Inflammation Flashcards
____-____ receptors recognize microbes.
___-___ receptors can sense cell damage.
Toll-like
NOD-like
Inflammation leads to the recruitment of _____.
Leukocytes
Causes of inflammation:
Infection
Tissue necrosis
Foreign body
Immune reactions, such as hypersensitivity
Cardinal signs of inflammation:
Redness, warmth, swelling, pain, loss of function
_____ is due to leakage of the fluid from a post capillary venules into the interstitial space. key mediators are ____ which causes endothelial cell contraction, and ___ ____ resulting in endothelial cells disruption.
Swelling
Histamine
Tissue damage
____ and ____ are due to vasodilation which results in increased blood flow via relaxation of arteriolar smooth muscle. Key mediators are ___, ____, and ____.
Redness
Warmth
Histamine
Prostaglandins
Bradykinin
Loss of function is from cellular and tissue damage related to ___ ___ ___ created by lysosomal enzymes.
Reactive oxygen species
The most important mediators of acute inflammation are:
Vasoactive amines, arachidonic acid derivative lipid products such as prostaglandins and leukotrienes, cytokines including chemokine, and products of complement activation
_____ come from mast cells and leukocytes. It causes vasodilation, pain and fever.
Prostaglandins
____ is produced by mast cells, basophils and platelets. It causes vasodilation, increase vascular permeability, and endothelial activation.
Histamine
_____ is produced by mast cells and leukocytes. It increases vascular permeability, chemotaxis, and leukocyte adhesion and activation
Leukotrienes
Cytokines such as ____, ___, and ____ are produced by macrophages, endothelial cells, and mast cells. Locally, they cause endothelial activation. Systemically, they produce a fever, metabolic abnormalities, and hypotension (shock)
TNF, IL-1, and IL-6
_____ are produced by leukocytes and activated macrophages. They cause chemotaxis and leukocyte activation.
Chemokines
____ comes from Plasma and is produced in the liver. It causes leukocyte chemotaxis and activation, direct target killing, and vasodilation
Complement
Diagram of mediators of inflammation:
Principal actions of arachidonic acid metabolites in inflammation:
Prostaglandins, bradykinin, and substance P are the main mediators of ____.
Pain
Lysosomal enzymes and reactive oxygen species are the main mediators of tissue damage, and ___ ___ ___.
Loss of function
Histamines and prostaglandins are the main mediators of ___ and ___.
Redness
Warmth
Histamines, serotonin, C3a and C5a, leukotrienes C4, D4, and E4 are the main mediators of increased ____ ____.
Vascular permeability
TNF, IL-1, chemokines, C3a and C5a, leukotriene B4 are the main mediators of ____ recruitment and activation.
Leukocyte
Inflammation allows inflammatory cells such as neutrophils and macrophages, lymphocytes, etc., plasma proteins, and fluid to exit the ___ ___ and enter the ___ ___.
Blood vessels
Interstitial space
____ inflammation is fast, onset in minutes or hours. Mainly neutrophils with prominent local and systemic signs.
Acute
____ inflammation can take days. It is mainly monocytes/macrophages and lymphocytes. The tissue injury is often severe and progressive. There are less local and systemic signs.
Chronic
Acute inflammation arises in response to ____ or ___ ____. It is characterized by the presence of edema and neutrophils. It is immediate response with limited ____.
Infection
Tissue necrosis
Specificity
Three Major components of the acute inflammatory response:
Vascular changes
Leukocyte recruitment
Leukocyte activation
Acute inflammation:
____ is mediated by histamines serotonin prostaglandins, leukotrienes, and complement. It increases blood flow and produces ____ (redness).
Vasodilation
Erythema
Acute inflammation:
____ ___ ____ is mediated by histamines serotonin, and kinins. The result is gaps between endothelial cells that allows for leakage of fluid, which causes ___.
Increased vascular permeability
Edema
Vascular changes allow movement of ___ ___ and ___ ___ from vascular space to site of infection/injury.
