Vaccines Flashcards
possible question: discuss current concepts of vaccines. Learn different T cells etc.
Immunisation
act of making someone. something immune to a particular disease
Vaccination
deliberate induction of adaptive immune response by injecting a vaccine (dead or attenuated - nonpathogenic) form of the pathogen
Immunological Memory
Ability of immune system to generate more rapid and more effective responses to antigens previously encountered
Memory Cells (B cells)
initial expansion of antigen specific cells -
some progeny don’t divide or develop to plasma cells
revert to small lymphocytes with same BCR as ancstors
Somatic hypermutation
alterations in variable regions of light and heavy chains of memory cells - random
increase affinity 1000x
Features of memory B cells (6)
Long lived Increased frequency proliferate more rapidly produce more antibody produce higher affinity antibody produce antibodies with better effector functions (IgG/IgA)
Memory T cells features (3)
long lived
high frequency
proliferate more rapidly
Memory T cells express
low levels of L-selectin not home to lymph nodes and so stay in circulation
CD450R associated with TCR and CD4 co-receptor
more effective transduce signal than naive
Naive T cell express
CD45RA - not associate with TCR
Vaccine must… (4)
Activate antigen presenting cells to process antigens and produce cytokines
Activate T and B cells, giving high yield memory cells
Generate T cells to several epitopes (parasite variation)
Provide constant and long lasting source of antigenin lymphoid tissue
Natural active
natural infection
Artificial active
immunisation
Natural Passive
Placental transfer IgG
Maternal IgA - colostrol transfer
Artificial Passive
human/animal IgG normal or immune
pooled specific immunoglobulin
animal sera (snake venom) anti- toxins/venoms
Passive immunisation - Passive Transfer
transfer specific high titre antibody from immune donor to non-immune
Passive Immunisation - Adoptive Transfer
transfer immune cells from immune donor
Passive Immunisation
immediate
transient - only last up to 6 months
Neonatal protection
trough at 3-6 months - decline maternal IgG, child’s still rising
Active Immunisation - vaccine types (5)
Live attenuated Killed Sub-unit Conjugate Recombinant
Requirements of effective vaccine (8)
Safe High level protection Long-lasting protection Right response type (local/systemic) (Ab/CMI) Low cost stable easy administration minimal SE
Killed Vaccine Examples (4)
Salk
Pertussis (Whooping cough)
Typhoid
cholera
Killed vaccine features (3)
important antigens must survive
possible SE
use formaldehyde to kill
Advantages of killed vaccine
stable in storage
not cause disease through residual virulence
Live Vaccines examples (6)
Mumps Measles Rubella Oral polio (sabin) BCG Yellow fever
Live vaccines feature
cold attenuated
host range mutants
Live vaccine positives (4)
single dose
natural route admission
local and systemic immunity
right response type
Live vaccine negatives (4)
Reversion to virulence
contamination
susceptible to inactivation
disease in immunocompromised
Recombinant sub-unit example
Hepatits B (first) protect against natural infection
purified sub-unit
purified component of pathogen
purified sub-unit example
Haemophilus Influenza B –> meningitis or pneumonia
purified capsular polysaccharides
purified haemagglutinin and neuraminidase
Conjugate example
Haemophilus vaccine conjugated to tetanus or diptheria toxoid
Conjugate mechanism
b cell bind polysaccharide and internalise and present peptide to T cells, B cell produce relevant antibody
Children not respond to polysaccharide antigen
link polysaccharide to protein (tetanus toxoid) to gain T cell dependent response
presents protein and stimulated to produce antibody to polysaccharide
Right type of immunity
HIV –> CTL
more harm than good otherwise
Cytosol - virus response
cytotoxic CD8
Macrophage vesicles response
TH1
Extracellular fluid response
TH2
Adjuvants
enhance immune response
keep store of antigen in individual
immunostimulatory response
e.g. alum better for antibody than cell mediated
NEW DNA vaccines
Injected with DNA encoding antigen
DNA vaccine plasmid
antigen expression unit produciton unit (amplification)
Plasmid delivery (3) and best place
intradermal
intravenous
intramuscular
skin and mucous membranes best - high conc dendritic cells, macrophages and lymphocytes
Gene Gun (biolistic)
sticky DNA to gold
accelerated by partial vacuum
Gene pathway for DNA vaccine
transcribed and translated into peptide
binds MHC 1
presented to CD8+ T cell (virus)
