Inflammation Part 1 and 2

Excessive inflammation can be pathogenic. Inappropriate inflammatory responses when there are no foreign substances to fight off leads to _________.

Autoimmunity

She reminded us at this point that transudate is just fluid while exudate will contain cells

Make sure that you can distinguish these two concepts, she emphasized them multiple times

Leukocyte recruitment to the site: chemokines 1. In the lumen: *__________, __________, and __________ to endothelium* 2. Migration across the endothelium and vessel wall 3. Migration in the tissues toward a _________ stimulus.

Margination, rolling, and adhesion to endothelium Migration in the tissues toward a chemotactic signal

On the oxygen-dependent system, ROS are produced by the rapid assembly and activation of the mulicomponent oxidase _______________ which is also called ________________. what is the reaction catalyzed by this enzyme?

NADPH oxidase (phagocyte oxidase), which oxidizes NADPH and, in the process, reduces oxygen to superoxide anion.

what are the dual actions of NO in inflammation?

NO has dual actions in inflammation: 1. it relaxes vascular smooth muscle and promotes vasodilation, thus contributing to the vascular reaction 2. but it is also an inhibitor of the cellular component of inflammatory responses

describe the reaction that synthesize NO

NO, is a soluble gas produced from arginine by the action of nitric oxide synthase (NOS)

Pathogenesis of acute inflammation: 3. Leukocyte emigration to extravascular tissues: leukoctyes accumulate at the site of injury in some types of inflammation. _________ are the predominant cell in and are characteristic of acute inflammation.

Neutrophils

Once leukocytes (particularly neutrophils and monocytes) have been recruited to a site of infection or cell death, they must be activated to perform their functions. The responses of these leukocytes consist of 1. Recognition of the offending agents by ________ and other receptors, described earlier, which deliver signals that 2. Activate the leukocytes to _________ and destroy the offending agents.

TLR Phagocytosis

Step 2 in phagocytosis: engulfment, with subsequent formation of a phagocytic vacuole. After a particle is bound to phagocytic receptors, extension of the cytoplasm (_________) flow around it, and the plasma membrane pinches off to form a vesicle (___________) that encloses the particle. This then fuses with a __________ granule, resulting in discharge of the granule's content into the ____________.

Pseudopods Phagosome Lysosomes Phagolysosome

_________, a _________ exudate, is an inflammatory exudate rich in leukoctyes (mostly neutrophils), the debris of dead cells and, in many cases, microbes.

Pus Purulent exudate

Give the pathological basis for each of the cardinal signs of inflammation

Redness and warmth are the result of the vasodilation of the arterioles and capillaries Swelling, pain and loss of function are due to vascular leakage and edema

Vascular Permeability mechanisms Which is the most common mechanism?

Retraction of endothelial cells resulting in increased interendothelail spaces

*the initial rolling interactions are mediated by a family of proteins called _____________*

Selectins *she emphasized knowing these molecules and what would happen in the case of a genetic deficiency

The expression of selectins and their ligand is regulated by what?

Cytokines produced in response to infection and injury (e.g. tumor necrosis factor (TNF), IL-1, and chemokines or chemoattractant cytokines)

What is the inheritance pattern in most cases of chronic granulomatous disease of infancy?

x-linked recessive in most cases, therefore usually in males

Firm adhesion of the leukocytes to the endothelium is mediated by a family of heterodimeric leukocyte surface proteins called ____________

*integrins* The combination of cytokine-induced expression of integrins ligands on the endothelium and increased integrin affinity on the leukocytes results in firm integrin-mediated binding of the leukocytes to the endothelium at the site of inflammation. The leukocytes stop rolling, their cytoskeleton is reorganized, and they spread out on the endothelial surface

What are the three processes involved in the emigration of leukoctyes into extravascular tissues?

