Table of Contents
The human’s body immune system combines cell-mediated and humoral components that interact in various ways to protect body cells from pathogens. Immune system is subdivided into a non-specific innate immune system.
Innate immune system
- The nonspecific (so-called innate) immune system includes undirected and immediate defence mechanisms that follow an pathogenic invasion. This involves among others the elimination of pathogens (bacteria) by phagocytes and natural killer cells (viruses and intracellular pathogens), the induction of a local and systemic inflammation (complement system, cytokines), including the attraction (chemotaxis) of non specific and specific immune cells to the focus of inflammation, the opsonization of pathogens for non specific and specific immune cells (complement system) and the activation of a specific immune response.
Adaptive immune system
- The specific (so-called adaptive) immune system is responsible for the late and targeted immune response in the course of symptomatic/asymptomatic infections. Contrarily to the innate immune system, it is highly specific to particular pathogens. Moreover, it is able to create an immunological memory and to distinguish between endogenous and foreign pathogens.
The adaptive immune system consists of B and T lymphocytes as well as the immunoglobulins which are secreted by activated B cells (plasma cells).
|Innate immunity||Adaptive immunity|
|Cell-mediated||phagocytes: macrophages, neutrophil granulocytes, NK cells||T lymphocytes (CD4+, CD8+)
|Humoral||complement system, cytokines||plasma cells respectively antibodies|
Secondary Lymphoid Organs: Lymph Nodes and Lymphoid Follicles
Antigens arrive in the lymph nodes (filtration stations) in the course of an infection with the circulating lymph. There they are presented to the naive lymphocytes, which circulate between bloodstream and lymphoid organs. If their surface receptors fit to the particular antigen, they are activated by the influence of various stimuli (see below), whereupon they proliferate and differentiate to so-called effector cells.
If certain antigens invade through the mucosa, they withhold in the mucosa-associated lymphoid tissue (lymphoid follicles, Peyer’s patches) and presented to the lymphocytes there.
Antigen Presentation to T cells by Dendritic Cells
In order that naive T lymphocytes are activated, they need to be presented an antigen by specialized antigen-presenting cells. This is happening within the secondary lymphoid organs (lymph nodes, Payer’s patches, tonsils, and others): dendritic cells present epitopes of an antigen by using special surface proteins called major histocompatibility complex proteins (MHC proteins) to the naïve T cells.
As soon as the T cell recognizes a matching antigen with the help of their antigen-specific T cell-receptor (TCR), a binding between TCR and the antigen presenting MHC protein is induced.
For T cell activation process to be completed, a second signal is required from dendritic cells. This second signal is given by the B7 protein expressed on surface of dendritic cells. The B7 protein binds to CD28 receptor on the T cell. This completes the activation of naïve T cell to an Effector T cell. The reason for the second signal is to confirm that the antigen epitope presented is a foreign antigen and not from our own body. This prevents the formation of autoimmunity.
As mentioned above, upon activation the naïve T cell becomes an effector T cell. Naïve T cells carry either CD4 or CD8 receptor on their surface. Activation of these two types of naïve T cells has a different response and is described below.
- CD4+ T cells (T helper cells) mature to Th1 cells or Th2 cells. Th1 cells release cytokines in order to activate macrophages (IFNy, IL2), whose mission it is to modulate local inflammation processes. Th2 cells express another cytokine pattern. They are necessary for the activation of B lymphocytes to plasma cells and play an essential role in antibody class switching (isotype switching) during the later humoral immune reaction (see below).
- CD8+ cells differentiate to cytotoxic T cells which are equipped with various lytic enzymes. Their mission is to destroy cells that are infected with intracellular pathogens (viruses).
Alike the existence of two different T cell populations with particular functions there are two classes of MHC proteins for different types of antigen presentation:
- MHC I proteins occur on the surface of all nucleated cells and present proteasomal degraded proteins that are synthesized by the antigen-presenting cell itself (endogenous peptide). This includes, cell-specific antigens, viral antigens which emerge there within viral replication. MHC 1 proteins interact with CD8+ T cells that differentiate to cytotoxic effector cells (cytotoxic T cells) when activated.
- MHC II proteins occur only on few cells, that is to say on dendritic cells, B cells and macrophages (so-called profession antigen-presenting cells, APC). They present various antigens, particularly those of bacterial pathogens, that were internalized before via phagocytosis and interact thereupon with naive CD4+ T lymphocytes, which then mature into so-called CD4-positive helper cells.
For the activation of naive B cells, it is not always necessary to have antigens presented by MHC molecules. For the detection of antigens, B cells use IgM or IgD molecules on their membrane surface (B-cell receptor), which are able to detect and bind soluble antigens in the blood or in the lymphoid tissue.
The subsequent activation (clonal expansion) and differentiation into immunoglobulin-secreting plasma cells take place inside the lymphoid tissue:
- T cell-dependent activation of B cells: After an antigen has bound the B-cell receptor is taken up into the cell, the antigen gets degraded in the lysosome and is thereupon ready for the presentation with MHC II surface proteins. These interact with the T-cell receptor of antigen-specific CD4+ cells. The T helper cells thus promote with the help of further costimulating signals (among others the interaction between CD 40 molecule of the B cell and CD 40 ligand of the T cell) the proliferation and differentiation of B cells into plasma cells. This initial activation takes place in the T cell zone (primary focus) of lymphoid organs and results in short-lived plasma cells secreting IgM. Later on, the B cells migrate from the primary focus to the B cell zones (follicle), where so-called germinal centres are built. In those germinal centres B cells develop a higher antigen affinity by means of complex cell-cell interactions, the cells undergo a change of their antibody pattern (isotype switching) and immunological memory cells are built. These newly emerged plasma cells are long-lived and show a modified spectrum of antibodies (IgG, IgE, IgA)
- T cell-independent activation of B cells: Various antigens, capsular polysaccharides of some bacteria among them, can cause a crosslinking of B cell receptors with succeeding B cell activation. In contrast to the T cell-dependent activation of B cells, there are no immunological memory cells built on this occasion. There is also none or hardly any immunoglobulin class switching from IgM to IgG.