[P] Week 2: Inflammation and Repair - Part 2 Flashcards by Geno Alinsub

Enumerate the steps of phagocytosis

Recognition and Attachment
Engulfment
Killing and Degradation

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STEPS OF PHAGOCYTOSIS

Involves the recognition and attachment of the particle to be
ingested by the leukocyte

Recognition and Attachment

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STEPS OF PHAGOCYTOSIS

this receptors enable phagocytes to bind and ingest microbes

Mannose receptors, scavenger receptors, and receptors
for various opsonins

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STEPS OF PHAGOCYTOSIS

Consists of the extension of the cytoplasm around the particle, and the plasma membrane pinches off to form an intracellular vesicle called the PHAGOSOME, which encloses the particle.

Engulfment

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STEPS OF PHAGOCYTOSIS - Engulfment

The phagosome then fuses with a lysosomal granule, which discharges its contents into the?

PHAGOLYSOSOME

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STEPS OF PHAGOCYTOSIS

Involves the killing of the microbe and degradation of the
ingested material

Killing and degradation

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STEPS OF PHAGOCYTOSIS

Killing of microbes is accomplished by? enumerate

Reactive oxygen species (ROS)
Reactive nitrogen species (mainly derived from and nitric oxide (NO))

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STEPS OF PHAGOCYTOSIS - Killing and degradation

produced by the rapid assembly and activation of a multicomponent oxidase nicotinamide adenine dinucleotide phosphate (NADPH) oxidase which oxidizes reduced NADPH and, in the process, reduces oxygen to superoxide anion–making it highly reactive

Reactive Oxygen Species

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STEPS OF PHAGOCYTOSIS - Killing and degradation

superoxide from the NAPDH oxidization can be converted to?

hydrogen peroxide

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STEPS OF PHAGOCYTOSIS - Killing and degradation

Hydrogen peroxide may not efficciently kill microbes, so it should be combined with?

myeloperoxidase (MPO)
Halide (such as chloride to convert to HCl)

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STEPS OF PHAGOCYTOSIS - Killing and degradation

give an example of an ROS

hydrogen peroxide myeloperoxidase (H2O2-MPO) halide system

most potent bactericidal system of the neutrophils

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STEPS OF PHAGOCYTOSIS - Killing and degradation

a soluble gas produced from arginine by the action of nitric oxide
synthase (NOS), also participates in microbial killing.

Reactive Nitrogen Species: Nitric Oxide

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STEPS OF PHAGOCYTOSIS - Killing and degradation

what are the three types of NOS

endothelial nitric oxide synthase (eNOS)
neuronal nitric oxide synthase (nNOS)
inducible nitric oxide synthase (iNOS)

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STEPS OF PHAGOCYTOSIS - Killing and degradation

constitutively expressed at low levels, and the NO they generate functions to maintain vascular tone and as neurotransmitter, respectively

eNOS and nNOS

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STEPS OF PHAGOCYTOSIS - Killing and degradation

This NO is type that is involved in microbial killing, is induced when macrophages are activated by cytokines.

iNOS

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STEPS OF PHAGOCYTOSIS - Killing and degradation

in macrophage what is the mechanism of NO so that it will attack and damage the microbe

NO reacts with a superoxide to
generate the highly-reactive free radical PEROXYNITRITE

NO + Superoxide = Peroxynitrite

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STEPS OF PHAGOCYTOSIS - Killing and degradation

Granules, may be categorized as?

Smaller specific (secondary) granules
Larger azurophilic (primary) granules

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STEPS OF PHAGOCYTOSIS - Killing and degradation

this granule contains the:

lysozyme, collagenase, gelatinase, lactoferrin, plasminogen activator, histaminase, alkaline phosphatase

Secondary granules

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STEPS OF PHAGOCYTOSIS - Killing and degradation

this granule contains the:

myeloperoxidase, bactericidal proteins such as lysozymes and defensins, acid hydrolases, and a variety of neutral proteases such
as elastase, cathepsin G, non-specific collagenase, and
proteinase 3

Primary granules

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STEPS OF PHAGOCYTOSIS - Killing and degradation

this granule contains the:

defencins, cathelicidins, lysozyme, lactoferrin, and the major basic
protein, which is usually present in eosinophils

Other microbicidal granule

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This mechanism are present in order to combat the action of these free radicals

Antioxidant Mechanism

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Antioxidant Mechanism may be in the form of?