1. Marination and rolling 2. Activation and adhesion 3. Transmigration

What are a list of causes of inflammation? (Not just the two types of offending agents)

1. Microbial infections, e.g pyogenic bacteria, viruses 2. Hypersensitivity reactions, e.g. parasites, tubercle bacilli 3. Physical agents e.g. trauma, ionizing radiation, heat, cold 4. Chemical e.g. corrosive acids, alkalis, reducing agents, bacterial toxins 5. Tissue necrosis e.g. ischemia 6. Foreign bodies (splinters, dirt, sutures) 7. Immune reactions (hypersensitivity reactions)

production of NO is thought to be an endogenous mechanism for controlling inflammatory response. what are the actions of NO that contribute to this function?

1. NO reduces platelet aggregation and adhesion 2. inhibits several features of mast cell-induced inflammation 3. inhibits leukocyte recruitment.

What are the mechanisms that result in increased vascular permeability in acute inflammation? (Just generally speaking)

1. Reatraction of endothelial cells 2. Endothelial injury, resulting in endothelial cell necrosis and detachment 3. Increased transport of fluids and protein, called trans cytosine, through the endothelial cell. *note: she emphasized the first two

What are the three sequential steps of phagocytosis?

1. Recognition and opsonization of the particle to be ingested by the leukocyte 2. Engulfment, with subsequent formation of a phagocytic vacuole 3. Killing or degradation of the ingested material

What are the cardinal signs of acute inflammation? **high yield

1. Rumor - redness 2. Color - warmth 3. Tumor - swelling 4. Dolor - pain 5. Loss of function - functio laesa was later added by Virchow She said that we needed to know both terms

The typical inflammatory reaction develops through a series of sequential steps 1. the offending agent, which is located in the __________ tissues, is recognized by host cells and molecules 2. __________ and _________ are recruited from the circulation to the site where the offending agent is located 3. These are activated and work together to destroy and eliminate the offending substance. 4. The reaction is controlled and terminated 5. ________________________________________________

1. The offending agent (microbes or necrotic tissue), which is located in the extravascular tissues, is recognized by host cells and molecules. 2. Leukocytes and plasma proteins are recruited from the circulation to the site where the offending agent is located 3. The leukocytes and plasma proteins are activated and work together to destroy and eliminate the offending substance 4. The reaction is controlled and terminated 5. The damaged tissue is repaired

What are the main components of the inflammatory response? (She split inflammation up into these two general events)

1. Vascular reaction 2. Cellular response Note: both are activated by mediators that are derived from plasma proteins and various cells

Pathogenesis of acute inflammation: what three main processes occur at the site of inflammation, due to the release of chemical mediators?

1. Vasodilation 2. Vascular leakage and edema 3. Leukocyte emigration to extravascular tissues

1. what is the inheritance pattern of Chediak-Higashi disease? 2. what are the symptoms? 3. what age range would you see it? 4. what is the likely basic defect in this disorder?

1. autosomal recessive 2. neutropenia, with recurrent infection, oculocutaneous albinism, abberrant granules in neutrophils and other WBCs - "giant" lysosomes, melanocytes - "giant" melanosomes 3. infants and children 4. basic defect is unkown - may be in microtubules

what are the different types of NOS? compare and contrast based upon when each is expressed and what the NO they produce is used for?

1. endothelial NOS (eNOS) - constitutively expressed, NO maintains vascular tone 2. neuronal NOS (nNOS) - constitutively expressed, NO acts as a neurotransmitter 3. inducible NOS (iNOS) - involved in microbial killing,induced when macrophages and neutrophils are activated by cytokines (e.g., IFN-γ) or microbial products

what are the oxygen-independent systems of killing ingested particles?

1. lysozyme 2. lactoferrin 3. major basic protein (important in eosinophilic toxicity to parasites) 4. defensins (cationic arginine rich granules) 5. lysosomes (these merge with phagosomes to form phagolysosomes, allowing activated enzymes to biodegrade the bacteria)

what are the two categories of mechanisms by which the killing and degradation of ingested material can occur?

