T Cell mediated immunity Tatiana Scorza Stfany Bazinet

T Cell mediated immunity • Tatiana Scorza • Stéfany Bazinet • Dept. Sciences Biologiques,

T Cell mediated immune responses The importance of T cell mediated immunity in selfdefence has been underlined by numerous examples of T cell deficiencies: • For instance, children with the syndrome of Di. George (absence of thymus since birth) do not have T cells • These children are vulnerable to any type of infection controlled by T cells • AIDS is also a consequence of the elimination of T cells; people with AIDS die because their immune system fails to function properly

Why is T cell-mediated immunity important? • T cells are responsible for the induction of specific and long-lasting defences to intracellular microbes: viruses, bacteria, protozoa • T cells are also responsible for the induction of specific and long-lasting defences to extra-cellular microbes: bacteria, fungi

How are T cells distinguished? • T cells belong to a group of white blood cells known as lymphocytes expressing a special receptor on their surface called the T cell receptor (TCR) • The abbreviation "T", in T cell, stands for thymus since it is the organ where T cells develop and differentiate

The T cell receptor plays an important role in T cell activation • The TCR serves to recognize little pieces of proteins (peptides) derived from pathogens/microbes, that are presented by antigen presenting cells or target cells (cells infected with the pathogen) on their surface • The TCR can only “see” these peptides if these are combined to molecules from the Major Histocompatibity Complex (MHC) on the surface of specialized cells called antigen-presenting cells or target cells • In absence of MHC molecules, the T cell cannot “see” the peptides, and fails to know that an intruder is in our body

T cell PEPTIDE FROM DIGESTED BACTERIA BOUND TO MHC CLASS II Video 1 : APC: T cell interaction

What happens when a T cell sees the peptide-MHC complex? 1. The T cell will become activated. 2. The T cells multiplies: a single cell will produce many cells, all capable of reacting against the same pathogen 3. The T cell will secrete substances that activate other cells (i. e. macrophages) and help them in the destruction of the pathogens or may help B cells to produce antibodies; in this case we call this T cell a T helper cell 4. Other types of T cells will bind directly to cells with pathogens inside and kill them; in this case we call these T cells cytotoxic T cells

Cytotoxic T cells will kill infected cells T helper will help other cells to produce protective substances such as antibodies B B cell messengers (Video 2: T cell killing)

How do we distinguish T helper cells from cytotoxic T cells? • T helper cells, apart from their TCR, express a molecule called CD 4 on their surface; we call these cells CD 4+ T cells • Cytotoxic T cells, apart from their TCR, express a molecule called CD 8 on their surface; we call these cells CD 8+ T cells • CD 4+ and CD 8+ T cells do not detect the same type of peptide-MHC complex

Infected cell

Where do T cells originate? • T cells originate from stem cells in the bone marrow • The T cell progenitor cells derived from stem cells migrate to the thymus and become thymocytes • New born thymocytes will go through a long process of differentiation to then become mature T cells • Mature T cells will either be CD 4 T cells or CD 8 T cells

Thymocytes will become T cells only if: • They express a TCR that can recognize our own MHC molecules: this will allow them to become activated only by our own antigen cells whenever they show peptides from pathogens • They have a TCR that will not react with a self-peptide (from any normal protein in our body): this avoids auto reactive immune responses • If thymocytes respond to these two criteria they become mature and leave thymus in search for signs indicating that pathogens are present • If they fail to respond to these two criteria they die in the thymus

Memory T cells assure rapid long-term protection • When T cells are activated, they act immediately to destroy the pathogen or help other cells to do so but • They also give raise to a population of memory T cells that will persist in the body, awaiting for a second encounter with the same pathogen • This second encounter may take place years after the initial contact and in this case, • memory T cells will respond quickly to destroy the intruder: this provides long-lasting and specific protection

Regulatory T cells Apart from T helper cells and cytotoxic cells, there is a third group of T cells with regulatory properties These T cells, called regulatory T cells participate in the prevention of autoimmune responses

Why are regulatory T cells important? • Some T cells capable of reacting with self-peptides (our own proteins) leave thymus (escape the inspection) • Regulatory T cells recognize these auto reactive T cells and induce their death by apoptosis or paralyze them • In absence of regulatory T cells we would develop auto-immune responses that would destroy our own tissues

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