Superoxide dismutase
Catalase
Glutathione peroxidase
Ceruloplasmin
Transferrin

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Extracellular fibrillar networks that provide a high concentration of antimicrobial substances at sites of
infection and trap microbes, helping to prevent their spread

NEUTROPHIL EXTRACELLULAR TRAPS (NETs)

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LEUKOCYTE-MEDIATED TISSUE INJURY

Leukocytes are important causes of injury to normal cells and tissues under several circumstances:

As part of the normal defense reaction against infectious
microbes, when ____ tissues suffer collateral
damage

Adjacent

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# LEUKOCYTE-MEDIATED TISSUE INJURY *Leukocytes are important causes of injury to normal cells and tissues under several circumstances:* In some infections that are difficult to eradicate, such as tuberculosis, and certain viral diseases, the ____ ____ ____ contributes more to the pathology that does the microbe itself.

prolonged host response

# LEUKOCYTE-MEDIATED TISSUE INJURY *Leukocytes are important causes of injury to normal cells and tissues under several circumstances:* When the inflammatory response is inappropriately directed against host tissues, as in certain _____ _____

Autoimmun diseases

# LEUKOCYTE-MEDIATED TISSUE INJURY *Leukocytes are important causes of injury to normal cells and tissues under several circumstances:* When the host reacts excessively to against usually harmless environmental substance, as in ____ ____, including asthma

Allergic diseases

# OTHER FUNCTIONAL RESPONSES OF ACTIVATED LEUKOCYTES Activated leukocytes play several other roles in host defense, enumerate

1. Produce **Cytokines** (either amplify or limit inflammatory reactions) 2. Produce **Growth Factors** (stimulate the proliferation of endothelial cells and fibroblasts and the synthesis of collagen, and enzymes that remodel connective tissues.) 3. Production of **Th17 (IL-17) cells** (induces the secretion of chemokines that recruit other leukocytes)

KINDLY CHECK

CLINICAL EXMPALES OF LEUKOCYTE INJURY, ACUTE AND CHRONIC PLEASE LANG

# DEFECT IN LEUKOCYTE FUNCTIONS (GENETIC) Match 1. Leukocyte adhesion def 1 2. Leukocyte adhesion def 2 3. Chronic granulomatous disease 4. MPO def 5. Chediak Higashi syndrome A. Mutations in fucosyl transferase B. Decrease oxidative burst C. Mutations in B chain of CD11/CD18 integrins D. Mutations affecting protein involved in lysosomal membrane traffic E. Defective MPO H2O2 system

1. C 2. A 3. B 4. E 5. D

# DEFECT IN LEUKOCYTE FUNCTIONS (ACQUIRED Match 1. Bone marrow suppression 2. Diabetes, malignancy, sepsis, chronic dialysis 3. Leukemia, anemia, sepsis, diabetes, malnutrition A. Adhesion and Chemotaxis B. Phagocytosis and Microbicidal activity C. Production of Leukocyte

1. C 2. A 3. B

# DEFECTS IN LEUKOCYTE FUNCTION defect in phagolysosome function seen in?

Chediak-Higashi syndrome

# DEFECTS IN LEUKOCYTE FUNCTION Inherited defects in ____ ____ like in chronic granulomatous disease wherein there is inherited defects in the genes encoding components of phagocyte oxidase

microbicidal activity

# DEFECTS IN LEUKOCYTE FUNCTION may lead to marrow suppression

Acquired deficiencies

# DEFECTS IN LEUKOCYTE FUNCTION cells in tissue that serve important functions in initiating acute inflammation.

Mast cells and macrophages

# DEFECTS IN LEUKOCYTE FUNCTION defect of integrins and selectin ligands which may lead to recurrent bacterial infection.

Inherited defect in leukocyte adhesion

# TERMINATION OF ACUTE INFLAMMATORY RESPONSE When the cells were able to control the infection, there must be a?

**termination** of the inflammatory response

# TERMINATION OF ACUTE INFLAMMATORY RESPONSE Note that inflammation is a?

DOUBLE-EDGED SWORD (it is protective but it can also cause damage to the normal cells or tissues)

# TERMINATION OF ACUTE INFLAMMATORY RESPONSE nfammation declines after the offending agents are removed simply because the mediators of inflammation: ENUMERATE

- Are produced in **rapid burst** as long as the stimulus persists - Have **short half-lives** - Are **degraded after their release** (easily destroyed)

# TERMINATION OF ACUTE INFLAMMATORY RESPONS it should produce what anti-inflammatories?

- anti-inflammatory lipoxins - anti-inflammatory cytokines - anti-inflammatory lipid mediators

# MEDIATORS OF INFLAMMATION substances that initiate and regulate inflammatory reactions.

Inflammatory mediators

# MEDIATORS OF INFLAMMATION Mediators are generated either from?

cells or from plasma proteins.

