Microbial invasion can be facilitated by the following:
Virulence factors assist pathogens in invasion and resistance of host defenses; these factors include
Some organisms (eg, certain strains of pneumococci, meningococci, Haemophilus influenzae type b Haemophilus Infections The gram-negative bacteria Haemophilus species cause numerous mild and serious infections, including bacteremia, meningitis, pneumonia, sinusitis, otitis media, cellulitis, and epiglottitis... read more ) have a capsule that blocks phagocytosis, making these organisms more virulent than nonencapsulated strains. However, capsule-specific opsonic antibodies can bind to the bacterial capsule and facilitate phagocytosis.
Bacterial proteins with enzymatic activity (eg, protease, hyaluronidase, neuraminidase, elastase, collagenase) facilitate local tissue spread. Invasive organisms (eg, Shigella flexneri Shigellosis Shigellosis is an acute infection of the intestine caused by the gram-negative Shigella species. Symptoms include fever, nausea, vomiting, tenesmus, and diarrhea that is usually bloody... read more , Yersinia enterocolitica Plague and Other Yersinia Infections Plague is caused by the gram-negative bacterium Yersinia pestis. Symptoms are either severe pneumonia or large, tender lymphadenopathy with high fever, often progressing to septicemia... read more ) can penetrate and traverse intact eukaryotic cells, facilitating entry from mucosal surfaces.
Some bacteria (eg, Neisseria gonorrhoeae Pneumococcal Infections Streptococcus pneumoniae (pneumococci) are gram-positive, alpha-hemolytic, aerobic, encapsulated diplococci. In the US, pneumococcal infection is a major cause of otitis media, pneumonia... read more , N. meningitidis Meningococcal Diseases Meningococci (Neisseria meningitidis) are gram-negative diplococci that cause meningitis and meningococcemia. Symptoms, usually severe, include headache, nausea, vomiting, photophobia... read more , H. influenzae, Proteus mirabilis Proteeae Infections The Proteeae are normal fecal flora that often cause infection in patients whose normal flora have been disturbed by antibiotic therapy. The Proteeae constitute at least 3 genera of gram-negative... read more , clostridial species Overview of Clostridial Infections Clostridia are spore-forming, gram-positive, anaerobic bacilli present widely in dust, soil, and vegetation and as normal flora in mammalian gastrointestinal tracts. Pathogenic species produce... read more , Streptococcus pneumoniae Streptococcal Infections Streptococci are gram-positive aerobic organisms that cause many disorders, including pharyngitis, pneumonia, wound and skin infections, sepsis, and endocarditis. Symptoms vary with the organ... read more ) produce IgA-specific proteases that cleave and inactivate secretory IgA on mucosal surfaces.
Organisms may release toxins (called exotoxins), which are protein molecules that may cause disease (eg, diphtheria Diphtheria Diphtheria is an acute pharyngeal or cutaneous infection caused mainly by toxigenic strains of the gram-positive bacillusCorynebacterium diphtheriae and rarely by other, less common Corynebacterium... read more , cholera Cholera Cholera is an acute infection of the small bowel by the gram-negative bacterium Vibrio cholerae, which secretes a toxin that causes copious watery diarrhea, leading to dehydration, oliguria... read more , tetanus Tetanus Tetanus is acute poisoning from a neurotoxin produced by Clostridium tetani. Symptoms are intermittent tonic spasms of voluntary muscles. Spasm of the masseters accounts for the name... read more , botulism Botulism Botulism is poisoning that is due to Clostridium botulinum toxin and that affects the peripheral nerves. Botulism may occur without infection if toxin is ingested, injected, or inhaled... read more , clostridial enterocolitis) or increase the severity of the disease. Most toxins bind to specific target cell receptors. With the exception of preformed toxins responsible for some food-borne illnesses (eg, botulism Botulism Botulism is poisoning that is due to Clostridium botulinum toxin and that affects the peripheral nerves. Botulism may occur without infection if toxin is ingested, injected, or inhaled... read more , staphylococcal or Bacillus cereus food poisoning), toxins are produced by organisms during the course of infection.
