11. Chronic Inflammation I Flashcards
GRANULOMATOUS INFLAMMATION
“Tissue aggregates of epithelioid macrophages as part of a ____ immune response”
Do not confuse “Granulomatous inflammation” with: • \_\_\_\_ • \_\_\_\_ Granuloma • \_\_\_\_ Granuloma
cell-mediated
chronic granulomatous disease (CGD)
pyogenic
periapical
Acute vs Chronic Inflammation
Acute Duration: \_\_\_\_ Etiology: \_\_\_\_ Sign: \_\_\_\_ Symptom: \_\_\_\_ Outcome: \_\_\_\_ Cells: \_\_\_\_ Biology: \_\_\_\_
Chronic Duration: \_\_\_\_ Etiology: \_\_\_\_ Sign: \_\_\_\_ Symptom: \_\_\_\_ Outcome: \_\_\_\_ Cells: \_\_\_\_ Biology: \_\_\_\_
if someone has pneumonia (acute) they will know due to systemic inflammations but with chronic there might not be at the beginning until tissue is ____, ex. Peridontal disease.
hour/days eliminated red/heat/swelling \+++ resolution/abscess/scar/fibrosis mast/PMN/mac vascular/exudative
weeks/months/yrs persists indurated/hard --+ destruction/fibrosis mac/lymp "round cells" proliferative
destroyed
Where do cells come from?
Initially macrophages involved in inflammatory reactions are derived from the same source as neutrophils - the ____. You have monocytes in the blood that once get into the tissue are ____ in inflammation. Tissue like skin, interstinal tract.
Other kind of macrophages that reside – ____ cells in liver, ____ macrophages in lung , ____ in the brain tissue. These are generated from the progenitor cells in the ____ and ____ liver.
Monocyte – looks similar to a band cell but it is much the nucleus is much ____ and stains ____ rather than blue.
When monocyte becomes macrophage it takes the shape on the right most image
bone marrow kupfer alveolar microglia yolk sac fetal
smaller
pink
Properties of neutrophils and Macrophages
Neutrophils Origin: \_\_\_\_ Lifespan in tissue: \_\_\_\_ Response to stimuli: \_\_\_\_ Degranulation: \_\_\_\_ ROS: \_\_\_\_ Cytokine production: \_\_\_\_ NET formation: \_\_\_\_
Macrophages Origin: \_\_\_\_ Lifespan in tissue: \_\_\_\_ Response to stimuli: \_\_\_\_ Degranulation: \_\_\_\_ ROS: \_\_\_\_ Cytokine production: \_\_\_\_ NET formation: \_\_\_\_
• M1 clascially activated macrophages (\_\_\_\_) M2 (TGFbeta firboris) (\_\_\_\_)
HSCs in bone marrow 1-2 hour rapid, short-lived major response rapidly induced (respiratory burst) low levels or none prominent
HSCs in bone marrow (inflam); SC in yolk/fetal liver (resident)
inflam (day/weeks); resident (years)
slow, prolonged, transcription/cytokine
not prominent
not prominent
Major: M1: TNF, IL-1, IL-12, IL-6, chemokines; M2: IL-10, TGFbeta
No
pro-inflam
anti-inflam
• Macrophaegs work with T cells
○ Macrophage digest particles, but limited comapred to neutrophils
○ Express on ____, activate T cells
§ Th1: cytokine is ____; target = macrophage, happens when ____ pathogen, autoimmunity/crhornic
§ TH2: allergy > ____, ____, ____; target = eosinphils, against helminths and allergy
§ TH17: produce ____ and ____; activate neutrophils, extracell immunity
IFNgamma
IL4, IL5, IL13
IL17, IL12
M1 and M2 Macrophages • M1 – Activated by endotoxin, \_\_\_\_, and \_\_\_\_ matters – Produce \_\_\_\_, lysosomal enzymes and cytokines that induce \_\_\_\_
• M2 – Activated by cytokines other than \_\_\_\_ – NOT \_\_\_\_ – Promote \_\_\_\_, collagen synthesis \_\_\_\_ activation of M1 and M2?
