Immune system and immunity

White blood cells (WBC), also called leukocytes, are the soldiers of your immune system that actually fight the antigens (foreign body) and eliminate them. WBCs account for about 1% of all the cells present in the blood—we have 4,000-11,000 WBCs per cubic millimetre (mm³) of blood. The number of WBCs in the body rises during an infection.

Unlike red blood cells, WBCs are able to slip out of blood vessels and into the site of tissue damage, a process called diapedesis.

The following are the types of white blood cells in the body, depending on whether or not they have granules in them:

• Granulocytes: Granulocyte cells have small granules (small sacs) inside their cytoplasm when seen under the microscope. There are three types of granulocytes:

  • Neutrophils: Neutrophils or polymorphonuclear neutrophils are the most abundant types of leukocytes—they constitute 40-75% of all circulating WBCs. These cells have a lobed nucleus (central compartment in a cell that contains the DNA) with about three to five lobes in each cell, which makes them easy to differentiate from other leukocytes. Neutrophils are the first immune cells that reach the infection or injury site. They are attracted inside tissues by various chemicals and cytokines and eliminate the pathogen either by phagocytosis (internalise and break down the pathogen to present it to other immune system cells to start a specific immune reaction against the pathogen) or release antimicrobial factors from their granules. 
  • Eosinophils: Eosinophils have a bilobed (two lobes) nucleus which appears like an old-style telephone receiver, and granules inside their cytoplasm. The term eosinophil comes from the fact that these cells take up the eosin dye (eosin-loving) and appear pinkish-red under the microscope. Eosinophils make up about 2.3% of all WBCs. Their numbers rise in blood in case of allergies and parasitic infections.  
  • Basophils: Basophils are the most rare type of WBCs which release histamines (an inflammatory chemical) in the body to attract other WBCs and to the inflammation site. Basophils have an S-shaped nucleus which can be seen in shades of blue under the microscope. Only 0.4% of all leukocytes are basophils.
• Agranulocytes: Agranulocyte white blood cells do not have apparent granules in their cytoplasm. There are two types of agranulocytes:
  • Lymphocytes: Lymphocytes make up 20-40% of all leukocytes and constitute about 99% of all cells in the lymph. Lymph is a clear liquid that flows inside the lymphatic system. Lymph mostly contains lymphocytes but it also contains chyle, which is a protein- and fat-containing liquid from the intestines. Lymphocytes have an oval or round nucleus inside them. There are mainly two types of lymphocytes:
    • B lymphocytes: B lymphocytes mature inside the bone marrow (hence the name B). A mature B cell contains antibodies on its surface—antibodies are proteins which can identify antigens. B cells also have various molecules on their surface like class 2 MHC (which help the B cells to present antigens to other cells) that help them interact with other immune system cells. 
    • T lymphocytes: T lymphocytes mature inside the thymus, which is a small organ located inside the chest. Mature T cells also have specific receptors on their membranes called T cell receptors or TCRs. However, unlike antibodies on B cells, TCRs cannot recognise free antigens—TCRs can only identify an antigen when the latter is presented to them by the MHC (major histocompatibility complex) on various cells in the body. Depending on a specific glycoprotein present on their surface, T cells are of two types:
      • CD4+: CD4+ cells have the glycoprotein CD4 on their surface. They recognise antigens bound to MHC class 2. CD4+ are often called T helper (T_h) cells. MHC class 2 present foreign antigens like pathogenic bacteria. Once they are activated, T helper cells activate more T and B cells and other immune system cells. There are two types of T helper cells, T_h1 and T_h2. Both these types of T_h cells produce cytokines; however, they are of different kinds. While the T_h1 cytokines are pro-inflammatory (increase and stimulate inflammation), T_h2 cytokines are anti-inflammatory. When the T_h1 response goes out of hand, it can lead to tissue damage. T_h2 counters the effect of T_h1 response.
      • CD8+: CD8+ T cells have the glycoprotein CD8 on their surface. They recognise antigens bound to MHC class 1. These are often called T cytotoxic (Tc) cells. MHC class 1 present self-antigens like cancerous proteins or virus-infected cells to T cells. On being activated, these cells convert to cytotoxic T lymphocytes (CTLs). CTLs can recognise altered self cells and destroy them. However, this breakdown of T_h and Tc cells is not always right in that both cells (in some cases) do the other cell’s functions.
• Monocytes: Monocytes are yet another type of agranulocytes that circulate in the bloodstream. Unlike lymphocytes, monocytes have a kidney-shaped nucleus and more cytoplasm space. Monocytes are the largest of the WBCs. They turn into tissue-specific macrophages (for example, alveolar macrophages in lungs and microglial cells in the brain) when they enter tissue space. Macrophages are five to ten times bigger than monocytes and they have a higher phagocytic activity than monocytes. Monocytes comprise about 5% of all circulating WBCs.
• Mast cells: Mast cells are usually present at the junction of tissues and the external environment like the skin and mucous membranes. These cells contain histamine granules, and along with basophils, play an important role in allergies and parasitic infections. 
• Dendritic cells: These cells have small projections on their surface and are mainly involved in phagocytosis and presentation of antigens to T_h cells through MHCs. There are different types of dendritic cells depending on their location, for example, circulating dendritic cells are present in the blood and Langerhans cells are found in the skin.

