Cells Of The Immune System

The Complement System
The Complement System is the first part of the immune system that meets invaders of the body, such as bacteria, and it is very quick to act, and deadly. It is called complement because it helps, (complements) antibodies to kill these invaders. Complement is a cascade of about twenty five-thirty proteins, which flow freely in the blood, and can quickly reach the site of an invasion, where they can react directly with antigens. (molecules that the body recognizes as foreign substances).
Complement, marks any cell which does not have protective proteins on their surface; (see HLA's) whereas antibodies lock on to specific foreign invaders, and in many cases , activates complement. Complement markers, with or without antibody, attract white blood cells, known collectively as Phagocytes.

When activated, the complement proteins can...
1) stimulate inflammation
2) facilitate antigen phagocytosis by attracting phagocyte eater cells such as macrophages to the area
3) coat (opsonize) intruders, so that eater cells are more likely to devour them.
4) kill some cells directly, with various immune functions, such as lyses (destroys and kills)
5) attract neutrophils to a trouble spot.
6) enhance the effectiveness of antibodies.

Complement is not "antigen specific", it is activated immediately in the presence of a pathogen and therefore it is considered as a part of innate immunity. ( Immunity which we are born with) Complement is in fact the major humoral component, of the Innate immune response. It is a part of humoral immunity because antibodies can activate some complement proteins . Complement, is also a very powerful inflammatory agent, and therefore it's activity is tightly regulated. (see link below)

Complement proteins circulate in the blood in an inactive form, and this combination of proteins are important in humoral immune responses. Complement proteins are activated by the antibodies IgM and IgG, which are located on the membrane of B cells. When these antibodies recognize and bind to antigens, a change of the IgM or IgG occurs. This means that its structure is slightly altered. This alteration results in the binding site for the first complement protein, Cl, to be exposed.

Once Cl binds to the "antigen -antibody" complex, (Ag-Ab Complex=the joining of antigen and antibody) more complements proteins can also bind. Once complement proteins 1-6 bind to the Ag-Ab complex, this forms what is called the MAC complex. MAC stands for Membrane Attacking Complex. This complex, as it implies, perforates, or punches holes in the target cell that is expressing the antigen. This allows surrounding water to flow into the cell and electrolytes to flow out of the cell resulting in cell death and therefore antigen death.(see picture below)

The "complement cascade" is set off when the first complement molecule, (C1), encounters an antibody bound to an antigen, in what is referred to as an "antigen-antibody complex". Each of the complement proteins performs it's specialized job in turn, acting on the molecule next in line. (going from C1 to C9) The end product is a cylinder that punctures the cell membrane and, by allowing fluids and molecules to flow in and out, dooms the target cell.

This group of proteins in blood serum, interact systematically as part of the body's immune response to destroy disease-causing antigens, especially bacteria. Complement proteins interact with antibodies and other chemical substances to cause the disintegration of foreign cells, and enhance other immune functions such as phagocytosis. (in which the blood cell engulfs the foreign body or damaged cell).

Fragments flung off during the course of the cascade can produce other consequences. One byproduct causes mast cells and basophils to release their contents, producing the redness, warmth, and swelling of the inflammatory response.
Another stimulates and attract neutrophils. Yet another, C3b, opsonizes or coats target cells so as to make them more palatable to phagocytes, which carry a special receptor for C3b.
The C3b fragment also appears to play a major role in the body's control of immune complexes. By opsonizing (coating) antigen-antibody complexes,(that are joined,) C3b helps prevent the formation of large and insoluble (and thus potentially damaging) immune aggregates. Moreover, receptors for C3b are also present on red blood cells, which appear to use the receptors to pick up complement-coated immune complexes and deliver them to the Kupffer cells in the liver.

Immune Complexes and the Complement System
Imune complexes are clusters of interlocking antigens and antibodies. Under normal conditions, immune complexes are rapidly removed from the bloodstream by macrophages in the spleen and Kupffer cells in the liver. In some circumstances, immune complexes continue to circulate, eventually becoming trapped in the tissues of the kidneys, lung, skin, joints, or blood vessels.
Where in the body these complexes actually end up, probably depends on the nature of the antigen, the class of antibody, for instance, IgG instead of IgM, and the size of the complex. There, they set off reactions that lead to inflammation and tissue damage. Immune complexes work their damage in many diseases. Sometimes, they reflect persistent low-grade infections.

