Summary of defence mechanisms

Bacterial evasion strategies

Many bacteria have developed ways of interfering with phagocytosis. Encapsulated bacteria do not display sugar molecules for recognition by receptors on phagocytes. They are only phagocytosed when coated with antibodies, so can proliferate in non-immune individuals in the first few days after infection. Even when taken up by phagocytes, many encapsulated bacteria resist digestion (e.g. Haemophilus influenzae, Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa) or can even kill phagocytes (e.g. streptococci, staphylococci, Bacillus anthracis). Mycobacteria, listeria and Brucella spp. are able to survive within the cytoplasm of non-activated macrophages and can only be killed by a cell-mediated immune response driven by T_H1 macrophage-activating lymphokines.

Damage caused by immune responses to bacteria

Group A β-haemolytic streptococci cause sore throat and scarlet fever, which resolve on induction of specific antibody. Certain components of some strains of streptococci contain epitopes that are cross-reactive with epitopes present on heart tissue. Antibodies that eliminate the infecting bacteria can bind to heart tissue and cause complement-mediated lysis and antibody-dependent cellular cytotoxicity (rheumatic heart disease). Furthermore, circulating immune complexes can deposit in synovia and glomeruli, causing complement-mediated joint pain and glomerulonephritis, respectively. Induction of cross-reacting anti-heart antibody by group A streptococci is illustrated in Fig. 10.1 (see also Fig. 23.2).

Fig. 10.1 Induction of anti-heart antibodies by group A streptococci.

Persistent infection of macrophages, e.g. with Mycobacterium tuberculosis or Mycobacterium leprae, provokes a chronic, local, cell-mediated immune reaction due to continuous release of antigen. Lymphokine production causes large numbers of macrophages to accumulate, many of which give rise to epithelioid cells or fuse to form giant cells (syncytia). These giant cells release high concentrations of lytic enzymes, which destroy the surrounding tissue. Incorporation of fibroblasts also occurs, and the persisting pathogen becomes walled off inside a fibrotic, necrotic granuloma. Because the macrophages in a granuloma are activated, this mechanism also enhances the activation of T-helper cells. Granulomas may replace extensive areas of normal tissue, e.g. in the lungs of tuberculosis patients.

Summary of defence mechanisms

Viral evasion strategies

Certain viruses can modify the structure of components that are targets for the immune response (antigenic variation). Point mutations in the genes encoding viral antigens cause minor structural changes (antigenic drift), while exchange of large segments of genetic material with other viruses changes the whole structure of the antigen (antigenic shift). Antigenic drift of influenza A virus haemagglutinin occurs before each winter’s minor influenza epidemic, while major epidemics, such as those of 1918, 1957, 1968 and 1977, were the result of antigenic shift of haemagglutinin and/or neuraminidase.

Viruses that can integrate their genes within the host cell genome, such as human herpesviruses, provoke only low-level immunity, which fails to clear the latently infected cells. Viruses that infect cells of the immune system may inhibit their function, e.g. Epstein–Barr virus (B cells); measles, human T lymphotropic virus type I, human immunodeficiency virus (HIV) (T cells); dengue, lassa, Marburg–Ebola, HIV (macrophages).

Some herpesviruses and poxviruses can secrete proteins that mimic and interfere with key immune regulators such as cytokines and cytokine receptors.

Damage caused by immune responses to viruses

Epstein–Barr virus is a potent T cell-independent polyclonal activator of B cells. It induces B cells, including those with anti-self BCRs which are normally inactive due to purging of the corresponding anti-self T-helper cells, to secrete antibodies. Several viruses, notably hepatitis B virus, can cause chronic autoimmune disease due to release of previously sequestered (i.e. non-tolerogenic) self antigens following tissue damage. Complexes of antivirus antibodies with antigen can activate complement in the blood vessels, joints and glomeruli, causing vasculitis, arthritis and glomerulonephritis. Cytotoxic T cells may destroy essential host cells displaying viral antigens, e.g. coxsackievirus (myocarditis), mumps virus (meningoencephalitis) and viruses causing damage to the myelin nerve sheath (postviral polyneuritis).

HIV and AIDS

At the end of the year 2008, approximately 40 million people worldwide had become infected with HIV and approximately 25 million had died of the acquired immune deficiency syndrome (AIDS) (see also Chapter 30). The virus causes depletion of CD4⁺ T-helper lymphocytes over many years. Patients eventually succumb to opportunistic infections (Pneumocystis carinii, M. tuberculosis, atypical mycobacteria, Histoplasma, Coccidioides, Cryptococcus, Cryptosporidium and Toxoplasma spp., herpes simplex, cytomegalovirus) and may develop Kaposi’s sarcoma, B cell lymphomas and other malignancies. Infection of the brain by HIV can cause dementia and encephalitis.

The major route of transmission of HIV is by sexual intercourse: male to female, female to male and male to male. It can also be transmitted from mother to foetus across the placenta, during delivery or by breast-feeding. Direct injection into the blood stream, e.g. by multiple use of needles and syringes for injection of drugs, also transmits HIV.

The life cycle of HIV is shown in Figure 10.2. The virus gains entry into target cells by binding its surface gp120 molecule (glycoprotein of 120 kDa) to CD4 on T-helper cells and a subset of macrophages. The latter can also take up opsonized HIV via Fc or complement receptors. A coreceptor is also required for infection of target cells: CXCR4, also known as fusin or LESTR, is the receptor for the chemokine SDF-1 and is the coreceptor for infection of T cells by HIV; CCR5, the receptor for chemokines RANTES, MIP-1α and MIP-1p, is the coreceptor for infection of macrophages. Viral gp41 cau/>