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TYPE 4 (T CELL-MEDIATED) HYPERSENSITIVITY-Delayed Type and Cell Mediated Cytotoxicity-Mechanism and Diseases

It is initiated by activated T-lymphocytes (Either helper T cells or cytotoxic T cells).
On the basis of this it has two forms:
1)-Delayed type hypersensitivity (mediated by helper T or CD4+ T cells)
2)-T-cell mediated cytotoxicity (mediated by CD8+ T cells or Cytotoxic T Cells)

1)- Delayed-type hypersensitivity (mediated by helper T or CD4+ T cells)

Mechanism: It is exemplified by tuberculin reaction in which the person is exposed first to protein antigens of Tuberculosis Bacilli. As their degradation is difficult, therefore they are taken by the macrophages and presented with MHC type II molecules to naïve CD4+ T cells which recognize them and are activated by differentiation to TH1 cells ( Helper T cells type 1) These TH1 cells secrete various cytokines like IL-2, IL-12, IFN-gamma, TNF and chemokines. All these mediators and factors help in strengthening the cellular immune response that is, recruitment of monocytes which transform to macrophages, epithelioid cells, giant cells and granuloma formation, thus eliminating the antigen (protein of T.Bacilli in this case).
Merits: This form of type IV hypersensitivity has a major defensive role against various intracellular pathogens like mycobacteria, fungi, certain parasites and is also involved in tumour immunity.
Demerits: Besides its beneficial role it can also cause transplant rejection, contact dermatitis, type 1 D.M, and multiple sclerosis when the TH1 cells attack the autologous tissue antigens.
type 4 hyper sensitivity image

2)-T-cell mediated cytotoxicity (mediated by CD8+ T cells)

Mechanism: In this form of cell-mediated hypersensitivity the antigen is presented by APC (Antigen Presenting Cells) in association with type I MHC molecules to naïve CD8+ T cells. These naïve CD8+ T cells recognize the antigen and are activated now called sensitized or activated cytotoxic T cells (CD8+ T cells). They attack and kill the antigen-bearing cells i.e. Virus-infected cells or tumour cells. They perform this function by two mechanisms.
1; Perforin granzyme dependent killing and
2;.Fas-Fas legend dependent killing.
Merits: Eliminate tumour cells and various virus-infected cells.
Demerits: Plays role in transplant rejection.

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