Chronic Inflammation Flashcards by Iseoluwa Ojo

Chronic inflammation is a response of prolonged duration (weeks or months) in which ______,______, and ______ coexist, in varying combinations.

inflammation, tissue injury and attempts at repair

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Chronic inflammation may follow:

_________, or
_____________

acute inflammation

may begin insidiously, as a low-grade, smoldering response.

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causes of chronic inflammation

•_______ infections by microorganisms that are difficult to eradicate, such as ______ and certain viruses, fungi, and parasites.

These organisms often evoke an immune reaction called ____________
•The inflammatory response sometimes takes a specific pattern called a ________ reaction.

Persistent; mycobacteria

delayed-type hypersensitivity

granulomatous

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Causes of chronic inflammation

• In other cases, an unresolved ______ may evolve into chronic inflammation,

acute inflammation

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Causes of chronic inflammation

______ evoke a self- perpetuating immune reaction that results in chronic tissue damage and inflammation; examples of such diseases are rheumatoid arthritis and multiple sclerosis.

Autoantigens

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Causes of Chronic inflammation

______ exposure to potentially toxic agents, either exogenous or endogenous.
• Silica is an __genous nondegradable inanimate material that, when inhaled for prolonged periods, results in an inflammatory ___ disease called ____

• Atherosclerosis is thought to be a (acute or chronic?) inflammatory process of the arterial wall induced partly by excessive production and tissue deposition of endogenous cholesterol and other lipids.

Prolonged

Exo; lung

silicosis

Chronic

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MORPHOLOGICAL FEATURES

• Chronic inflammation is characterized by:

Infiltration with mononuclear cells, which include _______,_____,______

Tissue destruction, induced by the __________ or _______
Attempts at healing by ________ replacement of damaged tissue accomplished by ________ and, in particular, _______

macrophages, lymphocytes, and plasma cells

persistent offending agent or by the inflammatory cells

connective tissue; angiogenesis

Fibrosis

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angiogenesis is the proliferation of __________

small blood vessels

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Macrophages

• The half-life of blood monocytes is about ______, whereas the life span of tissue macrophages is several __________

1 day

months or years.

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In inflammatory reactions, monocytes begin to emigrate into extravascular tissues quite (early or late?) , and within _________ they may constitute the predominant cell type.

Early

48 hours

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Extravasation of monocytes is governed by different factors to those that are involved in neutrophil emigration.

T/F

the same

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There are two major pathways of macrophage activation, called _____ and _______

classical and alternative.

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Classical macrophage activation may be induced by:
 _______ products such as _______, which engage TLRs and
other sensors;
 by _____ cell–derived signals, importantly the __________ , in immune responses;
 by ______ substances including crystals and particulate matter.

Microbial; endotoxin

T ; cytokine IFN-γ

foreign

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Classically activated (also called ___) macrophages produce _____ and ____ and upregulate lysosomal enzymes.

NO and ROS

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Alternative macrophage activation is induced by ________, such as _____ and ____, produced by _______ and other cells.

cytokines other than IFN-γ

IL-4 and IL-13

T lymphocytes

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Alternative macrophages are actively microbicidal and the cytokines may actually inhibit the classical activation pathway;

T/F

They are not

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Alternative macrophages’ cytokines may actually inhibit the classical activation pathway of macrophages

T/F

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The products of activated macrophages

 eliminate injurious agents such as microbes,
 initiate _______
 also responsible for much of the ________ in ______________ inflammation .

the process of repair

tissue injury

chronic inflammation

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Macrophages secrete mediators of inflammation, such as ________ and ______

cytokines (TNF, IL-1, chemokines, and others) and eicosanoids.

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Macrophages display antigens to T lymphocytes and respond to signals from T cells

T/F

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Role of Lymphocytes

•_____ and other environmental antigens activate T and B lymphocytes.
• These cells are often present in chronic inflammation and when activated, the inflammation tends to be _____ and _____
• Some of the strongest chronic inflammatory reactions, such as _______ inflammation are dependent on lymphocyte responses.
• Lymphocytes may be the dominant population in the chronic inflammation seen in _______ and other _____ diseases.
• Antigen-stimulated (effector and memory) T and B lymphocytes use various adhesion molecule pairs (selectins, integrins and their ligands) and chemokines to migrate into inflammatory sites.
• Cytokines from activated ______, mainly _____,____, and chemokines, promote leukocyte recruitment.

