Memory and vaccination Flashcards
What is the primary immune response?
First time an individual’s immune system comes across a pathogen involving an immune response to an infection/vaccination
Before T/B cells have met their antigen= NAIVE
What’s a secondary (tertiary, quaternary) immune response?
the 2nd/3rd/4th time individual comes across same pathogen
Cells are antigen experienced and have immunological memory
Qualitatively and quantitatively improved
asymptomatic/very mid
Levels of antibodies over the years
Over the years after a vaccination antibody (Ab) levels rarely decline= long term immunological memory (but T cells - CD4+ and CD8+ do decline)
What makes memory B cells so good in a secondary immune response?
Produce higher affinity antibodies than plasma cells
Produce class switched antibody
Produce antibody quickly
Can re enter germinal centre an undergo somatic hypermutation and affinity maturation for a 2nd time
Have higher levels of MHC and costimulatory molecules to attract T helper cell
Characteristics of a primary immune response
Ratio of antigen specific B cell= low
IgM produced first in response (IgM>IgG)
Low affinity for antibody
Low somatic hypermutation
Characteristics of a secondary immune response
Ratio of antigen specific b cells is higher
More isotypes made (IgG, IgA)
Affinity of antibody= high
Somatic hypermutation= high
2 types of memory T cells
Central memory T cell
Effector memory T cell
How do T memory cells differ?
Occur in different locations
Traffic differently to naive T effector cells
each= have different effector functions
How do naive/effector/memory T cells
They each produce different molecules
How can naive T cell go to lymph node?
Have CCR7 chemokine receptor
lymph node has chemokine CCL21
CCR7 and CCL21 are attracted
Takes it to lymph node
Molecules that memory T cells can make
CD44- Cell adhesion molecule
CD45R0- modulate TCR signalling
CD45RA- modulate TCR signalling
What do naive T cells have on their surface?
CCR7 receptor
CD45RA
How are T memory cells produced?
Naïve T cells are activated by dendritic APC in lymph nodes (costimulation, cytokines)
Naive cells differentiate to adopt different effector phenotypes (T helper, cytotoxic cells-perforin and FAS L-made when APC makes IL-2)
Some effector cells become memory cells
Most effector cells die by mitosis after a few days
Difference between central memory t cell and effector memory T cell?
Central memory cells= express CCR7 receptor (chemokine receptor) and stay in lymphoid tissue
Effector memory T cell= lack CCR7 and migrate to tissue
How do memory T cells survive?
Cytokines IL7 and IL-15 give memory T cells survival signals
What do effector memory T cells have on their surface?
CCR3- chemokine
CCR5- receptor for chemokine CCR3
CD45R0- modulates TCR signalling
Characteristics of effector memory T cells
- Stay in tissue (not lymph nodes)
- Immediate expansion in reinfection
- express receptors for inflammatory cytokines so can be recruited to site of inflammation
- Quickly produce IL-4, IL-5, IFN-gamma
- Committed to a lineage similar to Th1 and Th2
Characteristics of central memory T cells
- Stay in lymph node (like naive cells)
- need antigen presented to them again
- Long lived precursors- take longer to respond
- Not committed to Th1/Th2 type
Why is innate immunity referred to as ‘trained immunity’?
Trained immunity- involves epigenetic changes, metabolic changes improved effector functions
These support functions of innate immunity
Aim of vaccines?
Generate long lasting and protective immunity
Seek to generate antibodies to prevent damage by pathogen toxins or neutralise pathogen to stop infection
What must a vaccine do to work?
Incorporate an antigen into the body that the body will recognize as foreign B cell must be activated by Antigen from vaccine binding to BCR= APC (MHC II) T helper cell binds to B cell APC= Costimulation and cytokine production Triggers class switching and B cell to differentiate into plasma cells and memory cells
What do the best vaccines do?
Trigger T cell immunity
When will a vaccine not work?
If antigen is cleared by innate immunity
Which people are vaccines least effective in and why?
Young, old, immunocompromised
Weakened immune systems
What is herd immunity?
Also known as ‘population immunity’
A concept used for vaccination, in which a population can be protected from a certain virus if a threshold of vaccination is reached
% of population that needs to be vaccinated varies for each infection e.g for measales it is 93-95%
What are the requirements for a vaccine?
- Safe- must not cause illness/death
- Protective- must protect against illness caused by pathogen
- Give sustained protection- last several years
Practical considerations for a vaccine
Low cost per dose
Biological stability
Ease of administration
Low side effects (side effects from a vaccine means immune response is activated= effective)
What are adjuvants?
Compounds used to enhance immune response
Mixed with antigen/pathogen (used in subunit/toxoid vaccines)
Examples of adjuvants
Alum, mineral salts, bacterial cell wall components
Purpose of adjuvants
Enhance immunogenicity by giving danger signal (PAMPs)
Reduce amount of antigen needed
Aid delivery at mucosa
Why can organisms be ‘difficult’?
- Pathogen is hidden (malaria)
- Pathogen changes its surface proteins (trypanosomes- have lots of genes for surface antigens that they can change)
- Conserved (Mutated) antigens are hidden (HIV- can mutate and change- hide conserved proteins so antibodies cant target them and neutralise them)
- Antibodies aren’t effective (TB)- antibodies aren’t enough to remove pathogen
Future of vaccinations
- Reverse Vaccinology (Meningitis B vaccine)
- DNA vaccines (prostate cancer trials)
- CAR T cells (in leukaemia)
Reverse Vaccinology
- Examine genome of pathogen- identify best, novel antigens (usually surface proteins)
- Synthetically produce the protein
- Test for an effective immune response and antibody production
Advantages of reverse vaccinology
- Find many targets v quickly
2. Don’t need live organism
Disadvantages of reverse vaccinology
Need to chose antigen (peptides) large enough that dendritic cells can process
Antigen (peptide) may not be bound by everyone’s MHC II molecules
DNA Vaccines (prostate cancer trials)
- Produce DNA strand that codes for pathogenic protein
- Inoculate into body cells (normally muscle)
- Cells take up DNA and produce protein on their surface/secret it
- Immune system recognises this as a foreign= immune response- can get CD4+ and CD8+ response
Advantages of DNA vaccines
- Potentially effective against cancers
- Antigen presentation by MHC I and MHC II
- Long term persistence of antigen
Disadvantages of DNA vaccines
- Limited to protein antigens
- Risk of affecting genes involved in cell’s growth
- Possibility of inducing tolerance (attack body’s own antigens)
