Inflammation Flashcards
What is inflammation
Host defense response to infection and tissue damage intended to eliminate offending agents.
Causes of inlammation
Infections, Tissue Necrosis, Foreign bodies, immune reactions
Features of Acute Inflammation
Initial rapid response
Develops within minutes-hours
Features: Redness, swelling, heat,
Cells involved in acute Inflammation
Neutrophils, other phagocytes
Outcome of acute inflammation
Complete resolution, resolution with fibrosis (usually mild) or progression to chronic inflammation
Characteristics of Chronic Inflammation
Longstanding injury with tissue damage
How long does chronic inflammation last?
Develops over days to months
Local features of Chronic inflammation
Variable, related to extent and type of tissue damage
Cells involved in chronic inflammation
lymphocytes, plasma cells, monocytes, macrophages, fibroblasts
Outcome of chronic inflammation
Progressive and sometimes severe tissue damage with fibrosis
Acute inflammation phases
- Blood vessel changes
- Leukocyte recruitment
- Phagocytosis
During acute inflammation what happens with the blood vessel changes
Increased flow due to vasodilation, increased permeability
During acute inflammation what happens with leukocyte recruitment
Margination, rolling, adhesion
Diapedesis
Chemotaxis
During acute inflammation what happens with phagocytosis
receptor binding, engulfment and intracellular destruction
What does exudate mean
Leakage of fluid and proteins from blood vessels
Caused by increased interedothelial space
What does Transudate mean
Leakage of fluid from blood vessels
Caused by increase in hydrostatic pressure common in congestive heart failure
Phases to getting leukocyte out of the blood vessel
- Rolling
- Integrin activation by chemokines
- Stable adhesion
- Migration through endothelium
How does your body go about slowing down the leukocytes in your blood stream to get them out of the blood vessels?
Activation of P-selectin and E-selectin attach to proteins on the surface of the leukocyte cell, the cell attaches and then rolls along the endothelium
Once it starts rolling how does the leukocyte slow down?
Attaching to Integrin (in its high affinity state) which is when its considered to be in stable adhesion
What is the process of the leukocyte moving through the endothelium to exit the blood stream called
diapedesis
What happens after diapedesis?
The leukocyte has proteins on the outside that use chemotaxis to move towards the site of inflammation
What is chemotaxis
migration along a chemical gradient (chemoattractants). It can be exogenous (bacterial products like peptids and lipids) or endogenous (chemical mediators)
What are some of the chemicals that can aid in the chemotaxis of leukocytes?
C5a - part of the complement cascade
Aarachadonic acid metabolites like Leukotriene B4
Cytokines like IL-8
Cellular Infiltrate in acute inflammation
Neutrophils - 6-24 hours
Monocytes - 24-48 hours and thereafter (when they persist as macrophages)
*Infiltrate may be mixed if tissue injury is ongoing
What are the steps of microbial killing
- recognition and attachment where the microbes bind to phagocyte receptors
- engulfment - phagocyte membrane zips up around microbe
- killing and degradation - killing of microbes by ROS and NO, degradation of microbes by lysosomal enzymes in phagolysosome
What are the 3 major methods of microbial killing
- reactive oxygen species
- nitric oxide
- Lysosomal enzymes and proteins
How do ROS kill microbes
NADPH oxidase (phagocyte oxidase) generates superoxide anion Superoxide anion generates H2O2 which works with myeloperoxidase and Cl- to generate OCl2-
How does NO kill microbes
Inducible nitric oxide synthase (iNOS) generates NO in activated neutrophils and macrophages
This works with superoxide anon to generate peroxynitrite (ONOO-)
How do Lysosomal enzymes and proteins kill microbes
Lysozomes, collagenase, elastase, acid hyrolase degrade bacteria and can cleave complement components and other proteins
What are some protective mechanisms against microbial killing pathways
- Location - limited to lysosome, phagolysosome
- Antioxidants
- Antiproteases
Mediators of Acute Inlammation
- Vasoactive amines
- Aarachidonic acid metabolites
- Ctyokines and chemokines
- Complement system
What is a powerful target for therapeutic agents to block inflammation?
Block the inflammation cascade
Examples of vasoactive amines and their source
Histamine, Serotonin - preformed in mast cells and basophils - rapid release and action. Associated with vasodilation and increased vascular permeability
Serotonin
Preformed in GI endocrine cells and platelets, its a neurotransmitter
Arachadonic acid metabolites - where are they derived from and what do they do
Derived from cell membrane phospholipids
They bind to G-protein coupled receptors.
Downstream effects of AA mediators
Vasodilation, Vasoconstricton, increased vascular permeability and chemotaxis and leukocyte adhesion
Cell membrane phospholipids combine with phospholipases to form
Arachadonic acid
What are two mediators of arachadonic acid
Cyclooxygenase, 5-Lipoxygenase
how do steroids affect inflammation
Blocking phospholipases and preventing the downstream effects of arachodonic acids
Examples of cytokines
TNF and IL-1
What do cytokines do
recruit neutrophils and monocytes, recruit leukocytes, systemic effects
Local inflammation caused by cytokines is regulated by what
TNF, IL-1
They increase permeability of blood vessels by increasing gaps between endothelial cells by increasing the expression of adhesion molecules
Systemic protective effects of cytokines
TNF, IL-1,6 - in brain –> fever
IL-1,6 in liver –> acute phase proteins
TNF, IL-1,6 - in bone marrow –> leukocyte production
Systemic pathological effects of cytokines
TNF - in heart - Low output
TNF - in Blood vessels - increased permeability
TNF, IL-1 - in skeletal muscles - insulin resistance
What is the complement system
Has to do with the activation of normally present proteins in the blood stream that become activated and then cause a cascade to amplify its effects ending in inflammation
Complement system begins with
C3 thats cleaved into C3a and C3b
name the 3 complement system pathways
Alternative, classical, lectin
Describe the alternative pathway of the complement system
Microbe, C3 binds to microbe
Describe the classical pathway of the complement system
Antibodies bind to a microbe and then C3 binds
Describe the lectin pathway of the complement system
Mannose binding lectin binds to a microbe which then binds to C3
Describe a MAC
Membrane attack complex, a tube that allows for the contents of the microbe cell to exit the cell leading to its lysis
What are the roles of C5a and C3b
C5a (and C3a) recruit and activate leukocytes that lead to inflammation and destruction o f microbes by those leukocytes
C3b leads to phagocytosis of microbe
Causes of chronic inflammation
- persistent infections
- hypersensitivity diseases
- prolonged exposure to toxins
Morphologic features of chronic inflammation
mononuclear cell infiltration - macrophages, lymphocytes, plasma cells
tissue destruction
Attempts at healing
What is granulomatous inflammation
Special form of chronic inflammation
What cells are associated with granulomatous inflammation
Macrophages, giant cells, T lymphocytes ,variable necrosis
Etiology of granulomatous inflammation
- foreign material
- infection - mycobacterial, fungal
- immune reactions
Systemic effects of inflammation
- Fever
- Leukocytosis
- Sepsis and septic shock
Diagnostic proteins of inflammation
C-reactive protien (most common), fibrinogen, serum amyloid A, hepcidin
