2.1. Barrier

Breech of the integument leads to infections of skin, and subcutaneous connective tissue.

2.2. Phagocytic function

Defects in neutrophil function, either qualitatively or quantitatively are associated with infection. Decreased number of leukocytes associated with severe infections, bacteremia and fever at levels below 500 absolute neutrophils.

There are congenital deficiencies of chemotaxis, which result in infection. These are rare. Favorite board questions:

Chediak Higashi syndrome - Defective neutrophil chemotaxis occurs from inadequate signaling, abnormal receptors for chemo-attractants, or disorders of locomotion. S. aureus most common pathogen.

Abnormalities of microbial killing power are typically inherited. Most common is chronic granulomatous disease (CGD). The enzyme NADPH oxidase is deficient and H₂0₂ is not formed. Patients are at risk for infection with catalase positive organisms (S. aureus). Organisms that make their own hydrogen peroxide, like pneumococci and streptococci are killed by neutrophils. Myeloperoxidase is present and uses the H₂0₂ to make lethal oxygen free radicals.

2.3. Disorders of Humoral Immunity

Immunoglobulin deficiency may be congenital (Burton’s X linked agammaglobulinemia) or acquired (common variable). Acquired can also arise from protein losing states (nephrotic syndrome), cancer within cell lines that make immunoglobulins or burns. Generally infections occur in respiratory tract from organisms that are encapsulated (Pneumococcus, H influenzae). Spleen is source of complement and antibody producing G cells. Asplenia results in infections, which may be quite fulminant, ie. Overwhelming sepsis with encapsulated bacteria.

Complement deficiencies also predispose to infection with encapsulated bacteria. Neisseria are a special problem for patients with late component deficiencies.

2.4. Disorders of cell mediated immunity

Defects of macrophages and T lymphocytes lead to an increased risk of infection with bacteria viruses and fungi that survive intracellularly. Listeria monocytogenes is classic intracellular bacterium seen in patients with this defect. Parasite example is Toxoplasma gondii, viruses in Herpes family, fungi like cryptococcus.

Primary cell mediated immune deficiency is usually congenital – Dx in childhood and lethal. Acquired defects usually arise in transplantation (solid organ and bone marrow) through use of immunosuppressive drugs, or viral infection (HIV).

2.5. Temporal sequence

There is a general temporal sequence following transplantation.

1. Early post transplant –
   • postoperative complications. ICU type organisms
2. Months 1-4 –
   • CMV, Candida, Aspergillus.
3. Months 4-12 –
   • Cryptococcus, Listeria.

4.1. Readings