Inflammation & Healing (Part 2) Flashcards
What is chronic inflammation and when does it occur?
prolonged inflammation: weeks to years
- acute inflammation fails to eliminate inciting stimulus
- there are repeated episodes of acute inflammation
- virulence factors of microbes warrant it
What are mechanisms resulting in chronic inflammation?
What is granulomatous inflammation composed of?
macrophages, epithelioid macrophages, and multinucleate giant cells
What are 2 main forms of granulomatous inflammation?
diffuse granulomas
nodular granulomas
What is a diffuse granuloma?
Th2 cell-based response (humoral and Ig response)
poorly delineated, widespread distribution
What is a nodular granuloma?
Th1 cell-based response - recruit more cells like macrophages and NK
“tuberculoid” granulomas
What does a nodular granuloma look like?
central area of necrosis, bordered by epithelia macrophages, multinucleate giant cells and macrophages, which is further bordered by plasma cells, lymphocytes, and fibrous connective tissue
building a wall
What are 4 differentials for nodular granulomas?
parasites
fungi
foreign body
higher order bacteria
What kind of stain is this? What does it show?
H&E stain
all are macrophages and causes diffuse granulomas
Diffuse granulomas have a [Th1/Th2] response and nodular granulomas have a [Th1/Th2] response
diffuse: Th2
nodular: Th1
What is an acid-fast stain used for?
mycobacterium
Diffuse or nodular? Explain how you know
nodular
central area of necrosis bordered by a bunch of macrophages
further bordered by lymphocytes and plasma cells
further bordered by fibrous CT - which is the wall
What is the wall in nodular granulomatous inflammation?
fibrous CT
Diffuse or nodular?
nodular
What are eosinophilic granulomas?
dense infiltrates of eosinophils with macrophages, varying numbers of lymphocytes, and plasma cells
parasitic infection
What are the stages of chronic inflammation?
change in players of the game - macrophages, multinucleate giant cells, lymphocytes, plasma cells
tissue destruction
desmoplasia/fibroplasia
angiogenesis & neurovascularization
wound repair
How do they players of the game differ between acute and chronic inflammation?
acute: neutrophils/macrophages
chronic: macrophages, multinucleate giant cells, lymphocytes, plasma cells
How can desmoplasia / fibroplasia be troublesome?
bad in areas where gas exchange occurs - can replace normal tissue (hair follicles, lung (alveoli)
does nothing in terms of gas exchange
What are multinucleate giant cells a product of?
fusion of macrophages together to form a multinucleate giant cell
What is the function of multinucleate giant cells and epithelioid macrophages?
response to foreign bodies or persistent intracellular pathogens
What are the types of multinucleated giant cells?
langhans
foreign body
touton
What are langhans multinucleated giant cells?
named due to horseshoe arrangement of nuclei
What are foreign body multinucleated giant cells?
no arrangement - haphazard
doesn’t mean it’s a foreign body
What are touton multinucleated giant cells?
circular arrangement of nuclei
see with cholesterolic lesions - xanthomas
Which multinucleated giant cell type?
a. langhan
b. foreign body
c. touton
c. touton
Which multinucleated giant cell type?
a. langhan
b. foreign body
c. touton
a. langhan - horseshoe shaped!
Which multinucleated giant cell type?
a. langhan
b. foreign body
c. touton
a. langhan
Which multinucleated giant cell type?
a. langhan
b. foreign body
c. touton
c. touton
Which multinucleated giant cell type?
a. langhan
b. foreign body
c. touton
b. foreign body
Which multinucleated giant cell type?
a. langhan
b. foreign body
c. touton
c. touton
Which multinucleated giant cell type?
a. langhan
b. foreign body
c. touton
b. foreign body
Which multinucleated giant cell type?
a. langhan
b. foreign body
c. touton
b. foreign body
What are dendritic cells?
antigen presenting cells
everywhere - but numerous in skin and mucous membrane
in skin called langerhan’s cells
What is a histiocytoma?
neoplasm derived from dendritic cells
benign round cell tumor - subcategory of mesenchymal cells
Why does a histocytoma appear to be raised?
neoplastic cells pushing hair follicles out of the way
recruit lymphocytes and aggregate around base of tumor
What are gross characteristics of chronic inflammation?
gray to white
firm
nodular if granuloma
depressed - fibrosis - scar tissue
A dog has a white (cream, tan), firm, nodular mass. What are some of my differentials?
abscess
granuloma - nodular higher order
neoplasia
A cat’s lung has coalescing, white to cream, firm, nodular lesions. What is this?
pulmonary histoplasmosis - abscess granuloma neoplasia
What are some chronic inflammatory responses one can have?
chronic inflammation
chronic active inflammation
granulomatous inflammation
pyogranulomatous inflammation
granulomas
pyogranulomas
What is included in chronic inflammation?
fibroplasia and cellular infiltration
includes newly formed “immature” connective tissue with newly formed blood vessels to “mature” connective tissue that contains well-collagenized and remodeled granulation tissue
What is included in chronic active inflammation?
chronic white blood cells, neutrophils, +/- fibrin, plasma proteins
What is included in granulomatous inflammation?
