Difference between revisions of "Innate Immunity Cellular Responses"

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==Introduction==
 
==Introduction==
  
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[[Image:LH Macrophage Histology.jpg|thumb|right|200px|<p>'''Macrophage'''</p><sup>© Nottingham Uni</sup>]]
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[[Image:LH Macrophage Histology.jpg|thumb|right|125px|<p>'''Macrophage'''</p><sup>© Nottingham Uni</sup>]]
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Pathogens can invade the body if a breach occurs in the barriers formed by the skin and mucus membranes, for example a wound, they must be detected and destroyed by cellular and [[Humoral Factors of Innate Immune System|humoral]] means.<br />
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* If pathogens breach the barriers formed by the skin and mucus membranes, they must be detected and destroyed by cellular and humoral means  
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<br />
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* The cells involved with innate protection are:
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The cells involved in the cellular response to a wound are:
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** Blood granulocytes, or Polymorphonuclear Cells
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* Tissue [[Mast Cells|mast cells]] and '''[[Macrophages|macrophages]]''' that initially [[Phagocytosis|phagocytose]] and detect [[Bacteria|bacteria]] or [[fungi]]<br />
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*** Notable for their multi-lobed nuclei
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<br />
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*** '''Neutrophils''': phagocytose bacteria
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* The blood [[Blood Cells - Overview#White Blood Cells|granulocytes]], or polymorphonuclear (PMN: multi-lobed nuclei) cells
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*** '''Eosinophils''': kill parasites by the release of granules
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** The '''[[Neutrophils|neutrophils]]''' are the most abundant as they are the primary cells that phagocytose bacteria, and the larger fungi
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*** '''Basophils/ mast cells''': kill parasites by the release of granules
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** The '''[[Eosinophils|eosinophils]]''' and '''[[Basophils|basophils]] / [[Mast Cells| mast cells]]''' are only needed in rare circumstances as they are for killing parasites by the release of granules (exocytosis).
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** Blood '''[[Monocytes|monocytes]]''': phagocytose bacteria
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<br />
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** Tissue mast cells and '''macrophages''': phagocytose bacteria
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* Blood '''[[Monocytes|monocytes]]''': phagocytose bacteria
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*Effectively, innate cellular response seeks to hold off the infection until the [[Adaptive Immune System|adaptive response]] can back it up with a more specific attack
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<br />
 
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The main role of the innate cellular response is to delay systemic infection until the [[Adaptive Immune System|adaptive response]] can back it up with a more specific attack.
 
  
 
==[[Macrophages|Macrophages]]==
 
==[[Macrophages|Macrophages]]==
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[[Image:Monocytes.jpg|thumb|right|200px|Monocytes - J. Bredl, RVC 2008]]
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[[Image:Monocytes.jpg|thumb|right|150px|Monocytes - J. Bredl, RVC 2008]]
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The innate cellular response begins with recognition and phagocytosis by macrophages that precide in the tissue where the wound occurs. The populations of distinct, tissue-specific macrophages that are present are the:
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*The role of macrophages in Innate Immunity is to act as primary '''phagocytes'''
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* Alveolar macrophages (lung)
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* Macrophages are present within tissues and take the form of distinct, tissue-specific populations:
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* Tissue histiocytes
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** Alveolar macrophages
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* Glomerular macrophages (kidney)
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** Tissue histiocytes
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* Hepatic Küpffer cells (liver)
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** Glomerular macrophages
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* CNS microglia (central nervous system: brain and spinal cord)
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** Hepatic Küpffer cells
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* Sinus-lining macrophages of the lymph nodes and spleen
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** CNS microglia
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<br />
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** Sinus-lining macrophages of the lymph nodes and spleen
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* [[Monocytes|'''Monocytes''']] (immature macrophages) are circulating phagocytes
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When [[Phagocytosis|phagocytosis]] of the bacteria or fungi by the tissue macrophages occurs, they release a number of [[Cytokines|cytokines]] that have many effects. The first being the activation of the endothelium that results in the expression of adhesion molecules that allow leukocytes, in particular the [[Neutrophils|neutrophils]] to bind to the endothelium from the bloodstream and the subsequent [[Neutrophils#Exocytosis|extravasation]] (movement out of the bloodstream). Once the leukocytes are out of the bloodstream, the cytokines released by the tissue macrophages act as chemoattractants that enable the chemotaxis of the leukocytes to the site of infection. 
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** Circulate for 6-8 hours  
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<br />
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** Can function as phagocytes within the blood and as newly migrated cells in tissues
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<br />
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** Chiefly function to replace the various tissue macrophage populations
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[[File:Extravasation with Macrophage.png|thumb|right|300px|Diagrammatic Representation of the Innate Immunity Cellular Response - R.J.Francis, RVC 2012]]
 
