to protect against different strains
Activates all phases of immune system.
T cells, B cells – with local IgA, humoral IgG
local and systemic immunity - important when cell mediated reactions needed
strong immune response
May confer lifelong immunity, sometimes just after one dose
disadvantages with live vaccines
Possible reversion to virulence (recombination, mutation).
* Vaccine associated paralytic poliomyelitis (VAPP, ca. 1: 750,000 recipients) – very rare
can cause illness
cant give to immunosuppressed, or if live with immunosuppressed
Spread to contacts
* Spread to immunosuppressed/immunodeficient patients
Storage problems and handling difficult - not stable, potential for contamination
interverence by viruses/vaccines and passive immunity
what are the inactivated vaccines
Influenza (inactivated quadrivalent)
Cholera,
Bubonic plague,
Polio (Salk),
Hepatitis A,
Pertussis,
Rabies.
what are the component/subunit vaccines
Protein component of the microorganisms or synthetic virus like particles
Hepatitis B (HbS antigen),
HPV (capsid),
Influenza (recombinant quadrivalent - less commonly used)
what are the inactivated toxin vaccines
diptheria
tetanus
inactivated toxic components
what is virus specific T cell therapy
for EBV:
- Take blood from self/donor
- Take out white cell
- Stim blood cells by EBV in vitro
- -> EBV specific T cells
- -> put back in patient
Usually after transplant/cancer patient
Avoid risk of EBV related illness inc lymphoma
also used for severe persistent viral infection in immunocomp
what is tumour infiltratijng lymphocyte T cell therapy
Take out tumour
Culture with IL2
Select and expand the T cells – assume have specificity for cancer because was in body
Put T cells back in patient
what is TCR and CAR T cell therapy
Can take T cell from donor
Engineer to express specific T cell receptor
Put in T cells with the receptor – will recognise tumour with that specific epitope
Car T cells - Express chimeric ag receptor
* Express by normal domain
* At end is an Ab structure (variable segment)
* Recognise specific Ag
* eg Recognition of CD19 – used for leukaemia
use of CAR T cells
used against:
* ALL
* NHL
* autoimmune
variable fragment of CAR recognise CD19
CAR signals through CD3 in T cells - > T cell response -> kill tumour
less successful for solid tumours
summarise blocking immune checkpoint: PD-1
Immune checkpoint –ve reg immune response
PD-1 = program death 1
* Negative response
* PD-ligand on APC and tumour cells bind PD-1 –> reg T cell response
Monoclonal Ab – block either PD-1 or PD-ligands
Blocked program death signal -> live T cell activation
summarise monoclonal Ab against CTLA4
CD8 t cell express CD28 – activation signal
which binds to CD80 and CD86
CD80 and 86 - also bind to CTLA4 which is a negative signal
Balance = controlled
Ab against CTLA4 takes out -ve signal = T cell activation