Inflammatory cells
Plasma proteins
When there is no inflammation there is a ___ hydrostatic pressure and ___ colloid osmotic pressure.
Higher
Lower
When exudates and transudates form, hydrostatic pressure ____ and colloid osmotic pressure ____.
There is ____ interendothelial spaces allowing for fluid and protein leakage. When
Increases
Decreases
Increased
Decreased colloid osmotic pressure is caused from ____ protein synthesis (liver disease) or ____ protein loss (kidney disease).
Decreased
Increased
Increased hydrostatic pressure is caused from venous ____ obstruction (congestive heart failure).
Outflow
____ refers to when vasodilation slows blood flow and cells move to periphery of vessels
Margination
____ refers to the up regulation of selectins on endothelial cells. Leukocytes have ____ __ __ on the surface, which binds to selectins.
Rolling
Sialyl Lewis X
Endothelial adhesion molecules, ____ and ___, are up regulated by TNF and IL-1. Leukocyte ____ are upregulated by C5a and LTB4 and converted to their high affinity form. ICAM and VCAM are ligands for Integrins. This process is referred to as ____, which stops the cell rolling.
ICAM
VCAM
Integrins
Adhesion
Leukocyte adhesion deficiency is most commonly due to an autosomal recessive defect of ____.
Integrins
Migration:
_____ is expressed on both leukocytes and endothelial cells. It facilitates transmigration. This process is driven by ____ produced at the site of injury (chemotaxis). Neutrophils are attracted by bacterial products, ___, ___, and ___.
PECAM-1 (CD31)
Chemokines
IL-8
C5a
LTB
Diagram of acute inflammation- leukocyte recruitment:
Rolling, adhesion, and migration
_____ is a cytokine that is produced by macrophages, mast cells, and T lymphocytes. It stimulates expression of endothelial adhesion molecules and secretion of other cytokines. It has its systemic effects.
TNF
____ is a cytokine that is produced by macrophages, endothelial cells, and some epithelial cells. It is similar to TNF, but plays a greater role in fever.
IL-1
____ is a cytokine produced by T lymphocytes. It recruits neutrophils and monocytes.
IL-17
____ is a cytokine that is produced by macrophages and other cells. It produces systemic effects (acute phase response).
IL-6
_____ are cytokines that are produced by macrophages endothelial cells, T lymphocytes, and mast cells. It recruits leukocytes to sites of inflammation and plays a role in migration of cells in normal tissues.
Chemokines
There are 10 different kinds of ___-___ receptors, each for a different set of microbial molecules
Toll-like
_____ receptors bind to mannose, C3b, and Fc (antibodies).
Phagocytic
Picture of myocardial infarct, showing acute inflammation:
Graph of acute inflammation:
Removal of the offending agent:
_____ is mediated by phagocytic receptors ( ____, ___, ____ ___). It is facilitated by coating (opsonization) by the ____ IgG, C3b, and others.
Phagocytosis
Mannose, opsonin, scavenger receptors
Opsonins
Destruction of phagocytosed material is performed by ___ ___ ___. ___ ___ (NADPH oxidase) produces superoxide anion. ___ ___ ___ (NOS) with superoxide produces peroxynitrite.
___ ___ (proteases) also assist with destruction, but are less effective than ROS.
Reactive oxygen species
Phagocyte oxidase
Nitric oxide synthetase
Granule enzymes
Diagram of removal of offending agents:
Altered phagocytosis:
_______ syndrome is a protein trafficking defect characterized by impaired phagolysosome formation. Immunodeficiency, diminished hemostasis.
Chediak-Higashi
Altered phagocytosis:
____ ____ disease (CGD) is characterized by poor oxygen, dependent, killing due to NADPH oxidase defect. It is X-linked or autosomal recessive. Characterized by recurrent infections.
Chronic granulomatous
Altered phagocytosis:
____ ___ results in defective hypochlorite formation. Increased risk for candida infections, however, most patients are asymptomatic
MPO deficiency
During resolution of acute inflammation, neutrophils undergo ____ and disappear within 24 hours after resolution.
