Immunology Theme 3 Flashcards
why is there a lag phase after a virus is administered, outline what occurs after this
Lag phase because antigen needs to be taken up presented to T cells, which then initiate B cells.
B cells make antibodies immediately, but also make memory cells
what are the primary and secondary antibodies produced
- Primary – IgM antibodies
* Secondary – switch to IgG dominated response
outline the characteristics of memory b-cells and where do they develop
develop in lymph nodes
- Long-lived (quiescent alive but inactive), high affinity, class switched antibody
- Affinity maturation – antibody will be more complementary to the antigen/ evolved better to bind to it
- Undergo Somatic hypermutation allows antibody genes to produce a higher quality antibody- undergoes genetic rearrangement
- Recombination allows antibody to switch classes depending on the need
- Circulate and are more easily activated than naïve B-cells
- Memory T-cells also produced
outline the involvement of b-cell in the secondary immune response
• Secondary immune response is quicker, stronger and an IgG response predominates
what infections are IgG and IgA responses better for
IgG- tissue infection
IgA- mucosal infection
what occurred in the case of the small pox vaccine
after the vaccination antibody levels had no significant decline here where as T-cell memory declined
- Immunity is long-lasting
- Memory is maintained in the absence of antigen e.g. small pox
outline Variolation for smallpox
- Smallpox has a long history of pestilence
- Widely used in the 18th century
- Inoculation of live virus from pustules people with less severe symptoms of the disease, scratch the skin of someone who hadn’t got it- this provided some protection but killed those who were inoculated
- Mild disease and protective immunity
- Effective but killed 3%
outline how Vaccination against cowpox provides immunity against smallpox. mention why this may only be the case in some viruses
• These 2 viruses have similar antigens so if you develop immunity against cow pox you develop immunity against smallpox
antibody targeting one will eradicate both
- But most viruses have no non-pathogenic antigenically related counterpart
- Antigenic variability of small pox is very limited therefore vaccines are effective. Unlike vaccines against influenza in which there is great variability
what are the Features of effective vaccines
- Safe, protective, gives sustained protection, induces neutralising antibody, induces protective T cells and considers practical considerations (low cost per dose/ few side effects & ease of administration). Must be economically viable.
- The best vaccine will activate both arms of the immune response
- Must elicit t-cell response as then t-cell response is weak and won’t be sustained
- Many pathogens require t-cells to remove them (t-cell immunity)
outline some Infections with no completely effective vaccines
- Issue Is there is no effective immune response
- Malaria, tuberculosis, cholera, HIV, seasonal flu and measles.
- Measles - vaccine must be refrigerated to be effective, therefore difficult to get to parts of Africa.
outline the methods vaccination can be based on
Vaccines based on killed organisms
Vaccines based on attenuated organisms
Production of recombinant vaccines
conjugate vaccines
outline how Vaccines are based on killed organisms and what are the risks of this
- Chemically treated, heated or irradiated - viruses cannot replicate however may contain antigenic potential. Essentially neutralising it (removing ability to replicate).
- These viruses have nucleic acids susceptible to damage – irradiate it with UV light, or heat it
- Need large quantities of virus for vaccine
- Danger of infection due to inefficient killing e.g. Salk polio vaccine accidentally inoculating individual with pathogen
outline the process of Selection of attenuated viruses for use as vaccines
Empirical selection of non-virulent ‘live-attenuated’ organisms (by experiment)
Grow cells in the lab, culture the virus (need live cells), culture until you get a strain that will replicate but not cause disease- attenuated with respect to its ability to cause disease. - virus no longer grows well in human cells
• Live, attenuated virus will not cause disease however will confer resistance
- Mimics the natural type of infection but does not cause any pathology
• No damage caused virus cannot replicate in human cells
outline examples of Vaccines based on attenuated organisms
- Measles, mumps, rubella, Sabin polio vaccine (viruses)
- BCG vaccine for TB but level of protection highly variable: 50-80% in UK (effective protection in children but not adults)
- Salmonella typhi vaccine (typhoid fever)
outline features of Immune responses and live-attenuated vaccines
- Mimic natural infections in terms of interaction with immune response
- Better (long-lasting) immunity
- Not virulent as not presented by class I MHC
- Elicit CD4+ T-cells as well as CD8+ T-cells
- Inactivated viruses cannot produce cytosolic virus particles therefore can’t be presented with MHC class I
outline examples of Diseases caused by bacterial toxins:
• Some vaccines are available against some of these. These vaccines comprise of inactivated toxins e.g. DTP – Diptheria, Tetanus, Pertussis
outline the Production of recombinant vaccines and what vaccine is made that way
- Hepatitis B made this way
- Requires knowledge of the chemical properties of the pathogen
- Remove gene that encodes antigen
- Produce hepatitis B surface antigen
- Insert into yeast (lots produced quickly)
- Eukaryotic sophisticated method of modifying proteins i.e. glycosylation
outline how vaccines comprising of a specific polysaccharide antigen can be used against encapsulated bacteria
Encapsulated bacteria are difficult to develop vaccines against
requires a good complement response, specifically the classical pathway as this involved antibodies- alternative pathway is not sufficient
Capsular subunit vaccines (comprising purified specific polysaccharide antigen) give rise to a thymus independent immune response (no T cells made)
Thus Only IgM made, no class switching, no somatic hypermutation, no memory
This provides protective immunity in adults but not in children and the elderly (who require helper T-cells to activate B-cells-’linked recognition’)
outline Examples of conjugate vaccines
- Haemophilus influenzae type b (meningitis & serious chest infections)
- Neisseria meningitides serogroup C (meningitis)
(Meningitis is not one disease, it’s a symptom of many diseases (including measles)
outline how Conjugate polysaccharide vaccines are a more potent vaccine.
