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04. Component of CELL MEDIATED IMMUNITY

  Component of CELL MEDIATED IMMUNITY MHC MOLECULES Antigen presenting cells(APC) T helper cells(T H ) and T cytotoxic c...

 

Component of CELL MEDIATED IMMUNITY

  1. MHC MOLECULES
  2. Antigen presenting cells(APC)
  3. T helper cells(TH ) and T cytotoxic cells(TC )

 

A. MHC MOLECULES-(Human leucocyte antigen= HLA)

 

1) MHC molecules are found on the surface membranes of cells.

2) There are 2 CLASSES of MHC molecules

 

 

CLASS II MHC MOLECULES

CLASS II MHC MOLECULES

Found on:

all nucleated cells of the body

Surface of ANTIGEN PRESENTING CEELS (dendritic cells, macrophages and B cells),sperm

3 types:

HLA-A, HLA-B and HLA-C

HALA-DP,HLA-DQ and HLA-DR

Inherited:

Co-dominantly from parents so each has 2 set of gens on chromosome 6,
Also 2set of MHC Class I/II molecules found on the surface of our cells.

polymorphic genes:

large umber of alleles for the MHC Class I & class II genes

e.g. : HLA-A1, HLA-A2, HLA-A3 ,

e.g. : HLA-DR4, HLA-DR6
(2-12 different DR ,DP ,DQ  molecules )

Composition :

α chain and small polypeptide called β2 microglobulin.

α chain and β chain

Bind to:

Large number of different linear peptides (peptide antigen bind to peptide binding groove )
Then (peptide antigen + MHC Class I/II molecule) interact with the T cell receptor.

 

3) HAPLOTYPE: The set of genes inherited from one parent on one chromosome

4) GENOTYPE: both HAPLOTYPE together (one the each parent )

5) Genetic polymorphism: multiple forms of the same gene in one population

6) Different individuals have different genotypes and express different MHC molecules on their cells.

7) However every cell in a single individual expresses the same MHC molecules.

8) The host cell bind peptide antigens derived from within the cell.

9) If the cell is infected with a pathogen, peptides from the pathogen are also bound to the MHC, molecules.

10) This MHC/peptide complex can interact with a T cell receptor.

11) Then the T cell act to eliminate the intracellular pathogen.

12) The MHC is the most highly polymorphic gene system in the body and there is a diversity of MHC molecules within the population.

13) This ensures that each individual is capable of presenting a wide rang of peptide antigens derived from pathogens to the T cell receptor

 

T helper cells(TH ) ,T cytotoxic cells(TC ) and Antigen presenting cells(APC)

image

 

 

T HELPER CELLS (TH cells):

T Cytotoxic cells(TC )

surfaces marker :

CD4 marker

CD8 marker

antigen reorganization

  • TCR bind to (Antigen + MHC class II molecules) on Antigen presenting cells(APC)
  • Also, the CD4 molecule on the TH cell binds to the MHC Class II molecule.
  • TCR bind to (Antigen + MHC class I molecules) on Antigen presenting cells(APC)
  • Also, the CD8 molecule on the TC cell binds to the MHC Class I molecule.
  • They can recognize antigen when its present by any nucleated cell of the body

Type of antigen :

Exogenous antigens
because recognizes-antigens derived from phagocytosed pathogens

Endogenous antigens
Only recognizes antigen derived from protein synthesized in the cytoplasm (virally infected cells )

Functions :

Synthesizing and secreting CYTOKINES.

  • IL-2, IFN-γ and TNF-α by (Th1 cells)→development of delayed type hypersensitivity responses
  • IL-4, IL-5 and IL-10 by (Th2 cells ) promote allergic responses
  • Cytokines like gamma interferon activate macrophages and make them more efficient phagocytes.
  • Cytokines like IL-2 "help" T cells to proliferate and differentiate
  • Cytokines like IL-4  and gamma interferon "help" B cells to become activated and to proliferate and differentiate into plasma cells.
  • Promoted class switching of antibodies from IgM to other isotypes.
  • Cytokines activate NK cells, mast cells, eosinophils.
  • Cytokines like (GM -CSF) stimulate the bone marrow to produce more granulocytes and monocytes/macrophages.
  • Cytokines like gamma interferon  and IL-4  regulate the immune response by activating or suppressing effector cells.

 

  • Cytotoxic T cells act by killing all nucleated infected cells (LYSE the infected cells)(CYTOTOXICITY).
  • killing tumour cells and also in mediating graft rejection

 

The pathogen(virus) will generate foreign peptides in the cytoplasm →associate with MHC Class I molecules. →Expression peptide-MHC Class I complexes at the cell surface leads → recognition by cytotoxic T cells →killing of the infected cell.

 

Antigen presenting cells(APC) –(dendritic cells and macrophages)

  • These cells take up pathogens intracellularly
  • process pathogen proteins into linear peptide antigens
  • conjugate the antigens with Class II MHC molecules and display them on the surface membranes.