Immune cells may serve for vaccine technology and for gene therapy. They are basically of lymphocyte and dendritic cell types. These
cells can be of adoptive and educated forms .Dendritic cell based vaccine technology can be established through ;In-vitro, ex-vivo and/
or in-vivo procedures. Subunit target antigen loading onto DCs or through insertion of gene construct cloned into a specific viral or
plasmid vectors .Dendritic cell based vaccine designs are found of use for infectious and cancer diseases .Experimental dendritic cell
based vaccine specific for ;viral ,bacterial ,fungal and protozoal infectious diseases are being ongoing in current research. Tuberculosis
in man and animals is problematic at worldwide scale including our country. The approved BCG vaccine is being of questionable efficacy
in infants, immune-compromised and pulmonary tuberculosis patients .
The SO2 attenuated live tuberculosis vaccine is in its way
for clinical trials .Experimental dendritic cell based vaccine designs specific for tuberculosis are being of educated DCs loaded with the
target protein ,peptide or trans-fected with gene construct codes for these proteins .Laboratory animal immune evaluations have found
to be the inserted gene DC is superior to antigen loaded Dc based vaccines in sense of immune protectivity. The current layout of tuberculosis
vaccine is; BCG questioned ,SO2 is being in its way for clinical trials and DC-based vaccine still experimental. Approved Dc
based tuberculosis preventive and therapeutic forms are still the near future goal of vaccinologists all over the world.
Adopted, Dendritic Cell, Educated, Ex-vivo, In-vivo, Technology, Vaccine
Dendritic cell serves as critical vaccine adjuvant or vaccine design
for prevention and /or treatment of microbial infections ,allograft
rejection treatment of cancer and autoimmune diseases.The
objective of the present mini-review is to sum-up the current
attitude about the DCs based vaccine for the rather common disease
all in this area or over the world ,the tuberculosis[2,3,4,5,6] .
As a phagocyte and phagocytosis in turn, they definitely appeared
as functional professional phagocytes in earth worm with coelum
passing through the evolutionary animal group ranks up to
vertebrate[ 7] .Boney fish devoted from bone marrow with an
evident extra-medullary heamopoiesis[ 8] .From amphibian up to
mammals, bone marrow haemopoiesis were evident.In boney
fish ,however. mononuclear cell system appeared as Melanomacrophage
centres in spleen and in liver[9,10,11] .
Tracing the ontogeny of the mononuclear cell system ,it is rooted
back to embryonic yolk sac,then fetal liver and fetal bone marrow
during the embryonic life of the fetus.They arose as pluri-potent
stem cells[12,13] .
The embryonic stem cells are; self re-new-able ,multi-potent ,and
non-differentiate cells with a set of characteristic surface markers
.These surface markers can be changed on differentiation to definite
cell entity. Such cells have the ability to be differentiated to any cell type in accordance with the surrounding micro-environmental
tissue mellue .Among these cell entities are the mononuclear cell
Macrophage is a general term denoted to all cells of the mononuclear
cell system that have phagocytic activity. Mononuclear cell
system(MCS) is a group of human and mammalian leukocytes
harboring peripheral blood and the reticculo-endothelial organs
,with rather different surface markers, Table 1.They performed
an array of immunobiologic functions. Mature mononuclear
cell forms and functions varies in accordance with their own
surrounding tissue microenvironment Their nomenclature will
be; glail, alveolar ,kupffer ,dendritic ,Langerhans, monocyte and
osteoclasts harboring ;brain, lung ,liver, lymph node and bone
marrow ,skin, blood and bone respectively[15,16,17].
displayed the functions of; uptake, process, present and immune
recognize the antigens as a preliminary step in the immune
response events .In ,Pyres patchs ,MCS have the antigen delivered
by M cells, they take up and present it to helper T cells then
triggering B or T cell responses. At the lymph node interdigitating
dendritic cell delivered antigens directly presenting them to B
lymphocytes to initiate immune response events.
are skin defenders .Kupffer cells in liver on antigenic stimulation
undergoes shape changes and increase in numbers within the liver
paranchyma and contribute to the local liver immunity against
the invading pathogens .Resting alveolar macrophage in
lung tissue melliue are small ovoid in active, on stimulation they
appeared larger in size and becomes rather ameboid in shape
.Glail cells in brain and CNS tissues during infectious invasion
undergoes cell form changes to satellite appearance, increase in
numbers and produce cytokines as well as contribute in tissue
regeneration .Osteoclast contribute in bone tissue catabolism.
Monocytes are phagocytic ,antigen presenting, cytokine producer
and might be differentiated into immature dendritic cells then
to mature dendritic by local cytokine action.MCS, form the
model systems for testing; phagocytosis, macrophage inhibitory
factor, ex-vivo cytokine production and antibody production by B
DC is satellite in shape with irregular nucleus in mature form and
bean shaped nucleus and ameboid shaped in the immature form.
