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علم الاحياء : المناعة :

Immune response

المؤلف:  Zinkernagel, R. M

المصدر:  Medical Microbiology

الجزء والصفحة: 

6-11-2015

1455

Immune response

Immune response is a complex and regulated sequence of events involving several cell types .Its trigger when an antigen enters the body and encounters a specialized class of cells called antigen presenting cells (APC) .The cells (APC) capture a minute amount of the antigen and display it in a form that can be recognized by ag –specific helper T cell . Th cells become activated and promote the activation of other classes of lymphocytes ,such as B cells or cytotoxic T cell .the activated lymphocyte then proliferate and carry out their specific effectors functions ,which in most cases successfully inactivate or eliminate the antigen .

 At each stage in this process ,the lymphocyte and APC communicate with one another through direct contact or secretory regulated cytokine .they also may interact with other cell types or with components of the complement ,kinin ,or fibrinolytic system resulting in phagocytic activation .Responses to most proteinaceous immunogen can being only after immunogen has been captured ,processed and presented by APC  because T cell  recognize only peptide binding with MHC on the surface of other cells ,Th cells is necessary for  all immune response . 

Antigen presenting cells( APC )

This term usually refers only to these specialized cells that bears class II MHC proteins .These  cells are called professional APC include dendritic cell ,Macrophage  and B cells

Characters of dendritic cells 1-present in all tissue 2- important in primary IR 3- capture particulate ag by phagocytosis and small by pinocytosis or by receptor mediated endocytosis ( this pathway can be used by macrophage and B cells ) 4- present in activate form but activated by immunogen

Characters of macrophage 1- present in lymphoid and non lymphoid tissue 2- require opsonized immunogen 3- important in secondary IR .

B cells presented ag only after subsequent exposure to immunogen

Activation of helper T cell

Activation of Th cells require two signals 1- provided by binding of the T cell receptor to the antigen peptide MHC complex on the surface of APC  and its transmitted through the CD3 protein complex 2- costimulatory signal CD28 with B7.1or B7.2 on APC .The two signals induce the helper T cell to begin secreting cytokine known as IL-2 and expressing a specific high affinity IL-2R .

IL-2 is potent mitogenic factor for T cell

Activated B cells/ require two signals 1-specific ag binding   2- activated Th cell ,the most help occurred when protein called CD40  bind with CD40 ligand on Th cell .

Activated T cytotoxic cell 1- provided by binding of the T cell receptor to the antigen peptide MHC class I complex  and its transmitted through the CD3 protein complex.2- activated Th cell to induce high affinity of IL-2R .Tc cells  induces the target cell to commit suicide by apoptosis .the activated Tc also proliferate giving rise to additional Tc .

Mechanism of ag elimination

  1. toxin neutralization antibodies specific for bacterial toxin or for venom of insects or snakes bind these antigenic protein in many cases directly inactivated them by steric effect or by phagocytic
  2. virus neutralization
  3. opsonization and phagocytic activity
  4. Activation of complement
  5. Antibody dependent cytotoxicity
  6. Inflammation inflammatory leading directly or indirectly increase blood flow ,increased vascular permeability ,leakage of fluid into the extracellular space and pain .

Localization of immune response

 the initial response to an immunogen depends partially on it rout of entery into the body 1-.Most immunogen enter through blood stream detected by denderitic cell and macrophage in spleen which become the principle site of the immune response 

2- the skin and subcutaneous connective tissue detected by APC such asepidermal ,langerhans or dermal macrophage and may be carried via the lymphatic circulation into regional lymph nodes

3- mucosal surfaces of respiratory or gastrointestinal tract immediately encounter the submucosal lymphoid tissues which launch a response that is directed both locally and adjacent lumen.

Kinetic aspect of immune response

B cell activity can be easily monitored by the concentrations of specific antibodies in the serum an area of investigation is known serology at any given moment active T and B effector cells account for roughly 1% of the total lymphoid population in a normal host . these belong many different clones , most of which are probably involved ,low level IR against many ag encounter every day life ,as a result  the serum of normal healthy adult contains innumerable different types of ab each is present in only minute amounts about 20% serum protein each of those provides low level of protection against specific ag when a person or animal is exposed to significant amount of ag and mount B cell response .the concentration of serum ab against ag rises .serum from such immunized individual is often called specific antisera .It is important to remember , An individual is first encounter with a particular immunogen is called a priming event and lead to a relatively weak ,short lived response designated the primary immune response .This is divisible into several phases .The lag or latent phase is the time between the initial exposure to an immunogen and the detection of antibodies in the circulation which average about 1 week in human ,during this period activation of T and B cell is taking place . the exponential phase is marked by rapid increase in the quantity of circulating ab and reflects the increasing numbers of secretory plasma cells . after an interval during which the ab level remains relatively constant because seretion and degredation are occurring in at equal rates ( the steady state or plateau phase ) the ab level gradually declines (declining phase ) .the decline indicates that new plasma cells are no longer being produced and exciting plasma cells are dying or ceasing ab production .thus the duration of a humoral immune response is limited by the duration of ag stimulation and by short life spans of the plasma cells involved in response subsequent encounters the same immunogen lead to responses that similar to the primary response but marked quantitative differences .In a uch secondary or anamnestic ,IR ,lag is short ,ab levels rise more rapidly to much higher steady state level ,thereafter remaining in the      serum at detectable levels for much longer period .the large number of ag specific memory T and B cells generated during the primary response are responsible for the rapid kinetic and the greater intensity and duration of secondary responses .

 

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