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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

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