Frequently, immune complexes develop in autoimmune disease, where the continuous production of autoantibodies overloads the immune complex removal system.

A group of specialized molecules that form the complement system helps to remove immune complexes. The different types of molecules of the complement system, which are found in the bloodstream and on the surfaces of cells, make immune complexes more soluble. Complement molecules prevent formation and reduce the size of immune complexes so they do not accumulate in the wrong places (organs and tissues of the body).
Rarely, some people inherit defective genes for a complement molecule from their parents. Because these individuals cannot make a normal amount or type of complement molecule, their immune systems are unable to prevent immune complexes from being deposited in different tissues and organs.

Lymphocytes (T cells and B cells) white Blood Cells.
All blood cells, Leukocytes (White blood cells), and cells destined to become immune cells begin life as immature cells, produced by Hematopoietic (hema-toe-poy-etic) Stem Cells (blood cell forming, stem cells) in the bone marrow. There are two major types of immune cell which stem from immature precursor Myeloid cells, and immature precursor Lymphoid cells.

Myeloid cells, form the second part to the innate immune system, a group typified by the large , cell and particle-devouring white blood cells, known as phagocytes. Phagocytes are and include, monocytes, macrophages, neutrophils dendritic cells, and mast cells.
Other myeloid descendants, become granule-containing inflammatory cells, such as eosinophils, and basophils. These cells identify and eliminate pathogens, either by attacking larger pathogens through contact, or by engulfing and then killing micro-organisms.
Innate cells are also important mediators in the activation of the adaptive immune system.

Some lymphocytes remain in the bone marrow and mature there, and become B cells. Other lymphocytes shortly after birth, migrate to the Thymus, an organ in the top of the chest, where they mature to become T cells. Both T cells and B cells play an important role in recognising and destroying, infecting organisms such as bacteria and viruses.
Once mature, these lymphocytes enter the circulation and peripheral (around the body) lymphoid organs, the thymus, spleen and lymph nodes, where they survey for invading pathogens and/or tumour cells. Lymphocytes are responsible for specific or aquired immunity, (see immune system ) including producing antibodies by B lymphocytes, and distinguishing self from nonself by T -lymphocytes.

T cells and B-cells are the major cellular components of the adaptive/aquired immune response.
T cells are involved in cell-mediated immunity, (see cell mediated immunity) and B cells are responsible for humoral immunity. (see humoral immunity)

The function of T cells and B cells is to recognize specific “non-self” antigens, during a process known as antigen presentation, which is carried out by macrophages and dendritic cells. Once they have identified an invader, the cells generate specific responses that are tailored to eliminate specific pathogens or pathogen infected cells.
B cells respond to pathogens by producing large quantities of antibodies which then neutralize foreign objects like bacteria and viruses. In response to pathogens, some T cells, called Helper T cells, produce cytokines that direct or stimulate the immune response, whilst other T cells, called cytotoxic T cells, or Killer Tcells, produce toxic granules that induce the death of disease infected cells.
These B and T lymphocytes involved in adaptive/aquired immunity differentiate even further after exposure to an antigen.
They form Memory lymphocytes and Effector lymphocytes.
(an Effector cell is a molecule that binds to an enzyme, with an effect on its catalytic activity, i.e. either as an activator or inhibitor)

Following activation, B cells and T cells leave a lasting legacy of the antigens they have encountered, in the form of these memory cells. Throughout life, these memory cells will “remember” each specific pathogen encountered, and are able to mount a strong response if the pathogen is detected again.
Memory cells, remain in the peripheral (around and about the body) tissues and circulation, for an extended time, ready to respond to the same antigen should they encounter it again in the future. They live weeks to several years which is very long compared to other leucocytes. Effector lymphocytes function to eliminate the antigen, either by:- 1) Releasing antibodies (in the case of B cells) 2) Releasing cytotoxic granules (in the case cytotoxic T cells) 3) Signalling to other cells of the immune system (as in the case of helper T cells). Each B cell and T cell is specific for a particular antigen. This means that each is able to bind to a particular molecular structure, by a specific receptor for antigen. (A receptor selectively receives and binds a specific substance.)

