2.7 Immunisation Flashcards
There are many vaccines available today, and most were developed in the past 40 years:
• Most vaccines require booster shots (timing dependent on type of vaccine) → _____________ vaccines generally need less frequent boosters
Live attenuated
Live virus particles with very low virulence are given → recognised by the _______________ (production of memory B cells)
• Replicate in host and present antigens to immune system (mimics natural infection more closely than inactivated vaccine)
• More likely to stimulate both B-cell and T-cell arms of the adaptive immune system
Inactivated: Virus particles are cultured and killed → ______________ are recognisable enough to produce a response
Subunit: ____________ administered (may be given in another virus which then manufactures the harmless particle)
live attenuated;
humoral system;
protein antigens;
Partial viral particle
ACTIVE & PASSIVE IMMUNITY
[Active immunity (activate immune system)]
Vaccines: produce an immune response in the patient that confers protection
• Degree of protection is dependent on host immune response
• Usually lasts much longer than with passive immunity
[Passive immunity (from external source)]
Immunoglobulin preparations (human-derived): provide passive antibody rapidly
• Used prophylactically before or after exposure (instant protection)
• Only lasts for a relatively short time in circulation (1 – 3 months) → repeated doses may be needed
• Cannot be used to treat established disease (only prevention) → mostly ____________ the disease
________: animal-derived
attenuates ;
Antisera
Immunoglobulin Preparations
- IV Immunoglobulin: Replacement therapy and immunomodulation
- Varicella-zoster immunoglobulin (VZIG): Susceptible pregnant women, neonates or immunosuppressed patients exposed to chickenpox
- Hepatitis B immunoglobulin (HBIG): Prevention of HBV infection (in conjunction with vaccination)
- Normal human immunoglobulin (NHIG): Prevention of ___________ infection (limited efficacy)
- Rabies immunoglobulin: Useful adjunct to rabies vaccine following a significant rabies exposure (e.g. animal bite in a non-immune subject)
HAV, polio, measles
CELL-MEDIATED IMMUNITY
The adaptive immune system has various key features which can be exploited to produce effective vaccines, including:
1. Antigen specificity
2. Capacity for memory (allows the effects of vaccination to last many years after the vaccine has been cleared from the body)
3. Fast and effective secondary responses which can prevent infection and disease (even though initial primary response is slow)
T cell (cell-mediated) response
- Specific T cells are activated by APC presentation of antigen/vaccine
- Effects:
1. ____________ towards infected cells
2. Activation of _____
3. Generation of __________
B cell (humoral) response
- Specific B cells are activated by T cells or direct recognition of antigens (via BCR/IgM)
Effects:
1. Production of specific antibodies* (elimination of pathogen)
2. Generation of memory B cells
*Antibodies (immunoglobulins) are proteins produced by B cells in response to infection with foreign substances/antigens → binds to antigen to neutralise the infectivity
Cytotoxicity;
B cells;
memory T cells
The primary aims of vaccination are to prevent disease in the vaccinated person and prevent infection in the general populations (via herd immunity):
• Other members of the population (who cannot be vaccinated like the immunocompromised, elderly) can be protected by increasing herd immunity
• Prevention of infection is harder to achieve, but is important in herd immunity and eradication of an infectious agent (significant proportion of population may have asymptomatic infections → reservoir of infection)
Vaccination programmes are not designed to protect the individual child, but rather the entire population from disease (via herd immunity):
• Proportion of population requiring vaccination to be protected depends on the reproductive number of the particular infection
- Reproductive number (R0): Number of people in an ____________________ population who will be infected by a single case of a given disease each generation
- Population target: Calculated by _______________
*Higher R0 indicates a _____________ and a greater degree of vaccination required to provide herd immunity (e.g. very infectious diseases like measles require 92 – 94% vaccination for sufficient herd immunity).
