BIOM30002 Lecture 26: T5_L26-27_summary
12 Jun 2018
School
Department
Course
Professor
L26 & 27 HIV 2/3
Natural history (no treatment) of HIV disease
- Acute and chronic depletion of CD4 T cells
1. Particular in GIT
- Cause immunodeficiency
1. Acute HIV syndrome
2. Clinical latency (after set-point)
3. Rapid increase of HIV RNA copies
4. Death
Chronology of CD4 T cell loss and disease
Immune deficiency
Infection
Primary
Early
Intermediate
Advanced
CD4 count
/uL
500
-
1000 (drop)
>500
200
-
500
<200
Disease eg.
F
e
ver
Polymyositis
Tuberculosis
Herpes simplex
Note
Miss diagnosis
Inflammatory
Autoimmunity
-
Rare disease
CD4+ T cell homeostasis
Causes of CD4+ T cell decline
- Increased destruction
1. Direct infection
GIT>>blood
Incomplete reverse transcription in naïve T cells apoptosis in cytoplasm
2. Indirect effects
Syncytium formation: uninfected T cells stuck in infected T cells
Apoptosis
Immune activation: dividing and turnover much faster (over-stimulation)
Lymph node fibrosis: reduce source of T cells
- Impaired production
1. Thymus
2. CD34+ progenitor cells
Why is CD4+ T cell depletion variable
- Viral factors
1. CXCR4: accelerates T cell loss
2. Nef deleted: limits T cell loss
3. Co-infection: with other viruses
CMV: increase T cell loss
GBV-C: preserve T cells
- Host factors
1. Immune response
HLA type (human leukocyte antigen)
2. Genetic factors
CCR5Δ32 heterozygote slower disease progression
3. Age
Impaired thymic function in very young and very old increase disease
progression
HIV induced immunopathology: depletion and/or dysfunction of other cells
- CD8+ T cells
1. Abnormally high during acute phase
2. Decline at later stages
- NK cells
1. Impaired numbers
2. Impaired function
- Monocytes and macrophages
1. Defects in chemotaxis
2. Not able to promote T-cell proliferation
3. Defects in FcR function
- B cells
1. Increase production of IgG/IgA
2. Decrease antibody responses
- Overstimulation
HLA type is important for immune response
- Certain HLA molecules present HIV epitopes more effectively which enhances the adaptive
the immune response
- HLA types depend on which peptides are presented on APC
HIV causes chronic immune activation
- Markers of immune activation that are elevated in HIV infection
1. Cellular marker
2. Soluble marker
Causes of immune activation
- Mucosal depletion of CD4 T cells
1. Increased microbial translocation, crossing GIT barrier
2. Activation of TLR4 by bacterial products (LPS) innate response
- Activation of innate immune response (pDCs)
1. HIV RNA is a TLR7/8 ligand expressed on pDCs
2. Increased plasma IFN-alpha
- Cytomegalovirus (CMV)-specific response
- Loss of Treg cells
HIV-induced immunopathology – innate immune cells
Document Summary
Acute and chronic depletion of cd4 t cells: particular in git. Cause immunodeficiency: acute hiv syndrome, clinical latency (after set-point, rapid increase of hiv rna copies, death. Chronology of cd4 t cell loss and disease. Incomplete reverse transcription in na ve t cells apoptosis in cytoplasm. Syncytium formation: uninfected t cells stuck in infected t cells. Immune activation: dividing and turnover much faster (over-stimulation) Lymph node fibrosis: reduce source of t cells. Viral factors: cxcr4: accelerates t cell loss, nef deleted: limits t cell loss, co-infection: with other viruses. Hla type (human leukocyte antigen: genetic factors. Ccr5 32 heterozygote slower disease progression: age. Impaired thymic function in very young and very old increase disease progression. Hiv induced immunopathology: depletion and/or dysfunction of other cells. Cd8+ t cells: abnormally high during acute phase, decline at later stages. Monocytes and macrophages: defects in chemotaxis, not able to promote t-cell proliferation, defects in fcr function. Increase production of igg/iga: decrease antibody responses.