You can go back to previous lecture, for most part the classically activated
macrophages are the ones that are activated by microbial product and ____ and IFNy1 which is produced from ____ cells and they produce ROS, enzymes and will phagocytose bacteria but it is not a prominent function, its really the neutrophils that do
that. They can also produce ____, TNF, ____, IL-6, chemokines that produce
inflammation.
The alternatively activated macrophages are induced by a different set of cytokines they produce IL1-beta which are ____ and ____ which lays down collagen.
These macrophages are activated in repair and fibrosis and they are antiinflammatory.
It is possible to they are activated sequentially, M1 then M2.
Not everyone believe they exist but most people believe there are two types that have
different function
IGNgamma
particulate
ROS
inflammation
IFNgamma
microbicidal
angiogenesis
sequential
TLR1
Th1
IL1
IL12
antiinflammatory
TGFb
Acute vs Chronic Inflammation
• Acute ○ Congested BV, neutrophils, redness • Chrnic ○ Foci of \_\_\_\_ ○ Normal lung parenchyma replaced by \_\_\_\_ ○ \_\_\_\_ epithelial that’s normally not there
inflam cells
fibrotic tissue
cuboidal
Retrograde Infection
an infection that spreads along a tubule or duct against the ____
of secretions.
* Tissue destruction * Blocked \_\_\_\_… infection that is opposite to salivary flow
flow
salivary gland
Chronic Sialadentitis
• Inflammation of \_\_\_\_ • Foci of inlam cells ○ Not \_\_\_\_, but macros and lympho's • Normal glandular cells replaced by \_\_\_\_ and \_\_\_\_
salivary gland
neutrophils
foci
fibrosis
Persistence of Etiologic Agents
• Macrophages unable to kill bacteria:
–____ and ____ (→DTH)
• Macrophages unable to degrade bacteria:
– Certain strains of ____
- Viruses and fungi:
- T cell/macrophage-mediated (____)
• Caused by particulate or physical agents:
– Acid, ____, talc, asbestos, ____, gall stones
• Immunecomplexes:
– In blood vessels, ____, kidneys
• Uric acid = gout ○ \_\_\_\_, macro's cannot digest these • Immune complexes deposits…
tuberculosis leprosy streptococci DTH silica uric acid joints inorganic
Persistence of etiologic agents in Periodontal disease • Burst model: – Tissue destruction occurs in \_\_\_\_ followed by \_\_\_\_ periods. • Slow continuous model: • Homeostatic break down?
Persistence of etiologic agent in periodontal disease its been known that it is not a
continuous destruction in the bone. People with disease have bone destruction for a
period of time then its ____, then ____ up again.
Different models on to why it happens
The best model proposed was talked about with Dr. Hasengalis. Normally gingival
crevis has 100,000 types of bacteria that are commensal and symbiotic and happy and
good for you, but in susceptible individuals or during periodontal disease there is immune regulatory defect or systemic disease or other factors that contribute to
periodontal disease or you might have infection with ____ (ex, P.
gingivalis). There is a breakdown of ____, and the normal commensal bacteria
become ____ and involved in periodontal disease.
bursts
quiescent
quiet
flares
keystone pathogen
homeostasis
dysbiotic
• Perio is caused by ____ and bacteria in bioifilm
• Inflamed gingiva > periodontal bone loss (takes long)
• Current model:
○ Symbiotic microbitota > dysbitoic due to ____ > recruit neuetrophils in gingival crevice
○ Neutrophils try to protect (acute lasts for few days), but here, chronic, the neutrophils won’t be protective bc the etiology are persisent
○ Macro’s/T cells activated, produce cytokines (TNFalpha, IL1, IL17) which induce activation of ____
○ IL17 recruits ____, which also come in, and produce ROS and ____, and play a role in gingival tissue degradation
• NEUTROPHILS CONTRIBUTE TO ____
• LAD > HOW DO YOU GET PERIO DISEASE
○ Neutrophils are in BV but cannot get out, and cannot be effero, and providing signal for IL23 > producing IL17 causing bone loss
• Both LAD and perio it is due to infection
keystone pathogen osteoclasts neutrophils proteases periodontal bone loss
Rheumatoid Arthritis
Autoimmune (____ immune system, T and B cells activated), and mistakes part of body is ____
With Rheumatoid Arthritis we don’t know if the antigen is a microbe or self component.