1. oxygen-dependent 2. Oxygen-independent

Inflammation from an immunology standpoint is a protective response involving host cells, blood vessels and proteins. Explain how it is a protective response and then explain how it could potentially be a harmful process

A protective response (part of innate immunity) becasue 1. Eliminate the initial cause of cell injury 2. Remove necrotic cells and tissue 3. Initiate the process of repair Also a potentialy harmful process- components of inflammation that are capable of destroying microbes can also injury bystander normal tissue (ex: reperfusion injury in which surrounding cells are destroyed along iwth the blood clot)

The initial, rapid response to infections and tissue damage is called __________ inflammation. It typically develops within minutes or hours and is of short duration, lasting for several hours or a few days; what are the main characteristics of this response?

Acute inflammation Main characteristics are the exudation of fluid and plasma proteins (edema) and the emigration of leukocytes, predominantly neutrophils (also called polymorphonuclear leukocytes) (Recall from pathoma that the characteristics of acute inflammation are edema and neutrophils)

Compare and contrast the features of acute and chronic inflammation **High yield Tell which type of immunity 1. Onset 2. Cellular infiltrate 3. Tissue injury, fibrosis 4. Local and systemic signs

Acute inflammation - innate immunity 1. Onset - fast; minutes or hours or few days 2. Cellular infiltrate - mainly neutrophils (PMN) 3. Tissue injury, fibrosis - usually mild and self-limited 4. Local and systemic signs - prominent increased vascular permeability (vascular leakage) Chronic inflammation - adaptation immunity 1. Onset - slow: days 2. Cellular infiltrate - monocytes/macrophages and lymphocytes 3. Tissue injury - often severe and progressive 4. Local and systemic signs - less prominent; may be subtle (vascular injury is less prominent

Acute inflammation is one of the reactions of the type of host defense known as ________ immunity, and chronic inflammation is more prominent in the reactions of ___________ immunity.

Acute inflammation - innate immunity Chronic inflammation - adaptive immunity

What are the histological features of an acute bacterial pneumonia?

Acute pneumonia - acute lung inflammation characterized by neutrophils within alveoli (In a normal lung there would be a lack of cells in the alveoli where O2 exchange takes place) Note: neutrophils present in the exudate is an indication that it is an acute inflammatory response (she told us that the question would be asking us to distinguish between acute and chronic inflammatory responses)

What is the difference between an exudate and transudate?

An exudate is an extravascular fluid that has a high protein concentration and contains cellular debris. It's presence implies that there is an increase in the permeability of small blood vessels triggered by some sort of tissue injury and an ongoing inflammatory reaction. In contrast, a transudate is a fluid with low protein content (most of which is albumin), little or no cellular material, and low specific gravity. It is essentially an ultrafiltrate of blood plasma that is produced as a result of osmotic or hydrostatic imbalance across the vessel wall without across the vessel wall without an increase in vascular permeability (imbalance of the starling forces). Simple table comparing the major features of the two on slide 11

Review/Summary for each of the steps in leukocyte recruitment give the molecules that mediate the interaction 1. Rolling 2. Adhesion 3. Migration

Cytokines are involved in all of it, particular chemokines 1. Rollin - selectins 2. Adhesion - integrins 3. Transmigration - immunoglobulin superfamily called CD31 or PECAM-1 (platelet endothelial cell adhesion molecule)

Practice question: A clinical study is performed of patients with pharyngeal infections. The most typical clinical course averages 3 days from the time of onset until the patient sees the physician. Most of these patients experience fever and chills. On physical examination, the most common findings include swelling, erythema, and pharyngeal purulent exudate. Which of the following types of inflammation did these patients most likely have? A. Granulomatous B. Acute C. Chronic D. Resolving

B. Acute inflammation Reason: "clinical course averages 3 days" "Swelling, erythema, and pharyngeal purulent exudate"

Vascular leakage: 2. Endothelial injury, resulting in endothelial cell necrosis and detachment. Direct damage to the endothelial is encountered in severe injuries e.g. injuries due to _________, or by the actions of _______ and __________ that target endothelial cells. ____________ that adhere to he endothelium during inflammation may also injure the endothelial cells and thus amplify the reaction

