Immune Defense and Deficiency Flashcards
Immunodeficiency causes increased incidence and severity of what three conditions?
1) Infection 2) Malignancy 3)Autoimmunity
What are some clues in a patient’s history that may indicate immunodeficiency?
Childhood infections; Family Hx; Behavior; Medications
What are six aspects of infections may indicate immunodeficiency?
- More frequent - Respiratory (sinus, lung); PCP; Salmonella; VZV with HIV)
- More severe - bacteremia; ¬ tissue injury
- Prolonged - don’t resolve without therapy
- Recurrent - diarrhea; pneumonia; otitis; sinusitis; HSV; thrush [oral Candida]
- Poor response to Rx
- Unusual (opportunistic) pathogens - PCP; aspergillus; CNS Toxo; Listeria; Nocardia, Cryptococcus; Cryptosporidium
What are four common sources of immunodeficiency?
- Malnutrition
- HIV/AIDS
- Age (very young/very old)
- Other (esp. medications – corticosteroids, chemotherapy, anti-TNF antibodies)
What are the four basic components of the immune system?
1) Anatomic (skin, mucosal barriers) 2) Phagocytes (neutrophils and macrophages) 3) Cellular immunity (CD4+ T cells, CD8+ T cells (CTL), Natural killer cells (NK)) 4) Humoral (Specific antibodies (B cells) - Complement)
What are the two broad ways in which the basic components of the immune system may become defective?
Decreased number/concentration Decreased function
What are the frequency, genetic malfunction, and typical presenting age for primary immunodeficiency?
Rates are low (1: 10,000 live births) Most are single gene defects Most are present in childhood (e.g., XLA; SCID; Wiskott-Aldrich)
What are the most common immunodeficiencies in adults?
* IgA deficiency * Common Variable Immunodeficiency (CVID) • IgG(2) subclass deficiency • Hyper-IgE syndrome (Job’s syndrome)
What are the most common causes of immunodeficiency in the developing world?
Developing country - Malnutrition - HIV-1/AIDS - Measles - Age
What are the most common causes of immunodeficiency in the developed world?
Developed country - Chronic steroids - HIV-1/AIDS - Cancer Therapy - Transplantation
What are the three most common conditions that compromise immune defense by the skin, and what infecting agents are typically found?
Severe Eczema, Burns, IV Lines S. aureus, Ps. aeruginosa
What are the two most common conditions that compromise immune defense in the lungs, and what infecting agents are typically found?
Cystic Fibrosis, Post-viral infection Ps. aeruginosa, S. pneumoniae, S. aureus
What is the most common condition that compromises immune defense in the oral/GI tract, and what infecting agents are typically found?
Chemotherapy E. Coli, Candida
What is the concentration of neutrophils that defines neutropenia?
For neutrophils, neutropenia with substantially increased risk of infection is classically defined as less than 500 PMN’s/uL, and particularly less than 100 PMN’s/uL.
Chemotherapy induced neutropenia commonly leads to infections in what three areas?
- Intestine - GNR (E. coli), Candida; Enterococcus – Transcytosis (from epithelium); – Perirectal abscess
- Periodontal - Anaerobic abscess; oral streptococci
- Skin/Catheters - S. aureus (MRSA); Strept.; GNR (Ps. aer)
What is the disorder in Chronic Granulomatous Disease and what are the common infections and infectious agents that result?
• Sufficient phagocyte number but decreased function • Uncommon (1 in 125,000); young children • Defect in NADPH oxidase (oxygen radicals decreased) • Recurrent skin abscesses, severe prolonged pneumonia, bone • Staph. aureus*, Serratia*, Nocardia, Salmonella, Aspergillus* • Diagnose clinically, family history, NBT test of PMN (*Risk for catalase+ organisms that destroy own oxygen radicals; not Streptococci [catalase -])
What are six common causes of deficiency in cell-mediated immunity?
• Malnutrition • Immunotherapy/Oral steroids • Immunotherapy • Chemotherapy • Transplantation • HIV/AIDS
What types of infections result from cell-mediated immunodeficiency?
• Bacterial • Fungal • Viral • Protozoan • Helminths
What are the T-cell concentrations for early, intermediate, and advanced AIDS?
Cells / µL HIV-1 Stage Above 500 “Early” 200 - 500 “Intermediate” Under 200 “Advanced”; AIDS
What cells are affected by HIV and how are they affected?
- T cell defects - - Low CD4+ T cells number - Decreased CD4+ T cell function
- NK cell dysfunction
- B cell dysfunction - Hypergammaglobulinemia/↑activation - Decreased memory B cells (IgD-; CD27+) - Decreased response to new antigens - High rates of autoimmunity
- Phagocytic function - PMN and macrophages - OK (High rates of mucosal Candida but no candidemia)
What is the most common humoral immunodeficiency?
IgA deficiency most common (≈1:700) 1:300-1:1,000 adults
What are the associations and consequences of IgA deficiency?
Family history of IgA def. or CVID
Limited increase in infection - (except with IgG2 defiency) - protection by compensatory IgM
Increased autoimmune, ± malignancy
Transfusion reactions (with anti-IgA)
What are the three complement deficiencies and what infections commonly occur with each?
- C2 deficiency most common - C1-4 deficiency (classical pathway) present with pyogenic infections - C5-9 deficiency (terminal) show serious Neisserial infections
How does Ig trigger destruction of antigens?
Pathogen-specific antibody typically binds by its pathogen-specific antigen-binding variable Fab region and mediates its effector functions through the ability of its constant Fc region to act as a bridge to other host defense mechanisms (e.g., complement, phagocytes, and NK cells).