A Receptor is a molecule on a cell's surface, that allows only molecules that fit precisely to it, (just as a key fits in a lock) and thereby able to attach to it. Both B and T cells have surface receptors for antigen. Each cell has thousands of receptors of a single specificity; that is, with a binding site for a particular epitope. T-cell receptors (TCRs) enable the cell to bind to and, if additional signals are present, to be activated by and respond to an epitope presented by another cell called the antigen-presenting cell or APC. B-cell receptors (BCRs) enable the cell to bind to and, if additional signals are present, to be activated by and respond to an epitope on molecules of a soluble antigen. The response ends with descendants of the B cell, secreting vast numbers of a soluble form of its receptors. These are antibodies. There are many different receptors. The B cell receptor for antigen is called a (BCR) and the T cell receptor is called a (TCR).

T cells are the cells, which modulate pathogenic immune responses.
Studies suggest that the regulatory T cell population is diminished or functionally impaired in patients and animals with autoimmune disease.
T cells are distinguished from other lymphocyte types, such as B cells and Natural killer cells (NKC's ) by the presence of a special receptor on their cell surface called the T cell receptor (TCR).

Tcell receptors
The surface of each T cell displays thousands of identical receptors (TCRs) that bind to antigen fragments nestled in MHC molecules. T cells will respond to antigens. Some of them (CD4+) secrete lymphokines which act on other cells involved in the immune response. Others (CD8+, cytotoxic) are able to cause lysis (the death) of infected cells.
There are two types of T cells that differ in their TCR.
1) alpha/beta (αβ) T cells. Their TCR is a heterodimer of an alpha chain with a beta chain. Each chain has a variable (V) region and a constant (C) region. The V regions each contain 3 hypervariable regions that make up the antigen-binding site.
(see Genes)
2) gamma/delta (γδ) T cells. Their TCR is also a heterodimer of a gamma chain paired with a delta chain (see antibodies)

The following is a list of the alpha/beta (αβ) T cells, and the least understood one, the gamma/delta (γδ) T cells, will be placed last in this list.

All cells express ClassI MHC molecules containing fragments derived from self proteins. (see genes)
Many cells express ClassII molecules that also contain self peptides. (see genes)

This presents a risk to the host (the individual body) of the T cells recognizing these self-peptide/self-MHC complexes and mounting an autoimmune attack against them.
Fortunately, this is usually avoided by a process of selection that goes on in the thymus (where all T cells develop).
In most cases, T cells only recognize an antigen if it is carried on the surface of a cell by one of the body’s own , major histocompatibility complex, molecules. (MHC's/HLA's amounts to the same thing)
MHC molecules are proteins recognized by T cells when distinguishing between self and nonself. A self MHC molecule provides a recognizable scaffolding to present a foreign antigen to the T cell. Although MHC molecules are required for T-cell responses against foreign invaders, they also pose a difficulty during organ transplantations.
Virtually every cell in the body is covered with MHC proteins, but each person has a different set of these proteins on their cells.
If a T cell recognizes a nonself MHC molecule on another cell, it will destroy the cell. Therefore, doctors must match organ recipients with donors who have the closest MHC makeup, otherwise the recipient’s T cells will likely attack the transplanted organ, leading to graft rejection. (see genes MHC's)

Positive and Negative Selection
The "progenitors" or precursors of T cells which have migrated to the cortex of the Thymus, do not have a complete T cell Receceptor (TCR). In the thymus, they expand by cell division to make a large population of immature thymocytes. These early thymocytes have neither CD4 nor CD8 receptors, and are therefore classed as...
1) double-negative (CD4-CD8-minus) (DNcells).

As they progress through their development they become

2) double-positive thymocytes (CD4+CD8+plus) (DPcells), and finally mature to..