Burns Microbes and microbial toxins Neutrophils

Review of first year material: Selectins are cell-surface _______-binding proteins synthesized by endothelial cells (E-selectin), platelets (P-selectins) and white blood cells (L-selectin) E- or P-selectins bind to _________ on _______ L-selecting bind to _______ cells

Carbohydrate binding E- or P-selectins bind to oligosaccharide on white blood cells L-selectins bind to endothelial cells

The journey of leukocytes from the vessel lumen to the tissue is a multi step process that is mediated and controlled by adhesion molecules and cytokines called _________

Chemokines

3. Transmigration: __________ act on the adherent leukocytes and stimulate the cells to migrate through interendothelail spaces toward the __________. __________ __________ that is, toward the site of injury or infection where they are being produced

Chemokines Chemical concentration gradient

After exiting the circulation, leukocytes move in the tissues toward the site of injury by a process called __________, which is defined as locomotion along a chemical gradient.

Chemotaxis

When acute inflammation achieves its desired goal of eliminating the offenders, the reaction subsides, but if the response fails to clear the stimulus, the reaction can progress to a protracted phase that is called _____________

Chronic inflammation

Inflammation is induced by chemical mediators produced by damaged host cells - ___________ and other mediators.

Cytokines

Practice question: A 10-year-old child developed a sore throat and fever over a period of 24-hours. Her symptoms last for three days. Physical examination shows pharyngeal erythema and swelling. Laboratory finding include large number of neutrophils. Which of the following types of inflammation does this patient most likely have? A. Abscess formation B. Chronic inflammation C. Granulomatous inflammation D. Acute inflammation

D. Acute inflammation Onset - fast: minutes or hours or few days: cellular infiltrate - mainly neutrophils (PMN) - these were characteristics of acute inflammation listed in the chart at the beginning of the lecture

The vascular reaction of acute inflammation consist of changes in the flow of blood and the permeability of vessels, both designed to maximize what?

Designed to maximize the movement of plasma proteins and leukoctyes out of the circulation and into the site of infection or injury

Practice question: A 58 year old woman has had a cough with fever for 3 days. A chest radiograph reveals infiltrates in the right lower lobe. A sputum culture grows streptococcus pneumoniae. The clearance of these organisms from the lung parenchyma would be most effectively accomplished through generation of which of the following substances by the major infalmmatory cell type responding to this infection? A. Platelet activating factor B. prostaglandin E2 C. kallikrein D. leukotriene B4 E. hydrogen peroxide

E. hydrogen peroxide

The escape of fluid, proteins, and blood cells from the vascular system into the interstitial tissue or body cavities is known as _________

Exudation

T or F: edema only refers to the presence of exudate in the extravascular tissue

FALSE! Edema denotes an excess of fluid in the interstitial tissue or serous cavities; it can be either an exudate or a transudate

T or F: an inherited deficiency in MPO will cause a large increase in susceptibility to infection

False: despite it being the most efficient bactericidal system, inherited deficiency of MPO by itself leads to minimal increase in susceptibility to infection, emphasizing the redundancy of microbicidal mechanisms in leukocytes.

Inflammation is a beneficial host response to __________ and __________ (what are two situations that can trigger inflammation? - this is the answer to these blanks) but it may also cause tissue damage.

Foreign invaders and necrotic tissues (She has these labeled as the offending agents in her general features of inflammation slide)

Practice Question: A 20-year-old man has experienced painful urination for 4 days following spring break. A urethritis is suspected, and Neisseria gonorrhea is cultured. Numerous neutrophils are present in a smear of the exudate from the penile urethra. These neutrophils undergo diapedesis to reach the organisms. Release of which of the following chemical mediators is most likely to drive neutrophil exudation?

I don't know what the options were but the answer is complement C5A (I think some other options were histamine, prostaglandins and bradykinin amongs others so look for the answer choices)

Transmigration: Adhesion molecules such as members of the ___________ superfamily called __________ or _________ present in the intercellular junctions between endothelial cells are involved in the migration of leukocytes.

