Immune Defense and Deficiency Flashcards

1
Q

Immunodeficiency causes increased incidence and severity of what three conditions?

A

1) Infection 2) Malignancy 3)Autoimmunity

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2
Q

What are some clues in a patient’s history that may indicate immunodeficiency?

A

Childhood infections; Family Hx; Behavior; Medications

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3
Q

What are six aspects of infections may indicate immunodeficiency?

A
  • 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
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4
Q

What are four common sources of immunodeficiency?

A
  • Malnutrition
  • HIV/AIDS
  • Age (very young/very old)
  • Other (esp. medications – corticosteroids, chemotherapy, anti-TNF antibodies)
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5
Q

What are the four basic components of the immune system?

A

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)

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6
Q

What are the two broad ways in which the basic components of the immune system may become defective?

A

Decreased number/concentration Decreased function

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7
Q

What are the frequency, genetic malfunction, and typical presenting age for primary immunodeficiency?

A

Rates are low (1: 10,000 live births) Most are single gene defects Most are present in childhood (e.g., XLA; SCID; Wiskott-Aldrich)

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8
Q

What are the most common immunodeficiencies in adults?

A

* IgA deficiency * Common Variable Immunodeficiency (CVID) • IgG(2) subclass deficiency • Hyper-IgE syndrome (Job’s syndrome)

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9
Q

What are the most common causes of immunodeficiency in the developing world?

A

Developing country - Malnutrition - HIV-1/AIDS - Measles - Age

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10
Q

What are the most common causes of immunodeficiency in the developed world?

A

Developed country - Chronic steroids - HIV-1/AIDS - Cancer Therapy - Transplantation

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11
Q

What are the three most common conditions that compromise immune defense by the skin, and what infecting agents are typically found?

A

Severe Eczema, Burns, IV Lines S. aureus, Ps. aeruginosa

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12
Q

What are the two most common conditions that compromise immune defense in the lungs, and what infecting agents are typically found?

A

Cystic Fibrosis, Post-viral infection Ps. aeruginosa, S. pneumoniae, S. aureus

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13
Q

What is the most common condition that compromises immune defense in the oral/GI tract, and what infecting agents are typically found?

A

Chemotherapy E. Coli, Candida

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14
Q

What is the concentration of neutrophils that defines neutropenia?

A

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.

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15
Q

Chemotherapy induced neutropenia commonly leads to infections in what three areas?

A
  • 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)
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16
Q

What is the disorder in Chronic Granulomatous Disease and what are the common infections and infectious agents that result?

A

• 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 -])

17
Q

What are six common causes of deficiency in cell-mediated immunity?

A

• Malnutrition • Immunotherapy/Oral steroids • Immunotherapy • Chemotherapy • Transplantation • HIV/AIDS

18
Q

What types of infections result from cell-mediated immunodeficiency?

A

• Bacterial • Fungal • Viral • Protozoan • Helminths

19
Q

What are the T-cell concentrations for early, intermediate, and advanced AIDS?

A

Cells / µL HIV-1 Stage Above 500 “Early” 200 - 500 “Intermediate” Under 200 “Advanced”; AIDS

20
Q

What cells are affected by HIV and how are they affected?

A
  • 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)
21
Q

What is the most common humoral immunodeficiency?

A

IgA deficiency most common (≈1:700) 1:300-1:1,000 adults

22
Q

What are the associations and consequences of IgA deficiency?

A

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)

23
Q

What are the three complement deficiencies and what infections commonly occur with each?

A
  • C2 deficiency most common - C1-4 deficiency (classical pathway) present with pyogenic infections - C5-9 deficiency (terminal) show serious Neisserial infections
24
Q

How does Ig trigger destruction of antigens?

A

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).

25
How do complement, phagocytes, and NK cells kill pathogens?
Recognition of Fc by these immune components (e.g., complement, phagocytes, and NK cells) induces fatal injuries to the pathogen, on which antibody defense is dependent. Complement: Complement-dependent assembly of transmembrane pores (membrane attack complexes [MAC; C5-9]), Natural Killer cells: Release of antimicrobial agents (e.g, cytokines such as IFN-γ) can activate phagocytes (neutrophils and macrophages), Phagocytes: Binding to and engulfment by phagocytes upon linkage of Complement (Green forks) with complement receptors (CR1/3) and Antibody Fc with Fc receptors on the pathogen and phagocyte, respectively.
26
What is the most common serious primary defect in adults?
Common Variable Immunodeficiency
27
What is the basic defect in CVID, the common infections, and age group most often affected?
• ↓IgG, IgM, IgA; nl number of B cells; “normal” T cells • Recurrent pyogenic sinopulmonary infections (esp. S. pneumoniae); less than ↓Ig children • Chronic diarrhea (G. lamblia; C. jejuni) - GI lymphoid hyperplasia; ↑ bacteremia • some ¬ PCP, fungi, mycobacteria; recurrent HSV • Increased risk of non-Hodgkins lymphoma and gastric cancers, and others. • Onset in teens or 20’s; men = women
28
What are the four primary source of immune protection that may be defective in immunodeficiencies?
Anatomic Barrier Phagocytic Cellular Humoral Immunity
29
How do you test the cell number and function in phagocytic immunodeficiencies?
Test: - CBC and diff. (with smear) Number: - PMN Less than 100-500 Function: Nitro Blue Tetrazolium
30
How do you test the cell number and function in cellular immunodeficiencies?
Test: - CBC with diff - Flow cytometry Number: - CD4 less than 500; Lymphocytes less than 1500 Function: skin tests
31
How do you test the cell number and function in humoral immunodeficiencies?
Test: - Total Protein/albumin - Serum Protein Electrophoresis (SPEP) - Quant. IgG, IgM, IgA - CH50 Number: - ↓globulin Total protein - ↓γ globulin SPEP - ↓ IgG, (M, A) Quant. - ↓CH50 CH50 Function: - anti-A/B (RBC) - vaccination