3) single-positive (CD4+CD8- or CD4-CD8+) (SPcells).
These single positive T cells (thymocytes) are then released from the thymus to peripheral (around the body) tissues. About 98% of thymocytes die during the development processes in the thymus, by failing either positive selection or negative selection. The other 2% survive and leave the thymus to become mature immunocompetent T cells. (Having the normal bodily capacity to develop an immune response following exposure to an antigen).

Positive Selection
In the cortex of the thymus the double -positive thymocytes are presented with self-antigens (ie: self antigens that are derived from molecules belonging to the host of the Tcell). Only those thymocytes that bind MHC/antigen complex, with adequate affinity, (or bind tightly enough), will receive a vital "survival signal"
It is also determined during positive selection, whether a thymocyte becomes a CD4+ cell or a CD8+ cell.
Double-positive cells that are positively selected on MHC class II molecules will become CD4+ cells, and cells positively selected on MHC class I molecules become CD8+ cells.

These cells must be able to interact with MHC and peptide complexes in order to effect immune responses. During these developments, thymocytes that do not have adequate affinity ( do not bind tightly enough) cannot serve useful functions in the body, and therefore they die by apoptosis (programmed cell-death), in effect they commit suicide! Their remains are then engulfed by macrophages. This whole process is called positive selection.
However, this process does not remove from the population, thymocytes that would cause autoimmunity or a reaction with one's own cells. The removal of such cells is dealt with by Negative selection.

Central tolerance is not always complete. It is estimated that as many as 25–40% of T cells reactive to a self-peptide escape clonal deletion in the thymus. These T cells include low-affinity, autoreactive T cells, and T cells specific for self-antigens not presented in the thymus. T cells must remain tolerant (to ignore) to harmless environmental antigens found in the respiratory tract or intestines.
The existence of autoreactive T cells into the periphery (around the body) necessitates the role for DCs (Dendritic Cells) in peripheral tolerance to prevent autoimmunity.
The existence of self-reactive T cells circulating in the periphery is not problematic if T cells are naïve and if they remain within lymphoid tissues and do not enter normal tissues to induce tissue damage.
Self-reactive, naïve T cells therefore do not lead to disease, as long as they ignore or are separated from self-antigens. However, naïve, self-reactive T cells are potentially a problem during infection or inflammation.
Dendritic Cells will capture and present pathogenic antigens to induce T cell immunity, and they will also co-present numerous self-antigens captured during the steady-state.

There is an inherent risk that Dendritic cells (antigen presenting cells, ) co-presenting self-antigens during infection, might activate self-reactive T cells that recognize an autoantigen leading to effector T cell formation and the initiation of autoimmunity. In establishing peripheral tolerance in the steady-state by filtering out autoreactive T cells before an acute infection, Dendritic cells can effectively focus adaptive immunity on the pathogen and so avoid autoimmunity.

Negative Selection
The thymocytes which have survived positive selection move to the medulla of the thymus. There, those thymocytes whose TCR binds very strongly to complexes of self-peptide and self-MHC are destroyed by receiving an apoptosis signal, which results in their death. A small minority of the surviving cells are selected and will become Regulatory T cells (suppressor cells).
This process of negative selection is important as it eliminates self-reactive Tcells capable of generating autoimmune disease in the host.
It is one of the ways in which immune tolerance (the ignoring of) to self antigens is achieved.
The T cells which have survived these processes, will be able to recognise non-self antigens, which have undergone phagocytosis, by macrophages and dendritic cells, (see phagocytes) and fragments presented in combination, on the surface of a "self" receptor called a major histocompatability complex (MHC) molecule. (see Antigen below)
After a little more maturation, they exit the thymus to perform their role in immune responses.

An Antigen is a substance that is foreign to the body. A T lymphocyte, part of the immune surveillance system, cannot directly recognize an antigen. Therefore, the antigen is first engulfed by an antigen-processing cell called a macrophage. (see macrophage) Enzymes in the macrophage break the antigen into fragments, which it then presents on the surface of major histocompatibility complex molecules. This new antigen formation moves to the surface of the macrophage, is recognized by the T-lymphocyte receptor, and binds with the T lymphocyte. (see picture below)

1)Helper Tcells (or Th cells.) These cells co-ordinate immune responses by communicating with other cells. Some stimulate nearby B cells to produce antibody, others call in microbe-eating cells called phagocytes, still others activate other T cells.
Helper T cells only recognize antigens coupled to Class II molecules. Helper T cells regulate both the innate and adaptive immune responses and help determine which types of immune responses the body will make to a particular pathogen. These cells have no cytotoxic activity and do not kill infected cells or clear pathogens directly. They control the immune response by directing other cells to perform these tasks. Antigen presenting cells (APC's) present antigen on the Helper T cell's Class II MHC molecules (MHC2).