DCs are professional phagocytes and acting as antigen presenting
cells(APC).They process antigens through MHCI,MHCII and CD1
pathways .DCs circulating within the host capture and deliver
microbial and/or cancer cell subunit antigens.
starts from lymphoid tissue to peripheral blood and back to
lymphoid tissue. DCs differentiation path starts with lymphomyeloid
progenitor cells to pro-monocyte immature monocyte
then to mature monocyte .From monocyte by the effect of cytokine
to immature DCs then to mature DCs. The surface marker for
both mature and immature is basically the same but with marked
quantitative differences, Table 2 ,DCs are hetero-genus group
of cells that displayed difference in various anatomic sites ,cell
surface phenotypes and functions. Thus ,its sub-grouped into three
subsets, Table 3 .DCs expressed a sort of cell plasticity[23,24,25].
Dendritic Cell Technology:
Immune cells can be of use for vaccine or gene therapy
technologies. The most tempted immune cell types were
lymphocytes and dendritic cells[26,27,28].These cells are either
in adopted or educated forms. Hence several technologic trends
are currently useable for educating DCs to be valid as a base for
vaccine technology both for preventive and therapeutic vaccine
types .Details of the DCs based vaccine technology are being
stated in the followings;
i-Blood samples with anti-coagulants collected from patients
.dendritic cells are separated, purified and incubated with
the subunit antigen of the causal and re-injected back to the
ii-Ex-vivo approach involves the separation purification and
culturing of DCs in cell culture system. Then the target gene
construct is added through an appropriate vector to facilitate its
journey to the appropriate target cells.
iii- Blood samples with an anti-coagulant collected from the
patients, dendritic cells are separated, purified and cultured in
cell culture system in presence of antigen source, loading agent
,maturation agent .
iv-In-vivo within the host, antigen targeted to dendritic cell
through binding to ICAM3 DCs sign or to CD209 establishing
promising in-vivo loading of antigens to DCs.
Dendritic Cell Based Vaccines:
For an effective DC-based vaccine designs development against
polio, measles, and hepatitis B. These vaccines composed of
microbial antigens are often made with adjuvant ,Table 4 ,
that activate DCs .There are urgent need for both preventive and
therapeutic vaccine for tuberculosis replacing the currently blamed
as ineffective the BCG[ 31].Since till now no approved dendritic
cell based tuberculosis vaccine are developed, evaluated and
licensed. However several experimental DCs based tuberculosis
vaccine tested iv-vitro, ex-vivo and in-vivo to the rank of
laboratory animal evaluations are being documented all over the
DCs based vaccine induced Immune Conversion:
The M tuberculosis is obliged intracellular pathogen on invasion of
the host it will stimulate Th1 or Th1 and TH2 responses at the
week 4 up to the week 12,the immune conversion sought as cytokine
rise in concentration and/or specific antibody concentration
or titres together with immune protection percentages .Here we
abstracting two experimental vaccination protocols in laboratory
animal models to give a clue to the nature of post vaccination
i-Three groups of mice were the test laboratory animals;first wa
vaccinated with DC loaded with Ag85,the second with DC loaded
CD4/Cd8 T cell peptide and the third vaccinated with adeno-virus cloned with Ag85 gene transfected to DCs. The of IL12 and was
more immunogenic than group one and two. Comparing the first
group to the second and third. The third elicited a remarkably
higher levels of ex-vivo INFg at the weeks 2,6 and 12 postimmunization
which was paralleled with high frequency of
Antigen specific T cells.
ii- Two groups of mice were the test laboratory animal.The first
immunized with calf Mtbag-calf serum –DCs vaccine and the
second immunized with Mtb ag-mouse serum-DCs vaccine in a
three doses protocol, animal was watched in first ,second and third
dose in both groups for bacillary load after challenge, INFg level,
survival and immune protection percentages. The second group
have shown reduced bacillary load in lungs and spleen, increase
of survival times, and as well as increase of INfg producing
cells in lung and lymphoid tissue .DC based vaccine group two
pays critical role in induction of protective immunity against M
Dendritic cell based vaccine Evaluations:
NHI in here
monograph published in 1998,”Understanding Vaccines”
have been put-forward set of criteria for evaluation of prototype or candidate vaccines in this paragraph we apply this set of criteria
onto tuberculosis DC based vaccine and the evaluation layout is
depicted in the table 5 .
Dendritic Cell Based Vaccine In Brief:
The developed and laboratory animal evaluated experimental
DC based vaccine for tuberculosis own several immune features
depicted in the following points:
i-Gene construct inserted DC based tuberculosis vaccine are
more immunogenic and more protective than antigen loaded DC
ii-Mouse serum is better adjuvant than calf serum DCs based
tuberculosis vaccine in mouse model for immune conversion
iii-The laboratory animal evaluation parameters include INFg,
IL12,reduction in bacillary load, survival time, and immune
iv-Subcutaneous rout is rather better than ,intramuscular ,and
intravenous routs for DC based vaccine for tuberculosis.
v-The general vaccine NIH 1998 evaluation parameters are being
partly applicable on DC based vaccine for tuberculosis.
vi-The current tuberculosis vaccine layout is being as; BCG
questioned,SO2 in its way for clinical evaluation and DC-based
vaccine is still experimental.
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