# MEDIATORS OF INFLAMMATION this mediator are produced in response to active stimuli

Active mediators

# MEDIATORS OF INFLAMMATION TOF One mediator can stimulate the release of another mediator

eurt

# MEDIATORS OF INFLAMMATION TOF Mediators vary in their range of cellular suspect

False cellular target not suspect

# MEDIATORS OF INFLAMMATION Once activated and released from the cell, most of these mediators are?

Short lived

# ACTION OF PRINCIPAL MEDIATORS Give the source and action of the mediators: Histamine

Source: Mast cells (predominant), basophils, platelets Action: Vasodilation, increased vascular permeability, endothelial activation

# ACTION OF PRINCIPAL MEDIATORS Give the source and action of the mediators: Prostaglandins

Source: Mast cells and leukocytes Actions: Vasodilation, pain, fever

# ACTION OF PRINCIPAL MEDIATORS Give the source and action of the mediators: Leukotrienes

Source: Mast cells and leukocytes Action: Increased vascular permeability, chemotaxis, leukocyte adhesion and activation

# ACTION OF PRINCIPAL MEDIATORS Give the source and action of the mediators: Cytokines (TNF, IL-1)

Source: Macrophages, endothelial cells, mast cells Action: Local endothelial activation, fever/pain/anorexia/hypotension, decreased vascular resistance

# ACTION OF PRINCIPAL MEDIATORS Give the source and action of the mediators: Chemokines

Source: Leukocytes, activated macrophages Action:Chemotaxis, leukocyte activation

# ACTION OF PRINCIPAL MEDIATORS Give the source and action of the mediators: PAF

Source: Leukocytes, mast cells Action: Vasodilation, increased vascular permeability, leukocyte adhesion, chemotaxis, degranulation, oxidative burst

# ACTION OF PRINCIPAL MEDIATORS Give the source and action of the mediators: Complement (C5a, C3a, C4a)

Source: Plasma (produced in liver) Action: Leukocyte chemotaxis and activation, vasodilation

# ACTION OF PRINCIPAL MEDIATORS Give the source and action of the mediators: Kinins

Source: Plasma (produced in liver) Action: Increased vascular permeability, smooth muscle contraction, vasodilation, pain

this mediators are normally sequestered in intracellular granules and can be rapidly secreted by granule exocytos or are synthesized de novo

Cell-derived mediators

# CELL-DERIVED MEDIATORS * Important action in blood vessels * First mediators to be released

Vasoactive Amines: **Histamine and Serotonin**

# CELL-DERIVED MEDIATORS - Vasoactive Amine ▪ Mostly coming from mast cells; basophil, platelet

Histamine

# CELL-DERIVED MEDIATORS - Vasoactive Amine Stimuli that may trigger the secretion of this mediator: - Physical injury - Binding of antigen to IgE antibodies displayed on the surfaces of mast cell - Fragments of complement (anaphylatoxin) C3a & C5a - Histamine releasing protein derived from leukocytes - Neuropeptides (substance P) - Cytokines (IL-1, IL-8)

Histamine

# CELL-DERIVED MEDIATORS - Vasoactive Amine this mediator causes dilatation of arterioles and increased permeability of venules

Histamine

# CELL-DERIVED MEDIATORS - Vasoactive Amine Histamine vasoactive effects are mediated mainly via binding to?

**H1 receptors** on microvascular endothelial cells

# CELL-DERIVED MEDIATORS - Vasoactive Amine It is a vasoconstrictor, but the importance of this action in inflammation is unclea

Serotonin (5-hydroxytryptamine)

# CELL-DERIVED MEDIATORS - Vasoactive Amine A preformed vasoactive mediator present in platelets and certain neuroendocrine cells

Serotonin (5-hydroxytryptamine)

