Immune responses

The immune response to bacteria depends on whether it is growing inside or outside of human cells. Bacteria can release toxins that the immune system will try to eliminate. Bacteria outside cells and bacterial toxins are neutralised by antibodies. Bacteria coated with antibody are killed by complement, macrophages, and other phagocytic cells.

Paradoxically, a macrophage ingesting bacteria may become a host and breeding ground for bacteria that can live inside the cell, such as Mycobacterium tuberculosis, the agent that causes tuberculosis, and M. avium intracellulare (MAI).

Antibodies are unable to attack an organism inside a cell. Cytotoxic CD8 T-cells may kill infected macrophages if antigens from the bacteria are presented on the macrophage surface. HIV infection can severely inhibit the immune response to intracellular bacteria by damaging the communication between CD4 and CD8 T-cells and macrophages. This is one reason that people with advanced HIV infection are much more vulnerable to TB than uninfected people.

Cell-mediated immunity is mainly of importance in protecting patients from viruses and intracellular bacteria. By contrast, antibody-mediated immunity is mainly of importance in protection against extracellular bacteria.

Although viruses only replicate inside cells, they exist outside cells and this is the only time that antibodies specific to viral antigens can recognise a virus. Virus-infected cells usually display viral antigens with HLA class I on their surface. CD8 T-cells recognise viral antigen in association with HLA and respond by killing the infected cell with toxic molecules. They also release cytokines which attract macrophages to ingest the dying cell and enhance the resistance of nearby cells to infection.

Many viruses have the ability to alter their antigens and because of this, can evade a memory immune response. A new primary immune response to the altered antigen must then be initiated. Antigen alteration or shift is an important feature of HIV’s biology, which partly explains how it avoids clearance by the immune system.

Fungi are not usually susceptible to antibodies, so lymphocytes must secret cytokines to attract neutrophils and macrophages. Some fungi live and reproduce inside human cells. These organisms can also cause disease in HIV infection.