DNA vaccine into Dendrtic
CD4+ (T helper) and CD8+
DNA vaccine advantages (6)
Induce humoral and cell mediated antigens resemble native viral epitopes Produced quick Many differemt antigens in one dose Improper folding not a problem cheaper
DNA vaccine Negatives
Cannot substitute for polysaccharide vaccines - outer caspid
extended immunostim –> chronic inflammation
some antigens require processing
DNA tatooing
naked plasmid with thousands of punctures - multiple needle device
affects local cells in murine skin - strong specific response
Dengue in mice
DNA vaccine used to immunise
Serum from immunised mice reacts with all 4 serotypes
inhibited infection of naive cells
DNA vaccine looking to treat
cancer and virus
poor immunogenicity so far
Dendritic cells
main APC - broad range of effector cells
important in tumour specific immune response
Dendritic cells location and function
Immature - mucosal etc. - where efficiently phagocytose microbes, particulate antigens + take up soluble antigen
move to 2ndry lymphoid tissue and mature - present antigen to T cells
DC Antigen take up
engulfment of apoptotic bodies
macropinocytosis
receptor mediated endocytosis (mannose and Fc - CD32/64
DC source
CD34+ blood/bone marrow precursors
Immature DC cultured with
IL-4 and GM-CSF
derived from monocytes
Mature DC cultured with
IL-4, GM-CSF
derived from monocytes
with IL1beta, IL-6, TNFalpha and PGE2
Antigen preparation
Peptides - specific
tumour lysates - many antigens - not prefer T helper
RNA transfection - many tumour epitopes to MHC I
Objective response rate
disease not progressed
CBR
Clinical Benefit Ration - objective response and stable disease
Trials into
glioma, melanoma
prolong life
Interstitial DC induce
ig secreting plasma cells and trigger diff of follicular helper T cells
Langerhan cells induce
cytotoxic CD8+ T cells
Reverse Vaccinology
genome sequence used to predict proteins location in organism surface - make protein - see response
Advantages of Reverse Vaccinology (5)
fast use organisms can;t grow rare antigens identified antigens not in-vitro non-structural proteins
Disadvantage of Reverse Vaccinology
Not use non proteinous antigens
Benign pre-malignant melanomas in cervial cancer
CIN - cervical intraepithelial neoplasia
1-3 in severity
HPV vaccine
expensive
18 types associated with cervical cancer
HPV vaccine manufacture (2)
Gardasil
DNA free virus like particles VLP in yeast
express major caspid antigen L1 - strong response
HPV only works
prior to infection
HPV possible SE
Make room for similar viruses
Malaria (4)
Plasmodium species - protozoa, apicomplexa
Transmitted by female anopheles mosquito
sexual stage - mosquito
asexual stage - vertebrate host - infect 4 species
Plasmodium falciparum
most common
more fulminent - coma and renal failure
Malaria symptoms
headache, muscle ache, lethargy
fever - temp rise - shivering
lasts 30 minutes returns 48hrs
spleen and liver enlarge + anaemia
Malaria can relapse
store in liver
vivax and ovale
Malaria - pregnant
anaemia and reduced birth weight
death more common
Cerebral malaria (3)
sudden coma
can be fatal
can be more common in healthy
Falciparum fatal
cross blood brain barrier
Malaria lifecycle (5)
sporozoites travel to liver propagate in hepatocytes --> shizonts release merazoites - infect erythrocytes asexual reproduction in blood lysis of erythrocyte and infect RBC
Malaria life cycle sexual stage (4)
Merazoites form male and female gametoytes - circulate
taken up in new mosquito
fuse into zygote and penetrate gut membrane –> oocyst
divides and release sporozoites - travel to salivary gland
Different vaccine (3)
Pre-erythorcyte - block stages in hepatocytes
Blood stage - no disease, organisms still present
Transmission blocking - works in mosquito
Pre-erythocytic vaccine
protect and prevent invasion (30mins)
radiation-attenuated sporozoites
CD8+ Tcell response
Blood Stage Vaccine
Stops symptoms
work on naive population not one already exposed
Transmission Blocking Vaccine
Target sexual stage specific molecules
not yet effective enough
conjugate - detoxified exoprotein act as adjuvant
HIV Vaccine types being developed (not essential)
peptide epitope DNA recombinat viral protein live vector pseudovirions
Tuberculosis Vaccine
BCG - live attenuated - mycobacterium bovis
good in children
Blocking hypothesis
prior sensitisation to prior mycobacterium provide protection
but not against TB
and impairs BCG
Ideal new TB vaccine
Given at birth
transmitting blocking - decrease sputum smears
therapeutic vaccine used with therapy - shorten treatment
induce strong cell mediated
