Chronic Inflammation

Question 1

5 Major Cell Types Involved

Answer 1

• Monocytes/Macrophages
  
  • Largest WBCs, non-central nucleus, grey-blue vacuoles
  • Function - phagocytosis
  • Attracted to site by chemostatic stimuli
• Lymphocytes
  
  • Smallest WBCs, small round nuclei and dense chromatin, some basophilic cytoplasm
  • Can also see T cells (thymus derived) and B cells (bone marrow derived) occasionally
  • Function - components of cell-mediated immune response and anti-body immune response
• Plasma Cells
  
  • Small/intermediate size, clock face chromatin, perinucelear hof (prominent Golgi)
  • Function - derived from activated B cells - make 1 specific antibody
• Eosinophils
  
  • Small granulocytes, bi-lobed nucleus and bright red eosin granules (BASIC)
  • Function- important in response to parasitic infections and IgE-mediated allergic reactions
  • Activated and recruited by eotaxin
• Mast Cells
  
  • Part of Type I immediate hypersensitivity reaction
  • Have cell surface receptors that bind Fc of IgE antibody (associated w/ anaphylactic reactions)
  • Release histamine (vasoactive amine) and prostaglandins

Question 2

2 Types of Macrophage Activation

Answer 2

• 1- Classical - main goal is to kill microbes; induce by microbial products; produce ROS and NO + up regulate lysosomal enzymes to inc ability to kill and secreted cytokines
  - 2- Alternative- main goal is tissue repair; induced by cytokine IL-3 and IL-4 (made by T cells); secrete growth factors and cytokines to induce angiogenesis, fibroblast activation and collagen synthesis

Question 3

Relationship Between T Cells and Macrophages

Answer 3

• Macrophages present antigens to T cells yet T cells secrete cytokines that active macrophages
• TH1 - activates classical macrophage activation
• TH2- activates alternative path of macrophage activation

Question 4

Reticuloendothelial System

Answer 4

• Monocytes made in bone marrow then circulate in blood; migrate to tissues and become macrophages;
• Stimulated for migration by cytokines, growth factors, fragments of collagen breakdown and fibronectin and fibropeptides
• Activated by IFN-gamma (cytokine), bacterial endotoxins, chemical mediators
• Morphological changes- inc in cells size, inc proteolytic enzymes/metabolism, inc ability to phagocytose and kill microbes
• Phagocytosis
  
  • 1- recognition and attachment to particle to be ingested
  • 2- engulfment -form phagocytic vacuole
  • 3- kill/degrade ingested material

Question 5

4 Things Macrophages Produce

Answer 5

• ROS and NO (reactive nitrogen species) - toxic to microbes
  
  • Proteases/lysosomal enzymes - toxic to mcirobes
  • Cytokines/chemokines
    
    • Ex) TGF-beta - MOST IMPORTANT IN DEPOSITION OF PROTEINS AND FIBROSIS (healing); stimulate fibroblast migration and proliferation, inc collagen synthesis, breakdown ECM (TIMPs)
  • Growth factors and chemical mediators of fibrosis and angiogenesis

Question 6

Lymphocytic Thyroiditis (Hashimoto’s thyroiditis)

Answer 6

• chronic inflammation w/in thyroid w/ plasma cells (can test for antibodies)

Question 7

Inflammatory Bowel Disease and Chron’s

Answer 7

• Chronic inflammation in lower GI tract —> fibrosis (strictures) and ulceration or fistula formation; malignancy

Question 8

Pelvic Inflammatory Disease

Answer 8

• Usually from ascending infection (enteric bacteria, Chlamydia, Gonorrhea) into upper female genital tract
  
  • Can have devastating complications (peritonitis, adhesions, bacteremia, infertility)

Question 9

Granulomatous Inflammation

Answer 9

• Pattern of chronic inflammation; hallmark= local collection of activated epithelial-like macrophages
• Involved multi-nucleated giant cells (MNGCs)

Question 10

2 Types of Multinucleated Giant Cells

Answer 10

• 1- Foreign Body Type - scattered nuclei

- 2- Langhans Type - horseshoe-arranged nuclei; peripherally arranged

Question 11

What is a granuloma? 2 Types

Answer 11

• Granuloma = focal aggregate of activated macrophages, lymphocytes and sometimes plasma cells, necrotic debris, usually MNGCs; can develop rim of fibroblasts and connective tissue over time
• 1- Foreign Body Type - arises from persistent material that is too large/indigestible for clearance
  -
  2- Immune Type - arises from insoluble/persistent antigen that induces cell-mediated immune reaction (ex- tuberculosis)

Question 12

Chronic Granulomatous Disease

Answer 12

• Hereditary immunodef - macrophages cannot make ROS (defect in gene encoding NADPH Oxidase - makes superoxide anion) - so macrophages cannot digest pathogen —> infection granuloma forms
• Can diagnose b/c lack of superoxide prevents NBT reagent from changing color

Question 13

Pulmonary Alveolar Peritonitis

Answer 13

• Accumulate surfactant b/c macrophage defect prevents alveolar macrophages from being able to clear surfactant (caused by either mutation or auto-antibodies against GM-CSF)
• Use bronchoalveolar lavage - diagnose and relieve
• Can diagnose via serological analysis of fluid (sandy-colored and opaque); GM-CSF autoantibodies

Question 14

TGF-alpha v TGF-beta

Answer 14

TGF-alpha attracts macrophages

THEN TGF-beta released by macrophages to activate fibroblasts (fibrosis) and breakdown inhibited by TIMPs

(ALPHA BEFORE BETA)