Term
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Definition
| recognizing the non-self react to this stimulus: histamine release, phagocytosis, process the agent into small fragments, hence activate adaptive immune system. |
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Term
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Definition
| neutralizing/kill reactions that are specific to the offending agent: cytotoxic T cells, antibodies |
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Term
| Three tasks of innate immunity |
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Definition
Defend against bacterial/parasitic infections via neutralization of the pathogen with secreted cytotoxic proteins or by phagocytosis of the bacteria/parasite.
Phagocytosis initiate proteolytic digestion of the macromolecules to fragments (antigen) that are then presented together with MHC II proteins on the surface of the antigen presenting cells (APC) which activates the adaptive immune system
APC= macrophages and dendrites
3) The innate immune cells secrete a variety of cytokines that further amplify the response. |
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Term
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Definition
Transmembrane protein that bind to shared microbial component such as TLR4-LPS complex
TLR-ligand activates a cascade of events including expresion of pro-inflammatory cytokines, leading to further immune cell recruitment and activation of the inflammatory response |
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Term
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Definition
Enhances activity of NK cells
Attracts neutrophils and macrophages |
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Term
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Definition
Induces proliferation of antigen-primed T cells
Enhances activity of NK cells |
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Term
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Definition
Enhances activity of macrophages and NK cells
Increases expression of MHC molecules
Enhances production of IgG2a |
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Term
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Definition
Cytotoxic effects on tumor cells
Induces cytokines secretion in the inflammatory response |
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Term
| An additional degree of specificit with MHC II APCs |
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Definition
| provided by the interaction of CD28 on TH cells with proteins of the B7 family on APC; this “costimulatory signal” is required for TH activation. The activated TH cell secretes IL-2 and expresses the IL-2 receptor (IL-2R); this autocrine pathway stimulates further TH-cell proliferation and activation. IL-2 and other cytokines secreted by the TH cell activate not only TH cells, but also TC cells and B cells. |
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Term
| Costimulation in the T-Cell Activation Pathway |
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Definition
Co- stimulation ensures that the stimulation of a single receptor does not elicits
a damage immune reaction: signal 1->provides specificity, signal 2->permissive |
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Term
| Costimulation and the CD40–CD40L Interaction |
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Definition
| A. An antigen-presenting cell (APC) presents MHC class II-bound antigen to a CD4+ T cell. T-cell recognition of antigen initiates an intracellular signaling cascade that leads to expression of CD40 ligand (CD40L) at the T-cell surface. B. CD40L on the activated T cell binds to CD40 on the surface of the APC. Activation of CD40 generates an intracellular signaling cascade that leads to expression of B7 on the APC surface. C. Enhanced T-cell proliferation and differentiation are promoted by costimulation of the T cell by MHC class II antigen (which binds to the T-cell receptor), CD40 (which binds to T-cell CD40L), and B7 (which binds to T-cell CD28). Cytokines secreted by the activated APC augment T-cell proliferation and differentiation. |
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Term
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Definition
| Stored in the granules of mast cells/basophiles. Vasodilatation of arterioles and constriction of veins, constriction of endothelial cells: vascular permeability |
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Term
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Definition
| serine proteases activated by antigen-antibody binding. Complement triggers A) inflammatory stimulation (C3b), B) leukocyte chemotaxis (C3a, C5a). |
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Term
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Definition
| metabolites of arachidonic acid, prostaglandins, leukotrienes, lipoxines. Involved in inflammatory responses and tissue repair. |
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Term
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Definition
| proteins that act in paracrine manner to regulate leukocyte activity. Interleukins are cykines secreted primarily by cells of hematopoietic linage. |
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Term
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Definition
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Term
| Four phases of Inflammatory Response |
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Definition
Dilation of Vessels
Recruitment of cells
Chemotaxis
Phagocytosis |
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Term
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Definition
| Pathological state characterized by continued and inappropriate response of the immune system to the inflammatory stimulus |
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Term
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Definition
Release of growth factors and cytokines stimulating healing and scar formation through angiogenesis:
(cytokines, EGF, PDGF, TGF-β) |
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Term
| Arachidonic Acid Pathways |
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Definition
Phospholipase A2 acts on the phospholipids phosphatidylcholine (PC) to release arachidonic acid.
Unesterified arachidonic acid is used as substrate for the cyclooxygenase, lipoxygenase, epoxygenase pathways.
The cyclooxygenase pathways produce prostaglandins, prostacyclin, and thromboxane.
The lipoxygenase pathways produce leukotrienes and lipoxins.
The epoxygenase pathway produces epoxyeicosatetraenoic acids (EETs).
Non-enzymatic peroxidation of arachidonic acid generates isoprostanes. |
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Term
| Generation of Arachidonic Acid |
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Definition
Arachidonic acid is biosynthesized from the essential fatty acid precursor linoleic acid
Biotransformation of -linolenic acid into EPA and DHA (omega -3), also the precursors of resolvins, protectins and maresins.
Arachidonic acid is esterified to the membrane phospholipids and released from cellular phospholipids by the enzyme Phopholipase A2.
This reaction is the rate-determining step in the generation of eicosanoids. |
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Term
| Prostaglandin Biosynthesis and Function |
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Definition
Cyclooxygenases are membrane bound
heme-containing enzymes
COX1 and COX2 are found in humans
Each enzyme catalyzes two sequential reactions:
Arach. A->PGG2->PGH2 |
|
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Term
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Definition
| Two cyclooxygenase isoforms, COX-1 and COX-2 |
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Term
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Definition
| is constitutively expressed and is involved in “housekeeping” activities; vascular homeostasis, renal function, platelet function, and antithrombogenesis |
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Term
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Definition
| is inducible and involves in inflammation, fever, pain, transduction of painful stimulus in spinal cord, renal adaptation to stress, uterine contraction during labor.. |
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Term
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Definition
|
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Term
| lance between TxA2 and PGI2 levels |
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Definition
| The local balance between TxA2 and PGI2 levels is critical in regulation of systemic blood pressure and thrombogenesis |
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Term
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Definition
express only high levels of thromboxane synthase
TxA2 the main eicosanoid product of platelets
TxA2 is a potent vasoconstrictor and promoter of platelet adhesion and aggregation |
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Term
| Vascular endothelium express |
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Definition
express only prostacyclin synthase
PGI2 is the main ecosanoid product of vascular endothelium
PGI2 is vasodilator, and inhibitor of platelet aggregation |
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Term
| Leukotriene Biosynthesis, and Function, |
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Definition
Lipoxygenase catalyse the insertion of O2 into Arach.A.
HPETEs is reduced to HETE by GSP.
HPETE formed by 5-LOX is the precursor of leukotriene A4 (LTA4)
LTA4 is the precursor of all bioactive leukotriens
5-LOX is translocated to the nuclear membrane and activated by 5-lipoxygenase activating protein (FLAP)
LTB4/LTC4/LTD4 play role in psoriasis, artheritis, vascular diseases and asthma |
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Term
|
Definition
| the insertion of O2 into Arach.A. |
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Term
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Definition
|
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Term
|
Definition
| 5-LOX is the precursor of leukotriene A4 (LTA4) |
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Term
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Definition
| all bioactive leukotriens |
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Term
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Definition
| to the nuclear membrane and activated by 5-lipoxygenase activating protein (FLAP) |
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Term
| TB4/LTC4/LTD4 play role in |
|
Definition
| psoriasis, artheritis, vascular diseases and asthma |
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Term
|
Definition
| the phospholipids phosphatidylcholine (PC) to release arachidonic acid. |
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Term
| Unesterified arachidonic acid is used as substrate for |
|
Definition
| the cyclooxygenase, lipoxygenase, epoxygenase pathways |
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Term
| The cyclooxygenase pathways produce |
|
Definition
| prostaglandins, prostacyclin, and thromboxane. |
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Term
| The lipoxygenase pathways produce |
|
Definition
| leukotrienes and lipoxins. |
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Term
| The epoxygenase pathway produces |
|
Definition
| epoxyeicosatetraenoic acids (EETs). |
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Term
| Non-enzymatic peroxidation of arachidonic acid generates |
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Definition
|
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Term
| Arachidonic acid is biosynthesized from the essential fatty acid precursor |
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Definition
|
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Term
| Biotransformation of ______ to Generation of Arachidonic Acid |
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Definition
| Biotransformation of -linolenic acid into EPA and DHA (omega -3), also the precursors of resolvins, protectins and maresins. |
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Term
| Arachidonic acid is esterified to the membrane phospholipids and released from |
|
Definition
cellular phospholipids by the enzyme Phopholipase A2
This reaction is the rate-determining step in the generation of eicosanoids |
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Term
|
Definition
Lipoxin are derivates of arachidonic acid
Both LXA4 and LXB4 modulate the actions of leukotrienes and cytokines
Resolution of inflammation
LXA4 receptors are expressed in neutrophils, lung, spleen, and blood vessels
Lipoxin stops neutrophil chemotaxis, adhesion and transmigration, stimulate vasodilation (increase PGE2, PGI2), inhibit LTC4/LTD4-mediated vasoconstriction and inhbit LTB4 inflammatory effects.