Microbes

persistent and severe.

granulomatous

autoimmune; hypersensitivity

Macrophages; TNF, IL-1

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____+ T lymphocytes promote inflammation and influence the nature of the inflammatory reaction through _____ production.

CD4

cytokine

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There are three subsets of CD4+ T cells that secrete different types of cytokines and elicit different types of inflammation.

• TH1 cells produce the cytokine ______, which _____________________
• TH2 cells secrete _____,——,____, which recruit and activate ______ and are responsible for the _____ pathway of macrophage activation.
• TH17 cells secrete ____ and other cytokines, which induce the secretion of _______ responsible for recruiting _______ and _______ into the reaction.

IFN-γ; activates macrophages by the classical pathway.

IL-4, IL-5, and IL-13; eosinophils; alternative

IL-17; chemokines

neutrophils (and monocytes)

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Both TH__ and TH___ cells are involved in defense against many types of bacteria and viruses and in autoimmune diseases.

TH__ cells are important in defense against helminthic parasites and in allergic inflammation.

1; 17

Activated B lymphocytes and antibody-producing plasma cells are often present at sites of chronic inflammation. T/F

In some chronic inflammatory reactions, the accumulated ______, _______ cells, and _____ cells cluster together to form ______ tissues resembling ________ and are called ___________

lymphocytes; antigen-presenting plasma lymphoid Lymph nodes tertiary lymphoid organs

tertiary lymphoid organs is type of lymphoid organogenesis that is often seen in the ______ of patients with long- standing ______ and in the thyroid in __________.

synovium; rheumatoid arthritis Hashimoto thyroiditis

Other cell types may be prominent in chronic inflammation induced by particular stimuli. • Eosinophils are abundant in immune reactions mediated by ____ and in ____ infections. Their recruitment is driven by adhesion molecules similar to those used by neutrophils, and by specific chemokines (e.g., ____) derived from leukocytes and epithelial cells. Eosinophils have granules that contain major basic protein, a highly ____ protein that is toxic to _____

IgE; parasitic; eotaxin cationic parasites

Mast cells are widely distributed in connective tissues and participate in __________ inflammatory reactions.

both acute and chronic

Mast cells express on their surface the receptor (FceRI) that binds the ____ portion of _____ antibody.

Fc; IgE

In immediate hypersensitivity reactions, ____ antibodies bound to the cells’ ___ receptors specifically recognize antigen, and the cells ______ and release mediators, such as histamine and prostaglandins. This type of response occurs during _____ reactions to foods, insect venom, or drugs, sometimes with catastrophic results (e.g.,_________).

IgE Fc; degranulate allergic anaphylactic shock

Neutrophils are characteristic of acute inflammation, but many forms of chronic inflammation, lasting for months, continue to show large numbers of neutrophils, induced either by persistent microbes or foreign bodies. T/F

Granulomatous inflammation is a form of chronic inflammation characterized by collections of _______, often with ______, and sometimes associated with _______

activated macrophages T lymphocytes central necrosis.

Granuloma formation is an attempt to _________________

contain an offending agent that is difficult to eradicate.

In granuloma formation, The activated macrophages may develop ____ and begin to resemble ________ cells, and are called ______ cells. Some activated macrophages may ______, forming ________ cells.

abundant cytoplasm epithelial ; epithelioid fuse; multinucleate giant

There are two types of granulomas: •________ granulomas •________ granulomas

Foreign body immune

Foreign body granulomas - are incited by relatively _________, in the absence of ________________ responses.

inert foreign bodies T cell–mediated immune

Typically, foreign body granulomas form around materials such as talc (associated with _______), ______ , or other fibers that are large enough to preclude phagocytosis by a macrophage

intravenous drug abuse sutures

In foreign body granulomas The foreign material when viewed with polarized light appears ______ at the _______

refractile; center of granuloma.