# CELL-DERIVED MEDIATORS - Arachidonic Acid (AA) Metabolites AA converted by action of enzymes to produce?

prostaglandin and leukotrien

# CELL-DERIVED MEDIATORS - Arachidonic Acid (AA) Metabolites AAis a 20-carbon polyunsaturated fatty acid that is derived from?

dietary sources or by synthesis from a precursor molecule, **linoleic acid**

# CELL-DERIVED MEDIATORS - Arachidonic Acid (AA) Metabolites AA-derived mediators, also called

eicosanoids

# CELL-DERIVED MEDIATORS - Arachidonic Acid (AA) Metabolites AA-derived mediators, also called eicosanoids, are synthesized by two major classes of enzymes:

- **Cyclooxygenases** (which generate prostaglandins) - **Lipoxygenases** (which produce leukotrienes and lipoxins

# CELL-DERIVED MEDIATORS - Arachidonic Acid (AA) Metabolites Match Action: 1. Vasodilation 2. Vasoconstriction 3. Increase Vascular permeability 4. Chemotaxis, and leukocyte adhesin Eicosanoid: A. Leukotriene B4, HETE (Hydroxyeicosatetraenoic acid) B. Thromboxane A2, leukotrienes C4, D4, E4 C. PGI2 (prostacyclin), PGE1, PG32, PGD2 D. Leukotrienes C4, D4, E4

1. C 2. B 3. D 4. A

# CELL-DERIVED MEDIATORS - Arachidonic Acid (AA) Metabolites ▪ Produced by mast cells, macrophages, endothelial cells and other cells ▪ They are generated by the actions of two cyclooxygenases, called **COX-1 and COX-2.**

Prostaglandins (PGs

# CELL-DERIVED MEDIATORS - Arachidonic Acid (AA) Metabolites Prostaglandin are involved in pathogenesis of ____ and ____ in inflammation.

Pain and Fever

# CELL-DERIVED MEDIATORS - Arachidonic Acid (AA) Metabolites produced in leukocytes and mast cells by the action of lipoxygenase and are involved in vascular and smooth muscle reactions and leukocyte recruitment

Leukotrienes

# CELL-DERIVED MEDIATORS - Arachidonic Acid (AA) Metabolites Secreted mainly by ____, forming leukotrienes and lipoxines

leukocytes

# CELL-DERIVED MEDIATORS - Arachidonic Acid (AA) Metabolites There are three different lipoxygenases, ____being the predominant one in neutrophils

5-lipoxygenase

# CELL-DERIVED MEDIATORS - Arachidonic Acid (AA) Metabolites This enzyme converts AA to **5 hydroxyeicosatetraenoic acid**, which is chemotactic for neutrophils and is the precursor of the leukotrienes

lipoxygenases

# CELL-DERIVED MEDIATORS - Arachidonic Acid (AA) Metabolites hoiw many lipoxygenases lead to production of lipoxins?

12 lipoxygenases

# CELL-DERIVED MEDIATORS - Arachidonic Acid (AA) Metabolites inhibitors of inflammation inhibiting leukocyte recruitment & cellular components of inflammation

Lipoxins

Enumerate the Pharmocologic inhibitors of prostaglanding and leukotrienes

1. Cyclooxygenase inhibitors 2. Lipoxygenase inhibitors 3. Corticosteroids 4. Leukotriene receptor antagonists

# Pharmocologic inhibitors of prostaglanding and leukotrienes Enumerate what Cyclooxygenase inhibitors inhibits

COX-1 and COX-2

# Pharmocologic inhibitors of prostaglanding and leukotrienes Are broad spectrum antiinflammatory agents that reduce the transcription of genes encoding many proteins involved in inflammation

Corticosteroids

Produced mainly by macrophages, lymphocytes and dendritic cells

Cytokines

# Cytokines serve critical roles in leukocyte recruitment by promoting adhesion of leukocytes to endothelium and their migration through blood vessels.

TNF (tumor necrosis factor) and IL-1

Are a family of small (8 to 10 kDa) proteins that act primarily as chemoattractants for specific types of leukocytes.