Lipoxins stimulate the uptake and clearance of apoptotic neutrophils by macrophages-> resolution of inflammation
Lipoxin-leukotriene homeostasis may be a key factor in the pathogenesis of inflammation |
|
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Term
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Definition
|
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Term
| Both LXA4 and LXB4 modulate |
|
Definition
| the actions of leukotrienes and cytokines |
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Term
| LXA4 receptors are expressed in |
|
Definition
| neutrophils, lung, spleen, and blood vessels |
|
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Term
|
Definition
| neutrophil chemotaxis, adhesion and transmigration, stimulate vasodilation (increase PGE2, PGI2), inhibit LTC4/LTD4-mediated vasoconstriction and inhbit LTB4 inflammatory effects. |
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Term
|
Definition
| the uptake and clearance of apoptotic neutrophils by macrophages-> resolution of inflammation |
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Term
| Resolvins, Protectins, and Maresins: Omega-3-Derived Mediators |
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Definition
Specialized local mediators that limit neutrophil recruitment to the site of inflammation.
Stimulate macrophage dependent clearance of apoptotic cells
Inflammation resolution is an active process |
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Term
| The Allergic Response in Asthma |
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Definition
APC present the antigens to CD4+ T cells->TH2 lymphocytes.
Secreted IL-4, IL-13, and IL-5 recruit B cells and eosinophils.
The B cells differentiate into IgE-producing plasma cells.
The IgE binds to FcεRI receptors on mast cells and APC. The IgE-bound FcεRI is cross-linked, inducing the mast cell to degranulate and release inflammatory mediators including histamine, leukotrienes, platelet-activating factor, and other cytokines.
These cytokines cause acute airway inflammation. |
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Term
| Chronically Allergic Response in Asthma |
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Definition
Chronically, activated TH2 cells and mast cells produce circulating IL-5 that recruits eosinophils, and TH2 cells release products that stimulate local mast cells and neurons.
Together, the inflammatory mediators and catabolic enzymes produced by eosinophils, mast cells, and neurons cause chronic airway inflammation and lead to airway remodeling. |
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Term
| The Leukotriene Pathway in Asthma |
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Definition
Leukotrienes are some of the most potent bronchoconstrictors known and are important mediators of inflammation in the airway.
LTB4 is expressed in neutrophils and monocytes. It binds to BLT1 receptors expressed on leukocytes, leading to leukocyte chemotaxis, recruitment and promote cellular aggregation
LTA4 is converted to LTC4 in mast cells and eosinophils, which is transported out of the cell. LTC4 is converted to LTD4 /LTE4; all three of these cysteinyl leukotrienes bind to CysLT1 receptors expressed on airway smooth muscle cells, leading to bronchoconstriction and airway edema.
Drugs that inhibit leukotriene production or leukotriene receptor binding have a role in asthma therapy. The leukotriene pathway can be inhibited by the 5-lipoxygenase inhibitor zileuton or by the CysLT1 receptor antagonists zafirlukast. |
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Term
|
Definition
Chronic, systemic and autoimmune inflammatory disease
Primarily attacks joints, but also affects lungs, muscle and cardiovascular system
Secretion of TNF, growth factors, and IL-> induce COX-2 expression
Levels of COX-2 and PGE2 are elevated in synovial fluid of affected joints.
