Acute and chronic inflammation II Flashcards
Acute inflammation:
What is fibrinous inflammation?
Where is this common?
Fibrinous inflammation
–Increased vascular permeability = large molecules (fibrinogen) pass out of the blood.
–Fibrin is formed and deposited in the extracellular space
–Develops with
- Large vascular leaks, or
- A local procoagulant stimulus (e.g., cancer cells)
- Characteristic of inflammation in the lining of body cavities
–Meninges, pericardium, and pleura
- May dissolve (cleared by macrophages)
- If fibrin not removed
–Fibroblasts and blood vessels stimulated –> lead to scarring
What is fibrin?
Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is formed by the action of the protease thrombin on fibrinogen which causes it to polymerize. The polymerized fibrin together with platelets forms a hemostatic plug or clot over a wound site.
Acute Inflammation:
Purulent (suppurative) inflammation
Characterized by the production of?
The exudate contains what?
What is an abcess?
What is a sorrounding abscess?
•Purulent (suppurative) inflammation
–Production of pus
–Pyogenic pathogens = pus-producing bacteria
•Staphylococci–> liquefactive necrosis
–Exudate with PMNs, necrotic cells, edema fluid
–>Abscess: localized collection of pus
–Pyogenic bacteria seeds into a tissue
–Central region of necrotic WBCs, tissue cells
–Preserved PMNs around necrotic focus
•Surrounding abscess = chronic inflammation and repair
–Vascular dilation
-Parenchymal and fibroblastic proliferation
What is an ulcer?
Occurs when necrosis and inflammation are________ each other.
Where can they be found?
Chronic Inflammation
Causes?
What are some characteristic physiological features?
•Characteristic histologic features:
1.Collection of chronic inflammatory cells
- Macrophages
- Lymphocytes
- Plasma cells
- Tissue destruction
- Healing; replacement by connective tissue (fibrosis)
Cells that act during chronic inflammation?
Mast cells
What activates mast cells?
In their immediate response, what do they release?
What about in their delayed responses?
•Involved in acute and chronic inflammation
–Allergic reactions (anaphylaxis)
•Activated by:
- Tissue trauma
- Complement proteins C3a, C5a
- Cross-linking of surface IgE by antigen
•Immediate response:
–Quick release of histamine
- Vasodilation of arterioles
- Increased vascular permeability
- Delayed response:
–production of AA metabolites (LTs-_Leukotrienes_)
–LTs maintain acute inflammatory response
Eosinophils
What chemokine is required to recruit Eosinophils?
Very helpful in what tipe of infections?
•Recruitment similar to neutrophils
–specific chemokines (eotaxin) required
- Variety of inflammatory reactions
- Specific scenarios:
–Parasitic infections:
•MBP (Major Basic Protein): toxic to parasites (& epithelial cells)
–Allergic reactions
•mediated by IgE
Lymphocytes
What do Th1 lymphocytes secrete? What does it activate? Involved in what kind disease?
Th2 lymphocytes secrete what? What type of macrophages and cells do they activate? Defends against what type of parasites?
What do Th17 lymphocytes secrete? What cells do they recruit?
Macrophages also activate T cells by presenting antigen and using the__4____cytokine.
TH1 T lymphocytes secrete IFN-ɣ
–Activate classical pathway macrophages (M1)
–Defense against bacteria, viruses
–Involved in autoimmune disease
•TH2 T lymphocytes secrete IL-4, IL-5, IL-13
–Activates alternative pathway macrophages (M2)
–Activates eosinophils
–Defense against helminthic parasites
–Involved in allergic inflammation
•TH17 T lymphocytes secrete IL-17
–Recruitment of neutrophils and monocytes
–Defense against bacteria, viruses
–Involved in autoimmune disease
4- IL-12
**Both TH1 and TH17 cells are involved in defense against many types of bacteria and viruses and in autoimmune diseases.
**TH2 cells are important in defense against helminthic parasites and in allergic inflammation.
Macrophage
Liver macrophages are known as__________
CNS macrophages are known as________.
Are they involved in scar formation and fibrosis?
•Monocytes circulate for about a day
–Give rise to macrophages in tissues
•Macrophages inhabit most tissues in the body
–Organ-specific names
•Kupffer cells = liver macrophages
•Microglia = nervous system macrophages
•Central to inflammatory reaction & healing
Secrete inflammatory mediators
–Initiation and propagation of inflammatory reactions
- Cytokines (TNF, IL-1, chemokines, etc)
- Eicosanoids (AA metabolites; LTs and PGs)
•Ingest and eliminate microbes and dead tissues
–Present antigens to adaptive immune system
•Initiate the process of tissue repair.
–Involved in scar formation and fibrosis
•Tissue destruction if inappropriate, excessive activation
Macrophage activation
Classical pathway to activate macrophages is by? what is its main function?
