manipulating the ir to control infectious diseases

imiquimod

tlr7 agonist - treatment of some viral - HPV - and some melanoma

supressing innate immunity

blocking over exuberant immune responses - tlr-4 antagonists in trial for septic shock

septic shock

inflammatory response and activation of coagulation = loss of fluid in tissues, fall in bp, circulatory collapse, multiple organ failure

manipulating the adaptive ir - passive immunisation

delivering the products of b cells i.e. AB

manipulating the adaptive IR - active immunisation

delivering the appropriate ag(s) to induce and activate b and t cells (vaccination)

passive immunisation

immediately avaliable, but not long lived, only ab, mainly serum ab

why cant passive imm be used w t cells

cannot be activated because of diff mhc

sources of passive AB

immunised animals, monoclonal AB from mice, blood bank serum, recombinant human AB

monoclonal ABS used to treat human disease

decrease immunogenicity, maintain ag specficity

active immunisation

induction of components of “wildtype” IR - immunisation, vaccinationa

advantages active immunisation

long lived (naturally boosted), can involve humoral (Ab) and cell immunity, can maybe target specifc tissue locations

disadvantages active immunisation

takes time to induce, variable in very young and very old

systemic induction

thru muscle i.e. ir creates high iga response

mucosal induction

i.e. rotavirus taken orally

immunological memory

first exposure to ag induced pool of memory cells, repeat exposure to same ag increase magnitude of response

currently licensed vaccines use

live attenuated organisms, subunits, killed MOs, VLPs

we want vaccines to….

isotype (class) switching, high affinity AB, induction of memory B cellsho

how to induce efficient B cell activation…

Ag binding to BCR alone results in only iGm produced - plasma cells - no isotype switching, no affinity Ab, no memory b cells

to induce efficient b cell activation…

need help from activated t cells

t cell help to b cells

interaction w CD40L and appropriate cytokines induce isotype switching, high affinity AB, memory cells

for t cell help to b cells, vaccines must

contain epitopes which can also be recognsied by the t cell

CD4 T cells are needed to

provide help to B cells for Ab production, produce IFN-gamma, expand effector CD8 T cells, provide the singlas to promote cd8+ memory

CD8 T cells are needed to

lyse virus infected cells, lyse cells containing intracellular bacteria

vaccine induced cd4 t cells - signal one

any vaccine ag delivered to the tissues gain access to endosomes in APCs to enter the class II processing and presentation pathway for signal one

vaccine induced CD4 T cells - signal 2

need to induce the costim molecules CD80 AND CD86 on APC for signal 2 - induced by PAMPS interacting w PRRs on APCs

purpose of adjuvants

pamps/damps dictate which ck are released, thus can choose which adjuvants as to mediate a specific ck response

adjuvants

a substance that is added to a vaccine to enhance prolong or modify the IR to the Ag

adjuvants can

promote Ag uptake and presentation, activate iir thur prrs, create a depot effect that slows ag release, share the type of air