HTHSCI 1DT3 Lecture Notes - Lecture 15: Cd14, Apoptosis, Envelope Glycoprotein Gp120
23 Jun 2018
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HIV and the GI tract
HIV is a double-stranded RNA retrovirus with 9 genes encoding 15 proteins.
It replicates better in activated, not naïve T cells
There are two core receptors: CCR5 and CXCR4
CCR5 is a chemokine receptor; utilized for viral entry
CXCR4 is normally expressed late is disease; it is found in 50% of patients, and is
expressed in naive CD4 T cells
Drugs that target CCR5 inhibit reverse transcriptase, protease and DNA integrase
Natural history of HIV:
viral load set point (white vertical line) determines long-term risk and future
requirement for antivirals
main immune defect = loss of CD4 T cells, which sorms a short-term indication of
prognosis: <400 will risk Kaposi’s sarcoma, <200 will risk opportunistic infections e.g.
PCP and toxoplasmosis
Gut immunity
- 40% of the body’s CD4s reside in the gut (c.f. 2-5% in the peripheral blood)
- most are activated well-differentiated memory cells, which are opt to HIV replication
- The gut immune system is split into two structural and functional compartments:
1) inductive compartment
-Peyer’s patches & lymphoid follicles
-Naïve CD4 CC5 T cells
-Once activated, migrate to LN then recirculate back to gut
2) effector compartment
-lamina propria & intestinal villi
-contains activated T cells that have already been exposed to antigen; most express
the CCR5 co-receptor
Immunology of chronic HIV
1) CD4 depletion
2) Chronic immune activation
3) Ineffective T cell generation
4) Functional T cell exhaustion
-In acute infection there is a transient drop in peripheral CD4s but the drop of CD4s in
the gut is much more dramatic
Effects of HIV on T cells
-loss of naïve CD4 and CD8 cells and failure of memory T cells
-increased T cell turnover and accelerated CD4 death and CD8 exhaustion
-impairment of CD4 T cell response to new and recall antigens
-loss of CD4 T helpers for CD8, B cells, monocytes and macrophages
-progressive loss of killing and cytokine induction by CD8; there is proliferative loss,
anergy and cell death (but generally it is functional damage to the CD8 population)
Importance of immune activation
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Document Summary
Hiv is a double-stranded rna retrovirus with 9 genes encoding 15 proteins. It replicates better in activated, not na ve t cells. There are two core receptors: ccr5 and cxcr4. Ccr5 is a chemokine receptor; utilized for viral entry. Cxcr4 is normally expressed late is disease; it is found in 50% of patients, and is expressed in naive cd4 t cells. Drugs that target ccr5 inhibit reverse transcriptase, protease and dna integrase. Natural history of hiv: viral load set point (white vertical line) determines long-term risk and future requirement for antivirals. Main immune defect = loss of cd4 t cells, which sorms a short-term indication of prognosis: <400 will risk kaposi"s sarcoma, <200 will risk opportunistic infections e. g. pcp and toxoplasmosis. 40% of the body"s cd4s reside in the gut (c. f. Most are activated well-differentiated memory cells, which are opt to hiv replication. The gut immune system is split into two structural and functional compartments:
