Acute and Chronic Inflammation Flashcards
State the 5 cardinal signs of inflammation.
Swelling Redness Heat Pain Loss of function
Identify types of stimuli that lead to inflammation. (5)
Infectious agents Toxins Necrotic tissue Foreign bodies Autoimmunity
Name the major differences between acute and chronic inflammation. (5 categories)
Acute:
- Rapid onset
- Short duration
- Exudative edema
- Neutrophils and macrophages
- Non-specific immune response
Chronic:
- Insidious onset
- Long duration
- Fibrosis, vascular proliferation, and tissue destruction
- Lymphocytes, macrophages, plasma cells
- Immunospecific
Identify the stages in endothelial adhesion and transmigration.
Called DIAPEDESIS
- Margination: leukocyte redistribution to enable adhesion
- -Vascular changes produce slower flow (stasis) -> leukocytes become more peripheral - Rolling: selectins and ligands; low affinity with fast off rate, easily disrupted by blood flow
- Adhesion: activated integrins bind immunoglobulin family strongly
- Transmigration: WBCs secrete collagenases to pierce basement membrane
Name the four general families of adhesion molecules and give specific examples of each.
- Selectins:
- -P-selectin (platelets)
- -E-selectin (endothelium)
- -L-selectin (leukocytes) - Glycoproteins:
- -PSGL-1
- -ESL-1
- -CD34
- -Glycam 1 - Immunoglobulins
- -ICAM-1 (intercellular)
- -VCAM-1 (vascular)
- -PECAM-1 (platelet-endothelial) - Integrins (on leukocytes)
- -LFA-1, MAC-1
- -VLA-4
Identify which adhesion molecule family is generally complimentary to members of which other family.
Selectins bind glycoproteins
Integrins (on leukocytes) bind Ig family (on endothelium)
Name the endogenous and exogenous chemoattractants important in neutrophil chemotaxis. (3 endogenous, 1 exogenous)
Endogenous:
- Cytokines (IL-8)
- Complement (C5a)
- Arachidonic acid metabolites (LTB4)
Exogenous:
-N-formyl-methionine
Explain the neutrophilic mechanism for killing and degradation of bacteria.
Respiratory burst: coupling of phagocytosis with rapid oxidative reaction to generate ROS within the lysosome
—-Uses phagocyte oxidase in lysosomal membrane -> superoxide -> H2O2
H2O2-MPO-halide system: converts H2O2 -> bleach
Inducible NO synthase -> NO -> OONO (peroxynitrite, highly ROS)
Also have substances in granules (lysozyme, elastase, etc.)
Identify categories of disease caused by inappropriate activation of the inflammatory response.
Autoimmunity: inappropriate defense reaction against host tissue
Allergy: excessive defense reaction against harmless environmental agents
Toxic agents: prolonged exposure to non-degradable exogenous material/endogenous toxic agents -> damage
Name three causes of chronic inflammation.
- Persistent infections: DTH against difficult to eradicate pathogens, especially TB
- Immune-mediated inflammatory disease
- Autoimmunity
- Allergy - Prolonged exposure to toxic agents
Identify the characteristic cell types found in acute and chronic inflammation.
Acute:
- NEUTROPHILS
- Eosinophils (if allergy, parasites)
- Lymphocytes (if viral)
- Monocytes/macrophages
Chronic:
- MACROPHAGES
- T cells: CD4 -> macrophages, CD8 -> viral infections
- B cells
- Plasma cells
Describe the pathogenesis of granulomatous inflammation.
A collection of macrophages
Often appear epitheliod (open nucleus, lots of cytoplasm) or have fused “giant cells” with peripheral or random nuclei
Often surrounded by a “collar” of lymphocytes and plasma cells (in infectious types)
Name and define the four morphologic patters of acute inflammation.
Serous: thin, watery fluid from plasma or mesothelial cell secretion (as in skin blister [vesicle or bulla])
Fibrinous: increased vascular permeability allows larger molecules (fibrinogen) -> extravascular space -> fibrin deposits
Purulent (suppurative): composed of neutrophils, liquefactive necrosis, and edema
Ulcer: local defect of the surface of an organ or tissue produced by sloughing of inflamed and necrotic tissue
Define inflammation.
A coordinated and complex host response to a stimulus involving soluble mediators, vascular reaction, and cellular and humoral elements resulting in the movement of fluid and leukocytes from the blood to extravascular tissues
Define acute inflammation. List its three major components.
Rapid host response that serves to deliver leukocytes and plasma proteins (antibodies) to sites of infection or tissue injury
Major components: vasodilation, increased vascular permeability (most commonly from retraction of endothelial cells), emigration and activation of leukocytes to focus of injury
List the four types or receptors used to recognize microbes and dead tissue. Briefly state what each recognizes.
- Toll-like receptors: bacterial products (LPS), viral products (dsRNA)
- GPCRs: bacterial peptides (N-formylmethionyl residues), chemokines (C5a), lipid mediators
- Opsonin receptors: IgG, C3b, mannose-binding lectin
- Cytokine receptors: IFNgamma
How is an inflammatory response terminated?
Passive: neutrophils die and are degraded
Active:
- Switch from leukotrienes to lipoxins
- Macrophages -> anti-inflammatory cytokines (TGF-beta, IL-10)
- Anti-inflammatory mediators (resolvins, protectins)
- IL-13, IL-4
Define chronic inflammation. List its four main characteristics.
Inflammation of prolonged duration in which inflammation, tissue injury, and attempts at repair coexist in varying combination
- Mononuclear cell infiltrate (NO NEUTROPHILS; lymphocytes, plasma cells, macrophages)
- Tissue destruction
- Angiogenesis
- Fibrosis
Define scar. Why is scar formation bad? (3 reasons)
Replacement of nonregenerated parenchymal cells with connective tissue
Bad because:
- Has no function
- Can obstruct, block, or constrict normal tissue, thus diminishing or destroying their function
- Can bind together structures/tissues that should remain independent
Define adhesion.
When scar tissue binds tissue together
Define abscess.
Localized collections of suppurative (purulent) inflammation
–Neutrophils, liquefactive necrosis, edema fluid
Center = necrotic leukocytes and tissue cells
First ring = preserved neutrophils
Outer ring = vascular dilation, fibroblastic proliferation
Discuss changes seen in acute appendicitis. (2)
- -Extensive neutrophil infiltration
- -Ulceration of mucosa
Discuss changes seen in acute pyelonephritis of the kidney. (1) What causes this?
–Many neutrophils in interstitium
Cause: bacteria ascending the urinary tract
Define empyema.
Usually caused by an infection that spreads from the lung
Leads to a buildup of pus in the pleural space
