Mucosal Immunity in STIs

Adaptive Immunity
Adaptive Immunity

• Follows initial innate immune mechanisms

• Consists of:
• Humoral Immunity
• Cell-Mediated Immunity
Humoral Immunity

• Both systemic and locally produced immunoglobulins (mainly IgG)

are found in cervicovaginal secretions and semen
• IgG > IgA  unlike the GI tract (Peyer’s patches)  such tissue has
recently been described in the ectocervical TZ
• FGT  weaker local immunoglobulin responses than intranasal,
oral, or rectal
• The homing mechanisms of B lymphocytes are poorly defined, because the
absence of MadCAM-1
• MGT  Local responses to pathogens  appear to be weak
Humoral Immunity

• Vaccines HPV (bivalent and quadrivalent)  utilize the outer coat

protein (L1) formed as virus-like-particles (VLPs)
• produce high titre
• sustained levels of neutralizing antibodies several fold greater than that
produced naturally
Cell-Mediated Immunity

• Classic paradigm: antigens from pathogens  taken up by mucosal

DCs, LCs in stratifed squamous epithelium  invading  conveyed
to draining lymph nodes  CD4, CD8, and B lymphocytes were
generated and cycled back to the infamed epithelium
• Occurs in both initial and recurrent infections
• HSV and HIV:paradigm  markedly modified
• More complex involving cooperation of multiple subtypes of DCs
• Generation of local memory T cells
Cell-Mediated Immunity
Cell-Mediated Immunity
Cell-Mediated Immunity
Cell-Mediated Immunity

Important in the
mucosa
Genital vs Gastrointestinal Tract Immunity

• Similarities
• immunologically reactive, producing antimicrobial peptides, cytokines, and
chemokines and can present antigen
• Commensal bacteria
• lymphoid aggregates
Genital vs Gastrointestinal Tract Immunity

• Differences
• greater density of organized lympho-epithelial tissue in the gut
• ease of inducing local immunoglobulin
Specific Diseases

• HIV
• Genital Herpes
• Human Papilomavirus
• Chlamydia trachomatis
HIV

• The cellular targets (sexual transmission)

• activated and resting CD4 lymphocytes
• Macrophages
• DCs
• There is now strong evidence supporting the role of LCs  the major
HIV-infectable constitutive cell type in the anogenital stratifed
squamous epithelium, in HIV transmission
• Recent studiesHIV infection of DCs or LCs induces partial maturation
and enhanced migration
• The partial maturation is suffcient to enhance T lymphocyte stimulation
and might also enhance DC–T cell contact and viral transfer, thus
affecting both viral production and antiviral immunity
Genital Herpes

Immune Response to Human Recurrent Herpes in the Skin

• HSV- specific CD4 and CD8 T-lymphocytes play a central role in
controlling primary and recurrent HSV infections in humans
• The increased severity and persistence of recurrent herpes The
key role of T cells, especially CD4 T cells
Genital Herpes

Immune Response to Human Recurrent Herpes in the Skin

• HSV infection first IFN-b and b chemokines  then interleukin
(IL)-12  by IL-1 and IL-6
• b chemokines attract monocytes, and CD4 and CD8 lymphocytes
into lesions  HSV antigen-stimulated CD4 (and CD8) lymphocytes
 release cytokine  IFN-g and IL-12
• HSV-1/2 downregulate MHC I expression by keratinocytes
reversed by IFN-g  allowing CD8 lymphocytes to recognize
infected keratinocytes
Genital Herpes

Immune Response to Human Recurrent Herpes in the Skin

• IFN-g  upregulate MHC class II expression on keratinocytes
allowing recognition by CD4 T lymphocytes
• immune and vaccine control of HSV higher levels of IFN-g
produced by blood CD4 T lymphocytes  refected in a lower
frequency of recurrent herpes
Genital Herpes

Immune Response to Human Recurrent Herpes in the Skin

• After lesion healing and loss of HSV DNA from skin biopsies HSV-
2-specific CD8+ T lymphocytes persisted for more than 6 months at
the dermal–epider- mal junction, adjacent to peripheral nerve
endings, and were accompanied by persistence of CD4
lymphocytes and myeloid DCs deeper in the dermis
Human Papillomavirus

• HPVs are unique among many pathogens in showing multiple

immunoevasive mechanisms.
• The major mechanism is avoidance of antigen presentation by lack
of lysis of keratinocytes, expression of few proinfammatory
signals, and lack of systemic spread
• HPV specically infects keratinocytes in the strati- ed squamous
epithelium of the lower FGT and penile skin, with complete virion
production being intimately linked with the differentiation of
squamous epithelium