The lymphatic system is a complex network of lymphatic vessels, organs and tissues that are present throughout the body.

Our blood passes through capillaries (very thin blood vessels that connect arteries and veins) for exchange of nutrients and waste between tissues and blood. Once the exchange happens, not all the blood goes back into the bloodstream, a small part stays inside the tissues. This liquid, called lymph, is taken into the lymphatic capillaries and enters the lymphatic system.

Flowing in these lymphatic vessels, lymph passes through and is filtered by lymph nodes and gets collected into bigger ducts called the collecting ducts. There are two collecting ducts in the body—one on each side. These ducts are connected to the subclavian vein (a major vein right below the collarbone), hence returning the fluids to the bloodstream. This return of fluid helps maintain fluid balance in the body and prevents oedema (fluid buildup in tissues).

Lymphoid organs are of two types:

• Primary lymphoid organs: Primary lymphoid organs are those where lymphocytes mature into functional lymphocytes. There are two primary lymphoid organs in the body:
  • Bone marrow, where the B lymphocytes develop and mature
  • Thymus, where the T lymphocytes mature. T lymphocytes are formed inside the bone marrow before they move to the thymus to turn into functional T lymphocytes. If any T cells are formed against self or healthy cells, they are eliminated at this step.
• Secondary lymphoid organs: Secondary lymphoid organs are those where mature lymphocytes come in contact with antigens and fight those antigens. This type of lymphoid tissue either contains a diffuse collection of lymphocytes and macrophages, a sort of arrangement called lymphoid follicles, or proper organs including the spleen and lymph nodes.
  • Lymphoid follicles have primary follicles where some dendritic cells and B cells reside and secondary follicles which contains B cells surrounding an area called the germinal centre where rapid proliferation of B cells happens during infection along with an area with T helper cells, non-dividing B cells and some macrophages and dendritic cells. Less organised lymphoid tissues are present in various areas of the body including the appendix, Peyer's patches (inside intestines), tonsils and mucous membranes of the bronchi (airways), alveoli (lung sacs) and the gut. Together, these are called mucosal-associated lymphoid tissue.
  • Lymph nodes: Lymph nodes are small bean-shaped structures that are present at the junction of various lymphatic vessels and are responsible for filtering lymph (fluids coming from tissues). Lymph nodes have various types of cells in them including macrophages and dendritic cells that capture any pathogens passing by and present them to the T cells. B cells are also present in lymph nodes.
    In our body, lymph nodes are present in various areas including the armpits, groin, neck between lungs and in the gut. Cancer originating in one part of the body can spread to other parts through lymph nodes. Hence, in most cases of cancer, doctors check lymph nodes for the presence of cancerous cells.
  • Spleen: The spleen is present on the left side of the abdomen and it filters blood to trap any pathogens present in it. The spleen is supplied by blood vessels (instead of lymphatic vessels). Just like lymph nodes, the spleen also has both B and T lymphocytes and phagocytic cells that present antigens to T cells and helps mediate antigen-specific immune response in the body.