Chemokines

What are the 4 major groups of chemokines, they are arranged according to the arrangement of cysteine (C) residues in the proteins

1. C-X-C chemokines 2. C-C chemokines 3. C chemokines 4. CX3C chemokines:

# OTHER MEDIATORS OF INFLAMMATION - Phospholipid derived mediator that may cause platelet aggregation, vasoconstriction,bronchoconstriction * A variety of cell types, including platelets, basophils, mast cells, neutrophils, macrophages, and endothelial cells,can elaborate PAF in both secreted and cell-bound forms

Platelet Activating Factor (PAF)

What are the three outcomes of acute inflammatory

1. Complete resolution 2. Healing by connective tissue replacement 3. Progress to chronic

Enumerate the morphologic patterns of Acute inflmmation

1. Serous Inflammation 2. Fibrinous inflammation 3. Purulent Inflammation and abscesses 4. Ulcers | `

# morphologic patterns of Acute inflmmation * Outpouring of a thin fluid from plasma or secretions. * Accumulation of fluid in cavities called effusion.

Serous inflammation

# morphologic patterns of Acute inflmmation fibrinogen pass out of the blood, and fibrin is formed and deposited in the extracellular space.

Fibrinous inflammation

# morphologic patterns of Acute inflmmation Purulent inflammation is characterized by the production of pus

Purulent Inflammation and abscesses ## Footnote `

# morphologic patterns of Acute inflmmation A local defect, or excavation, of the surface of an organ or tissue

ulcers

Causes of Chronic inflammation

a) Persistent infections b) Immune mediated inflammatory response c) Allergic dose d) Prolonged exposure to potentially toxic agents

MORPHOLOGIC FEATURE of chronic inflammation

- Infiltration with mononuclear cells - Tissue destruction - Attempts at healing by connective tissue replacement of damaged tissue

# CELLS AND MEDIATORS OF CHRONIC INFLAMMATION Enumerate the cells

1. Macrophage 2. Lymphocytes 3. B Cells or Plasma Cells 4. Eosinophils 5. Mast cells 6. Neutrophils | recall nalang kayo sa hema, diko na iddump info dito

It is a form/pattern of chronic inflammation characterized by collections of activated macrophages, often with T lymphocytes, and sometimes associated with necrosis

Granulomatous Inflammation

Consisting of a microscopic aggregation of macrophages that are transformed into epithelium like cells, surrounded by a collar of mononuclear leukocytes, pricipally lymphocytes

GRANULOMA

# Granulomatous Inflammation are **activated macrophages**, which forms **epithelioid cells** (resembles epithelial cells) and it is surrounded by inflammation — lymphocytes

Granuloma

# CLASSIFICATION OF GRANULOMA Incited by relatively inert foreign bodies, like sutures, which induce inflammation in the absence of T cell-mediated immune responses.

Foreign Body Granuloma

# CLASSIFICATION OF GRANULOMA * They are caused by a variety of agents that are capable of inducing a persistent T cell-mediated immune response. * Inciting agent is poorly degradable or particulate * An example is granuloma in TB

Immune Granuloma

# SYSTEMIC EFFECTS OF INFLAMMATIO Inflammation, even if localized, is associated with cytokineinduced systemic reactions that are collectively called the?

acute-phase response

# CLINICAL AND PATHOLOGIC CHANGES OF ACUTE PHASE RESPONSE pyrogens that act by stimulating prostaglandin synthesis); LPS-exogenous; IL1, TNF-endogenou

Fever

# CLINICAL AND PATHOLOGIC CHANGES OF ACUTE PHASE RESPONSE CRP, fibrinogen, serum amyloid A protein

Acute phase proteins

# CLINICAL AND PATHOLOGIC CHANGES OF ACUTE PHASE RESPONSE a common feature of inflammatory reactions, especially those induced by bacterial infections.

Leukocytosis

# CLINICAL AND PATHOLOGIC CHANGES OF ACUTE PHASE RESPONSE In the clinics, we may observe on the patients what presentation?

increase pulse rate & bp, and decrease sweating

# DEFECTIVE OR EXCESSIVE INFLAMMATION results mainly in increased susceptibility to infection, delayed healing

Defective inflammation

# DEFECTIVE OR EXCESSIVE INFLAMMATION Most common cause is **leukocyte deficiency** due to replacement of the bone marrow by leukemias and metastatic tumors and suppression of the marrow by therapies for cancer and graft rejection

Defective inflammation

# DEFECTIVE OR EXCESSIVE INFLAMMATION - may lead to allergies and autoimmune diseases - It is the underlying cause of many human diseases

Excessive inflammation

[P] Week 2: Inflammation and Repair - Part 2 Flashcards

(107 cards)