The knowledge of fundamental immunological functions are essential for every physician, no matter if an exam in physiology or immunology lies ahead or not. We summarised relevant facts for you that you should bear in mind beyond your study for exams.

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Immune System

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Immune System

The human’s body immune system combines cell-mediated and humoral components that interact in various ways. Depending on the respective specifitiy regarding the pathogens and on the point they are coming to force one has to distinguish between two general systems:

  • 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.
  • 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 lymhocytes as well as the immunoglobulins which are secreted by activated B cells (plasma cells).

Innate immunity Adaptive immunity
Cell-mediated phagocytes: makrophagen, neutrophil granulocytes, NK cells T lymphocytes (CD4+, CD8+)
B lymphocytes
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 mucosa, they are withhold in the mucosa-associated lymphoid tissue (lymphoid follicles, Peyer’s patches) and presented to the lymphocytes there.

T-Lymphocytes

In order that naive T lymphocytes are activated they need to be presented an antigen by specialised 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 with the major histocompatibility complex proteins (MHC proteins) on their membrane surface.

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 and the antigen presenting MHC protein is induced. In order to activate the T cell to the so-called effector cell by means of clonal expansion and differentiation it is however necessary to have a costimulation via further receptor-mediated cell-cell interactions between dendritic cell and T cell.

T-Lymphocytes

T-Lymphocytes

Of capital importance is in this case a interaction between the surface receptor CD28 on the one hand, which is expressed by T cells, and the antigen-presenting cell associated B7 protein on the other hand. This second signal serves to ensure that the presented antigen is not one of the endogenous antigens of our own body and supresses the formation of autoreactive T cells.

In accordance to the respective marker they express on their surface two subpopulations of T cells can be distinguished that mature to different effector cells:

  • CD4+ T cells (T helper cells) can 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 nessecary for the activation of B lymphocytes to plasma cells and play an essential role in antibody class switching (isotype swichting) 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).

MHC-Proteins

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:

  • MCH 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, next to cell specific antigens, viral antigens which emerge there within viral replication. The loading of the peptide fragments takes place in the endoplasmatic reticulum. From here the antigen loaded molecules migrate to the cell membrane via Golgi apparatus. 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-presentic 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 to so-called CD4-positive helper cells.
Note: MHC I proteins present antigens of intracellular pathogens to cytotoxic T cells (→ Destruction of the infected cell). MHC II proteins present antigens of extracellular pathogens to CD4+ cells (→ B cell activation into plasma cells).

B-Cells

For the activation of naive B cells it is, contrarily to the T cell activation, not necessary to have antigens presented by MHC moleculs. 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 immunoglobuline secreting plasma cells takes 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 MCH 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)
Note: The early humoral immune reaction is classified by the synthesis of IgM, which is replaced by IgG in a later phase of infection.
  • 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 immunglobulin class switching from IgM to IgG.
T cell-independent activation of B cells

T cell-independent activation of B cells

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