Apoptosis
____/____ can result after acute inflammation in the healing connective tissue
Scarring/fibrosis
_____ of acute and chronic inflammation results in an ____ with persistent acute inflammation and surrounding chronic inflammation.
Combination
Abscess
Diagram of inflammation:
If unchecked or inappropriately directed against host tissues, the ____ itself becomes the offender. This underlies, many acute and chronic human diseases. Adjacent tissues to inflammation may suffer ___ ___.
Leukocyte
Collateral damage
The inflammatory response may be inappropriately directed against host tissues, causing ___ ___.
Autoimmune disease
The host may react excessively against usually harmless, environmental substances, causing ___ ___ and ___.
Allergic reactions
Asthma
Table of disorders caused by inappropriate immune system actions:
____ inflammation is characterized by the presence of macrophages lymphocytes and plasma cells in tissue. It is a delayed response but more ____.
Chronic
Specific
Persistent infections, hypersensitivity diseases, and prolonged exposure to toxic agents and foreign material can cause ___ inflammation.
Chronic
The _____ is the dominant cell in most chronic inflammatory reactions. It ingests and eliminates microbes, and dead tissue. Peak activity is 2 to 3 days after inflammation begins.
Macrophage
Macrophages, secrete cytokines such as ___, ___, ___, and others that initiate inflammatory reactions. Macrophages also display ____ and respond to signals from T cells.
TNF
IL-1
Chemokines
Antigens
Macrophage development occurs in the bone marrow starting with a ___ stem cell. In the blood, it is a ____ which gets activated into a macrophage by inflammation.
Hematopoietic
Monocyte
In the fetal liver, there is a ___ in the yolk sac which turns into a resident tissue ___.
Progenitor
Macrophage
Picture of monocytes and activated macrophages:
Diagram of classically activated versus alternatively activated macrophage:
____ refers to classically activated macrophage and ___ refers to alternatively activated macrophage.
M1
M2
Microbes and other antigens activate T & B lymphocytes. They amplify and propagate ___ ___. They generate ___ cells, allowing for persistent and severe reactions.
Chronic inflammation
Memory
_____ T lymphocytes promote, and influence the nature of the inflammatory reaction.
CD4+
____ cells secrete INF-gamma which activate macrophages by the classical pathway
Th1
____ cells secrete IL-4, IL-5, IL-13 which recruit and activate eosinophils and are responsible for the alternative pathway of macrophage activation
TH2
Diagram:
____ cells produce IL-17 which induces the secretion of chemokines responsible for recruiting neutrophils and monocytes into the reaction
Th17
____ is a cytokine produced by dendritic cells and macrophages. It increases production of INF-gamma
IL-12
____ is a cytokine that is produced by T lymphocytes and natural killer cells. It activates macrophages.
INF-gamma
Picture of plasma B cells in chronic inflammation:
Granulomatous inflammation:
A pattern of chronic inflammation induced by persistent ___ ___ in some infections, immune mediated diseases, and foreign bodies
T-cell response
Composition of granulomatous: Aggregates of activated ___ with abundant pink cytoplasm, peripheral lymphocytes, multinucleated giant cells (fusion of numerous ___), and sometimes central necrosis
Macrophages
Macrophages
____ plays a crucial role in evolution of macrophages to epithelioid cells and giant cells. ___ ___ therapy can cause granulomatous to break down. This could make a previously contained infection such as TB disseminate
TNF
Anti TNF
Picture of peripheral lymphocytes
Conditions with granulomas:
TB, bartonella henselae, listeria, treponema pallidum (tertiary syphilis)
Fungal: histoplasmosis
Parasitic: schistosomiasis
Conditions with granulomas non-infectious:
Sarcoidosis, crohn disease, primary biliary cholangitis, Churg-Strauss, giant cell arteritis, Takayasu arteritis, foreign body
____ is used when the predominating disease state is inflammation. If inflammation is not the main disease state, do not use the term ___.
-itis
-itis
