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C4-05 Complement and Mediators of Inflammation
I don't even know anymore.
17
Immunology
Professional
10/30/2010

Additional Immunology Flashcards

 


 

Cards

Term




Inflammation 101

Definition

-The inflammatory response is a process that occurs when tissues are injured by bacteria, trauma, or toxins.


-It is a localized, protective response of the microcirculation designed to destroy, dilute, or wall-off injurious agents before substantial tissue damage ensues.


-Characterized by the “classic” signs :


redness  (rubor)
heat  (calor)
swelling  (tumor)

pain  (dolar)

Term




Phase I of Inflammation

Definition

Detection:   Tissue macrophages, mast cells and complement components detect infection.

Response:  The induction of multiple inflammatory mediators.

Result:   Dilation and increased permeability of blood vessels, resulting in increased blood flow and leakage of fluid into the affected area.     (redness, heat, swelling)

 

Goal #1: Isolate the foreign substance from further contact with body tissues and from becoming systemic.

Term




Phase II

Definition

-Soluble inflammatory mediators also alter the adhesive properties of the vascular endothelium. 


-Circulating leukocytes are then recruited – they stick to the vessel wall and migrate between the endothelial cells and toward a chemokine gradient in the affected tissue.


Goal #2:Attract phagocytes which can engulf and destroy microorganisms and damaged cells.

 

       (i) neutrophils early, and in large numbers

       (ii) monocytes / macrophages later and in smaller numbers

Term




Recognition of pathogens

Definition

The surfaces of many pathogens bear repeating patterns of carbohydrate or lipid moieties that are not found on the surface of host cells.  Some of these patterns are recognized by pattern recognition receptors :

on the surface of the macrophage:   activate the macrophage directly
-macrophage mannose receptor – sugar molecules
  scavenger receptors – anionic polymers, acetylated lipids

  * toll-like receptors – pattern recognition receptors

secreted proteins:   activate the macrophage indirectly

  mannan-binding lectin – sugar molecules

  C1q – sugar molecules

Term




After encounter with a pathogen, macrophages 

Definition

-and mast cells release multiple types of inflammatory mediators!

Term




Proinflammatory cytokines

Definition

-induce and amplify the inflammatory response.


-The pro-inflammatory cytokines IL-1, IL-6, and TNF-a are produced by macrophages, and are responsible for a wide spectrum of actions that help to coordinate the body’s responses to infection.

Term




IL-6

Definition

-of particular importance in induction of systemic effects including the release of acute phase proteins from the liver.


-Acute phase proteins are secreted by the liver and then move into circulation.

 

-These proteins function much like antibodies, but instead of being epitope-specific, they have broad specificities for pathogen-associated molecular patterns.

Term




Local TNFa

Definition

-is protective, but high quantities of systemic TNFa (e.g., septic shock) can lead to low blood volume, vessel collapse, and disseminated intravascular coagulation.

Term




Lipid mediators

Definition

-primarily act to increase vascular permeability.


-Macrophage activation provides a stimulus to activate phospholipase A2, which then releases arachadonic acid from membrane phospholipids.

 

-The result is production of :

prostaglandins
thromboxane A2
leukotrienes

Term

 

 

 

 Inflammatory mediators 

Definition

-Endothelial cells are normally tightly bound together.  Inflammatory mediators (complement components, TNFa, chemokines, prostaglandins, leukotrienes, and histamine) cause the endothelial cells to separate, resulting in vascular permeability.


-The result is leakage of serum containing more complement components and circulating antibodies.


-These mediators also induce the expression of and activate adhesion molecules that facilitate the recruitment of neutrophils and other immune cells to the site of infection.

 

Term




Neutrophils

Definition

-Not normally present in tissue, but are abundant in the blood.  The influx of neutrophils (in response to IL-8 and other signals) usually peaks around 6 hours after the induction of the inflammatory response.


-These cells are phagocytic, and thus ingest and kill pathogens in much the same way that macrophages do.

Term




Complement:  the simple facts

Definition

-Activation of the system results in a cascade of precursor proteins that are converted to active enzymes – a number of complement proteins are proteases that are themselves activated by proteolytic cleavage. 


-Point #1:   the activation of a small number of complement proteins at the start of the pathway is amplified by each successive reaction, resulting in a large response with multiple effects.


-Point #2:  The precursor proteins (the zymogens) are widely distributed throughout the body (especially in serum) with no adverse effect.  At sites of infection, the system is activated locally and triggers a series of potent inflammatory events that are designed to eliminate the pathogen.

       

Term

 

 

 

Complement Activation (Three Things Can Happen)

Definition

The result is activation of the entire complement system, which has three purposes:

 

1.  opsonization – C proteins covalently bind to pathogens and induce phagocytosis by cells that have C receptors.

 

2.  chemoattraction – small fragments of some C proteins recruit more phagocytes to the site and activate them.

 

3.  killing – C proteins can create pores in the membranes of some bacteria.

Term

 

 

 

No matter what pathway Complement Activation came from.......

Definition

-The three pathways converge at the generation of the critical molecule – C3 convertase.


-(one C3 convertase can cleave as many as 1000 molecules of C3)


In turn, C3 convertase initiates a cascade of events (that are unnecessary to know) leading to the final outcomes.


Important to note – all of this is happening on the surface of the pathogen.   


Term




Opsonization

Definition

-The key protein is C3b – a product of C3 convertase that is bound to the surface of the pathogen.


-Binding of C3b to the receptor, plus binding of soluble complement components initiates the process of phagocytosis.

Term




Biological Functions of Complement :

Activation of the inflammatory response

Definition

-Important to note –  C5a and other soluble complement components can induce a generalized circulatory collapse when produced in large amounts or injected systemically.........

 

resulting in anaphylactic shock.

Term




Inflammatory responses influence the

adaptive immune response

Definition

-When an iDC ingests a pathogen in infected tissue, it becomes activated and then migrates to nearby lymphoid organs.


-The induction of the adaptive immune response occurs when a mature DC presents antigen to T cells and B cells.

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