The MHC2/antigen complex is also recognized by the Helper cell's CD4 co-receptor, (CD4+), which recruits molecules inside the T cell that are responsible for the T cell's activation.
The activation of a resting helper T cell, causes it to release cytokines and other stimulatory signals, that stimulate the activity of macrophages, Killer T cells, and B cells, the latter producing antibodies. The stimulation of B cells and macrophages succeeds a proliferation of T helper cells.
Helper T cells have a weaker association with the MHC:antigen complex than for killer T cells; meaning that many receptors (around 200–300) on the helper T cell must be bound by an MHC:antigen in order to activate the helper cell; while killer T cells can be activated by engagement of a single MHC:antigen molecule. Helper T cell activation also requires longer duration of engagement with an antigen-presenting cell.
The activation of a resting helper T cell causes it to release cytokines that influence the activity of many cell types.
Cytokine signals produced by helper T cells enhance the microbicidal function of macrophages and the activity of killer T cells. Through interaction with helper Tcells, Cytotoxic killer cells, can be transformed into suppressor Tcells, which prevent autoimmune diseases. (see killer Tcells and regulating Tcells.) In addition, helper T cell activation causes an upregulation of molecules expressed on the T cell's surface, which provide extra stimulatory signals typically required to activate antibody-producing B cells.

2) Killer T cell (also known as CD8+ /cytotoxic Tcells.) Through interaction with helper Tcells, these cells can be transformed into suppressor Tcells, which prevent autoimmune diseases. Killer T cells only recognize antigens coupled to ClassI molecules.(MHC1). Killer T cells are a sub-group of T cells, that kill cells infected with viruses (and other pathogens), or are otherwise damaged or dysfunctional cells. Each type of T cell recognises a different antigen, (as do B cells) and are activated when their T cell receptor (TCR) binds to this specific antigen, in a complex with the MHC Class I receptor of another cell. Recognition of this MHC antigen complex, is aided by a co-receptor on the T cell, called CD8. This T cell then travels throughout the body in search of cells where the MHC I receptors, bear this antigen.

When an activated T cell contacts such cells, it releases cytoxines such as perforin which form pores in the target cell's plasma membrane, allowing ions, (water and toxins) to enter. The entry of another toxin called granulysin (a protease) induces the target cell to undergo apoptosis (cell death.) T cell killing of host cells is particularly important in preventing the replication of viruses. T cell activation is tightly controlled and generally requires a very strong MHC/antigen activation signal, or additional activation signals provided by Helper T cells.

3)Natural Killer (NKt) Cells. These are another, special kind of lethal white cell, or lymphocyte that bridge the adaptive immune system with the innate immune system. Unlike conventional T cells that recognize peptide antigen, presented by Major Histocompatibility Molecules(MHC), NKT cells recognize glycolipid antigen presented by a molecule called CDId. Once activated, these cells can perform functions ascribed to both cytokine production, and release of cytolytic/cell killing molecules. Like killer T cells, NK cells are armed with granules filled with potent chemicals. While killer T cells look for antigen fragments bound to self-MHC molecules, NK cells recognize cells lacking self-MHC molecules. Thus, NK cells have the potential to attack many types of foreign cells. Both kinds of killer cells slay on contact. The deadly assassins bind to their targets, aim their weapons, and then deliver a lethal burst of chemicals.