- Toxin promotes t-cell response
- Amplifies normal immune response
- Conjugate vaccines have specific polysaccharide antigen chemically coupled to carrier protein e.g. tetanus toxin
- This converts the polysaccharide to a T-dependent antigen
- Stimulates CD4 T-cell response and hence B-cell help for a more effective vaccine
- Several experiments done and select the one with best immune response
- Conjugate a polysaccharide antibody will allow a more effective immune response
- Conjugate better than polysaccharide
outline how the Route of vaccination is an important determinant for vaccine success
• Many important pathogens enter via mucosal surfaces
• Most vaccine given by injection not by mucosal route
Except e.g. intra-nasal ‘flu vaccine (children only); oral polio vaccine (better immune response if injected)
• Injections induce systemic antibodies which may not prevent all disease symptoms responses
• Mucosal immunisation induces mucosal antibodies which are more effective against the disease
• Injected – destroyed in stomach otherwise
• Practical disadvantages - risk of infection/ requires skilled staff/ cost/ discomfort
what are Adjuvants
other substance which stimulates the immune system before the pathogen enters (squalene/ oil/ aluminium salts). Add to formulation of vaccine to make them work better
- Purified pathogen antigens do not elicit a good innate immune response
- Needed to activate immune responses e.g. APC to stimulate T-cells
- Substances added to vaccines to encourage inflammation
- E.g. ‘alum’ (aluminium salts), bacterial components of combination vaccines (e.g. B. pertussis toxin component of DTP), oils e.g. squalene
- Induces sterile inflammation (interact with NLR e.g. uric acid crystals will act with NLR causing gout)
- Mimics what happens naturally in infections
outline the distribution of of immunoglobulin isotypes between mother and child
passive immunity
Dimeric IgA – mucosal surfaces. Passed through in breast milk
Monomeric IgA goes around serum
IgG – protects most tissues
- Developing baby is protected by IgG passively
- IgG crosses placenta, IgM doesn’t cross the placenta as its too large
IgE – allergic reactions
IgA- After birth, child protected by IgA (mucosal) in mother’s milk
outline The development of immune responses in man
- IgM has 5 antibody molecules stuck together difficult to get across placenta
- IgG can easily cross the placenta
- Premature babies even more vulnerable because their immune system is behind. Babis still very susceptible until around 7 months when immune system starts to kick in
outline how passive immunity is attained in new borns as adaptive immunity does not fully function until 6 months post-partum
- IgG across the placenta-in utero and post-partum protection
- IgA from mother’s milk passive immunisation against gut pathogens
- Babies (and especially premature babies) are susceptible to infection- behind in bone marrow/immune system development
- Also n.b. (horse) antisera to snake and spider venom (and previously bacterial toxins e.g. tetanus) provides passive immunity. Rare event so no vaccines
outline The principle of herd immunity
if most of the population have protective immunity, then the susceptible minority are protected (nowhere for pathogen to go).
• Protects community
• Limited potential for pathogen to thrive in individual
• Mirco-organism has a low probability of finding non-immune host
• Chain of infection not created
• The more non-immune people in a population, the greater the likelihood of outbreaks and epidemics
• Therefore: routine childhood immunisation programme
• We are no longer measles free as threshold is 85-90%
hw can measles spread and what are symptoms
droplets in coughs and sneezes
cold-like symptoms, fever, tiredness, kopliks sports
what is an early sign of measles infection in the oral cavity
Koplik’s spots
outline the features of Measles and the MMR vaccine
- Measles vaccine introduced in 1968, MMR in 1988.
- MMR is combination vaccine- works better
- Average 100 deaths every year in the UK before the vaccine. 13 per annum before MMR.
- Deaths occur in unimmunised children and leukaemia patients in remission (immunosuppressed)
- Young people born between 1998/00 and 03/04 are most succeptive
- They go to festivals and university
- Uptake in 2016 & 2017 of first vaccine dose >95% but currently only 88% for the second
- New UK measles and rubella elimination strategy for 2019
iah 20 flashcards are in theme 2
so annoying i know
