Human Pathology Inflammation Flashcards
What are the five cardinal signs of inflammation?
Rubor= redness Calor= Heat Dolar= Pain Tumor= Swelling Functio Laesa= loss of function
What is inflammation?
A protective response that attempts to eliminate the initial cause of the cellular injury as well as necrotic cells and tissue.
What are the two components of Inflammation?
Vasodialation
Vascular Permeability
What is the goal of the inflammatory reaction?
To bring WBC to the site of injury
Where are lymphocytes and leukocytes found?
Circulating in the blood
What causes inflammation reaction to progress?
Chemical mediators that are produced by the host cells in response to the injurious stimuli.
Inflammation is normally controlled and self limited
Acute Inflammation
An immediate and early response to injury and infection
Vasodialation
Structural changes resulting in increased vascular permeability
What are the two major events to start inflammation?
Vasodialation and emigration of the leukocytes from circulation in the blood to the site of injury
Vascular permeability
Allow the protein rich fluid and C proteins to enter into the ECM
Stimuli for Inflammation
Infectious Agents Toxins Chemical Agents such as drugs Immunologic Reactions Necrotic Tissue
Characteristics of Inflammation
Short Duration within 24 hours
Exudation of fluid and proteins
Emigration of neutrophils and WBC
Platelets
Process of Emigration of WBC
Diapedisis
What is the duration of chronic inflammation?
Months to years
Edema
Excess interstitial or serous cavity fluid due to vascular permeability
Purulent Exudate
Inflammatory exudate rich in leukocytes and cellular debris
Exudate
Inflammatory extravascular fluid with a high protein content and SG of 1.020
Transudate
An extravascular fluid with a low protein content and SG less than 1.012
Pattern Recognition Sensors
WBC have receptors that are designed to recognize the presence of infectious pathogens as well as substances released from dead cells
What are the 4 major classes of pattern recognition sensors?
TLR
NOD like receptors
C type lectin receptors
RIG like receptors for viral nuclei
What do TLR recognize?
Microbes and their products
Where are TLR located?
Plasma membrane of endosomes
Where are NOD like receptors located?
Cytosol
What do NOD like receptors recognize?
Products of necrotic cells like uric acid and released ATP.
What type of receptor signals the inflammasome?
NOD like Receptor
Inflammasome
Multiprotein cytoplasmic complex
Triggering of inflammasome results in activation of caspase 1
Caspase 1
Cleaves the precursor forms of the inflammatory cytokine interleukin 1B into its biologically active form
Mediators of leukocyte recruitment
TNF and IL-1
What are the steps in the changes of vascular flow with the inflammatory response?
- Transient vasoconstriction
- Vasodialation
- Increased Vascular permeability
- Slowing circulation
- Leukocyte margination
Colloid osmotic pressure
at the post capillary venule that reabsorbs the fluid from the interstitial space
Mechanism of Vascular Leakage
Endothelial cell contraction with gap formation
Junctional retraction
Direct Endothelial Injury
Leukocyte dependent endothelial injury
Leakage from newly forming blood vessels
Increased transcytosis in which the molecules are transported through the endothelial cell
In inflammation, lymphatic flow is increased.
True or False
True
Inflammation of lymphatic vessels
Lymphangitis
Inflammation of lymph nodes
lymphadenitis
Recruitment
Leukocytes flow rapidly in the blood and they must be slowed down and brought to offending agent or site of the injured tissue
Margination
Leukocytes adhere to the periphery of the blood vessel
Chemotaxis
Leukocytes follow a trail of chemokines to tell where the injury is
What is the most abundant leukocyte in acute inflammation?
Neutrophil
What are the chemokines from complement?
C5a
C2a
C3a
Rolling
Leukocytes roll along the vessel wall transiently sticking by selectins and adhesion molecules
Where are the P selectins derived from?
Waibel Palade bodies activated
What activates E selectins?
TNF and IL-1
What interferon activates ICAM and VCAM?
IL-8
ICAM and VCAM adhere to?
Integrins on the neutrophil
P selectin bind to which molecule on the neutrophil?
Siayl Lewis X
What upregulates selectins on endothelial cells?
