IMMUNOPATHOGENESIS(L1) Pt.2

1.Transmission

2.Dissemination>↑ viral replication>↑ viral loads
Loss of CD4 cells, macrophages express CCR5 & CD4 , Dendritic are CD4 negative>capture HIV on CD209 molecules

3.Control

4. Seroconversion>>antibodies production(IgM>switches to IgG)(explained well in PT.1 notes)

Mucosal surface&MALT

Frontline defense against antigens

Largest in our body

Consequences of immune activation (s.28&29)!

Gut lumen

Cryt of lieberkuhn

Payer's Patches(2º lymphoid tissue)

Goblet cells>produce mucus>protect & lubricate epithelial layer

Disruption of Villous

Stem cells>protected by Paneth cells>secrete antimicrobial molecules

epithelial stem cells>new cells

AP , T & B cells activation>lymphoid follicle

Microfold(M)cells>deliver intact antigens via transcytosis to AP cells

HIV replication in lamina propria CD4+ T cells>mucosal immune activation>atrophy of villous>reduced absorptive surface

Pro-inflammatory cytokines>↑ gut permeability to pathogens>promote HIV replication

HIV infection & opportunistic organisms>>malabsorption of nutrients

Langerhans cells>express CD4 & CCR5(can be infected)

Activated Langerhans cells>produce cytokines(IL-1, 6 & TNFa)

Langerhans cells>1st to contact HIV>express CD270(Langerin)>capture the virus & binds to gp120>internalization & degradation of virus>act. cell into lymph nodes>AP to CD4+ t cell(can be infected)

Activation of CD8 & CD4 helper cells>↓ viral replication>↓ viral

Dendritic cells engulf virus>MHC 1&2>presnted to T cells ,

Lymphatic & arterioles(patrolling immune cells)

End organ disease(CVD, liver, dementia)

Impaired CD4 T cell recovery

Immune activation prevented by inhibiting microbial translocation,persistent HIV , co-infections,activation of PDC & Altered Treg/th17

Inhibition of immune activation>prevents lymph node fibrosis, T cell exhaustion & inflammation