MECHANISMS OF INFLAMMATION I (LECTURE 92)  DR.

LEE
 Definitions of inflammation:
o a localized reaction that produces redness, warmth, swelling, and pain as a result of infection,
irritation, or injury. Inflammation can be external or internal (how we get it)
o an adaptive response that is triggered by a noxious stimuli and/or condition (what causes it)
o a protective response to an invading pathogen, noxious stimuli or injury resulting in redness, warmth,
swelling, pain and loss of function related to the removal of the pathogen/noxious stimuli ultimately
leading to the repair of damaged response (protective response)
 Five cardinal signs of inflammation: heat, redness, swelling, pain, and loss of function
 PAMPS (Pathogen-associated molecular patterns): outside the body; for infections  exogenous microbial
products
 DAMPS (damaged-associated molecular patterns): inside the body; for sterile inflammation  endogenous
molecules released by damaged tissues and necrotic cells
 1st step of wound-healing is inflammation
 NFkB is one of the primary cell signaling pathways associated with inflammation

1. Demonstrate a basic understanding of acute patterns of inflammation, the cellular components, mediators
and systemic effects
 Acute Inflammation: early (almost immediate) response of tissue to injury; normal response that is beneficial
 removal of offending agent and repair of tissue
o positive feedback loop: complex, multiple players, and longer time to return to normal
o mainly neutrophils

Acute Disorders Cells and Molecules Involved in Injury

Acute respiratory distress syndrome Neutrophils
Asthma Eosinophils; IgE antibodies
Glomerulonephritis Antibodies and complement, neutrophils,
monocytes
Septic shock Cytokines

2. Demonstrate a basic understanding of chronic inflammation, patterns of inflammation, the cellular

components, mediators and systemic effects
 Chronic Inflammation: the sum of responses mounted by tissues against a persistent injurious agent
(bacterial, viral, chemical, immunological etc)
o Either unable to resolve or unable to remove offending agent (agent could be pathogen, toxin, or
chemical)
o Damaging effects of inflammation > repair….increased damage and/or fibrous tissue (scarring) leads to
loss of function
o Anti-inflammatory drugs can be beneficial by stopping damaging effects of inflammation and facilitating
resolution
o Mainly monocytes, macrophages, and lymphocytes

Chronic Disorders Cells and Molecules Involved in Injury

Arthritis Lymphocytes, macrophages, antibodies(?)
Asthma Eosinophils; IgE antibodies
Atherosclerosis Macrophages, lymphocytes
Pulmonary fibrosis Macrophages, fibroblasts
3. Describe the time course of the vascular and cellular events responsible for the acute inflammatory
response to injury and discuss the receptors and ligands that are responsible for these events
 Patterns of Acute Inflammation
1. Recognition of offending agent and/or damage
 Cells: resident and recruited cells
 Chemical mediators: PAMPs and DAMPs
 PRR: danger signals
2. Recruitment of leukocytes and proteins
 1st vasoactive changes: transient vasoconstriction followed by more
permit vasodilation  increased blood flow result in redness and
increased temperature
 2nd increase capillary permeability: caused by either endothelial
swelling or damage  results in exudate and inflammatory edema
 Signals: chemokines, diapedesis
 Edema: transudate vs exudate
3. Leukocytes and proteins (complement) destroy/eliminate offending agent
 Activation of leukocytes; cells include neutrophils, macrophages,
dendritic cells
 Phagocytosis and intracellular killing
4. Inflammation resolves
 Pathogen is removed (No DAMPs or PAMPs); cellular debris is also
removed meaning no chemical mediators no inflammation
 Anti-inflammatory signals and clonal contraction
5. Damaged tissue is repaired
 Activation of fibroblast to replace damaged ECM  this may or may
not be 100% successful depending on tissue and degree of damage
 Angiogenesis and re-epithelization (skin)
 Maturation and remodeling

 Step 0 is hemostasis; stops blood with clotting then can move on to inflammation
o Not included inflammation…more closely associated with trauma resulting in bleeding both external and
internal
o Sets stage for inflammation to follow  vasoconstriction, platelet activation, clot formation
o Clot becomes reservoir for chemical/ inflammatory mediators
o Starts process of recruitment and activation of leukocytes

4. Describe phagocytosis and the molecular mechanisms of intracellular killing

 Macrophages and neutrophils both kill pathogens using phagocytosis and the release of toxic molecules and
enzymes. Phagocytosis is most effectively triggered by
pathogens that have been opsonized by complement or
IgG. A phagosome is formed by the ingestion of particulate
matter
 Oxidative burst: after phagocytosis, three interrelated
enzyme pathways are activated that produce toxic
molecules, which further damage pathogens. The enzymes
produce H2O2, hypochlorous acid, and nitric oxide
o Nitric oxide acts as an important messenger; has a role
as a neurotransmitter and in maintaining vascular tone
5. Discuss the chemical mediators of inflammation, classifying them with respect origins, targets and
mechanisms of action (SHOUT OUT TO EMILY HUDSPETH FOR FILLING OUT THIS TABLE 😊)
NOTE: I had this starred, and I’m not sure why, so I am going to include this just in case

