Term Test 2 - Inflammation Flashcards
what leukocyte is present in most lesions of acute inflammation
neutrophils (at least some)
pus implies what
bacterial infection
what are some examples of causes of neutrophilic inflammation
trauma, burns, immune complexes, foreign material, thrombosis, necrosis
neutrophils enter tissues within _______
hours
pus takes __________ days to form
several
abscess has what specific connotations
implies fibrosis, which takes at least a week (4-5 days to start)
What is the fate of a neutrophil
typically death once they enter a tissue
What are the four outcomes of suppurative inflammation
1) resolution - if the stimulus is removed
2) chronic suppurative inflammation - if stimulus persists
3) stimulation of fibrosis
4) containment - abscess formation
Do neutrophilic infections always produce pus
NO. If the neutrophils are contained in many compartments (ex. alveoli) or non-liquid, pus will not be produced
What are the steps in neutrophil recruitment (8 total)
1) bacteria enter tissue
2) bacteria are recognized by antibodies, phagocytes, complement…
3) release of inflammatory mediators
4) inflammatory mediators act on the endothelium and leukocytes
5) rolling adhesion (mediated by selectins)
6) firm adhesion (mediated by integrins)
7) diapedesis
8) chemotaxis
What are 3 mediators of chemotaxis
IL-8, C5a, LTB4
Rolling is mediated by ______ on leukocytes and ___________ on endothelium
carbohydrates ; L-selectin/P-selectin
Firm adhesion is mediated by ______ on leukocytes and ___________ on endothelium
integrins (ex. LFA1 aka CD11a/CD18); ICAM-1
How do neutrophils undergo chemotaxis
Extension of lamellipodia that adhere to the tissue matrix
What is an example of a chemotactic molecule for neutrophils
IL-8
What is an example of a chemotactic molecule for eosinophils
RANTES
What is an example of a chemotactic molecule for both neutrophils and eosinophils
C5a
IgG binds to _________ and is an opsonin of ____________ immunity
FcγR; acquired
C3b binds to ________ and is an opsonin of ____________ immunity
CR3; innate and acquired
SP-A and MBL are opsonins of _____________ immunity
innate
What TLR recognizes bacterial lipoproteins
TLR1, 2, 6
What TLR recognizes bacterial LPS
TLR4
What TLR recognizes CpG DNA
TLR9
What TLR recognizes dsRNA
TLR3
What TLR recognizes flagellin
TLR5
What TLR recognizes ssRNA
TLR7,8
what are 4 mechanisms by which neutrophils kills bacteria
bactericidal proteins, oxidative killing, proteolytic enzymes, NETs
what are 4 types of antimicrobial proteins in neutrophil granules
lactoferrin, lysozyme, defensins, cathelicidins
what are 4 types of ROS
superoxide anion (O2-), hypochlorite (HOCl-) , peroxide (H2O2), myeloperoxidase
what are 3 types of proteolytic enzymes
elastase, collagenase, cathepsin G
How do leukocytes recognize bacteria (3)
1) opsonins, 2) PAMPs, 3) cytokines from other cells
How do leukocytes kill bacteria (4)
1) bactericidal enzymes, 2) oxidative killing, 3) proteolytic enzymes, 4) NETs
What is the stimulus for eosinophils (2)
Parasites and allergy
What are eosinophil effector functions
1) not phagocytic
2) oxidative injury
3) damage to cell membranes from granule proteins
What are eosinophil granule proteins (3)
Eosinophil myeloperoxidase, eosinophil major basic protein; eosinophil cationic protein
T/F low amounts of immune complexes are characteristic of many immune reactions
True
In what cases do immune complexes cause disease
Persistent infection/immune response or defective removal via phagocytosis and complement
Where do circulating immune complexes tend to deposit
synovium, glomeruli, skin
what is the Arthus reaction
when antigen localized to vessel walls reacts with circulating antibody
What is a granuloma
nodular mass of activated (epitheloid) macrophages, with or without giant cells, surrounded by lymphocytes and/or fibrous tissue
what is granulomatous inflammation
inflammation dominated by activated macrophages
T/F granulomatous inflammation often includes giant cells, epitheloid macrophages and fibrosis
T
What is pyogranulomatous inflammation