PGE2 stimulates pain pathways and COX-2 derivated eicosanoids and leukotrienes recruit inflammatory cells
Macrophages release collagenase and proteases that further contribute to joint damage
Common symptoms: synovitis, leukocytosis, rheumatoid nodules and the presence of rheumatoid factor (spec antibody against IgG) |
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Term
| Proposed Roles for Tumor Necrosis Factor in Rheumatoid Arthritis |
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Definition
TNF is secreted by activated macrophages in an affected joint,
TNF activates endothelial cells to up-regulate expression of cell surface adhesion molecules that promote leukocyte adhesion and diapedesis.
TNF has a positive feedback effect on nearby monocytes and macrophages, promoting their secretion of cytokines such as IL-1.
IL-1 activates T cells, and the combination of IL-1 and TNF stimulates synovial fibroblasts to increase their expression of matrix metalloproteases, prostaglandins (especially PGE2), and cytokines (such as IL-6) that degrade the joint cartilage.
Synovial fibroblasts also secrete IL-8, which promotes neutrophil diapedesis |
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Term
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Definition
TxA2 is an important mediator of thrombosis in acute coronary syndrome and other cardiovascular diseases (therapeutic target)
COX-inhibitor aspirin is an effective antiplatelet agent in prophylaxis and treatment of these diseases.
Intravascular leukotriene production during rupture of atheromatous plaques also contribute to acute coronary syndrome.
5-LOX, FLAP and LTA4 are genetically linked to myocardial infarction (therapeutic targets). |
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Term
| NSAIDs and GPIIb–IIIa antagonists inhibit |
|
Definition
| steps in thromboxane A2 (TxA2)-mediated platelet activation. |
|
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Term
|
Definition
COXs, leading to decreased TxA2 production. The platelets lack the ability to synthesize new enzyme molecules.
Aspirin is mostly used as antiplatelet agent to prevent arterial thrombosis leading to ischemic attack, stroke and myocardial infarction. |
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Term
| GPIIb–IIIa antagonists, small-molecule antagonists inhibit |
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Definition
| GPIIb–IIIa antagonists, such as the monoclonal antibody abciximab and the small-molecule antagonists eptifibatide and tirofiban, inhibit platelet aggregation by preventing activation of GpIIb–IIIa, leading to decreased platelet cross-linking by fibrinogen. |
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Term
| What is the role of the innate immune system |
|
Definition
Defend against bacterial/parasitic infections via neutralization
Recognizes non-self agent |
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Term
| Which statement is correct for the MHC-I proteins |
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Definition
|
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Term
| Which combination is true for MHC-II proteins |
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Definition
| MHC-II protein displays endocytic proteins; and has a CD4 recognition site |
|
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Term
| What is true about COX enzymes: |
|
Definition
They are involved in the prostaglandins biosynthesis from arachidonic acid
COX2 plays role in fever, pain and vasodilation |
|
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Term
| Which of the following is true about cyclooxygenase pathway? |
|
Definition
PGE2 is involved in vasodilation and bronchoconstriction
Prostaglandines are not cytoprotective
Prostacylins (PGI2) are vasodilators and promote platelet aggregation |
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Term
| Which of the following statements are true for Leukotrienes … |
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Definition
|
|
Term
| Which of the following cells are primarily responsible for this reaction? |
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Definition
|
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Term
| The action of lymphocytes attempting to eliminate this antigen is an example of.. |
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Definition
|
|
Term
| NSAIDs and GPIIb–IIIa antagonists inhibit |
|
Definition
| steps in thromboxane A2 (TxA2)-mediated platelet activation. |
|
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Term
|
Definition
COXs, leading to decreased TxA2 production. The platelets lack the ability to synthesize new enzyme molecules.
Aspirin is mostly used as antiplatelet agent to prevent arterial thrombosis leading to ischemic attack, stroke and myocardial infarction. |
|
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Term
| GPIIb–IIIa antagonists, small-molecule antagonists inhibit |
|
Definition
| GPIIb–IIIa antagonists, such as the monoclonal antibody abciximab and the small-molecule antagonists eptifibatide and tirofiban, inhibit platelet aggregation by preventing activation of GpIIb–IIIa, leading to decreased platelet cross-linking by fibrinogen. |
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