MECHANISMS OF INFLAMMATION II (LECTURE 93)  DR. LEE

1. Describe systemic changes seen in inflammation
 Cardinal signs
 Flu-like symptoms
o Fever  IL-1b, TNF-a, IL-6
o Leukocytes  neutrophilia (bacterial infections) and lymphocytosis (viral infections)
o Acute phase proteins, chills, fatigue, headaches (prostaglandins and bradykinins), loss of appetite,
and muscle soreness
 Edema: transudate vs exudate
o Transudate: due to increased hydrostatic pressure; low protein content (clear); does not coagulate on
standing; low specific gravity (dissolve more); no inflammatory cells; can occur early in inflammation
 Don’t have big holes to let the cells out
o Exudate: due to increased vascular permeability; rich in protein especially fibrin; coagulates on
standing; high specific gravity; contains inflammatory cells; occurs late in inflammation
 Types: serous (clear fluid few cells); serofibrinous (rich in fibrin), and pus (thick, turbid, rich in
cells, turbid means it has lots of proteins, won’t be able to see through it)
2. Explain metabolic consequences of changes in levels of serum proteins (acute phase reactants) and other
mediators due to inflammation
 Types of acute inflammation: suppurative (purulent) vs non-suppurative  pus or non-pus

3. Summarize the possible pathological outcomes of inflammation

Possible outcomes: resolution, abscess, ulcers, fistula formation, chronic inflammation, scar formation, and
allergic reaction (?)

4. Discuss factors that determine which outcomes are seen under which circumstances
Didn’t discuss????

5. Recognize and classify the major types of inflammatory patterns that can be present in histologic sections
MECHANISMS OF INFLAMMATION III: CHRONIC INFLAMMATION (LECTURE 96)  DR. LONGLEY
1. Compare and contrast acute, chronic, and granulomatous inflammation with respect to the major cell
type(s) involved in the process

 Histamine and
Serotonin 
mast cell, platelets
 Bradykinin  plasma substrate  pain
 C3a  plasma protein via liver  opsonic fragment (C3b)
 C5a  macrophages  leukocyte adhesion, activation
 Prostaglandins  mast cells, from membrane phospholipids  vasodilation, pain, fever
 Leukotriene B4  leukocytes  leukocyte adhesion, activation
 IL-1 and TNF  macrophages  acute-phase reactions, endothelial activation

 Chronic Inflammation: a response of prolonged duration (weeks or months) in which inflammation, tissue
injury, and attempts at repair coexist in varying combination
o nothing is ever resolved immediately; the main thing is the time interval
 Granulomatous inflammation

 Granulomatous inflammation is a form of chronic inflammation characterized by collections of activated

macrophages, often with Th1 lymphocytes and sometimes associated with central necrosis (dead tissue in the
core)
 Characteristics: activation of Th1 lymphocytes which leads, in turn, to macrophage (histocyte) activation which
causes injury to normal tissues; activated macrophages appear to transform by IFN-gamma to epithelial like
cells which are termed “epithelioid cells”; other macrophages fuse together to form multinucleated “giant
cells”
 There are two types of granulomas:
o Foreign body granulomas: can form around materials such as talc, glass, suture fibers, food particles,
or anything that does not induce phagocytosis by macrophages or inflammation
o Immune granulomas: caused by agents capable of inducing a cell-mediated immune response. Agent
is difficult to eradicate such as a persistent microbe or self antigen. Macrophages activate T cells to
produce cytokines, like IL-2 and IFN-gamma which perpetuate the response

2. Identify the types of etiologic agents that produce each type of inflammation
Causes of Chronic Inflammation
 Persistent infections caused by microorganisms which are difficult to eradicate and invoke delayed-type
hypersensitivity reactions  mycobacteria (acid-fast positive bacilli), viruses, fungi, and parasites
 Hypersensitivity Diseases
o Rheumatoid arthritis: inflammation within the joints
o Multiple Sclerosis: T cells getting into the brain space constant attack and repair of the myelin
o Inflammatory bowel disease: mostly lower bowel; can be controlled but not cured
o Bronchial asthma: can get over it; depends on when it comes up in life
 Prolonged exposure to toxic agents (exogenous or endogenous)
o Particulate silica (silicosis: body’s response to something it can’t get rid of)  lung disease
o Atherosclerosis: excessive deposition of endogenous cholesterol in the arterial wall; NOT
arteriosclerosis (hardening of arteries)
o Alzheimer disease, Type I and II diabetes, and certain cancers
3. Describe the mechanisms of tissue injury seen with different types of inflammation
Morphologic Features of Chronic Inflammation
 Infiltration of site with: macrophages, lymphocytes, and plasma cells (B cells)
o Macrophages: the most prevalent cells in many chronic inflammatory reaction
 Secrete cytokines and growth factors, destroy foreign invaders and tissues, and activate
other cell types, primarily T and B lymphocytes

o Macrophage actions: ingest and eliminate microbes and dead tissue; initiate process of tissue
repair; secrete mediators of inflammation; display antigens to T cells and respond to signals
o B lymphocytes and plasma cells: antibodies produced may not be specific for any one antigen
 Cluster together to form a lymphoid type “organ”
 “Tertiary” lymphoid organs: can be seen in synovium of patients with rheumatoid
arthritis and other organ clustered cells that form a pseudo-lymphoid organ
 Other cell types found in chronic inflammation
o Eosinophils: granules containing major basic protein (MBP) which is toxic to parasites but also
host tissues
o Mast cells: prominent in chronic inflammation as producers of many different types of cytokines
o eutrophils: found primarily in acute inflammation however, they hang around for months in
chronic inflammation sites and produce chronic tissue damage
o
 Tissue destruction mediated by: organism or physical agent (pathology of organism) and inflammatory cell
damage
 Attempts at healing: angiogenesis (formation of new blood vessels) and fibrotic tissue replacement (no
function except to protect the body)

4. Provide examples of pathologic conditions in which these can be found