unaffected, unprotected;
1 – (1/R0);
higher infectivity
The conditions required for successful eradication of a disease include the following:
- Infection is limited to humans with no animal/environmental reservoir (prevents external re-introduction of the disease into the population)
- Virus/bacterium should be __________ with only one/very few strains
- Virus should not __________ (reduce opportunity for transmission)
- Vaccine must induce a lasting and effective immune response
antigenically stable;
persist in the host
The current MMR vaccine contains the ______________ strain (measles), __________ strain (mumps) and __________ strain (rubella):
• Use of the __________ strain of mumps in the MMR vaccine was discontinued as it caused an unacceptable level of meningitis
• Led to significant reduction in the incidence of all 3 diseases (similar for other vaccines like diphtheria → rapid decrease in incidence and mortality; Haemophilus influenzae vaccine led to 96% decline in cases in children < 1 year of age)
Measles: Usually self-limiting but can be severe for immunocompromised or malnourished children (causes 700000 deaths per year):
• ___________________ is common
• Other features: pneumonitis (secondary bacterial infections), croup (harsh barking cough), bronchiolitis, encephalitis, myocarditis, thrombocytopenia, subacute sclerosing panencephalitis (SSPE)
Mumps: May cause significant complications including ____________________, pancreatitis, oophoritis (ovarian inflammation), meningitis and deafness, orchitis (testicular inflammation)
Rubella: Generally mild (with few complications), but it may be __________________:
• Congenital rubella syndrome: cataracts, heart defects, mental retardation, deafness
Edmonston-Enders;
Jeryl Lynn;
RA27/3;
Urabe;
Otitis media (middle ear inflammation);
parotitis (parotid gland inflammation);
teratogenic (causes significant malformations in the unborn child, especially in the 1st trimester)
ONCOVIRUS VACCINES
There is an increasing number of viruses which have been shown to cause cancer, and are thus potentially vaccine-preventable
- Cervical cancer: Human papillomavirus (HPV)
- Primary liver cancer: Hepatitis B and C (HBV/HCV) → effective against HCC
- Lymphoma: ___________________
- Nasopharyngeal carcinoma: ______________
- Kaposi sarcoma: _______________
Two vaccines against HPV have recently been introduced, and are both effective against antigen types 16 & 18 (major causes of cervical cancer):
• One of these is effective against antigen types 6 & 11 (major causes of genital warts)
• Proved effective in preventing the
development of ______________
Epstein-Barr virus (EBV), Hepatitis C (HCV), HTLV-1 ;
Epstein-Barr virus (EBV), human papillomavirus (HPV);
Human herpesvirus 8 (HHV8);
cervical intraepithelial neoplasia grade 2/3 (CIN2/3)
TYPES OF VACCINES
- Live attenuated: Replicate in the host → larger and broader antigen challenge to immune cells e.g. ________________
- Inactivated: Do not replicate in the host and less ____________ than live vaccines; safer in immunocompromised patients (can be used in highly lethal infections like rabies) e.g. Pertussis, rabies, inactivated polio vaccine (IPV), HAV, typhoid
- Recombinant protein: Produced artificially by ______ containing the HBV surface antigen DNA sequences (inserted using recombinant DNA technology) e.g. HBV
- Subunit: Contains only the antigenic parts of the pathogen e.g. ___________
- Conjugate: Proteins (not very antigenic) attached to a carrier protein (makes them more potent) e.g. _____________
- Toxoid: Toxin produced by certain pathogens e.g. Tetanus, diphtheria
MMR, rotavirus, yellow fever, BCG, oral polio vaccine (OPV), VZV, typhoid
immunogenic;
yeasts;
Influenza, meningococcal A/C, pneumococcal, typhoid;
Haemophilus influenzae B (HIB), meningococcal C, pneumococcal conjugate vaccine (PCV)
OTHER VACCINES
- Rotavirus: Rotavirus is highly infectious (_________ infectious dose) and infects all children by the age of 5 → immense morbidity and costs
• Need for the rotavirus vaccine (at _______________)
Bacillus Calmette-Guerin (BCG)
- Live attenuated strain of M. bovis given _____________ (only used to prevent latent infections) → given after tuberculin test (unless < 3 months old)
Rabies: Inactivated rabies virus used ___________________
• Given in conjunction with HRIG post-exposure
Rubella: Used in _____________ (prevent rubella from spreading to the foetus during pregnancy and then causing congenital defects) Diphtheria, polio
Used in people if not previously immunised during childhood HAV, HBV, rabies
For at-risk groups (in case of exposure)
*Vaccines (especially live attenuated ones) must have proper storage and cold-chain before use
100 particle;
6 weeks and 1 month;
intradermally;
pre-exposure (if at risk) or post-exposure (due to relatively long incubation period of rabies):
seronegative women
CONSIDERATIONS
It is not advisable to give the _________________ during pregnancy even though they may not be teratogenic or transmissible:
• Virus in the oral polio vaccine is excreted in the stools of immunised individuals
• Live vaccines should be avoided in patients having chemotherapy for malignancies, patients < 6 months after BM transplant or children on high-dose steroids and cytotoxic drugs
• HIV patients should be given _______________, but not the BCG vaccine (IPV can be used in symptomatic patients):
o CD4 __________: live vaccines are safe (MMR should be given if susceptible)
Most adverse reactions to vaccines are mild and self-limiting (e.g. __________________), while severe reactions are uncommon:
rubella, polio, MMR vaccines as well as live vaccines (especially BCG or polio);
inactivated vaccines (e.g. HIB, TDaP);
> 200;
fever, rash, injection site reactions
complications of Tdap?
Anaphylaxis, protracted crying. Encephalopathy, shock
Complications of OPV/ IPV?
Poliomyelitis (for OPV). Guillain-Barre syndrome
complications of measles vaccine?
Anaphylaxis, Thrombocytopenia
complications of rubella vaccine?
Acute arthritis