Immunoglobulin superfamily CD31 or PECAM-1 (platelet endothelial cell adhesion molecule)

Define inflammation

Inflammation is a response of vascularized tissues to infections and damaged tissues that bring cells and molecules of host defense from the circulation to the sites where they are needed, in order to eliminate the offending agents

Leukocyte activation results from signaling pathways that are triggered in leukocytes, resulting in increase in ______________ and activation of enzymes such as ________ and __________.

Intracellular Ca2+ and activation of enzymes such as protein kinase C and phospholipase A2

Retraction of endothelial cells is elicited by what chemical mediators? This response is called the _______ ________ response because it occurs rapidly after exposure to the mediator and is usually short-lived (15 to 30 minutes)

It is elicited by histamine, bradykinin, leukotrienes, and other chemical mediators Immediate transient response Note after this it says in some forms of mild injury (e.g. after burns, irradiation or ultraviolet radiation, and exposure to certain bacterial toxins)

what does the suffix "itis" indicate?

Itis means that there is inflammation to that particular organ. Examples arthritis, salpengitis, pancreatitis, gingivitis

**look at the diagram on slide 7 of the general features of inflammation, it gives a broad overview of the progression of the inflammatory response. What are the cell types that are already located in the tissue which can recognize the offending agent? What are the three responses that occur at the site of infection as a result of the amines/cytokines released by these cells?

Macrophages Dendritic cells Mast cells 1. Recruitment of leukocytes (leading to elimination of microbes, dead tissue) 2. Plasma proteins are released into extravascular space and act as Mediators of inflammation, elimination of microbes. 3. Vasodilation, increased vascular permeability leading to edema (Recall how pathoma said the histological features of acute inflammation were edema and neutrophils and acute inflammation results in the accumulation of cells, plasma proteins, and fluid at the site of inflammation)

Leukocytes express ______-selectin at the tips of their micovilli and also express ligand for ____ and _____-selecting, all of which bind to complementary molecules on the _________ cells.

L-selectin E- and P-selectin Endothelial cells

What are the types of selectins? Where are they expressed?

L-selectin = expressed on leukocytes E-selectin = expressed on endothelium P-selectin = expressed on platelets and endothelium

The loss of fluid and increased vessel diameter lead to ________ blood flow, concentration of ________ in small vessels, and increased __________ of the blood.

Lead to slowed blood flow, concentration of red cells in small vessels, and increased viscosity of the blood

Recognition of microbes or dead cells induces several responses in leukoctyes that are collectively called ______ _______

Leukocyte activation

There can be genetic deficiencies in the molecules involved in leukocyte recruitment to sites of inflammation: What diseases are caused by mutations in integrin? Selectins?

Leukocyte deficiency 1 - mutation in integrin Leukocyte deficiency 2 - mutation in selectins

Leukocyte recruitment: key concepts Leukocytes are recruited from the blood into the extravascular tissue where infectious pathogens or damaged tissues may be located, migrate to the site of infection or tissue injury, and are activated to perform their functions. Leukocyte recruitment is a multi step process consisting of loose attachment to and rolling on endothelium (mediated by _______); firm attachment to endothelium (mediated by _________); and migration through interendothelial spaces (_____________)

Loose attachment and rolling on endothelium - selecting Firm attachment - integrins Migration through interendothelial spaces - immunoglobulin superfamily

Chronic inflammation is of longer duration and is associated with more tissue destruction, the presence of _______ and _________, the proliferation of _____ ______, and the deposition of _____ _____.

Lymphocytes and macrophages Proliferation of blood vessels and the deposition of connective tissue

________ predominate in the early inflammatory infiltrate and are later replaced by _________ and __________

Neutrophils Monocytes and macrophages

Re-call Starling's law: the hydrostatic pressure of the blood is normally balanced by the ____________ pressure. What are circumstances there this can become imbalanced and what is the result of an imbalance?