Dominated by activated macrophages and neutrophils
T/F granulomatous inflammation can be acute or chronic
FALSE, it is ALWAYS CHRONIC
What are four causes of granulomatous inflammation
1) foreign material
2) fungi
3) mycobacterium
4) DTH reaction
What is the pathogenesis of granulomatous inflammation
Response to inert foreign material OR immune response stimulated by Th1 cells
What are some sequelae of granulomatous inflammation
cachexia, space occupying lesion, impingement on a vital structure
How do macrophages become activated during granulomatous inflammation
Macrophages present antigen to Th1 cells -> Th1 cells produce IFNγ -> IFNγ activates the macrophages
What are the effector functions of macrophages
Phagocytosis and killing of bacteria
How does granulomatous inflammation differ from neutrophilic inflammation
In granulomatous, there are resident populations of macrophages that are ready for rapid responses AND there is better coordination between the immuno-inflammatory responses
What are some common causes of delayed type hypersensitivity
plants, textile fibres, dyes, cleansers, topical medications, shampoos, disinfectants, rubber, latex, plastics, metals
What is the time from exposure to the stimulus to onset of immune complex mediated disease
8 hours
What is the time from exposure to the stimulus to onset of delayed type hypersensitivity
24-72 hours
How would you describe the exudate formed by neutrophilic inflammation on mucosal surfaces
catarrhal or mucopurulent
What is hypopyon
neutrophilic inflammation in the anterior chamber of the eye; interferes with vision
endothelial activation is associated with an _______ in tissue factor _______ in protein C and ________ in thrombomodulin
increase, decrease, decrease
what colour does eosinophilic inflammation impart on tissues
green
What are three ways that neutrophils may damage host tissue
space occupying lesion, proteolytic/oxidative injury, induction of fibrosis and scarring
what are giant cells
macrophages with multiple nuclei (5-20)
T/F there are tons of lymphocytes in a granulomatous reaction to foreign bodies
FALSE
What are histiocytes
macrophages, monocytes, dendritic cells
Inflammatory lesions formed by lymphocytes +/- plasma cells without other leukocytes suggests
protozoal, viral, or immune-mediated disease
What is SIRS
Systemic consequences of localized or disseminated inflammation
What is sepsis
SIRS caused by infection
What is bacteremia
Bacteria in systemic circulation (with or without clinical disease)
What is septicemia
Bacteremia + clinically apparent disease
Name examples of systemic distribution of the causes of SIRS
- bacteremia
- anaphylaxis
Name examples of localized distribution of the causes of SIRS
- sterile pancreatitis
- bacterial pneumonia
What are examples of cytoplasmic receptors
NOD like receptors and RIG-I like receptors
What are three examples of soluble receptors
complement, antibody, collectins
What are examples of cell surface receptors
TLRs, Fc receptors, complement receptors
Changes in tissue factor, thrombomodulin and protein c promote _____________ when local
endothelial activation and hypercoagulability -> thrombosis
Changes in tissue factor, thrombomodulin and protein c promote __________ when disseminated
cogaulation -> DIC -> consumptive coagulοpathy
Name 5 consequences of SIRS
- acute phase response
- vasodilation (systemic hypotension)
- increased vascular permeability (edema)
- leukocyte activation (release of proteases and free radicals)
- endothelial activation
What tissues are the first to suffer from SIRS
liver, heart, brain, kidney, intestine, lung
T/F acute phase response is static
False, it is adaptive
Define the acute phase response
systemic changes in physiologic processes during disease; adaptive
Name 3 acute phase proteins
CRP, fibrinogen, haptoglobin
Name 3 beneficial functions of acute phase proteins
control pathogens, quell inflammation, minimize tissue damage
Name 2 acute phase proteins in ruminants
haptoglobin, fibrinogen
Name 2 acute phase proteins in dogs
SAA, CRP
Name 2 acute phase proteins in cats
SAA, α1 acid glycoprotein