Endotoxin is a lipopolysaccharide produced by gram-negative bacteria and is part of the outer membrane of these organisms. Endotoxin triggers humoral enzymatic mechanisms involving the complement, clotting, fibrinolytic, and kinin pathways and causes much of the morbidity in gram-negative bacterial sepsis.
Some microorganisms are more virulent because they do the following:
Impair antibody production
Destroy protective antibodies
Resist the lytic effects of serum complement
Resist the oxidative steps in phagocytosis
Many microorganisms have mechanisms that impair antibody production by inducing suppressor cells, blocking antigen processing, and inhibiting lymphocyte mitogenesis.
Many mucosal pathogens, including Neisseria gonorrhoeae, N. meningitidis, S. pneumoniae, and H. pneumoniae, produce proteases that cleave immunoglobulin A (IgA). IgA is the predominant immunoglobulin class produced at mucosal surfaces.
Resistance to the lytic effects of serum complement confers virulence.
Some organisms resist the oxidative steps in phagocytosis. For example, Legionella Legionella Infections Legionella pneumophila is a gram-negative bacillus that most often causes pneumonia with extrapulmonary features. Diagnosis requires specific growth media, serologic or urine antigen... read more and Listeria Listeriosis Listeriosis is bacteremia, meningitis, cerebritis, dermatitis, an oculoglandular syndrome, intrauterine and neonatal infections, or rarely endocarditis caused by Listeria species. Symptoms... read more either do not elicit or actively suppress the oxidative step, whereas other organisms produce enzymes (eg, catalase, glutathione reductase, superoxide dismutase) that mitigate the oxidative products.
Some viruses and bacteria produce superantigens that bypass the immune system, cause nonspecific activation of inordinate numbers of naive T cells, and thus cause excessive and potentially destructive inflammation mediated by massive release of proinflammatory cytokines (eg, staphylococcal and streptococcal toxic shock syndrome Toxic Shock Syndrome (TSS) Toxic shock syndrome is caused by staphylococcal or streptococcal exotoxins. Manifestations include high fever, hypotension, diffuse erythematous rash, and multiple organ dysfunction, which... read more ).
Adherence to surfaces helps microorganisms establish a base from which to penetrate tissues. Among the factors that determine adherence are adhesins (microbial molecules that mediate attachment to a cell) and host receptors to which the adhesins bind. Host receptors include cell surface sugar residues and cell surface proteins (eg, fibronectin) that enhance binding of certain gram-positive organisms (eg, staphylococci Staphylococcal Infections Staphylococci are gram-positive aerobic organisms. Staphylococcus aureus is the most pathogenic; it typically causes skin infections and sometimes pneumonia, endocarditis, and osteomyelitis... read more ).
Other determinants of adherence include fine structures on certain bacterial cells (eg, streptococci Streptococcal Infections Streptococci are gram-positive aerobic organisms that cause many disorders, including pharyngitis, pneumonia, wound and skin infections, sepsis, and endocarditis. Symptoms vary with the organ... read more ) called fibrillae, by which some bacteria bind to human epithelial cells. Other bacteria, such as Enterobacteriaceae (eg, Escherichia coli Escherichia coli Infections The gram-negative bacterium Escherichia coli is the most numerous aerobic commensal inhabitant of the large intestine. Certain strains cause diarrhea, and all can cause infection when... read more ), have specific adhesive organelles called fimbriae or pili. Fimbriae enable the organism to attach to almost all human cells, including neutrophils and epithelial cells in the genitourinary tract, mouth, and intestine.