Oncotic pressure of plasma proteins Increased hydrostatic pressure can occur with venous outflow obstruction e.g. congestive heart failure Decreased colloid osmotic pressure (decreased protein synthesis, e.g. liver disease; increased protein loss e.g. kidney disease) Both of these options would lead to an imbalance and the leakage of fluid across the capillary leading to edema. Specifically this leakage is transudate

The functional responses that are most important for destruction of microbes and other offenders are ____________ and intracellular killing.

Phagocytosis

The increased permeability that is a hallmark of acute inflammation occurs in which vessels?

Postcapillary venules

As stasis develops, blood leukoctyes, principally _________, accumulate along the vascular endothelium. At the same time, endothelial cells are activated by mediators produced at sites of infection and tissue damage, and express increased levels of _______ molecules.

Principally neutrophils Adhesion molecules Note: leukocytes then adhere to the endothelium and soon afterward they migrate through the vascular wall into the interstitial tissue, in a sequence that is discussed later in cellular events

what would be the morphological pattern of exudate in the case of serous inflammation?

Serous contains low MW proteins, especially albumin. Clear yellow fluid. No cells.

**see slide 24 on leukocyte activation

She expected us to have already known all the outcomes of the activation process on the diagram but there wasn't a good way to test it - left side shows the signals for adhesion and chemotaxis and the right two show the signals needed for the most important effect of leukocyte activation - phagocytosis and intracellular killing

These above changes result in engorgement of small vessels with slowly moving red cells, a condition termed ________, which is seen as _________ ________ and localized redness of the involved tissue

Stasis Vascular congestion

Pathogenesis of Acute Inflammation: 2. Vascular leakage and edema: increased vascular permeability. Loss of intravascular fluid and other blood components which results in _________ of blood flow and the accumulation of fluid (exudate) in the interstitial tissues and/or body cavities.

Stasis of blood flow

Various cytokines promote expression of selectins and integrin ligands on endothelium (________, _______) increase the avidity of integrins for their ligands (__________), and promote directional migration of leukocytes (also __________); many of these cytokines are produced by tissue __________ and other cells responding to pathogens or damaged tissues.

TNF, IL-1 Chemokines Also chemokines Macrophages

which is the more efficient system of killing of ingested particles?

The H2O2-MPO-halide system is the most efficient bactericidal system in neutrophils. (oxygen-dependent system)

What is the functional significance of these weak rolling interactions between selectins?

These weak rolling interactions slow down the leukocytes and give them the opportunity to bind more firmly to the endothelium.

What are the major opsonins?

The major opsonins are IgG antibodies, the C3b breakdown product of complement, and certain plasma lectins, notably mannose-binding lectin, all of which are recognized by specific receptors on leukocytes

What are the exogenous and endogenous chemoattractants?

The most common exogenous agents are bacterial products, including peptides that posses an N-formylmethionine terminal amino acid and some lipids. Endogenous chemoattractants include several chemical mediators 1. Cytokines, particularly those of the chemokines family (e.g. IL-8) 2. Components of the complement system, particularly C5a 3. Arachidonic acid (AA) metabolites, mainly leukotrienes B4 (LTB4) (On our slides was listed cytokine TNFalpha but it wasn't in her notes and she didn't mention it in lecture)

What are the affinity characteristics and timeline for the interactions of the selectins with their ligands?

These are low-affinity interactions with a fast off-rate, and they are easily disrupted by the flowing blood. As a result, the bound leukocytes bind, detach, and bind again, and thus being to roll along the endothelial surface

Vascular leakage mechanisms: 1. Increased transport of fluids and proteins, called _________, through the endothelial cell. This process may involve intracellular channels that may be stimulated by certain factors such as ______________, that promote vascular leakage. However, the contribution of this process to the vascular permeability of acute inflammation is uncertain.

Transcytosis Vascular endothelial growth factor (VEGF)

T or F: during the step 2 engulfment phase of phagocytosis, the phagocyte may also release granule contents into the extracellular space

True

T or F: inflammation is normally controlled and self limited

True

Why does a leukocyte only migrate across the blood vessel at the site of inflammation?

