الفهرس 
Immunity to InfectionOnly 14 pages are availabe for public view
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Abstract
HPVs are DNA viruses that belong to the family
papovaviridae. The DNA genome is divided into 3 main
regions; the LCR, region of early proteins (E1-E8) and region
of late proteins (L1, L2).
HPV infection is confined to keratinocytes. HPV
replication inside the cells occurs in a silent manner. There is no
cytolysis or cell death and virus laden keratinocytes die of
natural causes as desquamation or apoptosis. Viral proteins are
only expressed at the upper layers of epidermis which are away
of APCs.
Clinical manifestations vary according to HPV type, the
anatomical location and the immune status of the host. Warts
have high prevalence during childhood. Sexual abuse is the
main cause of 50% of all anogenital verruca in children, most
frequently in girls and the incidence increases with the age of
the child. Also, pregnant females have higher risk of developing
HPV infection due to the existing immunological depression
and the higher concentration of steroid hormones.
Warts are treated with different modalities. Their
combination usually has better results. Destructive methods are
common but their main disadvantage is scarring. There are also
virucidal and antimitotic methods. Every single wart must be
treated with the previous mentioned methods.
Different agents are used as an immunotherapy such as
candida, MMR vaccine, PPD tuberculin, BCG vaccine and
tricophyton. One or two target warts are injected; this clears not
Summary
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only the local warts but also distant warts unlike traditional wart
therapies.
Nowadays, prophylactic vaccines are used to prevent
viral entry. They are type-specific. They are directed against
L1and L2 and aim to produce high levels of L1 specific serum
neutralizing antibodies and immune memory cells.
The current available vaccines are bivalent HPV 16/18
and the Quadrivalent HPV 6/11/16/18 vaccines. They are
directed against the high risk HPV types which turn to be
carcinogenic. Also, there are therapeutic vaccines that eliminate
infected cells expressing the viral onco-proteins E6 and E7.
These vaccines are still under trial.
Many researches used PPD tuberculin as an
immunotherapy. Number of injections varied from 3, 4, 6 up to
12 injection times at 2-4 intervals. Side effects were reported as
pain, edema and erythema at or around site of injection. None
of them was severe for treatment to be discontinued. Most of
them did an intradermal skin test before injection.
Immunotherapies elicit delayed type hypersensitivity
towards the injected antigen and also towards the viral antigens.
This therapy has been found to be associated with the
production of Th1 cytokines which activate Tc and NK cells to
eradicate HPV infection. The local effect induced either by
induction of a non specific inflammatory reaction or specific
reaction by stimulating the action of Tc and T memory cells.
The exact mechanism of action of immunotherapy is still
unknown. It is believed that Th1 plays a major role in the
immune response against HPV and both IL-12 and IFN-γ have
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antiviral activities. During the primary response to antigen, IL-
12 and IFN-γ are the cytokines which direct Th1 differentiation,
and IL-4 directs differentiation of Th2 populations. Interleukin-
12 and IFN-γ coordinate the link between pathogen recognition
by innate immune cells and the induction of specific immunity,
by amplifying the Th1 response.
Interleukin-12 is an IFN-γ inducer and also the antiviral
activity of IL-12 is mediated through endogenous IFN-γ.
Interleukin-12 acts in synergy with other activating cytokines
such as IL-2, IL-18 and IL-27 for IFN-γ production.
In this study, we measured IL-12 and IFN-γ levels before
and after intralesional PPD tuberculin treatment in warts. Also,
we compared their levels with levels in normal health
individuals as a control. Patients had elevated pre-treatment
levels of IL-12 and IFN-γ levels when compared to control
individuals, which ensure their immunological role against
HPV.
There was no significant difference between pretreatment
and post-treatment levels of IL-12 and IFN-γ. It is
suggested that their maximum concentration was reached. Other
factors play a role and affect resultant response to treatment.
Interleukin-12 acts in synergy with IL-2 for IFN-γ
induction from T-cells, NK cells. Similar synergy occurs with
IL-18 on macrophages, dendritic cells, and B cells. Also, IL-12
synergizes with IL-27 on naïve T-cells. On the contrary, IL-10
acts as an immunosuppressive cytokine. It is a negative
regulator for IL-12 and also inhibits IFN-γ production. As TGFSummary
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β stimulates IL-10 production, so elevation of any of them will
drive the immune system towards Th2 differentiation.
These cytokines and these target cells are not the
suspected to be deficient in this study, as IFN-γ is significantly
elevated than in the control.
IFN-γR deficiency may be the cause of HPV persistence.
There are various forms of IFN-γR deficiency, partial or
complete IFN-γR1 or IFN-γR2 deficiencies. Mutations in IFN-
γR1 or IFN-γR2 genes result in defective IFN-γ mediated cell
activation.
This suggests that the outcome of viral infection in
patients with IFN-γR deficiency depends partially on inherited
factors, and that patients with IFN-γR deficiency may be
resistant to certain viruses and susceptible to others.