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The [[Monocytes|'''Monocytes''']] are immature macrophages that are circulating phagocytes. They circulate for 6-8 hours and function as phagocytes within the blood and as newly migrated cells in tissues. Their primary function, however, is to replace the various tissue macrophage populations at the latter stages of the immune response.
 
  
 
==[[Neutrophils|Neutrophils]]==
 
==[[Neutrophils|Neutrophils]]==
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[[Image:Neutrophil 2.jpg|thumb|right|200px|Neutrophils - J. Bredl, RVC 2008]]
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[[Image:Neutrophil 2.jpg|thumb|right|150px|Neutrophils - J. Bredl, RVC 2008]]
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[[Neutrophils|Neutrophils]] are the principal, highly active '''[[Phagocytosis|phagocytes]]''' in the blood and comprise 30-70% of all white blood cells depending on species. Their main function is to kill and digest microbes in a similar way as macrophages. They also have another function of extracellular bacterial killing by disrupting bacterial membranes by the secretion of small antibacterial peptides, for example defensins and bactenecins.
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* Neutrophils are the principal, highly active '''phagocytes''' in the blood
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<br />
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** Comprise 30-70% of white blood cells depending on species
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<br />
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** Kill and digest microbes in a similar way as macrophages
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Neutrophils also produce vasoactive peptides, for example, histamine and bradykinin which, as their name suggests, activate the endothelium to become more "leaky" causing a great increase in extravasation of blood granulocytes and [[Monocytes|monocytes]], and the diffusion of plasma proteins to the site of infection. These peptides, released from other cells as well as neutrophils, are responsible for the classical signs of [[Inflammation - Introduction|inflammation]]: redness ('''rubor'''), heat ('''calor'''), swelling ('''tumour'''), and pain ('''dolor'''), often accompanied by loss of function. Neutrophil activation in an inflammatory lesion also results in the release of '''prostaglandins''' which are responsible for vasoactive changes and for pain (N.B. These are reduced with cyclo-oxygenase (COX) inhibition for example with the [[NSAIDs|NSAIDs]] (non-steriodal anti-inflammatory drugs) aspirin and ibuprofen).
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* Neutrophils can also cause extracellular bacterial killing by disrupting bacterial membranes
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<br />
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** Secrete small antibacterial peptides
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<br />
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*** E.g. defensins and bactenecins
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It is for the reasons above that neutrophils have been described as the archetypal cell associated with [[Acute Inflammation - Introduction|acute inflammation]].
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* Neutrophils produce vasoactive peptides
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<br />
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** E.g. histamine and bradykinin
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<br />
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** Cause a great increase in extravasation of blood granulocytes and [[Monocytes|monocytes]] and plasma proteins at the site of infection
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To move the neutrophils from the blood to the sites of inflammation a system of various chemoattractants exist. These include [[Complement|complement components]], in particular C3a and C5a; [[Cytokines|cytokine]] production, in particular the chemokine class of cytokines, for example CXCL8 (IL-8); and the activation of the endothelium of post-capillary venules.
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* Neutrophils are the archetypal cell associated with [[:Category:Inflammation|acute inflammation]]
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<br />
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** Are attracted to sites of inflammation by:
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<br />
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*** Complement activation
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Their removal from the site after the removal of infection is an important step in the resolution of the lesion. Under physiological conditions the neutrophils undergo a process called '''apoptosis''' (or ''Programmed Cell Death''), and are then cleared by [[#Macrophages|tissue macrophages]] (see above). However, if there are too few macrophages to clear the cells, or the infection is resulting in the death of the neutrophils, they undergo a process called '''necrosis'''. When these neutrophils that have undergone necrosis accumulate at the site of infection it forms '''pus'''.
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*** Cytokine production
 +
*** Changes to vascular endothelium
 +
** Neutrophil activation in an inflammatory lesion results in the release of '''prostaglandins'''
 +
*** Responsible for vasoactive changes and for pain
 +
* The accumulation of dead and dying [[Neutrophils|neutrophils]] at the site of infection is called '''pus'''
 +
** Their removal from the site after the removal of infection is an important step in the resolution of the lesion
  
