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51 terms

411 Exam 3 - Vaccines

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innate immunity
the first line of defense against infection; provide initial defense against infections; includes epithelial barriers, phagocytes, complement, and NK cells; within 12 hours after infection
adaptive immunity
responds later after infection, but produces a more specific response and is able to have memory of the microbe; includes B lymphocytes, antibodies, T lymphocytes, and effector T cells; occurs 1-21 days after infection; can eliminate disease through cell-mediated and humoral immunity, as well as surviving memory cells
pathway of adaptive immunity
antigen recognition (APCs, naive T and B cells), lymphocyte activation (clonal expansion, differentiation of B and T cells), antigen elimination (humoral immunity, cell-mediated immunity), contraction (homeostasis; apoptosis), memory (surviving memory cells)
vaccination
prepares the body for infection, eliciting the primary response, thus the secondary response will be stronger and faster (memory B cells made)
BCR
B cell receptor
B lymphocytes
recognize soluble antigens in circulation (don't recognize infected cells), mature to plasma cells that can secrete antibodies
antibodies
can have a myriad of functions - neutralization of microbes, phagocytosis, complement activation
helper T lymphocytes
recognize antigens presented on surface of APCs in MHC Class II; must be CD4+, become activated and secrete stimulatory cytokines; don't kill directly
stimulatory cytokines
stimulate different mechanisms of immunity and inflammation - cause activation of macrophages, inflammation, and activation (proliferation and differentiation) of T and B cells
TCR
T cell receptor
APC
antigen presenting cell
CTL
cytotoxic T lymphocyte, killer T cell
Killer T cells
recognize antigens presented on surface of infected cells in MHC class I; must be CD8+; need 2 signals before they can kill the cell (activation and TCR specific for antigen); TCR binds to presented antigen and kills by releasing cytotoxic vesicle of perforin and granzyme B; receptors have more limited diversity than T or B cell antigen receptors to recognize and kill their targets
regulatory T cells
suppress and prevent immune response, e.g. to self antigens
dendritic cells
professional APCs
anatomy of an infection
dendritic cells engulf free antigens at site of infection, transported via lymphatics into regional lymph node, naive B and L cells migrate in and are activated (clonal expansion and differentiation into effector and memory cells), cells and antibodies enter circulation, antigen eliminated by T cells, memory lymphocytes wait in tissues and secondary lymphoid organs for the next infection
TLR
toll-like receptor; most characterized pathway that activates APCs w/danger signals; some are expressed in endosomes and some on the cell surface; different receptors recognize different pathogens
TLR signaling pathway
recruitment of adapter proteins; recruitment and activation of protein kinases; activation of transcription factors; gene transcription; expression of inflammatory cytokines, chemokines, endothelial adhesion molecules, costimulatory molecules, and antiviral cytokines
B cells as APCs
receptor mediated endocytosis of antigen, antigen processing and presentation (Class II MHC-peptide complex), T cell recognition of antigen --> activated CD4+ T cell
goal of drug delivery
get drug to tissue/cell of interest so it can exert its mechanistic action
antigen
what the disease looks like; a representative surface marker from the bacteria, virus, toxin, cancer cell, etc, that you would like the immune system to recognize
adjuvant
increases specific immune response to the antigen (creates a depot effect, stimulates the APC to upregulate activation markers, secrete cytokines, etc...); aluminum salts (alum), alum + monophosphoryl lipid A (ASO4), MF59 (squalene, span85, tween80)
target cells
dendritic cells, macrophages, B cells; T cells
routes of delivery
often delivered into the skin to avoid serum degradation, protein binding, and to create a depot effect; can bbe intradermal, subcutaneous, intramuscular
activation of APCs
APC circulate throughout the body searching for antigens and activation, constantly sampling their environment; they can be activated by many mechanisms (TLRs) and many adjuvants activate in this manner; once they are activated, they retreat to draining lymph nodes, mature, and present antigen
antigen from epithelium and connective tissue
captured by lymph nodes
blood-borne antigens
captured by APCs in the spleen
CD4 T cells
specifically bind to MHC Class II on APCs, soluble antigen is endocytosed, CH4 cells help B cells make antibodies against soluble antigens (circulating viruses/bacteria)
CD8 T cells
specifically bind to MHC Class I on APCs, surface bound antigens on infected cells recognized, CD8 cells recognize infected cells based on the antigens presented in MHC I on the surface (based on intracellular proteins)