4) Memory T cells. These are a subset of antigen-specific T cells that persist a long time after an infection has resolved. They quickly expand to large numbers of effector T cells upon re-exposure to their antigen, thus providing the immune system with "memory" against past infections. Memory T cells comprise two subtypes: 1) central memory T cells (TCM cells) and 2) effector memory T cells (TEM cells). (able to alter the function of other cells) Memory T cells may be either CD4+ T ( regulating Tcells) or CD8+. killer Tcells)

5) Regulatory (or Suppressor) T cells . These are white blood cells that helps to end an immune response. Through interaction with helper Tcells, these cells can be transformed into suppressor Tcells, which prevent autoimmune diseases. These are the cells which are under intense research. An important question in the field of immunology is how the immunosuppressive activity of regulatory T cells is modulated during the course of an ongoing immune response.

The immunosuppressive function of regulatory T cells prevents the development of autoimmune disease. Reg Tcells are crucial for the maintenance of immunological tolerance. (Having the ability to ignore self antigens and respond to only non-self antigens.) Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus. Two major classes of CD4+ regulatory T cells are:- 1) Innate occurring T-reg.cells, and the adaptive T-reg cells. Naturally occurring (innate) T-reg cells (also known as CD4+CD25+FoxP3+ Treg cells) arise in the thymus. 2) adaptive T-reg. cells (also known as Tr1 cells or Th3 cells) may originate during a normal immune response.
Naturally occurring (innate) T-reg.cells can be distinguished from other T cells by the presence of an intracellular molecule called FOX P3. Naturally occurring regulatory T cells represent five to ten percent of CD4+ T cells and possess potent immunoregulatory functions essential to peripheral (around the body) self-tolerance. (the ability to recognise and ignore self antigens)

Regulatory T cells express Foxp3. Foxp3a is a Master Control gene for regulatory T cells, and identifies these cells as a distinct subset of T cells.
Genetic insufficiency of Foxp3 causes autoimmune and inflammatory disease. In humans, defects in the Foxp3 gene underlie loss of self-tolerance and immune dysregulation. These results raise the prospect of novel approaches to controlling autoimmunity.
Mutations of the FOXP3 gene can prevent regulatory T cell development, causing the fatal Autoimmune disease IPEX .

6)Autoaggressive Tcells.
These are a unique T cell subset that are characterized by the expression of CD40. CD40 is associated with antigen-presenting cells, but is also expressed on a subset of T helper cells. Th40 cells are found in all individuals but occur at drastically expanded percentages in autoimmune subjects. This is true of autoimmune humans and mice.
For eg:- Th40 cells from type 1 diabetic subjects respond to known self-antigens, whereas Th40 cells from non-autoimmune subjects do not respond to those antigens.

A crucial role of CD40 on T cells is to induce RAG1 and RAG2, the VDJ (variable, Diversity, & linking ) recombinase proteins, (see genes) responsible for altering the T cell receptor. The TCR is the means by which T cells are able to recognize antigens. It is required that RAG1 and RAG2 be expressed only in the thymus, during T cell development. However, RAGs are re-expressed in peripheral T cells, and CD40 engagement on Th40 cells induces RAGs expression. Following RAG expression, changes in TCR occur. This means that Th40 cells are capable of adapting throughout an individual's lifetime. This process of altering TCR expression in the periphery is called TCR revision. Revision can be responsible for expanding the T cell repertoire, but also could result in the generation of autoaggressive T cells. TCR revision is therefore another means of T cell self-tolerance.

7)Gamma/Delta (γδ) T Cells
A minor sub-type are the γδ T cells that recognise intact antigens that are not bound to MHC receptors.
The function of the γδ T cells within the human immune system is largely unknown. Gamma/Delta Tcell receptors (γδ TCRs ) seem to recognize antigen directly, similar to immunoglobulins (Igs),
but they do not require presentation by an MHC protein or other molecules and do not depend on antigen processing.
The diversity of the γδ TCR is limited, suggesting that the ligands (see below) for the γδ TCR are conserved and invariant.
γδ T cells have been shown to recognize self-peptides, such as stress-associated antigens expressed on epithelial cells, tumor lines, and primary carcinomas.
Recognition of self-peptides and the production of cytokines early during an immune response indicate that γδ T cells play a role in the development of an immune response against self-tissue, ie : Autoimmune response.
Definition of Ligand= (When a protein binds to another molecule, that molecule may be referred to as a ligand. The site where the ligand is bound is known as the binding or active site of the protein.)

