Sexual transmission of HIV Flashcards
Routes of HIV transmission
- heterosexual intercourse
- MSM
- vertical
- injection drug use
- needle-stick injury
- blood transfusions
Population most at risk of HIV acquisition
- women aged 25-29
When does peak of HIV infection in men occur?
30-34 years
4 regions of the FGT
- keratinised stratified squamous epitheliam (opening)
- vaginal mucosa
- external region of the cervix (ectocervix)
- endocervix
Components of the transformation zone
- ectocervix (stratified squamous epithelium)
- endocervix (single layer of columnar epithelial cells)
Structure of lymphoid aggregates in the endometrium
- B cell core
- surrounded by memory CD8 T cells
- encapsulated by macrophages
HIV target cells
- CD4+ T cells
- DCs
- macrophages
- Langerhans cells
HIV binding sequence
- CD4 attachment
- Co-receptor binding
- virus-cell fusion
Role of Langerhans cells as HIV target cells
- internalize R5 strains
- transfer virus to CD4 T cells
- also bind C-type lectin receptor (Langerin)
- may result in virus endocytosis and degradation
Role of DCs as HIV target cells
- express C-type lectin receptors (DC-SIGN) which may capture HIV
- HIV endocytoised or transferred to CD4 and CCR5 receptors on DCs
- viral-cell membrane fusion and infection
- endocytosed HIV degraded/transferred to CD4 T cells or macs
Immune barriers in the FGT
- epithelial layer
- antimicrobial peptides
- immune cells
- lactobacillus
- mucus
How could the epithelial barrier be protective?
Multiple layers of squamous cells and continuous sloughing off of the superficial layer
Characteristics of mucus
Negatively charged high-molecular weight glycoproteins = mucins
Antimicrobial proteins released by epithelial cells in the FGT
- defensins
- interferons
- SLPI
- lactorferrin
How do lactobacilli protect the vagina?
- directly inhibit HIV
- compete for receptor sites
- inhibit pathogens
- capture the virus through lectin molecules
- regulate immune response during health and disease
How does HIV cross the epithelial barrier?
- disruption of the mucosae
- columnar epithelial cells endocytose cell-free and cell-associated virus + transcytose to LP
- DCs extend processes between epi cells + capture virus
Factors that increase susceptibility to HIV
- BV/STIs/parasites
- menstrual cycle phase
- injectable hormone contraceptive use
- douching
- sexual activity
- ectopy
Role of inflammatory cytokines in HIV
- recruit/activate/differentiate HIV target cells
- induce NF-kB (binds to HIV long terminal repeat and directly promotes transcription)
- disrupts epi cell tight junctions
What phase of the menstrual cycle is the “window of vulnerability”?
- secretory/luteal phase
Why are women more susceptible to HIV in the luteal phase?
- cell-cell adhesion proteins and antiproteases are reduced
- leukocyte recruitment elevated
- extravasation proteins elevated
Possible mechanisms for increased HIV risk with progestin-based injectable use
- increased or decreased cytokines
- thinning of epithelial barrier
- increased or decreased HIV target cells
- altered immune cell activation
- changes in mucus
- decreased lactobacilli
- increased HIV uptake and transcytosis
Epithelium of urethra of males
pseudostratified columnar epithelium
Immune defense mechanisms in the MGT
- PRRs
- antimicrobial proteins
- mucus
- plasma cells in urethra
- NK cells in mucosa of urethra
- T cells abundant
How may seminal plasma suppress mucosal transmission of HIV?
- contains cationic polypeptides and ROS (antiviral)
- blocks HIV attachment to DC-SIGN
- decreases cell surface expression of CD4 and CXCR4
- increasing FGT epithelial monolayer integrity
