Chapter 3 part 3 Flashcards by Kristen Hemmersmeier

In what settings does chronic inflammation occur?

persistent infections
hypersensitivity diseases
prolonged exposire to toxic agents

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Morphologic features of chronic inflammation

infiltration with mononuclear cells (macrophages, lymphocytes, plasma cells), tissue destruction, attempts at healing (angiogenesis and fibrosis)

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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

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Mononuclear phagocyte system

circulating monocytes
macrophages in tissues
specific macrophages based on tissue (e.g. Kuppfer cells in liver)

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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

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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

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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

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What do CD4+ T lymphocytes promote?

inflammation

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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

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What are Th1 and Th2 cells involved in defense against?

bacteria and viruses

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What are Th2 cells important in defense against?

helminthic parasites and allergic inflammation

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Tertiary lymphoid organs

accumulation of lymphocytes, antigen presenting cells, and plasma lymphoid tissue resembling lymph nodes

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Function of eosinophils

abundant in immune reactions mediated by IgE and in parasitic infections; toxic to parasites and causes lysis of mammalian epithelial cells

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Function of mast cells

express FceR1 on surface that binds to FC portion of IgE antibody, release histamine and prostaglandins, respond to allergic reaction

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In what chronic diseases are neutrophils persistent in?

bacterial infection of the bone (osteomyelitis), in lungs from smoking

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Define granulomatous inflamation

chronic inflammation characterized by activated macrophages and T lymphocytes, sometimes with necrosis

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What is a foreign body granuloma?

group of macrophages around a foreign body without a T cell-mediated response

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What is an immune granuloma?

group of macrophages that induce a T cell-mediated response; caused by a persistent microbe or self Ag

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What cytokines are involved in immune granuloma formation?

IL-2 (from macrophages), IFN-gamma

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What is the morphology of a granuloma?

activated macrophages resemble epithelia and are surrounded by lymphocytes, contains giant cells, resembles a caseous necrosis grossly

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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