Chapter 3 part 3 Flashcards
In what settings does chronic inflammation occur?
persistent infections
hypersensitivity diseases
prolonged exposire to toxic agents
Morphologic features of chronic inflammation
infiltration with mononuclear cells (macrophages, lymphocytes, plasma cells), tissue destruction, attempts at healing (angiogenesis and fibrosis)
Where are macrophages derived from?
hematopoietic stem cells in the bone marrow and from progenitors in embryonic yolk sac and fetal liver during early development
Mononuclear phagocyte system
circulating monocytes
macrophages in tissues
specific macrophages based on tissue (e.g. Kuppfer cells in liver)
Classical macrophage activation pathway
induced by microbial products which engage TLRs and other sensors and by IFN-y; produce NO and ROS and up regulate lysosomal enzymes
Action: phagocytosis and inflammation
Alternative macrophage activation
induced by cytokine other than IFN-y (IL-4 and IL-13); secrete growth factors that promote angiogenesis, activate fibroblasts, and stimulate collagen synthesis
Actions: tissue repair, fibrosis, anti-inflammatory effects
Functions of macrophages that make them central to development and persistence of chronic inflammation
1) ingest and eliminate microbes and dead tissues
2) secrete mediators of inflammation
3) display antigens to T lymphocytes and respond to signals from T cells
What do CD4+ T lymphocytes promote?
inflammation
3 subsets of CD4+ T lymphocytes and their products
1) Th1 cells: IFN-y which activates macrophages by classical pathway
2) Th2 cells: IL-4, IL-5, and IL-13 recruit and activate eosinophils and activate alternative macrophage activation pathway
3) Th17 cells: IL-17 which induces chemokine for recruitment of neutrophils
What are Th1 and Th2 cells involved in defense against?
bacteria and viruses
What are Th2 cells important in defense against?
helminthic parasites and allergic inflammation
Tertiary lymphoid organs
accumulation of lymphocytes, antigen presenting cells, and plasma lymphoid tissue resembling lymph nodes
Function of eosinophils
abundant in immune reactions mediated by IgE and in parasitic infections; toxic to parasites and causes lysis of mammalian epithelial cells
Function of mast cells
express FceR1 on surface that binds to FC portion of IgE antibody, release histamine and prostaglandins, respond to allergic reaction
In what chronic diseases are neutrophils persistent in?
bacterial infection of the bone (osteomyelitis), in lungs from smoking
Define granulomatous inflamation
chronic inflammation characterized by activated macrophages and T lymphocytes, sometimes with necrosis
What is a foreign body granuloma?
group of macrophages around a foreign body without a T cell-mediated response
What is an immune granuloma?
group of macrophages that induce a T cell-mediated response; caused by a persistent microbe or self Ag
What cytokines are involved in immune granuloma formation?
IL-2 (from macrophages), IFN-gamma
What is the morphology of a granuloma?
activated macrophages resemble epithelia and are surrounded by lymphocytes, contains giant cells, resembles a caseous necrosis grossly
What are giant cells (Langhans giant cells)?
consist of large amounts of cytoplasm and many nuclei, derive from the fusion of multiple macrophages
What organism causes tuberculosis?
Mycobacterium tuberculosis
What organism causes leprosy?
Mycobacterium leprae
What organism causes syphilis?
Treponema pallidum
What organism causes cat-scratch disease?
Gram-negative bacillus
What causes Crohn disease?
Immune reaction against intestinal bacteria, possibly self Ags
What is the tissue reaction of tuberculosis?
caseating tubercle with activated macrophages, fibroblasts, lymphocytes, histiocytes and Langhans giant cells
What is the tissue reaction of leprosy?
non-caseating granulomas with acid-fast bacilli in macrophages
What is the tissue reaction of syphilis?
Enclosing wall of histiocytes with plasma cell infiltrate and necrotic central cells
What is the tissue reaction of cat-scratch disease?
Rounded granuloma with granular debris and neutrophils, giant cells unlikely
What is the tissue reaction of sarcoidosis?
Noncaseating granulomas with many activated macrophages
What is the tissue reaction of Crohn disease?
Occasional noncaseating granulomas in the intestine with chronic inflammatory infiltrate
What cytokines are most commonly involved in an acute-phase reaction?
IL-1, IL-6, and TNF, type 1 interferons may also contribute
What are the most common clinical and pathologic changes in an acute-phase reaction?
Fever, acute-phase proteins, leukocytosis, increased pulse and blood pressure, decreased sweating, shivering and chills, widespread cytokine release
What is the temperature change involved in a fever?
Increase in body temp by 1 to 4 degrees celsius
What are pyrogens?
Substances that induce a fever?
What molecule causes an increase in body temp and how is it made?
Prostaglandins produced in vascular cells of hypothalamus, release is stimulated by leukocytes releasing IL-1 and TNF increasing the amount of prostaglandins present
What is the action of PGE2 as it relates to fevers?
Causes the production of neurotransmitters that reset the body temp to a higher level.
What are the most common acute-phase proteins?
CRP, fibrinogen and serum amyloid A
What cytokines cause the release of acute-phase proteins?
IL-6 causes the release of CRP and fibrinogen, IL-1 or TNF causes the release of serum amyloid a
What are the main actions of acute phase proteins?
Binding to microbial cell walls to act as opsonins and fix complement, may also bind chromatin and aid in clearing the necrotic cell nuclei
What is the action of fibrinogen?
Binds red cells and causes them to form rouleaux that sediment more rapidly than regular RBCs
What is erythrocyte sedimentation rate?
Test used for an inflammatory response
What does the presence of hepcidin cause in an inflammatory reaction?
elevated plasma concentrations of hepcidin reduce iron level and cause anemia
What is leukocytosis?
increase of leukocytes to 15-20k cells/mL, may increase to 40-100k cells/mL (leukemoid reaction)
What is a left shift?
accelerated release of cells and a rise in immature neutrophils
Definition of neutrophilia
Increase in neutrophils due to bacterial infection
Definition of lymphocytosis
Absolute increase in number of lymphocytes due to a viral infection
Definition of eosinophilia
Increase in absolute number of eosinophils due to parasites or allergies
Define leukopenia
Decrease in number of white blood cells caused by certain infections like typhoid fever, some protozoa and viruses
What is the clinical triad of septic shock?
intravascular coagulation, hypotensive shock, and metabolic disturbances (insulin resistance and hyperglycemia)
What are the main causes of defective inflammation?
leukocyte deficiency from bone marrow replacement and suppression of marrow for transplants
