Immune CellsThe role of immune networks is to defend the body against foreign invasion. Microbes such as bacteria invade the body and activate innate antibacterial systems, such as the complement cascade. Polymorphonuclear leukocytes are attracted to this activity and attempt to ingest the bacteria.
The surfaces of the body are protected by cells on duty much like a military organization defends a country. The interior body surfaces are lined with a moist mucous-secreting surface that senses and reacts to the ambient environment. Antigens are protein molecules that are recognized by immune cells. Any chemical can link to a protein and become an antigen. Immune sensors or lymphoid tissues are present in the surface linings or mucosa of the intestine and respiratory tract (MALT).
These sensors are mast cells, macrophages and mobile lymphocytes of both T and B varieties. B and T-helper lymphocytes can only see antigen presented by macrophages and other antigen-presenting cells (APC).
The purpose of the surveillance is to detect and respond to foreign antigens. In the gut, lymphocytes are also contained in follicles, the solitary lymphoid nodules (SLN), found along the length of the intestine and in much of the upper and lower respiratory tracts. SLNs sample the soluble and particulate matter from the environment. The gut-associated lymphoid tissues (GALT) and the lung or bronchus-associated lymphoid tissues (BALT) are sensing agents for the whole body, identifying antigens for later detection by internal immune defenses. Both GALT and BALT and SLNs, contain predominantly B cells in which the major immunoglobulin classes synthesized are IgM and IgA.
Antigen Presenting CellsImmune responses often begin with macrophages, dendritic cells and other antigen-presenting cells (APC) that ingest process and then present antigens on their surface. The antigen signal attracts other immune cells who recognize it and are activated by it. Antigen is presented adjacent to the major histocompatability complex (MHC) proteins on the surface of APCs. The details of how APCs ingest, digest and then express foreign antigens are being worked out. The antigen moves through the cell membrane and is incorporated into a phagosome which interacts with acts endoplasmic reticulum, a protein transfer system that moves the antigen via a transporter to a location in the cell where the antigen binds to MHC class I molecules. The antigen-MCH complex is then moved thorough the cell membrane to appear on the outside as a receptor.
Molecules on bacterial membranes activate toll-like receptors (TLRs) on macrophages and dendritic cells. These cells respond by secreting proinflammatory cytokines as well as proteins such as CD86 and CD40 that activate other cells amplifying the original signals and exciting an inflammatory cascade. Dendritic cells (DCs) discover antigens in peripheral tissues and then migrate to the local lymph nodes, where they encounter CD4+ or CD8+ T cells, which are activated by the presentation of antigen-derived peptides in association with major histocompatibility complex (MHC).
DCs take up antigen through different receptor families, such as Fc receptors for antigen-antibody complexes, C-type lectin receptors (CLRs) for glycoproteins, and pattern recognition receptors, such as Toll-like receptors (TLRs), for microbial antigens. Geijtenbeek et al suggested that:” DCs are continuously sampling and presenting self- and harmless environmental proteins to silence immune activation. Uptake of self-components in the intestine and airways are good examples of sites where continuous presentation of self- and foreign antigens occurs without immune activation. In contrast, efficient antigen-specific immune activation occurs upon encounter of DCs with nonself-pathogens. Recognition of pathogens by DCs triggers specific receptors such as TLRs that result in DC maturation and subsequently immune activation. Here we discuss the concept that cross talk between TLRs and CLRs, differentially expressed by subsets of DCs, accounts for the different pathways to peripheral tolerance, such as deletion and suppression, and immune activation.”
Monocytes are circulating macrophages that can enter tissue spaces and promote inflammation. Macrophages are found within the endothelium generally and are concentrated in the lung, liver and spleen where they remove antigen and immune complexes from the blood.
Some tissues have resident macrophages such as the Langerhan's cells in the skin. Killer T-cells recognize antigen presented on MHC class I on all types of somatic cells. The purpose of the surveillance is to detect, and respond to foreign antigens. Since most antigens are proteins and foreign proteins arrive daily in the food ingested, I am interested in the mechanisms by which food proteins activate immune cells and cause disease.
APCs can ingest foreign protein and process them into peptides in proteasomes. Peptides are then transported into the endoplasmic reticulum to MHC class I molecules for presentation. Houde et al, for example, showed that latex beads labelled with fluorescent ovalbumin (egg white protein) were ingested and fluorescence could be detected in the cytoplasm, indicating that proteins are moved from outside into the cyoplasm for degradation by proteasomes. They showed that phagosomes are a site of loading onto MHC class I molecules on the cell surface, leading to T-cell stimulation.
LymphocytesTwo major groups of lymphocytes are recognized as Thymus dependent or T-lymphocytes; and Bursa dependent or B-lymphocytes. Adaptive immune responses require B cells to provide antibody and T cells to provide cell-mediated immunity. Cell surface receptors recognize antigens. B-lymphocytes learn make antibodies to specific antigens. Although T and B cells share a common progenitor, their development occurs in different locations in the body. B cells develop in the bone marrow and mature in lymphoid tissue. T lymphocyte progenitors leave the bone narrow and travel to the thymus where they mature.
The identity of a foreign molecule, microorganism or cell, is recognized by an antigenic determinant, an amino acid sequence, usually contained in an intact protein. Once an antigenic determinant is recognized, its sequence is remembered by clones of antigen-specific B and T-memory cells which can activate other B lymphocytes that make antibodies against the antigen. T memory cells are also referred to a as helper T cells which are activated by the binding of a specific antigen encountered in the past, a signal that initiates defense against familiar pathogens.
One of the growing complexities in immunology is the description of cell surface receptors for a growing list of cytokines. Research reports are dense with acronyms, abbreviations and codes that may deter even an experienced reader. Some of these markers are described as CD followed by a number; CD122, for example is a receptor for interleukin 2- . In addition some descriptions emphasize the presence or absence of a well-studied receptor; CD122 + or -. CD receptors may be associated with other surface molecules in complexes. For example, natural killer T lymphocytes (NKT) have CD94-NKG2 complexes that bind to major histocompatibility complex (MHC) class Ib, aka Qa-1, on the surface of antigen presenting cells. CD8+ suppressor T cells regulate peripheral immune responses.
The frequencies of blood lymphocyte subsets are monitored by flow cytometry using monoclonal antibodies to identify subtypes: for example, OKT4 identifies CD4+, T-helper cells and OKT8 identifies CD8+, T-suppressor cells.
Virus-specific CD8 and CD4 T lymphocytes play an important role in controlling HIV replication; however CD4 and CD8 lymphocytes are infected by HIV virus. Identifying and counting CD4 cells is a major tool in following patients with AIDs taking antiretroviral medications.
See Immunology Notes at Alpha Online