Class II MHC
extracellular antigen presented by macrophages of B cells to CD4 helper T cells, which activated the macrophages or B cells and eliminate the extracellular antigens
Class I MHC
cytosolic antigens are presented by nucleated cells to CD8 CTLs, which kill/lyse the antigen-expressing cells
humoral immune response
immune responses initiated by recognition of antigens by B cells and helper T cells; activated cells migrate towards each other and interact, resulting in B cell proliferation, differentiation into antibody-secreting cells, and early isotype switching; late events occur in germinal centers and include affinity maturation of the response and additional isotype switching, and memory B cell generation
types of vaccines
attenuated live virus, inactivated/dead virus, subunit vaccine, DNA encoding antigen
attenuated vaccines
against virus, bacteria, parasite; attenuated by irradiation (UV light), chemical means (formaldehyde, beta-propiolactone), repeated passage in vitro, or genetic means; H1N1 vaccine, M(NLS-88R)
M(NLS-88R)
3 mutation included in vaccine formulation to make the virus less pathogenic (even at high infectious doses), yet still able to replicate in vivo; caused decreased viral titers in lung/brain/nose of mice tested, mice showed no weight loss after vaccine
HPV
human papillomavirus; causes cervical caner, some head and neck cancers; HPV 16 causes more than 50% of cervical cancers worldwide
Gardasil
subunit vaccine; quadravalent (HPV 6, 11, 16, 18); approved for women and men, ages 9-26; adjuvant is aluminum hydroxyphosphate sulfate; yeast expression system to manufacture protein antigens
Cervarix
subunit vaccine; bivalent (HPV 16, 18); approved for women only; ASO4 adsorbed onto aluminum hydroxide salt as adjuvant; vaculovirus (insect cell) expression system used to make protein antigens
DOTAP/E7 complex
therapeutic cervical cancer vaccine of MHC class I peptide antigen and lipid adjuvant; about 100nm; nanoparticles taken up in vivo and activate dendritic cells; vaccine uptake by DCs in draining lymph node after 4 hours; causes tumor regression in vivo
Provenge
recently approved therapeutic vaccine for prostate cancer; recombinant antigen composed of PAP and GM-CSF; blood is isolated from the patient, leukocytes are purified, cells are stimulated w/tumor associated antigen-cytokine fusion proteins, lymphocytes are activated against TAA (tumor associated antigen); repeat cycle 3 times
vaccines NC pharmacists can administer
influenza, pneumococal, zoster vaccines, per the NC Administrative Code; cannot give vaccines to those under age 18; must have PCP consultation before giving pneumococcal or zoster vaccines
preparing influenza virus vaccine (split virus)
propagated in embryonated chicken eggs; virus-containing fluids harvested, inactivated w/formaldehyde, concentrated, and purified; virus disrupted w/Triton X-100; split virus created; stabilizers and preservatives added; injectable vaccine ready
allantoic fluid
from chicken eggs, used in many cases for virus propagation
TIV
trivalent inactivated influenza vaccine, suspension for IM injections, split virus and subunit vaccines; Afluria, Fluarix, FluLaval, Fluzone, Fluzone High-Dose; Agriflu, Fluvirin
preparing influenza virus vaccine (subunit)
propagated in embryonated chicken eggs; virus-containing fluids harvested, inactivated, concentrated, and purified; removal of internal proteins via cationic surfactant and centrifugation; surface antigens only remain; stabilizers and preservatives added, injectable vaccine ready
LAIV
live, intranasal influenza vaccine,
FluMist, pre-filled, single-use, half dose in each nostril, live trivalent vaccine, genetically modified, cold-adapted/temperature-sensitive so no replication at body temperature (attenuated), don't give to people on aspirin therapy
H5N1 influenza virus vaccine
for national stockpile, for 18-64 yr olds, split virus, monovalent, 2 IM injections 28 days apart, multi-dose vial w/thimerosal
pneumococcal vaccines
work against streptococcus pneumonia, given to children (highest risk of invasive pneumococcal disease); Prevnar (4 dose series), Prevnar 13 (4 dose series, more serotypes), Pneumovax 23 (given to age 50+ as single injection)
Zostavax
live attenuated virus vaccine for prevention of herpes zoster (shingles) in age 60+, single injection (SC suspension), lyophilized preparation; no preservative b/c it is a single-dose vial; no adjuvant b/c it is a whole, live virus
thimerosal
preservative in multi-dose vaccines; causal relationship drawn by parents, viewing vaccines as dangerous and unnecessary; think that repeated vaccination may lead to high Hg levels in infants; from epidemiological evidence, no link was found; paper linking autism w/MMR vaccine was fully retracted from published record in 2/10
VAERS
Vaccine Adverse Event Reporting System, exists to catalog adverse events due to vaccines