Recognition of pathogens by the innate immune system is facilitated by receptors on macrophages, NK cells, and neutrophils that recognize conserved pathogen motifs called pathogen-associated molecular patterns (PAMPs), including lipopolysaccharide of gram-negative bacteria, lipoteichoic acid of gram-positive bacteria, mannans of yeast, and specific nucleotide sequences of bacterial and viral DNA. Recognition of PAMPs by the innate immune system leads to the production of cytokines and chemokines that initiate inflammation and recruit inflammatory cells, induce an acute phase response (e.g., C-reactive protein, mannose binding lectin, complement), and activate the adaptive immune system. Complement proteins kill pathogens by facilitating uptake by phagocytic cells or by lysis of pathogens. Polymorphonuclear neutrophils ingest pyogenic bacteria and some fungi. Macrophages are effective in killing facultative intracellular organisms such as Mycobacterium, Toxoplasma, and Legionella. In addition NK lymphocytes mediate cytotoxic activity against virus-infected cells and cancer cells.
The key features of the adaptive immune system are antigen specificity and the development of immunologic memory, produced by expansion and maturation of antigen-specific T cells and B cells. Antibodies (immunoglobulin) produced by B cells neutralize toxins released by pathogens, opsonize pathogens to facilitate uptake by phagocytic cells, activate complement causing cytolysis of the pathogen, and direct NK cells to kill infected cells through antibody-mediated cytotoxicity. T cells kill virus-infected cells and cancer cells, activate macrophage to kill intracellular pathogens, and deliver the necessary signals for B-cell antibody synthesis and memory B-cell formation. Immunodeficiency can result from defects in one or more components of innate or adaptive immunity, leading
Aspiration syndromes (gastroesophageal reflux, ineffective cough, foreign body) Cleft palate, eustachian tube dysfunction Adenoidal hypertrophy
Nasal polyps Obstruction of paranasal sinus drainage (osteomeatal complex disease), encephaloceles
Tracheoesophageal fistula, bronchobiliary fistula Pulmonary sequestration, bronchogenic cysts Vascular ring Tumor, foreign body, or enlarged lymph nodes
Primary ciliary dyskinesia syndromes, Young syndrome Cystic fibrosis Bronchopulmonary dysplasia Bronchiectasis
Allergic disease (allergic rhinitis, asthma)
Burns Chronic atopic dermatitis Ureteral obstruction, vesicoureteral reflux IV drug use Central venous line, artificial heart value, CSF shunt, peritoneal dialysis catheter, urinary catheter Dermal sinus tract
CSF, Cerebrospinal fluid.
to recurrent, opportunistic, or life-threatening infections. Primary immunodeficiency diseases are relatively rare individually, but together they cause significant chronic disease, morbidity, and mortality (Table 72-3).