Alternatively actvated is important in the resolution of?
Different stimuli activate monocytes/macrophages to develop into functionally distinct populations.
-Classically activated: induced by microbial products and cytokines, (IFN-γ); phagocytose and destroy microbes and dead tissues ; potentiate inflammatory reactions.
Classical: induced by
- microbial products (endotoxin) engage TLRs and other sensors;
- T cell–derived signals, importantly the cytokine IFN-γ, in immune responses;
- foreign substances including crystals and particulate matter.
1. produce NO and ROS and upregulate lysosomal enzymes = enhanced ability to kill ingested organisms,
2. secrete cytokines that stimulate inflammation.
important in host defense against microbes and in many inflammatory reactions.
*The same activated cells are capable of injuring normal tissues.
-Alternatively activated: important in tissue repair and the resolution of inflammation.
Alternative: induced by
-cytokines IL-4 and IL-13, produced by T lymphocytes and other cells.
NOT actively microbicidal and the cytokines may actually inhibit the classical activation pathway;
- function is in tissue repair.
- secrete growth factors that promote angiogenesis, activate fibroblasts, and stimulate collagen synthesis.
Granulomatous inflammation
Nodules of what are seen?
They form around some organism to prevent their spread which menas that the organisms may remain_____.
•Pattern of chronic inflammation
–Nodules of enlarged macrophages
–Surrounded by lymphocytes
•Form around some organisms, prevent spread
–May remain viable (and infectious)
•Fibrosis around longstanding granulomatous inflammation
Granuloma formation is a cellular attempt to contain an offending agent that is difficult to eradicate.
In this attempt there is often strong activation of T lymphocytes leading to macrophage activation, which can cause injury to normal tissues.
The activated macrophages may develop abundant cytoplasm and begin to resemble epithelial cells, and are called epithelioid histiocytes .
Some activated macrophages may fuse, forming multinucleate giant cells.
Granulomatous inflammation: Foreign body type
Do they incite specific or inflammatory immune response?
Granulomatous inflammation: Immune type
•Macrophages activate T cells to produce cytokines
–IL-2: Activates additional T cells
–IFN-γ: Activates macrophages
–IL-4 or IFN-γ: cause transformation into epithelioid Histiocytes, multinucleate giant cells
Granulomatous inflammation; Uric acid crystals
A special type of granulomatous inflammation—uric acid crystals
These are interesting because although they are technically a “foreign” substance, they are not inert
They incite an inflammatory response—specifically they initiate the inflammasome.
Systemic effects of inflammation:
Acute Phase Reaction
Happens as a result of what inflammatory mediators?
- AKA: Acute phase reaction
- Result of inflammatory mediators
–TNF, IL-1, and *IL-6
–Become systemically distributed
–Produce generalized effects
What are some consequences of it?
- Pyrexia (fever)
- Increased acute phase proteins in the blood
- Leukocytosis: increased WBCs in the blood
- Other physiologic effects:
–tachycardia, hypertension, hypohidrosis, rigors, chills, anorexia, somnolence, malaise
Acute phase reaction: Fever
Vascular cells in hypothalamus stimulated by pyrogens to produce prostaglandins (esp. PGE2) that act locally to cause a central increase of body temperature
Exogenous pyrogens (e.g. bacterial components) cause leukocytes to release endogenous pyrogens (IL-1, TNF) which then act on the hypothalamus vasculature cells.
Exogenous pyrogens also act directly on the hypothalamus vasculature cells
The increase in body temperature is thought to aid in fighting some infections.
Acute phase reaction:
Acute phase proteins
What do hepatocytes respond to?
What two APP are known to adhere to cell wall and act as opsonins?
What does fibrinogen binds to? What test allows us to perform for the presence of inflammation.
Increased acute phase proteins in the blood.
In response to IL-6 hepatocytes produce several proteins in greater abundance.
Clinically used to detect and monitor the progress of inflammatory processes.
Two of these: C-reactive protein (CRP) and serum amyloid A (SAA) protein are known to adhere to cell walls and may act as opsonins.
Fibrinogen binds red blood cells causing them to form stacks that quickly form sediments. This forms the basis for the erythrocyte sedimentation rate (ESR), a long-used test for the presence of inflammation
Acute phase reaction:
Leukocytosis
Early release of immature white blood cells is commonly referred to as?
Leukocytosis: increased leukocytes in the blood
White blood cells often increased systemically during inflammation
Under the influence of TNF & IL-1 more leukocytes are released from the bone marrow
May see an increased number of immature white blood cells (early release): commonly referred to as a “left shift” of the leukocytes
Continued inflammation leads to increased production of colony stimulating factors (CSFs) that increase bone marrow production of leukocytes (as opposed to releasing more cells that have already formed).
Acute phase reaction