Which is most likely to trigger an acute phase response
A) bacterial pneumonia
B) dehiscence of GI tract
C) liver abscess
D) granuloma in cat liver
B (tons of bacteria, huge surface area affected)
Where is edema commonly localized to during SIRS
lung
Define autoimmune disease; what breaks down
Disease caused by an immune response against self-antigens (Ab mediated and cell mediated); breakdown of self tolerance
Name three mechanisms of tissue damage in autoimmune diseases and give an example of each
1) immune complex disease (vasculitis, polyarthritis, glomerulonephritis, uveitis)
2) antibody-mediated cytotoxicity (IMHA, thrombocytopenia, myasthenia gravis, pemphigus)
3) T cell-mediated cytotoxicity (myositis, discoid lupus)
What is inflammation
The active response of tissues to injury which stimulates a return to homeostasis
Neutrophils eliminate
extracellular bacteria
Eosinophils eliminate
metazoan parasites (worms)
Macrophages eliminate
Mycobacteria, fungi, foreign material
Cytotoxic T cells eliminate
viruses, protozoa
Name 4 goals of inflammation
1) eliminate the injurious stimulus or pathogen
2) contain the injury
3) remove necrotic tissue
4) initiate tissue repair
Humoral responses of inflammation include (5)
Fibrinogen, edema, antibody, innate defense proteins, complement
What occurs physiologically during cachexia and why
Catabolism of muscle to provide amino acids for tissue repair
The plasma concentration of acute phase protein increases within _____________ hours after the onset of tissue injury
5-10
The plasma concentration of acute phase proteins returns to normal within by _________ hours after the inflammatory response subsides
48 (2 days)
Measuring the concentration of _____________ is helpful to detect inflammatory responses in ruminants
plasma haptoglobin
What are the most frequent sites for bacteremic spread
pericardium, pleura, peritoneum, meninges, synovial surfaces
What well vascularized tissues are prone to population from bacteria
Cancellous bone, growth plate of bones, spleen, liver, kidney, lung, uvea, heart valves
What is a consequence of hypercoagulability in horses
laminitis
What are four ways in which autoimmune diseases damage tissues
1) antibody mediated opsonization/complement activation
2) formation of immune complexes
3) pro inflammatory/cytotoxic effects of autoreactive T cells
4) actions of T helper cells
What three changes indicate that an inflammatory reaction is occuring in a patient
1) fever
2) leukocytosis
3) changes in acute phase proteins
What are the three MAIN organs that get affected during SIRS/sepsis
kidney, liver, lung
T/F neutrophils secrete cytokines that can trigger thrombosis, leading to ischemia
T
what is activated upon immune complex deposition
- activation of complement
- activation of macrophages and neutrophils
what causes vasculitis
neutrophil-mediated damage to vessel walls (by being recruited to the vessel wall)
T/F well vascularized tissues are the most susceptible to immune complex disease
T
What are two consequences of immune complex deposition
- vasculitis (due to the neutrophils)
- activation of platelets and thrombosis -> infarction and ischemia
T/F Mycobacterium = mycoplasma
F
T/F macrophages activated by IFNγ are better equipped at killing intracellular pathogens
T
upon re-exposure to an antigen that elicited a TH1 response, what happens
TH1 cells secrete cytokines that induce an inflammatory response and IFNγ that activates macrophages
Type 1 sensitivity takes how many mins to develop
30
Type III sensitivity takes how long to develop
8 hours
Type IV sensitivity takes how long to develop
24-72h
what are three consequences of vasculitis from immune complex deposition
edema, petechiae, infarcts
How does the histologic appearance of a chronic allergic disease differ from that of the immediate reaction following injection of an allergen?
chronic: mast cells, eosinophils, lymphocytes
acute: degranulated mast cells, edema
In pemphigus foliaceus, how does the immune response cause pustules/ vesicles/ blisters in the epidermis?
Autoantibodies target desmosomal proteins