Whatever it is, it would be processed by macrophage and presented to T cell in context of MHC.
The T cells produce cytokines which activate B cell and macrophages and
leads to the formation of R-factor which leads to ____ formation which
deposits within the ____ and eventually bring in neutrophils.
Also cytokines produced activate Fibroblasts and chondrocyte to promote their
proliferation. Cytokines also activate endothelial cells and when endothelial cells are
activated they increase expression of ____ molecules to help bring in leukocytes.
The result is the formation of ____, bone destruction, fibrosis and ____.
In the figure you can see the normal joint. There is synovial fluid in-between the joint,
which is important for the joint to function properly. In rheumatoid arthritis, you get
neutrophil recruitment because of immune complexes, because of activated B cells you
get antibodies, macrophages are activated, dendritic cells are there, and lymphocytes
are there. All these chronic inflammation cells are there and you get the formation of
pannus. (Missing from this slide): Pannus consist of ____ cells, ____ tissue,
____ connective tissue. It under goes fibrosis ankylosis, and instead of fluid between
the joints you have ____ tissue bridging the two parts of the joint.
It can also undergo ____, and you can have bony ankylosis, related to more
of a severe arthitis.
adaptive
foreign
immune complex
joints
adhesion
pannus
ankylosis
inflammatory
granulation
fibrous
fibrous conenctive
ossification
- Acute Abscess
- Chronic Abscess
- Acute: ____ material only
- Chronic: ____ tissue that is encapsulating ____ exudate; and when heals it leads to scar and fibrosis
- Acute, chronic and granulation can go on at same ____
purulent
granulation
purulent
time
Localized chronic duodenal ulcer
Another example is localized duodenum stomach ulcer. In the stomach, there are
____ forces that are trying to damage mucosa, ex. gastric acidity and peptic
enzymes, but you also, have ____ forces and whether you have homeostatic
disease matters which factor is stronger.
Defensive forces include, surface ____,
____ secretion, and regenerative property of ____ cell, and elaboration of
____ which help to maintain homeostasis.
This hemostasis can breakdown by impaired defense mechanism, or increase damage.
Examples of both are listed on the slide.
Chronic peptic acid - if you have more acid than normal, than it will act as a irritant that
damage epithelial cells and you will get an acute ____.
Non specific acute inflammation will try to wall off acid, but if the etiology persist for a long time, the acute inflammation
will lead to the formation of ____ tissue and eventually ____. As long as the
acid persist you will have damage (____), ____ inflammation, ____ tissue formation and ____, a dynamic interaction between each factor.
damaging
defensive
mucosa
bicarb
epithelial
prostaglandins
ulcer
granulation fibrosis ulcer acute granulation fibrosis
BRONCHIECTASIS
Permanent ____ of one or more bronchi
• Destruction of ____ and ____ supporting
- Predisposing factors:
- Bronchial ____
- ____
- Aspirated Foreign materials
- Localized to the obstructed lung segment
- Congenital:
- ____ (obstruction caused by mucus)
- Immunodeficiency (Immunoglobulin deficiencies)
- ____ Syndrome (Structural Abnormality in cilia)
- Pneumonia:
- Caused by ____ organisms (e.g. Staph Aureus)
- Post-____ Bronchiectasis
dilation
muscle
elastic
obstruction
neoplasm
cystic fibrosis
kartagener
virulent
tuberculosis
Virulent (pyogenic) > PA abscess > ____
acute/chronic osteomyelitis
Osteomyelitis
• Acute or Chronic.
