TYPE IV HYPERSENSITIVITY

Type 4 hypersensitivity, detailed description of type 4 hypersensitivity mechanism, CD8 cells role, and CD4 cells activity

1. TYPE IV HYPERSENSITIVITY -M QASIF MASIS -B841305 -II MSc

2. HYPER SENSITIVITY Several environmental antigens may stimulate an adaptive immune response, immunologic memory These overreactions of the immune system to harmless environmental antigens is called hypersensitivity This may produce tissue injury and other serious diseases, often referred to as auto-immune diseases In other words hypersensitivity means that our immune system reacts to something in such a way that it ends up damaging itself instead of protecting it

3. TYPES OF HYPERSENSITIVITY There are 4 types of hypersensitivity, based upon the effector mechanisms by which they are produced-

4. TYPE IV HYPERSENSITIVITY This type of hypersensitivity is mediated by antigen specific effector T-cell The duration between exposure to antigen and the response is about 48-72 hours , hence it is also referred to as delayed type hypersensitivity In type-IV hypersensitivity, cytotoxic CD8 T-cells and helper T-cells (CD4) leads immunogenic response

5. CONTD. Antigen is picked up antigen presenting cells(APCs) i.e. dendritic cell or macrophages Carried to nearest lymph mode Where this APC present antigen using either MHC-II or MHC-I receptor

6. CD4 T-CELL MEDIATED TYPE IV HYPERSENSITIVITY APC present antigen using MHC-II receptor, serving platter for CD4 T-cell T h cell recognise antigen and binds to it using co-receptor arm (CD4 arm) T h cell also produces CD28 protein that binds to B7 protein on the surface of APC APC releases IL-12 cytokines that matures T h cell into T h 1 cell T h 1 cell relese IL-2 cytokines that helps in proliferation of T h 1 cells Also releases IFN  that activates macrophages and creates more T h 1 cells

7. CONTD. Also macrophages releases cytokines like TNF, IL1, IL6 These cytokines causes leakiness in endothelial barriers and more immune cells are recruited, leading tp redness edema , and sometimes fever Lysosomal enzymes, reactive oxygen species are also produced that leads to tissue damage

8. EXAMPLES D ermatitis- caused by poison ivy or by wearing iron or nickel Apart from skin diseases, systemic diseases like multiple sclerosis where T h 1 cells damage myelin around nerve fibre Tuberculin reaction- if person is exposed to tuberculosis previously, T h 1 cells migrate to reaction site and inflammatory response, that makes skin thick and hard

9. These are killer T-cells, these cells destroys cell directly APC present antigen on MHC-I molecule (present on every nucleated cell) MHC-I molecule present antigen present inside the cell E.g.- Virus infected cells, cancerous cells After CD8 cell binds to antigen , CD8 cell releases cytokines perforin and granzymes Perforin forms pores in cell membrane and granzymes enters cell that induces apoptosis CD8 T-CELL MEDIATED TYPE IV HYPERSENSITIVITY

10. Fig.- CD8 cell in action

11. EXAMPLES- Hashimoto thyroiditis- where CD8 cells attack thyroid epithelial cells Type 1 Diabetes- CD8 cells target pancreatic  -cells