Medical Microbiology and Infection at a Glance. Stephen H. Gillespie

varying components of humoral and cell immunity. Organisms each contain many antigens, within which are many different epitopes.

      The adaptive immune response comprises two main components: the humoral and cellular immune system.

      In the humoral response, B‐lymphocytes develop into clones of antigen‐producing cells, elaborating antibodies against antigens of the invading organism. Repeated exposure allows for increasing maturation of the response with the initial IgM response being replaced by IgG and IgA. Clones of B‐cells produce antibodies that recognize and bind to unique pathogen antigens and inhibit key possesses. This process can be critical for recovery from invasive infection: the lysis stage of pneumococcal pneumonia (see Chapter 20). We also use this in vaccination to protect against specific diseases that generate memory B‐cells, most optimally when the disease depends on a single antigen (e.g., toxin in tetanus) or a pathogen with a single serotype (e.g. measles) (see Chapter 13).

      In the cellular response, clones of cytotoxic lymphocytes develop, which can destroy cells bearing the foreign antigens, which results in control of infection. T‐cells can interact with other cells of the system to enhance defences by releasing molecules such as cytokines that can, for example, activate macrophages and increase killing efficiency.

      The overall effectiveness of both the humoral and the cellular immune response depend for their amplification on CD4 helper T‐lymphocytes. In their absence of effective CD4 cells as in the case of HIV infection, new infections cannot be overcome by cellular immune responses, and new antibody responses are inefficient.

Damaging immunity

      On occasion, the immune response can be damaging. Sepsis is associated with immune dysregulation and can result in multi‐organ failure. Although not fully understood, pattern‐recognition receptors (e.g., Toll‐like receptors) trigger the release of pro‐ and anti‐inflammatory mediators. Multiple cytokines e.g., tumor necrosis factor (TNF) and others, activate complement and clotting cascades generating micro‐thrombi. Breakdown of pathogen components can cause uncontrolled stimulation of the system, resulting in shock and sudden death (see Chapter 55). Uncontrolled cellular responses in, for example, tuberculosis can cause tissue damage in lung cavitation. Another example is Immune Reconstitution Inflammatory Syndrome, which is an inflammatory condition that occurs when a patient experiences a recovery of immune activity against the antigens of an established infection that had previously been suppressed. It is described in HIV‐infected patients after starting anti‐retroviral therapy, but also occurs when patients recover from general or pathogen‐specific immunosuppression. It presents with fever, increased new lymphadenopathy, skin inflammation, pleural or pericardial effusions, ascites, shock or sudden death (see Chapter 53).

3 The ‘normal’ flora in health and disease

      The innate immune system is a natural barrier to infection that can be overcome as a result of organism pathogenicity (Chapter 4), trauma or medical intervention. It is complemented by the normal flora that acts to compete with invading pathogenic organisms.

Normal flora

      The body is colonized by a wide range of species known as the normal flora that outnumber human cells in the body. The normal flora provides protection by competing with pathogens for colonization sites and producing antibiotic substances (bacteriocins) that suppress other bacteria. Anaerobic bacteria produce toxic metabolic products and free fatty acids that inhibit other organisms. In the female genital tract lactobacilli produce lactic acid that lowers the pH, so preventing colonization by pathogens.

      Antibiotics can kill normal flora allowing colonization and subsequent infection by naturally resistant organisms, such as Candida albicans or carbapenemase‐producing Enterobacteriaceae. Hospital patients and especially those in high dependency areas are at particular risk due to frequent antibiotic prescription and their underlying disease. The infective dose of primary pathogens, e.g. Salmonella typhi, is lowered by concomitant antibiotic use. Antibiotics may upset the balance between organisms in the gut allowing one to proliferate disproportionately. Clostridium difficile carrying natural resistant determinants can overgrow and produce severe diarrhoeal disease and spread widely in hospitals and elderly care facilities (see Chapter 24).

Physical and chemical barriers

      The skin is a physical barrier; secreted sebum and fatty acids inhibit bacterial growth. Many pathogens can penetrate the skin by the bite of a vector (e.g. Aedes aegypti that transmits dengue) or by invasion through intact skin (e.g. Leptospira and Treponema). Some organisms colonize mucosal surfaces and invade by this route (e.g. Streptococcus pneumoniae into the lungs and sinuses).

      Mechanisms and consequences of deficiency

Component	Compromise	Consequence
Normal flora
Pharynx	Antibiotics	Oral Candidiasis
Intestine	Antibiotics	Pseudomembranous colitis; colonization with antibiotic‐resistant organisms
Vagina	Antibiotics	Vaginal Candidiasis
Skin	Burns, vectors	Cutaneous bacterial infection, systemic viral, bacterial, protozoal and metazoal infection
Turbinates and mucociliary clearance	Kartagener’s syndrome, cystic fibrosis, bronchiectasis	Chronic bronchial sepsis
Lysozyme in tears	Sjögren’s syndrome	Ocular infection
Urinary flushing	Obstruction	Recurrent urinary infection
Phagocytes, neutrophils, macrophages	Congenital, iatrogenic, infective	Chronic pyogenic infection, increased susceptibility to bacterial infection
Complement	Congenital deficiency	Susceptibility to capsulated bacterial infection, especially Neisseria spp. See Chapter 66.

      If skin integrity is broken by intravenous cannulation or by medical or non‐medical injection, blood‐borne viruses, such as hepatitis B or the human immunodeficiency virus (HIV) may gain access. Eczema or burns, permit colonization and invasion by pathogens (e.g. Streptococcus pyogenes or Pseudomonas aeruginosa).

      Mucociliary