Vaccines Flashcards
the memory response can be so effective there is no
prodrome
what does vaccination do
primes the immune response without exposure to pathogenic agent
herd immunity
sufficient immune members of a population limit spread of a pathogen in a population
vaccines are composed of
whole pathogenic organisms or antigens from pathogens
lymphatic system
returns lymph back to circulation into the subclavian veins
lymph nodes
sample antigens from the lymphatics and display to lymphocytes (secondary lymphoid tissue)
spleen
performs a similar function of sampling antigens for the blood (secondary lymphoid tissue)
leukocytes are generated in
the bone marrow
leukocytes are educated
for self vs non-self discrimination in the bone marrow or the thymus (primary lymphoid tissues)
two arms of the adaptive immune response
humoral immunity - B cells
cell-mediated immunity - T cells
humoral immunity
B cells
extracellular targets
antibodies secreted into the serum
binds to targets and directs effector responses
the major outcome of most vaccines
cell-mediated immunity
T cells
intracellular antigens
eliminates infected or damaged cell
clonal selection theory
education/deletion in the bone marrow or thymus removes auto-reactive cells
binding a specific antigen stimulates clonal proliferation to make a population of B or T cells expressing the same receptor
B and T cells diversity is
encoded in the germline and expressed by recombination
BCR recombination
diversity of immunoglobulin generated by recombination of V, D and J segments
requires RAG1/2 - lymphoid specific recombinase
heavy chains
43 V, 21 D, 6 J = 5658 combinations
light chains
have 204 or 165 different combinations
terminal deoxytransferase
add non-templated additional nucleotides at each junction to increase diversity
b cells encounter antigen and T cells in
lymph nodes
how do B cells encounter antigen and T cells in lymph nodes
antigen from the periphery travels to the lymph nodes in the lymph
follicles contain FDCs and B cells
FDCs trap antigen
B cells continually circulate to different lymph nodes and sample antigen
B cell that finds antigen move to the paracortex (T cell zone)
activated B cells form a
germinal center (GC)
germinal center
sites of somatic hypermutation (SMH) and class switching
both require activation-induced cytidine-deaminase (AID)
somatic hypermutation increases
affinity and diversity of antibody responses
class switching changes
the effector functions of antibodies (new Fc regions)
types of B cell antigens
repetitive antigens can activate B cells if there is TLR or complement bound to the antigen
no co-stimulation (TLR, complement, or T cell) leads to B cell anergy (absence of response)
TD antigen, TI-1 antigen, TI-2 antigen
qualities of a good B cell antigen
non-self
large - many epitopes
chemically complex
can be degraded and presented on HLA (T-dependent)
protein»_space; carbohydrate»_space; lipid
antibodies link _____ with _____
link antigen recognition (Fab) with specific effector functions (Fc)
antibody-dependent enhancement of infection
non-neutralizing antibodies bind (especially targeting different serotype) bind to virions
Fc portion of IgG binds to Fc receptors on monocytes
low pH in the endosome leads to fusion, entry and subsequent replication
second infection with dengue leads to worse disease (hemorrhagic fever)
antibody-dependent enhancement of infection is especially observed in
flaviviruses
dengue, zika, west nile, yellow fever
adaptive immunity - cytotoxic T cells
express CD8 and recognize antigen in the context of HLA class I
if cytotoxic T cell recognizes its cognate antigen it will attempt to kill the cell
preformed granules contain
perforin and granzyme B
granzyme B stimulates
apoptosis by the intrinsic pathway (damaging mitochondria)
Fas ligand will
stimulate apoptosis by the extrinsic pathway (signal from another cell)
B cell epitopes must be
on the surface of the antigen
T cell epitopes can be
anywhere in a protein sequence
are there more T or B cell epitopes available in a pathogen
T cell
what is common for B cell epitopes
antigenic drift
antigenic drift for T cell epitopes is
uncommon and likely represents a higher genetic barrier
active immunity (viral) vaccine strategies
attenuation
inactivation
fractionation
cloning
inactivated vaccines
whole viruses or bacteria that are inactivated using radiation, heat or chemicals (formaldehyde, formalin)
-prevents replication but maintains antigenicity
-do not infect cells - mostly humoral response
-requires boosting
attenuated vaccines
whole organism weakened or adapted to growth in non-human cells
-less virulent and less replication
-mild to no disease symptoms
-infects cells - humoral and cell mediated response
-boosting not often required
toxoid vaccines
bacterial exotoxins purified from culture
-toxins inactivated with chemical treatment (formaldehyde)
-stimulate neutralizing antibody responses
-diphtheria and tetanus exotoxins
recombinant subunit vaccines
generate antigen in yeast culture and purify
-requires cloning antigen that generates a protective response
-stimulate neutralizing antibody responses
(HBV and Shingrix)
virus-like particles (VLP)
viral capsids self-assemble in a concentration-dependent manner
some viral capsids do not require viral genomes - form non-infectious virus-like particles
HPV vaccine
VLPs stimulate protective antibodies responses
prevents cervical and some esophageal cancer and genital warts
genetic vaccines and the strategies
gene encoding an antigen into human cells
strategies: DNA on a plasmid, mRNA, modified virus vector
for genetic vaccines DNA and RNA require a
platform allowing entry into cells, such as liposomes or electroporation
genetic vaccines can generate
humoral or a cell mediated response
COVID-19 vaccine
mRNA lipid nanoparticle (LNP)
taken into cell
escapes the endosome
ionizable lipids are uncharged at neutral pH and positive charge at low pH
contributes to disruption/fusion/payload delivery