• Very serious condition causing destruction of large amounts of bone
• Spread of infection into ____ spaces
• Most cases arise after ____ infection or ____ fractures
• ____ predilection
• ____>MX
Predisposing factors • Chronic systemic diseases • \_\_\_\_ status • Conditions that may cause bone hypovascularity – \_\_\_\_ • \_\_\_\_, alcohol, \_\_\_\_ • Malnutrition
• Manidble is more affected than maxilla ○ Difference in \_\_\_\_ supply • \_\_\_\_ health ○ Do not generate OM
bone marrrow odontogenic jaw male MD
immunocompromised
radiation
tobacco
IV drugs
blood
good
Acute osteomyelitis
• Clinical: – Severe \_\_\_\_ – Fever – \_\_\_\_ – Lymphadenopathy
• Histology:
– ____ bone
– Bacteria
– Inflammation
• Local \_\_\_\_, but a \_\_\_\_ manifestation • Know differences between systemic and local maniser ○ \_\_\_\_, vascular \_\_\_\_, \_\_\_\_ recruitment, \_\_\_\_ § local ○ \_\_\_\_, \_\_\_\_ § systemic • \_\_\_\_ are empty (no osteocytes) • Mostly neutrophils, and a lot of fluid, and bacteria • Dying bone - lacunae are all empty - bone is being resorbed
pain
leukocytosis
non-vital
response
systemic
vasodilation
permeability
neutrophil
edema
fever
leukocytosis
lacunae
Acute osteomyelitis
• Radiographs
– ____ or
– ____ radiolucency
• Sequestration of necrotic bone
• Treatment: – Difficult to treat – Culture/Sensitivity – \_\_\_\_ not common – High dose, long term antibiotics – Drainage – Remove dead bone?
• Radiopacity due to dead bone • \_\_\_\_ to treat ○ Tough to get antibiotics in there • Biopsy uncommon because difficult to get
unremarkable
ill-defined
biopsy
difficult
Chronic Osteomyelitis
• Clinical: – \_\_\_\_ – Pain – \_\_\_\_ formation – Purulent discharge – \_\_\_\_ loss – Pathologic fracture
• Histology: (Biopsy) – Soft tissue consisting of: • \_\_\_\_ cells • \_\_\_\_ tissue • \_\_\_\_ • “Pockets of \_\_\_\_”
• Etiology persists • Histology is different and clinical • Clinical presentation is \_\_\_\_ than acute • Foci of inflammatory • Sequestra ○ More pieces of \_\_\_\_ in chronic than in acute • Pockets of abscess • Acute and chronic exist in the same \_\_\_\_, but clinical manifesations is not as serve as in acute
swelling
sinus
tooth
chronic inflammatory fibrous sequest abscess milder dead bone tissue
Chronic osteomyelitis
• Radiograph:
– Patchy ____ radiolucency
– Often, central radiopaque ____
• Treatment:
• Even more difficult to treat
– Dead bone and bugs are shielded by ____ tissue
– Limited ____ supply
• ____ dose, long-term intravenous antibiotics
• ____ intervention mandatory
– Remove all infected tissues down to good bone
– May need resection with immediate ____
* Because of dead bone - patchy (\_\_\_\_) * Radioopaque sequestra - pieces of \_\_\_\_ bone * Here, remove the dead bone (mandatory) and reconstruct
ill-defined
sequestra
fibrous
blood
high
surgical
reconstruction
radiolucency
live
Less virulent (non-pyogenic) > ____ > ____ or ____
PA granuloma
PA cyst
phoenix abscess
Periapical Granuloma
Chronically inflamed ____ tissue at apex of non-vital tooth
Etiology: \_\_\_\_ Clinical: \_\_\_\_, \_\_\_\_, \_\_\_\_, \_\_\_\_ EPT: \_\_\_\_ Histopath: \_\_\_\_ Treatment: \_\_\_\_, \_\_\_\_, \_\_\_\_
• See BV and fibroblasts, and chronically inflam cells • Well defined \_\_\_\_ • Nectotic pulp due to microbe, but the microbe is non-pyogenic, that is casuing \_\_\_\_ death of the pulp • \_\_\_\_ - different from PA abscess • PA radiolucency but no \_\_\_\_ - PA granuloma • PA surgery > make sure it's not a neoplasm • What you do depends on the extent If left untreated - bigger, and can transform into \_\_\_\_
granulation necrotic pulp asymptomatic no mobility or sens. to percussion ~75% of apical inflam. lesions found on routin radiogrape exam
no response
granulation tissue/fibrosis
root canal
PA surgery
extraction
asymptomatic
symptoms
PA cyst
Periapical (Radicular) cyst
____-lined, ____-filled cavity at the apex of a non-vital tooth
Epithelial ____-tissue breakdown
