A brief outline of Immune response to HIV

1. Immune Response to HIV
The meek challenges the mighty…

2. Complexities of HIV infection
HIV primarily infects the CD4+ T-cells.
Establishes Chronic Immune Activation.
Thrives on CD4+ T-cell activation.
Error prone HIV reverse transcription.
Establishment of latent reservoir.

3. Events that happen in an HIV infection

4. Course of HIV Infection
Kuby’s Immunology, 7th edn.

5. Host Response to HIV

6. Immune escape
Humoral Immunity
Neutralizing Antibodies
Hypervariability of Primary
sequence of the envelope.
Extensive Glycosylation of the
envelope.
Conformational masking of the
neutralizing epitopes.
Cellular Immunity
CD8+ T cells
Early:
Development of escape
mutants.
Late:
Apoptosis – Expression of PD1
molecule.
Malfunctional CD8+ T cells.

7. Mechanisms of CD4+ T cell depletion
Loss of plasma membrane due to viral budding
Accumulation of unintegrated viral DNA
Apoptosis
Aberrant intracellular signalling events.

8. CD4+ T cells
T Follicular helper cells
Humoral Immunity & B cell
development
Staphylococcus,
Streptococcus,
Pseudomonas,
E. coli
Brucella,
Listeria,
Chlamydia,
M. tuberculosis,
Salmonella.
http://www.bloodjournal.org/content/112/5 (adapted)

9. Monocytes & Macrophages
Normal in Number. But functionally deficient.
HIV is less cytopathic to monocytes.
Hence play a role of reservoir of infection.
Increased cellular activation generates a large
pool of monocytes/macrophages

10. Dendritic cells
Crucial role in the establishment of HIV
infection in the host.
Main APCs for the HIV infection.
A target for vaccine.

11. Natural Killer cells (NK)
Normal in number.
Abnormal CD56-/CD16+ cells predominate.
NK cell – Dendritic cell interaction.

12. Evolution of Humoral response
Adapted from Zelda Euler et al. 2012

13. Take Home Message
The primary immunopathogenic lesion in HIV infection
involves CD4+ T cells.
The dysregulated immune activation of the host serves to
maintain the HIV persistence.
HIV develops a latent reservoir in the host making the
eradication of the virus difficult.
HIV sets up an evolutionary race with the host B cells and
till today has managed to win it.

14. Further reading
Harrison’s Principles of Internal Medicine, 18th edn.
Chapter 189. Human Immunodeficiency Virus
Disease.(a must read)
Kuby’s Immunology, 7th edn., Chapter 18.
Immunodeficiency Disorders. (a must read)
HIV Immunology, Immunological Reviews 2013.
Vol. 254: 5–9. (optional)

15. Thank You!