Vascular endothelium in its normal, inactivated state does not bind circulating cells or impede their passage. In inflammation, the endothelium is activated and can bind leukocytes as a prelude to their exit from the blood vessels

Pathogenesis of Acute Inflammation: 1. __________: increased blood flow. There is actually an initial ____________ (_______) followed by the __________ of arterioles and capillaries.

Vasodilation: increased blood flow There is actually an initial vasoconstriction (pallor) followed by the vasodilation of arterioles and capillary

The efficiency of phagocytosis is greatly enhanced by what?

When microbes are opsonized by specific proteins (opsonins) for which the phagocytes express high-affinity receptors.

Components of the inflammatory process include ________ and _________ normally present in the blood. What is the inflammatory processes goal as regards these agents?

White blood cells Plasma proteins Goal is to bring these to the site of infection and/or tissue damage

what is the basic defect in chronic granulomatous disease of infancy?

basic defect is in NADPH oxidase - resulting in a deficiency of oxygen-dependent generation of H2O2 and microbial killing

As discussed earlier, these oxygen-derived free radicals bind to and modify what?

cellular lipids, proteins, and nucleic acids and thus destroy cells such as microbes

people with chronic granulomatous disease of infancy are subject to recurrent infection, especially by what types of organisms? (the category and then specific examples)

especially by catalase-producing microorganisms 1. C-candida 2. A - S. aureus 3. t 4. A - P. Aeruginosa 5. L - listeria 6. A - Aspergillus 7. S - Serratia 8. E - E. coli (see pathoma for explanation of why these microbes)

CGD of infancy, affects infants and children and presents with a variety of histopathologic patterns, especially _________

granulomas

H2O2 can also be converted to ________ antoher powerful destructive agent

hydroxyl radical

Deficiencies in the inflammatory response are analogous to immunodeficiencies and result in increased ____________________________________________. some are inherited whereas others are acquired.

increased susceptibility to infection

she said that she didn't expect us to memorize the table on page 33 (slide 28)

maybe just look over it, if she asks a specific question on a name of an FC receptor it doesn't seem worth the time to memorize where it is distributed for just one question but maybe glance at functions and cell distribution I think the point of the slide was that the FC receptor binding to its substrate is a means of leukocyte activation

The ROS species produced by the oxygen-dependent system are located where inside of the cell?

the ROS are produced within the lysosome and phagolysosome, where they can act on ingested particles without damaging the host cell.

what are some examples of serous inflammation?

the skin blister resulting from a burn or viral infection is a good example of the accumulation of serous effusion either within or immediately beneath the epidermis of the skin. (fluid in serous cavity is called an effusion. eg. second degree burn, common skin blister after repeitive trauma, skin blisters caused by varicella (chicken pox), herpes simplex virus)

Describe the remainder of the reactions and enzymes involved in the oxygen-dependent system

the superoxide radical produced from oxygen by NADPH oxidase is then converted to hydrogen peroxide (H2O2) mostly by spontaneous dismutation (pathoma says by SOD). H2O2 is not able to efficiently kill micobes by itself. however the azurophilic granules of neutrophils contain the enzyme myeloperoxidase (MPO), which, in the presence of halide such as Cl-, converts H2O2 to hypochlorite (the active ingredient in household bleach). The latter is a potent antimicrobial agnet that destroys microbes by halogenation (in which the halide is bound coavelently to cellular constituents) or by oxidation of proteins and lipids (lipid peroxidation).

oxygen-derived radicals may be released extracellularly from leukocytes after exposure to microes, chemokines, and antigen-antiody complexes or following phagocytic challenge. These ROS are implicated in _____ ______ accompanying inflammation

tissue damage

T or F: NO also participates in microbial killing

true

The morphological patterns of acute inflammation can aid in determining the underlying cause, particularly you will look at the type of __________.

type of exudate 1. differences in the degree of vascular permeability 2. type of prominent leukocyte infiltrating tissues 3. type of predominant protein in the exudate