Chapter 31 Infections in the Compromised Host Flashcards
What are the primary factors that affect innate immune system, compromising the host?
complement deficiencies, phagocyte cell deficiencies
What are the secondary factors that affect innate immune systems, compromising the host?
burns, trauma, major surgery, catheterization, foreign bodies (e.g. shunts, prostheses), obstruction
What are the primary factors affecting the adaptive immune system?
T-cell defects, B-cell deficiencies, severe combined immunodeficiency
What are the secondary factors affecting the adaptive immune system?
malnutrition, infectious diseases, neoplasia, irradiation, chemotherapy, splenectomy
What causes primary immunodeficiency?
inherited or occurs by exposure in utero to environmental factors or by other unknown mechanisms. It is rare, and varies in severity depending upon the type of defect.
What causes secondary or acquired immunodeficiency?
underlying disease state or as a result of treatment for a disease
What is one of the best know examples of a primary defect of innate immunity?
chronic granulomatous disease, an inherited failure to synthesize cytochrome b-245, which leads to failure to produce ROS during phagocytosis. As a result, neutrophils cannot kill invading pathogens
What congenital defects are primary defects of innate immunity?
congenital defects in the synthesis of early components in generating classical C3 convertase, particularly C4 and C2
What type of defense system do burns, traumatic injury and major surgery disrupt, and how?
Disrupt the body’s mechanical barriers: Destroy the continuity of skin and may leave poorly vascularized tissue near the body surface, providing a relatively defenseless site for pathogens to colonize and invade.
What is the result of a defect in the stromal microenvironment in which lymphocytes differentiate?
failure to produce B cells (Bruton-type agammaglobulinemia) or T cells (DiGeorge syndrome)
Name and describe the most common form of congenital antibody deficiency?
common variable immunodeficiency; characterized by recurrent pyogenic infections and probably heterogeneous mechanism. Number of immature B cells in marrow tend to be normal, but the peripheral B cells are either low in number or in some cases absent. Where present, they are unable to differentiate into plasma cells in some cases or to secrete antibodies in others.
What is transient hypogammaglobulinemia of infancy?
Occurs naturally in human infants as the maternal serum IgG concentration decays. Serious problem in very premature babies as, depending on gestational age, maternal IgG may not have crossed the placental barrier. characterized by recurrent respiratory infections, associated with low serum IgG concentration, often normalizes abruptly by 3-4 years of age
What is the most common and important cause of acquired immunodeficiency, and what results from it?
malnutrition. The major form, protein-energy malnutrition (PEM) presents as a wide range of disorders, with kwashiorkor and marasmus at the two poles. Results in:
What are the results of the most common and important cause of acquired immunodeficiency?
protein-energy malnutrition results in:
- drastic effects on structure of lymphoid organs
- gross reductions the synthesis of complement components
- sluggish chemotactic responses of phagocytes
- lowered concentrations of secretory and mucosal IgA
- reduced affinity of IgG
- serious deficit in circulating T cell numbers-> inadequate cell-mediated responses
What are the histological features of the thymus in children with protein-energy malnutrition?
acute involution, lobular atrophy, loss of distinction between cortex and medulla, depletion of lymphocytes and enlarged Hassall’s corpuscles
How do lymphocyte counts compare between healthy and malnourished patients?
T cells are decreased in malnourished patients compared to healthy controls. B-cell counts are usually unaltered, and lymphocytes lacking T- and B-cell markers are increased.
What are three examples of treatments causing immunosuppression?
- Cytotoxic agents such as cyclophosphamide and azathioprine cause leukopenia or deranged T- and B-cell function.
- Corticosteroids reduce the number of circulating lymphocytes, monocytes and eosinophils and suppress leukocyte accumulation at sites of inflammation.
- Radiotherapy adversely affects the proliferation of lymphoid cells.
What causes patients receiving treatment for neoplastic disease to be immunocompromised?
treatment and disease
What characteristic skin lesion is caused by Pseudomonas aueruginosa, an opportunist Gram-negative rod that has a long and infamous association with burn infections?
ecthyma gangrenosum
What type of damage to burns cause?
damage the body’s mechanical barriers, neutrophil function and immune response
What kind of pathogens are the major pathogens in burns? Name the most important ones
Major pathogens in burns are aerobic and facultatively anaerobic bacteria and fungi.