Epithelial Cell ____
Mass of epithelial cells-____-____ press
____ Bodies
• Take histology of bag ○ Epithelial cells (\_\_\_\_), slothing into cyst and lumen ○ They prolfierate in response to \_\_\_\_ that are produced in lesion ○ Pushing into cavity, and they die, and they contain protein, creation of \_\_\_\_ gradient, and leads into cravicular fluid
epithelial fluid proliferation death osmotic calcification-rushton
squamous
EGF
osmotic
Periapical (Radicular) cyst
• Clinical and Radiological: – No symptoms unless \_\_\_\_ inflam. Exacerbation – Tooth does not respond to \_\_\_\_ – Radiology : identical to \_\_\_\_ • Treatment: – Same as \_\_\_\_
* If tooth is infected with more virulent, and gets into cyst, and acute, then you may see symptoms * But if that doesn't occur, no symptoms (like PA grnauloma) * Only time to tell when cyst is following \_\_\_\_
acute
EPT
PA granuloma
PA granuloma
removal
Less virulent (non-pyogenic) > ____
phoenix abscess
Phoenix abscess
• ____ abscess arising within a ____
• Due to changes in ____ or host ____
• Presents with ____
• Painful, and swelling - requires urgent treatment to relive pain and swelling ○ \_\_\_\_, \_\_\_\_, or \_\_\_\_
acute
microbial flora
defenses
radiolucency
antiobiotics
RCT
extraction
Condensing Osteitis:
Localized area of ____ at the apex of a non-vital tooth
- Reactive ____ of bone
- Induced by long standing, ____
- More common in patients under ____
- Usually lower ____
- Pulp: Necrosis/____ pulp test
- Treat: Endo or Extraction
- ____
- Months and years to develop
- Test status of pulp; negative = dead
sclerosis hyperplasia low grade pulp infection 30 1st molar negative radioopacity
Images left to right: Heart muscle, H and E staining, Deposition of collagen, Trichrome
staining deposition of collagen.
Scar formation, in the context of ____ healing, the scar acts as a Band-Aid to keep the heart together to enable function, we refer to this as wound healing.
(Scar = ____ healing).
When the scar tissue is extensive and interferes with the heart we call this fibrosis, and
its associated with loss of function and chronic inflammation
(____ = loss of function/ chronic inflammation).
So when one has a myocardial infarct, initially there is ____, then ____ coming in, then ____ tissue formation which becomes a ____ or ____ depending on the extent of damage.
wound
wound
fibrosis
acute inflammation macrophages granulation scar fibrosis
- Liver cirrhosis
- Chronic alcoholic - damaging the hepatocytes - not able to proliferate - bring in ____ from BM - differentiate into fibroblasts and ____ - collagen and contract - fibrosis without involvement of ____ that you see in heart
SC
myofibroblasts
acute/macro’s/granulation
Pneumoconioses (Silicosis) • Pneumon (lung) konis (dust) = Dusty lung • Non-\_\_\_\_ reaction to inhaled dust • \_\_\_\_, \_\_\_\_ and Asbestos • Particles 1-5μm in diameter
* Impraired lung function * Most important pneumconiose > \_\_\_\_ * Breath in silica, and <1-5um is removed; but bigger, gets into lung and cannot be \_\_\_\_
neoplastic coal dust silica silicosis removed
Silicosis:
•The most prevalent chronic ____ disease in the world
•~2.0 million construction workers in the US are exposed to respirable crystalline silica
•~300,000; brick manufacturing
* When silica get into lung - alveolar macros try to engulf - but silica is \_\_\_\_ so they cannot digest - macro's may die, secrete cytokines - recruit fibroblasts - going to proliferate - synthesize \_\_\_\_ [present: macro's, fibro's, lymphocytes and collagen] * As long as etiology persists… * Lung parenchyma replaced by nodules of \_\_\_\_
inorganic
collagen
collagen
Silicosis
• Stain lung with trichrome - filled with collagenous fibrotic tissue • Can see some normal parenchyma, but most of lung is fibrotic and inflam cells • Chronic inflammation: ○ Persistence of \_\_\_\_ ○ (\_\_\_\_ destruction) ○ Fibrosis > \_\_\_\_ ○ COD > loss of lung function
etiology
tissue
loss of cuntion
