Immunology

Lecture- 5

Adaptive Immunity

T- cell

Cell Mediated Immunity

• An adaptive immunity mediated by response specific cells of immune system, that recognize foreign

antigens on the surface of cells, organisms or tissues.

• T cell have an antigen receptor that recognize and react to a specific antigen ( T cell receptor)

• Requires constant presence of antigen to remain effective

- Involves cytokines

T lymphocytes ( T- cell) ( The main agent of cellular immunity)

Helper T cell Cytotoxic T cell

• T-cell do not produce antibody but instead attack foreign antigen directly

• T cell regulate the proliferation and activity of other cells of immune system: B cell, macrophages,

neutrophil and natural killer cells

• Each type of T cell

• Respond to different types of antigen presenting cells ( dendritic cells, macrophages, B cells) • Activated by different antigen presentation • has different effector function

T- Cell

• Principle function of T cells

• response and eliminate intracellular pathogen and expressing foreign antigens.

• Eliminate tumor cells

• Native T cell circulate between blood stream and the lymphatic system

• Native T cell response only to Antigen presenting cells.

Cell-Mediated Immunity – T Cells

- T cells bind to small fragments of antigens that are bound to normal cell-surface proteins called MHC

molecules

- Infected cells produce MHC molecules which bind to antigen fragments and then are transported

to the cell surface in a process called antigen presentation

- A nearby T cell can then detect the antigen fragment displayed on the cell’s surface

- Depending on their source peptide antigens are handled by different classes of MHC molecules

- Antigen activates effector T cells and produces memory T cells and cytotoxic T cells that lyse virus-

infected cells, tumor cells

Antigen Recognition

- Lymphocytes respond to antigens bound to either class I or class II MHC proteins

- T cell membranes contain CD markers

- CD3 markers present on all T cells

- CD8 markers on cytotoxic and suppressor T cells

- CD4 markers on helper T cells

T- cell receptors

T cell

• Induction of cell mediated immunity : Depend on nature of antigenic stimulus

• Defenses against

• Best develop after following infection by Bacteria and viruses that are inside host cells (

intracellular) and are inaccessible to antibodies.

• Fungi, protozoa

• Tumor cells

• Live vaccine highly stimulus

• Killed vaccine not very effective but effective if contain adjuvant

Types of T cells

Major types of effector T cells

• 1- Cytotoxic T cells

• (attack foreign cells) Recognize antigen on surface of virus infected cells , tumor cells, allograft

cells with MHCI and sectored lymphokines and destroy target cells.

• Kill infected host cells that bear a foreign antigen on contact.

• Directly kill certain cells; Cells infected with viruses and other intracellular pathogens Abnormal

(tumor ) cells

• Distinguished by the CD8 cell-surface glycoprotein

• may possess fc receptors for IgG. It functions by killing target cell through antibody-dependent cell-

mediated cytotoxicity or through perforin formation, killing cells without prior sensitization

• Produce cytokines, which promote phagocytosis and inflammation.

Cytotoxic T cells

Types of T cells • 2- Helper T cells

• Stimulate ( help) B cells to produce antibodies.

• produce cytokines; secrete interleukin 2 (I-2) which stimulates cell division of T cells and B cells (recruit even

more cells to help fight the pathogen).

• Induce formation of cytotoxic T cells.

• Most are CD4 (identifier- forming part of larger structures such as the T-cell receptor)

• Recognize antigen on the surface of antigen presenting cells (e.g. activate macrophage)

• serves in the defense against intracellular agents, including intracellular bacteria (eg, mycobacteria), fungi,

protozoa, and viruses.

• 2 types • Type 1 helper T cell (TH 1) • Assist cytotoxic T cells • Express CD26 and a cytokine receptor named CCR5

• Type 2 helper T cell (TH 2) • Assist B cells • Have cytokine receptors CCR3 and CCR4

Helper T Cell

Types of T cells

3- Suppressor T cell - ( regulatory T cell)

- inhibit the activation of T and B cells

- regulate immune response

- suppress induction of effector T cells ( autoimmune disease, organ transplantation)

- inhibiting, suppressing, or helping to stop an immune response by releasing signals to other immune cells.

Types of T cell

• 4- Memory T cells • jump- start an immune reaction upon re-infection.

• function during a second exposure to antigen

• These cells remain dormant after the initial exposure to an antigen. If the same antigen presents

itself again, survive a long time (even if it is years later).

• the memory cells are stimulated to convert themselves into cytotoxic T cells and help fight the pathogen.

• Can stimulate memory B-cells to produce antibodies

Memory T cell

Major Histocompatibility Complex ( MHC)

Glycoprotein family of cell surface molecules which controls a major part of the immune system.

T cell activation involves recognition of antigens combined with MHC on the surface of cells.

The major function:

bind to peptide fragments derived from pathogens and display them on the cell surface for recognition

by the appropriate T-cells.

MHC molecules mediate interactions of leukocytes

The MHC determines compatibility of donors for organ transplant, as well as one's susceptibility to an

autoimmune disease via cross reacting immunization.

• There are 2 major classes of MHC associated with T- cell function, namely:

• MHC class I: found on all cells

• display antigens on surface of nucleated cells, display peptide antigens to cytotoxic T cells.

• MHC class II: found on phagocytes

• located mainly on dendritic cells, macrophages, and B cells display antigens to helper T cells, resulting in

activation of immune cells

MHC classes

MHC

MHC

Antigen presenting Cell

• Express MHC and can present antigen to the T cells

• Can present antigen to the T cells via a histocompatibility molecule.

• Depending on the antigen presented and the type of the histocompatibility molecule, several types of T cells can become activated.

• For T-Cell Receptor (TCR) recognition, it must be processed into small fragments inside the cell and presented to a T-cell receptor by MHC. Antigen by itself is not capable to elicit the immune response without the help of an Immunologic adjuvant.

• Macrophages

• B- cell

• Dendritic cells

Antigen Presenting cell

T cell and Superantigens

• Reaction has drastic consequences

• Superantigens are a form of a virulence factor

• Provoke overwhelming immune responses by large numbers of T cells

• – Release of cytokines

• – Blood vessel damage

• – Toxic shock

• – Multiorgan damage