TNF and IL-1
What is the role of selectins?
To ensure that the binding of leukocytes is restricted to the endothelium at sites of infections and injury
Integrins
Transmembrane heterodimeric glycoproteins that also function as cell receptors for ECM.
Present on leukocytes in low affinity until activated by a cytokine
Transmigration of the neutrophils is mediated by which adhesion molecule?
PECAM CD31
VCAM binds
VLA-4 Integrin on neutrophil
ICAM binds
CD11.CD 18 integrin on neutrophil
GlyCam 1 binds
L -Selectin on neutrophil
PECAM CD 31 binds
CD 31 on neutrophil
What mediators affect upregulation of P selectin?
Histamine
Thrombin
PAF = platelet activating growth factor
Exogenous chemotactic agents
bacterial products
Endogenous chemotactic agents
components of the complement system in liver
Products of lipoxygenase pathway from cell membrane PLA2
What does the lipooxygenase pathway produce?
Leukotrienes
What starts the cyclooxygenase and lipooxygenase pathways?
Arachnodonic Acid
How do leukocytes make products to destroy the bacteria?
Oxygen Burst
Opsonin
Tag microbe with C3b
Which part of the complement system starts the classical pathway?
C1 binds to the antigen antibody complex on the Fc portion of the antibody
What is the enzyme that starts the oxygen dependent pathway in the production of ROS?
oxidase
What enzyme turns hydrogen peroxide back into water?
Catalase
Glutathione peroxidase
What enzyme makes hydrogen peroxide turn into bleach?
MPO and Cl-
What does binding the C3b do to the microbe?
Tag it for phagocytosis
What enzymes does the oxygen independent killing mechanism use?
Bacterioacidal permeabiluty increasing protein
Lactoferin
lysozyme
Major Basic protein
Defensins
NETS
Neutrophil Extracellular Traps
Extracellular fibrillar networks produced by neutrophils in response to infections which contain a framework of chromatin and granule proteins that trap bacteria when the neutrophil dies
How does the leukocyte induced tissue injury occur?
lysosomal enzymes leak out
ROS
Products of arachidonic acid metabolism
What conditions cause a defect in phagocytosis and microbial activity of leukocytes?
DM
Sepsis
Anemia
Malnutrition
What conditions cause a defect in adhesion and chemotaxis?
DM
Chronic dialysis
Sepsis
Malignancy
Leukocyte Adhesion Deficiency
Defective Leukocyte adhesion due to mutations in the b chain of the CD 11/CD 18 integrins
Leukocyte Adhesion Deficiency 2
Defective leukocyte adhesion deficiency due to mutation in fucosyl transferase required o make sialyted oligsaccharide
Chronic Granulomatous Disease
Decreased oxidative burst ( phagocyte oxidase)
Membrane bound X linked
Cytoplasmic autosomal recessive
Myeloperoxidase Deficiency
Decreased microbial killing due to defective MPO-H2O2 system
Stop Signals of Inflammation
TGF-B
IL-10
Neural impulses (cholinergic) which inhibit the production of TNF in macrophages
Vasoactive amines of the inflammatory response
Histamine
Serotonin
Histamine
Released by Mast Cells, Basophiles and platelets.
Cause dialation of arterioles and increased vascular permeability
Serotonin
Present in platelets and enterochromaffin cells
What releases arachidonic acid from the plasma membrane?
phospholipase A2
What inhibits phospholipase A2 in arachidonic acid metabolism?
Steroids
What inhibits cycloxygenase?
COX 1
COX 2
Prostaglandin GI2
Cause vasodialation and inhibit platelet aggregation
Thromboxane A2
Cause vasoconstriction and promote platelet aggregation
PGD2
Prostaglandin that promotes vasodialation and vascular permeability
PGE2
Prostaglandin that promotes vasodialation and vascular permeabilty.
Responsible for fever initiation by influencing the hypothalamus
Leukotriene C,D,E
Bronchospasm and increased vascular permeability
Lipoxin A4 and Lipoxin B4
Inhibit neutrophil adhesion and chemotaxis
Leukotriene B4
Chemotaxis promotion
PAF
Platelet Activating Factor