Skin is the largest organ of our body. It not only presents a mechanical barrier to the entry of pathogens inside the body (the skin cells are packed very close together and do not allow any pathogen to enter the body via the skin) but also has various immune system cells inside the dermis (the lower layer of skin) that fight off foreign invaders. Here are some types of cells and their functions inside the skin:

• Keratinocytes: Keratinocytes are specialized epithelial cells (present on the outer layer of skin) that secrete various cytokines (a type of signalling molecule) to initiate inflammation in the damaged tissue/area. Keratinocytes also have MHC 2 on their surface and can hence present antigens to T helper cells. 
• Langerhans cells: Langerhans cells have long projections coming out of their surface. They phagocytose (engulf) antigens and move to lymph nodes to change into something called interdigitating dendritic cells which have MHC 2 on their surface and present the antigen to T helper cells.
• Intraepidermal lymphocytes: Intraepidermal means inside the epidermis. These lymphocytes mostly consist of CD8+ T cells that specialize in targeting antigens that enter through the skin surface. The dermis layer also contains CD8+ T cells along with CD4+ T cells and macrophages which were made on a previous occasion when an antigen had entered the body.
• Skin also has other cells like neutrophils, eosinophils and mast cells.

The mucous membrane is the inner lining of our gastrointestinal tract, respiratory tract and the urogenital tract. Just like the skin, it provides a mechanical barrier to prevent pathogens from entering into circulation.

Mucous membranes secrete a slimy substance called mucous and have various bacteria on them that prevent pathogens from attaching to their surface. They also have tiny hair-like projections called cilia that push the pathogens and harmful substances out of the body. 

Additionally, mucosal surfaces have something called mucosal-associated lymphoid tissue (MALT), which is a type of secondary lymphoid tissue. It comprises unorganised areas like the lamina propria inside the intestines and more organised areas like the tonsils (in the mouth), the appendix (to the right of the abdomen) and Peyer's patches (in the intestines). MALT has a large number of antibody-producing cells (more than those found in the spleen or lymph nodes). 

A special type of cells called M cells helps pass the pathogens from the gut, respiratory or urogenital system inside MALT in the area. Once the pathogen reaches the lymphoid tissue, various immune system cells including macrophages, B cells and T cells identify it and start fighting against it. 

The five types of antibodies are as follows:

• IgG: IgG is the most abundant of all the immunoglobulins, accounting for about 80% of all immunoglobulins. This is the only type of immunoglobulins that can cross the placenta. IgG helps in fighting bacterial infections and viral infections. 
• IgM: IgM is the first immunoglobulin that is formed at the time of infection and the first type of antibody that forms in newborns. IgM antibodies make up about 5-10% of all the serum immunoglobulins.
• IgA: About 10-15% of all serum immunoglobulins are IgA type. IgA antibodies are majorly present in all the secretions of the body, including tears, breast milk, saliva and mucus. 
• IgE: IgE is mainly involved in allergic reactions along with mast cells and basophils. They are normally not present in very high numbers in the blood.
• IgD: IgD only comprises about 0.2% of all antibodies in our serum. Not much is known about this immunoglobulin. However, it is believed to be a major immunoglobulin on the surface of B cells and play a role in the activation of B cells on exposure to antigens.

Regardless of type, antibodies have a specific Y-shaped structure with two heavy chains and two light chains (both heavy and light chains are made of amino acids) attached together by disulphide bonds.

The upper ^v region of the antibodies has two parts. The lower constant region determines the way an antibody will target the antigen, it is different in the five types of immunoglobulins. The upper variable region is further subdivided into hypervariable region or complementarity determining region, which is the actual region in the antibody that makes contact with the antigen and the lower framework region that makes sure that the hypervariable region is in the right position to be in contact with the antigen.

Simply put, the upper ^_v region (remember the Y shape of antibodies) can bind with specific sites on the pathogen, to neutralise and eliminate it. Once an antibody binds to the antigen, the constant region of the heavy chain then interacts with other immune system cells to eliminate the antigen in one of the following ways:

• Macrophages and neutrophils phagocytose the pathogen, and the organism is destroyed.
• A serum glycoprotein called complements is activated; complements can break down the cell membranes of pathogens or mark them for phagocytosis. The complement system also triggers inflammation.
• Apoptosis or programmed death of a cell that is marked by antibody binding is done by a special type of cell called NK (natural killer) cells.