The reactions of the immune system to the wide variety of micro-organisms are varied. Antibodies released by B-cells can be abundant in bodily secretions where they can react to specific antigens in tears, saliva and fluids in the lung and gut. Sometimes specific antibodies will eliminate a micro-organism at the skin, lung or gut barrier before it invades the body tissues or enters the bloodstream. Many vaccines work by producing this kind of response.

Bacteria

When dealing with bacteria the responses depend on whether the bacteria are growing inside or outside human cells. Bacteria can produce and release poisonous molecules called toxins which the immune system will also try to eliminate. Bacteria outside cells and bacterial toxins are dealt with by antibodies released by B-cells. Bacteria coated with antibody are killed by the immune factor complement and also by macrophages and other phagocytic cells.

Intracellular bacteria

Paradoxically, macrophages ingesting bacteria may become a host and a 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. The mechanism to kill these bacteria is therefore mediated by cytokines from CD4 T-cells to macrophages. Cytotoxic CD8 T-cells may also kill macrophages if specific antigens from the bacteria are recognised on the surface of the macrophage with HLA class I. HIV infection can severely inhibit the immune response to intracellular bacteria by damaging the response of CD4 and CD8 T-cells, as well as macrophages. Unsurprisingly, tuberculosis and MAI are common diseases during HIV infection.

Viruses

Viruses can exist outside cells, when they are encased in a coat, but they can only replicate themselves inside a host cell. Specific antibodies can recognise specific viral antigens when the virus is outside cells but when it is inside cells. However, virus-infected cells usually show viral antigens with HLA class I on their surface. CD8 T-cells recognise HLA in association with viral antigen, responding by releasing cell-killing molecules to kill the infected cell, and cytokines which attract macrophages to ingest the dying infected cell and encourage nearby cells to become resistant to infection by the virus.

One feature of some viruses is their ability to alter their antigens. This can help the virus avoid the efficient immune response to previous antigens generated by immune memory. The immune system has to start an immune response to a new antigen, like a game of cat and mouse. Antigen alteration or shift is an important feature of HIV's biology, which partly explains how it can avoid clearance by the immune system.

Fungi

Fungi are not usually susceptible to antibodies and the immune response is carried out by lymphocytes secreting cytokines to attract neutrophils and macrophages. Some fungi live and reproduce inside human cells. These organisms may also be more likely to cause disease in HIV infection.