macrophages
What is included in pyrogranulomatous inflammation?
chronic white blood cells, neutrophils - even mix
What is included in granulomas?
nodular
diffuse
What is included in pyogranulomas?
nodular granuloma (macrophages) + neutrophils
Define Th1 and Th2 responses (you should know this already)
What is the purpose of Th1 response?
recruit more cells to a site - i.e. cell-mediated
What do antigen presenting cells need to function properly?
co-stimulatory molecules - B7
What does interferon-gamma do?
recruits macrophages
- negative feedback on TH2 to not turn into TH2 response
- talk to B cells and set them up on reserve
What does TNF-alpha do?
activate and recruit macrophages and NK cells
- get B cells ready if you need TH2 response
What does IL-2 do?
tells cell to proliferate
acts on TH1 for B cell proliferation
What does IL-4 do?
promotes TH cell to turn into TH2
- tell B cells to differentiate into plasma cells
What does IL-10 do?
negative feedback to become TH1 cell - NO
promotes Th2 differentiation
Know those that have feedback on antigen presentation response
What are effector cells of chronic inflammatory response?
fibroblasts
macrophages
dendritic cells
mast cells
eosinophils
endothelial cells
lymphocytes
What are fibroblasts and its function? Acute or chronic inflammation?
mesenchymal cell lineage
contribute to cell’s structural integrity
have abundant RER to synthesize collagen
produce ECM proteins, cytokines, MMP’s and chemokines
chronic inflammation
What are macrophages/monocytes and its function? Acute or chronic inflammation?
hallmark cell of chronic inflammation
strategically located in tissue (resident macrophages)
functions:
- respond to acute inflammation
- migrate (due to chemotaxis)
- phagocytize
- antigen present
both acute and chronic
What are lymphocytes and its function? Acute or chronic inflammation?
perivascular pattern in viral infections
CD4/CD8: help regulate Th1 vs Th2 responses
B lymphocytes - can be APC’s, differentiate into plasma cells and produce antibody
Treg lymphocytes: influence balance of TH1 vs Th2 response
What is perivascular cuffing?
the accumulation of leucocytes in the perivascular space between the endothelial and the parenchymal basement membranes
consider a virus
What is lymphocyte trafficking?
What are plasma cells and its function?
result from B cell differentiation
antibody producer
predominate in chronic inflammation
What are eosinophils and its function?
allergic or parasitic responders
stimulated to proliferate by IL-5 and eotaxin
What are mast cells and its function?
histamine - leukotrienes and many others
IgE induced granulation
act as APC, phagocytes
type I hypersensitivity reactions
What is septicemia?
form of bacteremia, complicated by toxemia, fever, malaise and septic shock
“seeding” of bacteria into tissues
What are the usual sequelae of advanced septicemia?
septic shock
DIC
What factors are involved in advanced septicemia ?
LPS (+), TNF
TNF, IL-1- diffuse vascular permeability; endothelial damage, leads to profound circulatory disturbances
IL-6
What is the role of TNF in septic shock?
What is septic shock?
endotoxin - LPS gram negative bacteria
peptidoglycan layer of gram positive bacteria
bacterial exotoxins
What are the four phases of wound healing?
hemostasis
acute inflammation
proliferation (granulation)
remodeling (maturation, contraction) and wound repair
What is the proliferation (granulation) phase?
angiogenesis - new blood vessels
fibroplasia/desmoplasia (fibroblasts and CT)
epithelialization
What is the remodeling / maturation: wound repair?
remodeling granulation tissue from immature to mature collagen
provides time for tissue to return to normal tensile strength
wound contract: myofibroblasts
What is first intention wound healing?
apposing edges
rapid healing
if delayed, then healing by second intention
retained tensile strength
What is second intention wound healing?
non-opposing edges, or presence of microbes, foreign bodies
CT is haphazardly synthesized and arranged- little organization
fibrous CT fills the gaps
diminished tensile strength
resolves as hyperplastic scar, loss of hair, or remain ulcerated
What is the extracellular membrane?
composed of proteins and hydrated gel of proteoglycans
surrounds and interconnects cells in CT
degreased largely by MMP’s
What is collagen?
What is a vaccine induced fibrosarcoma?
mesenchymal malignant sarcoma - fibroblasts
What is this?
granulation tissue - comprised of tissue fibers, fibroblasts, and blood vessels
often red and hemorrhagic and bleeds easily due to fragility of newly formed capillaries
How do fibroblasts and CT grow regarding granulation tissue?
parallel to wound surface and are arranged perpendicularly to the proliferating capillaries
What is proud flesh?
hypertrophic scar of excessive granulation tissue
What is angiogenesis?
formation of capillary bud at margins of wound
Describe what happens with angiogenesis
formation of capillary bud at margins of wound
migration of immature endothelial cells towards wound
proliferation of endothelial cells “hollow vessels?
establishment of inter endothelial gaps
recruitment of smooth muscle cells, vascular remodeling
What is epithelialization?
epithelial hyperplasia “fill the wound”
intact basement membrane enhances re-epithelialization - provides a “path”
differentiation of epithelial cells
