Lymphatics and Immunity 3: Cell-Mediated Immunity

What is adaptive immunity then?

Adaptive or specific immunity responds to specific antigens through the coordinated action of T and B cells. It is only developed after birth. Adaptive immunity involves both cell-mediated and antibody-mediated immunity. Cytotoxic T cells provide cell-mediated immunity, providing defence against abnormal cells and pathogens inside cells. B cells provide antibody-mediated immunity, providing defence against antigens and pathogens in body fluids.

There are four properties of immunity:

1. Specificity - response to only a specific type of antigen
2. Versatility - production of many types of lymphocytes
3. Memory - active lymphocytes stay in circulation and provide immunity against new exposure
4. Tolerance - immune system ignores normal antigens

What is cell-mediated immunity?

T cells only recognise antigens that are bound to glycoproteins in a plasma membrane. These are termed major histocompatibility complex proteins. These proteins differ between individuals and are a group of proteins with a 'flagging' or 'signalling' protein. There are two types of major histocompatibility complex proteins:

1. Class 1 proteins are in the membranes of all nucleated cells and are involved in cell-mediated immunity.
2. Class 2 proteins are found in the membranes of antigen-presenting cells and are found in lymphocytes.

Class 1 MHC proteins pick up small peptides in cells and carry them to the surface. T cells ignore the normal peptides, however abnormal peptides or viral proteins activate T cells to destroy that cell:

1. Antigen presentation by class 1 MHC proteins is triggered by a viral or bacterial infection of a body cell.
2. The infection results in the abnormal appearance of peptides in the cytoplasm.
3. The abnormal peptides are incorporated into a class 1 MHC protein as they are synthesised at the endoplasmic reticulum.
4. After export to the Golgi apparatus, the MHC proteins reach the plasma membrane within transport vesicles.
5. The abnormal peptides are displayed by class 1 MHC proteins on the plasma membrane.
6. T cells recognise the MHC proteins and induce a response.

Class 2 MHC proteins bind to antigenic fragments from the antigenic processing of pathogens, which are then inserted into the plasma membrane to stimulate T cells:

1. Phagocytic antigen presenting cells engulf the extracellular pathogen
2. Lysosomal activity produces antigenic fragments
3. The endoplasmic reticulum produces class 2 MHC proteins
4. Antigenic fragments are bound to class 2 MHC proteins
5. Antigenic fragments are displayed by class 2 MHC proteins on the plasma membrane
6. T cells recognise the MHC proteins and induce a response

Antigen presenting cells can be either phagocytic or non-phagocytic.

Cluster of differentiation markers (CD markers) exist in T cell membranes are are molecular mechanisms of antigen recognition. There are more than 70 types, but the two main ones include:

1. CD8 markers, found on cytotoxic and suppressor T cells which respond to Class 1 MHC proteins
2. CD4 markers, found on helper and memory T cells which respond to Class 2 MHC proteins

In T cell-mediated immunity, it is the cytotoxic T cells that seek out and immediately destroy target cells. The way in which they do this is summarised below:

1. Antigen recognition occurs when a CD8 T cell encounters an appropriate antigen on the surface of another cell, bound to a class 1 MHC protein.
2. Costimulation activates a CD8 T cell
3. Antigen recognition results in T cell activation and cell division, producing active cytotoxic T cells and memory T cells.
4. Active cytotoxic T cells destroy the antigen-bearing cell through:
• Destruction of plasma membrane by perforin release (like natural killer cells in immunological surveillance)
• Stimulation of apoptosis by cytokine release (like interferons)
• Disruption of cell metabolism by lymphotoxin release

Active helper T cells secrete cytokines. Cytokines help stimulate B cells to produce antibodies which augment the activity of the working cytotoxic T cells. Some B cells act as chemotaxis, which lure cells into an invaded area. This keeps the cells within the area by the macrophage migration inhibition factor.