Cell Mediated Immunity - CMI

Cell groups share in CMI

1-Group A-non specific cells Phagocytic cells e.g Macrophages

2-Group B – APC: DC-1

3-Group C-T-lymphocytes:  including Th1 – CD4 Th1 – CD8 T cytotoxic

4-Mediators: IL-2, IL12, IFNδ

Intercellular Ag attacked by 2 ways:

1-Non-specific

Activated macrophages: in infected host activated macrophage has phagocytic killing power 100 time more than normal macrophages in non-infected host

Phagocytic pathway: by macrophage and dendritic cells

2-Specific

T-cytotoxic cells --- specific CD-8 T lymphocytes responsible for destruction infected cells containing m.o

Endogenous pathway

When the pathogen escape phagocytosis e.g. HIV

Hepatitis virus infect its target cell ---Hepatocyte

                                 Viral protein released inside Hepatocytes

                              Before assembly to virion it undergo

                         Viral protein bind to intercellular protein Upiquitin

                          Viral protein become labeled as Ubiquitinated viral protein

                          Transfer to proteasome (Tubular enzymatic structure)

               Fragmentation of ubiquitinated viral protein into small peptides in the proteasome

                            Release of of fragmented ubiquitinated viral protein in the cytoplasm

                                   Transfer Associated Protein ( TAP1&TAP2)

                 Transfer of small viral peptides into the lumen of endoplasmic reticulum(ER)

                  Binding of small viral peptides with newly synthesized MHC-I inside ER

             Release of vesicles of MHC class I-peptide complex to the cytoplasm

                            Vesicles passé through golgi apparatus

                           Release of MHC-I with viral peptides on Hepatocyte surface

 Exogenous pathway

When viral infect other cells, e.g.  Dendritic cell type-1(DC-1) that can express both arms MHC II and MHC1 on its surface

TLRs present in sentinel cells e.g DC-1 bind to specific epitope will define both the releasing cytokines together with the use of MHC-1 or MHCII or both   

a-MHC II arm

The viral protein constitute inside the infected -DC1

DC-1 act as APC process viral protein and display it through its surface via MHC-II

MHC II stimulate Th1 that connected to DC-1 through TCR & CD4 (2signals)

Moreover DC-1 stimulates Th1 through secretion of cytokine IL-12 (3^rd signal)

Th1 undergoes proliferation and differentiation

Effector Th1                                    Memory Th1

Secrete cytokines

IL2-IFN Ɣ

Stimulate CD8 T cytotoxic in the lymph node

CD8 T cytotoxic migrates and attacks the infected cells through binding its TCR and CD8 to MHC1 with viral peptide on surface of infected hepatocyte

Destruction of the infected cell through

Perofrin make pores in the target cell membrane then Ganzym enter the pores hydrolyses the nucleic acid of infected cell

b- MHC 1 arm

On the other hand CD8 cytotoxic bind to DC1 MHC1 arm through TCR and CD8(2 signals)

And activated by cytokines from Th1 IL2-IFN Ɣ ( other 2 signals)

T cytotoxic undergoes proliferation and differentiation into:

Effector T cytotoxic                             Memory T cytotoxic

Effector CD8T cytotoxic leave lymph node to circulation and migrate to the infected hepatocyte,

And most prominently that epitope presented by DC-1 will define the type of effector CD8 cytotoxic cell

2 different pathway of killing infected hepatocyte:

1- CD8 T cytotoxic migrates and attacks the infected cells through binding its TCR and CD8 to MHC1 on surface of infected hepatocyte

Destruction of the infected cell through

Perofrin make pores in the target cell membrane then Ganzym enter the pores hydrolyses the nucleic acid of infected cell

2-Any cell has FAS which is known as death receptor, CD8 T cytotoxic secrete CD 95 that bind to FAS ,

Fragmentation and shrinkage of DNA of infected cell (Blebbing) death without necrosis