Immune Response to HIV

Immune Response to HIV

The meek challenges the mighty…

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.

Events that happen in an HIV infection

Course of HIV Infection

Kuby’s Immunology, 7th edn.

Host Response to HIV

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.

Mechanisms of CD4+ T cell depletion

Loss of plasma membrane due to viral budding

Accumulation of unintegrated viral DNA

Apoptosis

Aberrant intracellular signalling events.

CD4+ T cells

T Follicular helper cellsHumoral Immunity & B cell

development

Staphylococcus, Streptococcus, Pseudomonas,E. coli

Brucella,Listeria,Chlamydia, M. tuberculosis, Salmonella.

http://www.bloodjournal.org/content/112/5 (adapted)

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

Dendritic cells

Crucial role in the establishment of HIV

infection in the host.

Main APCs for the HIV infection.

A target for vaccine.

Natural Killer cells (NK)

Normal in number.

Abnormal CD56-/CD16+ cells predominate.

NK cell – Dendritic cell interaction.

Evolution of Humoral response

Adapted from Zelda Euler et al. 2012

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.

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)

Thank You!