Gamma/delta T cells differ from the alpha/beta in several ways:
1) Their TCR is encoded by different gene segments.
2) Their TCR binds to antigens that can be intact proteins. (just as antibodies do) as well as a variety of other types of organic molecules.

3) Are not "presented" within class I or class II histocompatibility molecules;
4) Are not presented by "professional" antigen presenting cells(APCs) such as Dendritic cells
5)Most of these T cells have neither CD8 nor CD4 on their surface. This makes sense because they have no need to recognize class I and class II histocompatibility molecules.
6) Gamma/ Delta Tcells like alpha/beta T cells, develop in the thymus. From there, they migrate into body tissues, especially epithelia (eg.intestine, skin, lining of the vagina), and don't recirculate between blood and lymph nodes. (they represent no more than 5% of the T cells in the blood and are even rarer in lymph nodes)
7) They encounter antigens on the surface of the epithelial cells that surround them rather than relying on the Antigen presenting cells found in lymph nodes.

The Function of γδ Gamma Delta T cells
That is still something of a mystery. Situated as they are at the interfaces between the external and internal worlds, they may represent a first line of defence against invading pathogens. Their response does seem to be quicker than that of αβ (Alpha Beta) T cells.
Curiously, many of the antigens to which γδ T cells respond, are found not only on certain types of invaders (eg. Mycobacterium tuberculosis, the agent of tuberculosis) but also in host cells that are under attack by pathogens.
Knockout Mice that cannot make γδ T cells are slower to heal injuries to their skin. They are also much more susceptible to skin cancers than normal mice. Perhaps,immune surveillance is one of the functions of γδ T cells?

CD Markers. Cluster of Differentiation (CD)
What those CD numbers mean:
The cluster of differentiation (CD) is a protocol used for the identification and investigation of cell surface molecules present on leukocytes. CD molecules can act in numerous ways, often acting as receptors or ligands (the molecule that activates a receptor) important to the cell. A signal cascade is usually initiated, altering the behavior of the cell. Some CD proteins do not play a role in cell signalling, but have other functions, such as cell adhesion. There are approximately
250 different proteins.
Uses as cell markers
The CD system is commonly used as cell markers; this allows cells to be defined based on what molecules are present on their surface. These markers are often used to associate cells with certain immune functions or properties.

While using one CD molecule to define populations is uncommon (though a few examples exist), combining markers has allowed for cell types with very specific definitions within the immune system.
It is important to note that, while CD molecules are very useful in defining leukocytes, they are not merely markers on the cell surface. While only a fraction of known CD molecules have been thoroughly characterised, most of them have an important function. In the example of CD4 & CD8, these molecules are critical in antigen
CD molecules are utilized in cell-sorting using various methods including flow cytometry. Cell populations are usually defined using a '+' or a '–' symbol to indicate whether a certain cell fraction expresses or lacks a CD molecule. For example, a "CD34+, CD31–" cell is one that expresses CD34, but not CD31. This particular CD combination, typically corresponds to a stem cell, opposed to a fully-differentiated endotheliel cell.

Types of cells, and their CD markers.
Stem Cells
CD34+, CD31-
All Leukocyte Groups
CD45+, CD15+ Monocytes CD45+,CD14+
T Lymphocytes
T Helper Cell CD45+,CD3+,CD4+
Cytotoxic Tcell CD45+,CD3+,CD8+ B Lymphocyte CD45+,
D19+ CD45+, CD19+ or CD45+,CD20+
Natural Killer cell
CD16+, CD56+, CD3-

Two commonly used CD molecules are
CD4 and CD8, which are, in general, used as markers for helper (CD4) and cytotoxic T cells, (CD8) respectively. When defining T cells, these molecules are defined in combination with CD3+. Other leukocytes also express these particular CD molecules. Some macrophages express low levels of CD4. Dendritic cells (antigen presenting cells) express high levels of CD8. The relative abundance of CD4+ and CD8+ T cells is often used to monitor the progression of an HIV infection. http://en.wikipedia.org/wiki/List_of_human_clusters_of_differentiation