 
==[[Eosinophils|Eosinophils]]==
 
==[[Eosinophils|Eosinophils]]==
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[[Image:Eosinophil.jpg|thumb|right|200px|Eosinophil - J. Bredl, RVC 2008]]
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[[Image:Eosinophil.jpg|thumb|right|150px|Eosinophil - J. Bredl, RVC 2008]]
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Eosinophils are less common than [[Neutrophils|neutrophils]], with eosinophils making up less than 5% of the leukocytes in normal blood. They are still described as granulocytes but they are not phagocytic.
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* Eosinophils are less common than [[Neutrophils|neutrophils]], and they are not phagocytic
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<br />
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** Make up <5% of the leukocytes in normal blood
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<br />
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* Eosinophil numbers are increased:
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It has been found that eosinophil numbers are increased slightly during the resolution phase of inflammation, but many-fold in parasite-infected animals. It is therefore the presence of a large proportion of eosinophils in a blood smear that is highly indicative of parasitaemia.
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** Slightly during the resolution phase of inflammation
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<br />
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** Many-fold in parasite-infected animals
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<br />
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*** The presence of a large proportion of eosinophils in a blood smear is highly indicative of parasitaemia
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The eosinophils mainly function by targeting the surface of parasites by means of a specific [[Immunoglobulins|antibody]] or [[Complement|complement component]]. Once the parasite has been recognised the eosinophils release, through a process called exocytosis (the fusion of granules to the plasma membrane), a large range of toxic molecules that break down the parasite integument.<br />
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* Mainly function by targeting the surface of parasites by means of specific antibody or complement
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<br />
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** Release a large range of toxic molecules that break down the parasite integument
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Intrestingly, eosinophils are also prominent in [[:Category:Allergic Diseases|allergic]] (anaphylactic) reactions.
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* Prominent in [[:Category:Allergic Diseases|allergic]] (anaphylactic) reactions
  
 
==[[Basophils|Basophils]] / [[Mast Cells|Mast Cells]]==
 
==[[Basophils|Basophils]] / [[Mast Cells|Mast Cells]]==
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[[Image:Basophil and Lymphocyte.jpg|thumb|right|200px|Basophil - J. Bredl, RVC 2008]]
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[[Image:Basophil and Lymphocyte.jpg|thumb|right|150px|Basophil - J. Bredl, RVC 2008]]
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The basophils and the mast cells are principally localised at epithelial surfaces with very small numbers present in blood, making up less than 0.5% of circulating leukocytes.
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* Basophils/mast cells are principally localised at epithelial surfaces
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<br />
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** Very small numbers are present in blood
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<br />
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*** Less than 0.5% circulating leukocytes
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These two cell types have two principal functions:
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* They have two principal functions:
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<br />
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*# Induction of [[:Category:Inflammation|acute inflammation]]
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<br />
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*#* Trauma and/ or bacterial infection causes the production of '''cytokines''' by the mast cells that induce a classical acute inflammatory response
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The first is the induction of [[Acute Inflammation - Introduction|acute inflammation]]. They do this through the production of '''[[Cytokines|cytokines]]''' by the mast cells in response to trauma and/or bacterial infection which then induces a classical acute inflammatory response.
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*# Response to parasite infection
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<br />
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*#* Specific [[Immunoglobulins|IgE]] binds cells
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<br />
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*#* Subsequent contact with antigen causes the mast cells to degranulate
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The second is to respond to parasite infection. They do this specifically by interacting with the Fc region of the [[IgE|IgE]] class of antibody. When the IgE then comes into contact with antigen, Fc receptors on the surface of the mast cells and basophils can interact with the antibody which causes the mast cells and basophils to degranulate. This causes the release of enzymes and vasoactive substances that can result in a high level of mucus secretion and smooth muscle contraction. As the granules contain a much greater concentration of these peptides, the degranulation of mast cells and basophils creates a much more powerful response than that by neutrophils alone (it is for this reason that they can cause [[Type I Hypersensitivity|Type I hypersensitivity reactions]]). These cells also produce factors that influence local host cell physiology
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*#* Release enzymes and vasoactive substances that can result in a high level of mucus secretion and smooth muscle contraction
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and various mediators that increase the ratio of phagocyte to microbe (in particular [[Cytokines|cytokines]]).
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* Also produce factors that influence local host cell physiology
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<br><br>
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** Various mediators increase the ratio of phagocyte to microbe
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{{Robert J Francis
 