Biofilm is a slime layer that can form around certain bacteria and confer resistance to phagocytosis and antibiotics. It develops around Pseudomonas aeruginosa Pseudomonas and Related Infections Pseudomonas aeruginosa and other members of this group of gram-negative bacilli are opportunistic pathogens that frequently cause hospital-acquired infections, particularly in ventilator... read more in the lungs of patients with cystic fibrosis Respiratory Cystic fibrosis is an inherited disease of the exocrine glands affecting primarily the gastrointestinal and respiratory systems. It leads to chronic lung disease, exocrine pancreatic insufficiency... read more and around staphylococcal bacterial species on synthetic medical devices, such as IV catheters, prosthetic vascular grafts, orthopedic fixation devices and prosthetic joints, and suture material.
Factors that affect the likelihood of biofilm developing on such medical devices include the material’s roughness, chemical composition, and hydrophobicity.
Genetic variability among microbes is inevitable. Use of antimicrobial drugs eventually selects for survival of strains that are capable of resisting them.
Emergence of antimicrobial resistance may be due to spontaneous mutation of chromosomal genes. In many cases, resistant bacterial strains have acquired mobile genetic elements from other microorganisms, usually of the same species but sometimes from different ones. These elements are encoded on plasmids or transposons and enable the microorganisms to synthesize enzymes that
Modify or inactivate the antimicrobial agent
Change the antimicrobial agent's ability to accumulate in the bacterial cell
Resist inhibition by the antimicrobial agent (eg, alteration in the target sites of antibiotics is a common mechanism of resistance)
Minimizing inappropriate use of antibiotics in humans and in animal and crop farming is important for public health.
Defects in Host Defense Mechanisms
Two types of immune deficiency states affect the host’s ability to fight infection:
Primary immune deficiencies are genetic in origin; > 100 primary immune deficiency states have been described. Most primary immune deficiencies are recognized during infancy; however, up to 40% are first recognized during adolescence or adulthood.
Acquired immune deficiencies are caused by another disease (eg, cancer, HIV infection, chronic disease) or by exposure to a chemical or drug that is detrimental to the immune system.
Defects in immune responses may involve
Cellular deficiencies Cellular immunity deficiencies Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more are typically T-cell or combined immune defects. T cells contribute to the killing of intracellular organisms; thus, patients with T-cell defects can present with opportunistic infections such as Pneumocystis jirovecii Pneumocystis jirovecii Pneumonia Pneumocystis jirovecii is a common cause of pneumonia in immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV) and in those receiving systemic... read more or cryptococcal infections Cryptosporidiosis Cryptosporidiosis is infection with the protozoan Cryptosporidium. The primary symptom is watery diarrhea, often with other signs of gastrointestinal distress. Illness is typically self-limited... read more . Chronicity of these infections can lead to failure to thrive, chronic diarrhea, and persistent oral candidiasis.
Humoral deficiencies Humoral immunity deficiencies Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more are typically caused by the failure of B cells to make functioning immunoglobulins. Patients with this type of defect usually have infections involving encapsulated organisms (eg, H. influenzae Haemophilus Infections The gram-negative bacteria Haemophilus species cause numerous mild and serious infections, including bacteremia, meningitis, pneumonia, sinusitis, otitis media, cellulitis, and epiglottitis... read more , S. pneumoniae Streptococcal Infections Streptococci are gram-positive aerobic organisms that cause many disorders, including pharyngitis, pneumonia, wound and skin infections, sepsis, and endocarditis. Symptoms vary with the organ... read more ). Patients can present with poor growth, diarrhea, and recurrent sinopulmonary infections.
A defect in the phagocytic system Phagocytic cell defects Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more affects the immediate immune response to bacterial infection and can result in development of recurrent abscesses or severe pneumonias.
Primary complement system defects Complement deficiencies Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more are particularly rare. Patients with this type of defect may present with recurrent infections with pyogenic bacteria (eg, encapsulated bacteria, Neisseria species) and have an increased risk of autoimmune disorders Autoimmune Disorders In autoimmune disorders, the immune system produces antibodies to an endogenous antigen (autoantigen). The following types of hypersensitivity reactions may be involved: Type II: Antibody-coated... read more (eg, systemic lupus erythematosus).