Immune granulomas are caused by a variety of agents that induces a ______ response. • In such responses, ______ activate T cells to produce cytokines, such as IL-__, which activates other T cells, perpetuating the response, and _____ which activates the macrophages.

persistent T cell–mediated immune macrophages 2 IFN-γ,

MORPHOLOGY of granulomas • Activated macrophages in granulomas have ____ colored granular cytoplasm with indistinct ______ and are called _____ cells.

pink; cell boundaries epithelioid bby

MORPHOLOGY of granulomas • The aggregates of epithelioid macrophages are surrounded by a _____ • Older granulomas may have a rim of ___________ • Frequently, but not invariably, _______ cells 40 to 50 μm in diameter are found in granulomas; these are called _______ cells.

collar of lymphocytes. fibroblasts and connective tissue. multinucleated giant;

In granulomas associated with certain infectious organisms (most classically Mycobacterium tuberculosis), a combination of ____ and _____- mediated injury leads to a _____ zone of necrosis. • Grossly, granular, cheesy appearance called _______ necrosis is seen.

Hypoxia; free radical central caseous

In Granulomatous inflammation, Microscopically, this necrotic material appears as (granular or amorphous?) , structureless, ____philic, granular debris, with complete loss of _____

Amorphous eosino cellular details.

The granulomas in Crohn disease, sarcoidosis, and foreign body reactions do not have necrotic centers and are said to be _________.

noncaseating

Granulomas is usually accompanied by ________

fibrosis

Granulomas are encountered in certain specific pathologic states; • ________ responses to certain microbes (e.g., M.tuberculosis, Treponema pallidum, or fungi), • Granulomas may also develop in some ______-mediated inflammatory diseases, notably ______ disease, • In a disease of unknown etiology called _____.

Persistent T-cell immune Crohn sarcoidosis

Causes of sarcoidosis?

Unknown

Tuberculosis is the prototype of a granulomatous disease caused by infection and should always be excluded. • In this disease the granuloma is referred to as a ______.

tubercle

Systemic Effects of Inflammation • Inflammation, even if it is localized, is associated with cytokine-induced systemic reacti ons that are collectively called the __________

acute-phase response.

The cytokines TNF, IL-1, and IL-6 are important mediators of the acute-phase reaction; other cytokines, notably type I interferons, also contribute to the reaction. T/F

• The acute-phase response consists of several clinical and pathologic changes: • Fever, characterized by an elevation of body temperature, usually by —“ to ___ C, is one of the most prominent manifestations of the acute-phase response, especially when inflammation is associated with infection.

1° to 4°C

Bacterial products, such as LPS (called ___genous _____), stimulate leukocytes to release cytokines such as IL-1 and TNF (called ____genous _____) that increase the enzymes (________) that convert AA into prostaglandins. • In the hypothalamus, the prostaglandins, especially PG___, stimulate the production of neurotransmitters that reset the temperature set point at a higher level.

Exo; pyrogens Endo; pyrogens cyclooxygenase E2

NSAIDs, including _____, reduce fever by _____

aspirin inhibiting prostaglandin synthesis.

Acute-phase proteins are plasma proteins, mostly synthesized in the liver • Three of the best-known of these proteins are __________,_______, and _______

C-reactive protein (CRP), fibrinogen, and serum amyloid A (SAA) protein.

Leukocytosis is a common feature of inflammatory reactions, especially those induced by _____ infections. • The leukocyte count usually climbs to ________ or ———— cells/mL, but sometimes it may reach extraordinarily high levels of ______ to _______ cells/mL.

bacterial 15,000 or 20,000 40,000 to 100,000

These extreme elevations of leukocytes are referred to as ______ reactions, because ______________________

leukemoid they are similar to the white cell counts observed in leukemia and have to be distinguished from leukemia.

• In severe bacterial infections (sepsis), clinical manifestation may include; • ————————————, •_________, and • metabolic disturbances including ___________ and ________. • This clinical triad is known as __

disseminated intravascular coagulation Hypotensive shock insulin resistance and hyperglycemia