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|date = May 3, 2012}}
 
  
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{{Jim Bee 2007}}
 
 
[[Category:Innate Immune System]]
 
[[Category:Innate Immune System]]
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[[Category:Robert J Francis reviewed]]
 

Revision as of 15:59, 13 August 2010

Introduction

Macrophage

© Nottingham Uni
  • If pathogens breach the barriers formed by the skin and mucus membranes, they must be detected and destroyed by cellular and humoral means
  • The cells involved with innate protection are:
    • Blood granulocytes, or Polymorphonuclear Cells
      • Notable for their multi-lobed nuclei
      • Neutrophils: phagocytose bacteria
      • Eosinophils: kill parasites by the release of granules
      • Basophils/ mast cells: kill parasites by the release of granules
    • Blood monocytes: phagocytose bacteria
    • Tissue mast cells and macrophages: phagocytose bacteria
  • Effectively, innate cellular response seeks to hold off the infection until the adaptive response can back it up with a more specific attack

Macrophages

Monocytes - J. Bredl, RVC 2008
  • The role of macrophages in Innate Immunity is to act as primary phagocytes
  • Macrophages are present within tissues and take the form of distinct, tissue-specific populations:
    • Alveolar macrophages
    • Tissue histiocytes
    • Glomerular macrophages
    • Hepatic Küpffer cells
    • CNS microglia
    • Sinus-lining macrophages of the lymph nodes and spleen
  • Monocytes (immature macrophages) are circulating phagocytes
    • Circulate for 6-8 hours
    • Can function as phagocytes within the blood and as newly migrated cells in tissues
    • Chiefly function to replace the various tissue macrophage populations

Neutrophils

Neutrophils - J. Bredl, RVC 2008
  • Neutrophils are the principal, highly active phagocytes in the blood
    • Comprise 30-70% of white blood cells depending on species
    • Kill and digest microbes in a similar way as macrophages
  • Neutrophils can also cause extracellular bacterial killing by disrupting bacterial membranes
    • Secrete small antibacterial peptides
      • E.g. defensins and bactenecins
  • Neutrophils produce vasoactive peptides
    • E.g. histamine and bradykinin
    • Cause a great increase in extravasation of blood granulocytes and monocytes and plasma proteins at the site of infection
  • Neutrophils are the archetypal cell associated with acute inflammation
    • Are attracted to sites of inflammation by:
      • Complement activation
      • Cytokine production
      • Changes to vascular endothelium
    • Neutrophil activation in an inflammatory lesion results in the release of prostaglandins
      • Responsible for vasoactive changes and for pain
  • The accumulation of dead and dying neutrophils at the site of infection is called pus
    • Their removal from the site after the removal of infection is an important step in the resolution of the lesion

Eosinophils

Eosinophil - J. Bredl, RVC 2008
  • Eosinophils are less common than neutrophils, and they are not phagocytic
    • Make up <5% of the leukocytes in normal blood
  • Eosinophil numbers are increased:
    • Slightly during the resolution phase of inflammation
    • Many-fold in parasite-infected animals
      • The presence of a large proportion of eosinophils in a blood smear is highly indicative of parasitaemia
  • Mainly function by targeting the surface of parasites by means of specific antibody or complement
    • Release a large range of toxic molecules that break down the parasite integument
  • Prominent in allergic (anaphylactic) reactions

Basophils / Mast Cells

Basophil - J. Bredl, RVC 2008
  • Basophils/mast cells are principally localised at epithelial surfaces
    • Very small numbers are present in blood
      • Less than 0.5% circulating leukocytes
  • They have two principal functions:
    1. Induction of acute inflammation
      • Trauma and/ or bacterial infection causes the production of cytokines by the mast cells that induce a classical acute inflammatory response
    2. Response to parasite infection
      • Specific IgE binds cells
      • Subsequent contact with antigen causes the mast cells to degranulate
      • Release enzymes and vasoactive substances that can result in a high level of mucus secretion and smooth muscle contraction
  • Also produce factors that influence local host cell physiology
    • Various mediators increase the ratio of phagocyte to microbe
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