Phagocyte

B cells

ReceptorB Cell

Naïve B cell

B cells and antibodies

daughter cells produce antibodies

phagocyte consumesan antibody coated virus

Antibodiesneutraliseantibodies

B cell attaches toantigen cloning ofdaughter cells

Cytotoxic CD8 cells

CD8 cells can recognisemarkers on the outsideof infected cells

CD8 destroys infected cell which stops cell from producing more virus or bacteria

Antigen presenting cells

These cells can engulf

invading organisms

The foreign organism is broken up into smaller

pieces

Antigenspresented to CD4 cells

CD4 cell

Analogy for the immune system

Naïve and Memory B cells Naïve B cell

Once activated it divides many times making two types of clones

The plasma cell which makes and releases large amounts of the appropriate antibody

The memory B cell which can live for years

Memory B cells The existence of memory B cells means

that the body can respond much more quickly

CD4 and CD8 Cluster of Differentiation

Molecules on the surface of the cells that help the T cell attach to the antigen

CD4 cells Th1 (humoral response) Th2 (cell mediated

response) Th0 (??) CD8 cells

Cytotoxic lymphocytes (CTL) CD45RA – Naïve cells CD45RO – Memory cells

CD4 count viral load over timeViral Load CD4

Count

Set PointLevels in the Blood

Below the limit of the test

Seroconversion Asymptomatic Symptomatic

HIV virion

Reverse transcriptase enzymeProtein p24

Protein p18

Fatty(lipid bilayer)

membrane

Glycoprotein gp120

Vaccine - Ideal characteristics Prevent transmission by mucosa &

injecting Excellent safety profile Single dose administration Offers protection for a long time Low cost Stability and ease of administration Works against a wide range of

different strains

Immune system responses Humoral response

Based on antibodies and the B cells that produce them

Cell-mediated response Based on cytotoxic CD8 cells

Mucosal immunity The above but concentrated in the mucosal

membranes where most transmission occurs

Current trend is to aim to stimulate a sufficient HIV-specific CTL

response to control or prevent HIV infection

Types of vaccine Live attenuated vaccines

Defective or weakened form of the virus Previous example original smallpox vaccine, vaccinia Research in monkeys indicates may slowly lead

to immune disease Inactivated or 'killed' vaccines Recombinant sub-unit envelope vaccines Recombinant vectored vaccines DNA vaccines and replicons Combination vaccines or ‘prime and boost’

Types of vaccine Live attenuated vaccines Inactivated or 'killed' vaccines

Second classic technique (e.g. Dr Jonas Salk in creating the world's first successful polio vaccine)

No-one has yet claimed any significant success Maybe difficult to distinguish between vaccine

immune response and infection Recombinant sub-unit envelope vaccines Recombinant vectored vaccines DNA vaccines and replicons Combination vaccines or ‘prime and boost’

Types of vaccine Live attenuated vaccines Inactivated or 'killed' vaccines Recombinant sub-unit envelope vaccines

Seek to stimulate antibodies to HIV by mimicking proteins on the surface of HIV (e.g. gp120)

Initial research was strain-specific and produced poor antibody responses

Recently more hope Recombinant vectored vaccines DNA vaccines and replicons Combination vaccines or ‘prime and boost’

Types of vaccine Live attenuated vaccines Inactivated or 'killed' vaccines Recombinant sub-unit envelope vaccines Recombinant vectored vaccines

incorporate harmless bits of HIV into established vaccines

• ALVAC series of vaccines are canarypox based vaccines

• Vaccine strains of adenovirus• recombinant rabies virus vaccines

DNA vaccines and replicons Combination vaccines or ‘prime and boost’

Types of vaccine Live attenuated vaccines Inactivated or 'killed' vaccines Recombinant sub-unit envelope vaccines Recombinant vectored vaccines DNA vaccines and replicons

involve HIV genetic sequences which, once injected, induce expression of HIV antigens by human cells.

In the case of replicons, these sequences are wrapped in the outer coat of an unrelated virus.

Combination vaccines or ‘prime and boost’