The most important pathogens in burn wounds are:
-Pseudomonas aeruginosa and other Gram-negative rods
-Staphylococcus aureus
-Streptococcus pyogenes
-other streptococci
-enterococci
Candida spp. and Aspergillus account for ~5% of infections. Anaerobes are rare in burn wound infections.
Which factors predispose the burned host to Pseudomonas aeruginosa infection?
- abnormalities in antibacterial activities of neutrophils
- deficiencies in serum opsonins
What virulence factors make Pseudomonas aeruginosa a devastating Gram-negative pathogen of burned patients?
production of elastase, protease, and exotoxin
Describe the treatment of Pseudomonas aeruginosa.
Difficult because of its innate resistance to many antibacteria agents. A combination of aminoglycoside, usually gentamicin or tobramycin, with a beta-lactam such as ceftazidime or imipenem, but resistance to these is common.
What is the most common fungal pathogen in compromised patients, and what conditions does it cause?
Candida causes: -vaginal and oral thrush -skin infections -endocarditis, particularly in injecting drug users
How does Histoplasma capsulatum infection compare between healthy and immunocompromised patients?
this highly infectious fungus causes acute but benign pulmonary infection in healthy people, but can produce chronic progressive disseminated disease in the compromised host
Which fungus is increasingly reported as a cause of invasive disease in compromised patients, usually in profoundly neutropenic patients or those receiving high-dose cortcosteroids?
Aspergillus spp.
Which atypical fungus causes symptomatic disease in people whose cellular immune mechanisms are deficient? and how is the rest of the population safe from it?
Pneumocystis jirovecii;
a large proportion of the population has antibodies to it
Name two pathogenic genera in the family Actinomyces, relatives of mycobacteria but resembling fungi in that they form branching filaments
Actinomyces and Nocardia
Describe Nocardia asteroides infectionsW
have been reported in immunocompromised, especially renal transplant, patients. Lung is usually primary site, but infection can spread to skin, kidney or CNS
Which protozoan parasites cause severe diarrhea in AIDS patients?
Cryptosporidium and Cystoisospora
Which viral infections are more severe and more common in compromised patients, requiring regular surveillance?
- EBV (can lead to tumor development)
- Respiratory virus infections: respiratory syncitial virus, influenza, parainfluenza, adenoviruses
Which viral infection can result in disseminated disease in immunocompromised hosts, particularly pediatric and adult bone marrow transplant patients?
adenovirus (high mortality rate)
What is the likely cause of jaundice in bone marrow transplant recipients?
Hepatitis B virus infection after cytotoxic T cells have lysed hepatitis B surface-antigen-bearing hepatocytes, indicating hepatitis B re-activation post-transplantation
How does HCV infection lead to liver necrosis and multi-organ failure in bone marrow transplant patients?
venous congestion owing to non-specific vasculitis; multi-organ failure can be precipitated because of increased capillary permeability throughout the body
How are polyomaviruses acquired, and where can they be detected in bone marrow transplant recipients?
BK or JC viruses are polyomaviruses acquired via the respiratory tract that lie latent in the kidney, and may be detected in the urine of bone marrow transplant recipients.
Which urinary condition is BK viruria associated with?
hemorrhagic cystitis
What conditions can JC virus cause in individuals with AIDS and how?
JC virus can reactivate and disseminate to cause CNS infections such as progressive multifocal leukoencephalopathy in individuals with AIDS
In addition to being infected by pathogens capable of infecting immunocompetent individuals, what other types of pathogen can infect immunocompromised individuals?
opportunistic pathogens
If a pathogen is suceptible to antimicrobial therapy in in vitro, will it always kill the pathogen in vivo? Why or why not?
effective antimicrobial therapy is often difficult to achieve in the absence of a functional immune response, even when the pathogen is susceptible to the drug in vitro
Which bacterial opportunist is especially important in neutropenic patients and those with major burns?
Pseudomonas aeruginosa
Which bacterial opportunist is especially important in patients with plastic devices in situ?
Staph. epidermis
What type of bacterial opportunists are predominant?
intracellular pathogens benefiting from the lack of cell-mediated immunity
Which types of infections are patients with neutropenia following cytotoxic therapy and advanced HIV infection susceptible to, especially when the patient has received previous antibacterial therapy?
fungal infections (e.g. Candida, Aspergillus, Cryptococcus)
