Chronic Inflammation Flashcards
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
Chronic inflammation may follow:
_________, or
_____________
acute inflammation
may begin insidiously, as a low-grade, smoldering response.
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
Causes of chronic inflammation
• In other cases, an unresolved ______ may evolve into chronic inflammation,
acute inflammation
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
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
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
angiogenesis is the proliferation of __________
small blood vessels
Macrophages
• The half-life of blood monocytes is about ______, whereas the life span of tissue macrophages is several __________
1 day
months or years.
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
Extravasation of monocytes is governed by different factors to those that are involved in neutrophil emigration.
T/F
F
the same
There are two major pathways of macrophage activation, called _____ and _______
classical and alternative.
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
Classically activated (also called ___) macrophages produce _____ and ____ and upregulate lysosomal enzymes.
M1
NO and ROS
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
Alternative macrophages are actively microbicidal and the cytokines may actually inhibit the classical activation pathway;
T/F
F
They are not
Alternative macrophages’ cytokines may actually inhibit the classical activation pathway of macrophages
T/F
T
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
Macrophages secrete mediators of inflammation, such as ________ and ______
cytokines (TNF, IL-1, chemokines, and others) and eicosanoids.
Macrophages display antigens to T lymphocytes and respond to signals from T cells
T/F
T
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
____+ T lymphocytes promote inflammation and influence the nature of the inflammatory reaction through _____ production.
CD4
cytokine
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)
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
2
Activated B lymphocytes and antibody-producing plasma cells are often present at sites of chronic inflammation.
T/F
T
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
T
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
T
• 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
