CELLS INVOLVED IN IMMUNE RESPONSE (Lymphocytes)
1) CELLS INVOLVED IN IMMUNE RESPONSE (Lymphocytes)
1.5) Types of T Cells
1.6) B-CELLS or B Lymphocytes
What is immune Response ?
- The immune response involves a coordinated set of interactions among host cells and the protective molecules they produce upon encountering a pathogen or antigen.
- The purpose of which is to prevent dangerous incursions and then to restore homeostasis.
Cells of immune response
T- cells or T lymphocytes
- A type of white blood cell that is of key importance to the immune system and is at the core of adaptive immunity, the system that tailors the body’s immune response to specific pathogens. The T cells are like soldiers who search out and destroy the targeted invaders.
- Large numbers of antigen-specific T cells are produced in the thymus from circulating T cell precursors derived from stem cells in the bone marrow. Each T cell has receptors specific for only one antigen that are generated by gene rearrangement from multiple, inherited germline genes. T cells then undergo selection to remove those that are highly self-reactive. In the process, two different kinds of T cells develop. T helper (Th) cells, of which there are two types (Th1 and Th2), express CD4 and provide help for B cell growth and differentiation. T cytotoxic (Tc) cells express CD8 and recognize and kill virally infected cells. Functionally mature T cells then migrate to secondary lymphoid tissues to mediate protection.
Production of T Cells
- T cells originate from stem cells which are produced in the bone marrow.
- T cells then migrate to the thymus gland, in the anterior mediastinum, to undergo the process of maturation. They enter the cortex and proliferate, mature and pass onto the medulla of the thymus.
- From the medulla, mature T cells enter the circulation. These mature T cells are now capable of responding to antigens in the periphery.
- The thymus shrinks as we age and so provides fewer T cells over time.
Types of T Cells
1. Helper T Cells
- They become activated when they are presented with peptide antigens by MHC Class II molecules, which are expressed on the surface of antigen presenting cells (APCs).
- Helper T cells help in the maturation of B cells into plasma cells and memory B cells. They also help activate cytotoxic T cells and macrophages.
- Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or assist in the active immune response. There are various subtypes present within the immune system that are able to secrete different cytokines depending on the immune response occurring.
2. Cytotoxic T Cells
- Cytotoxic T cells cause lysis of virus-infected and tumour cells. They are also involved in transplant rejection. These cells recognize their targets by binding to antigen associated with MHC Class I molecules which are present on the surface of all nucleated cells.
3. Natural Killer T Cells
- They bridge the adaptive immune system with the innate immune system. Whilst most T cells function based on recognition of MHC class molecules, natural killer T cells are able to recognise other antigen classes. Once activated they are also able to perform the same functions as Helper T cells and Cytotoxic T cells.
- These cells are distinct from natural killer cells.
4. Memory T cells
- Once they come into contact with an antigen naive T cells differentiate into effector cells (Helper T cell and Cytotoxic T cells) and memory T cells. Memory T cells are long-lived and can quickly expand to large numbers of effector T cells upon re-exposure to the antigen.
- They provide the immune system with “memory” against previously encountered pathogens. Memory T cells may be either Helper T cell and Cytotoxic T cells.
How T-Cells Works
- T lymphocytes eliminate nascent tumors and intracellular microorganisms such as viruses and some bacteria, and regulate the strength of adaptive immune responses. Functionally, T lymphocytes lyse malignant or infected cells, induce inflammatory responses, and synthesize and secrete soluble intercellular messengers called cytokines.
- Antigen-presenting cells must bind the processed antigens, first by using the major histocompatibility complex (MHC) and then presenting it to the T lymphocytes.
- With the help of other assistive molecules, the T lymphocytes are activated to secrete effector proteins for clearing antigens. There are many ways to classify the T lymphocytes; most accepted subpopulations are T help (TH), T cytotoxic (TC), and T regulatory cells (T reg). TH cells have CD4 glycoprotein on their surfaces, TC cells have CD8 glycoprotein, and T reg cells have CD4 on their membranes.
- After encountering the right antigen-MHC complex, TH cells do not clear the antigens directly but activate the B cells and TC cells to kill the pathogens. However, TC cells are responsible for secreting proteins to destroy the pathogen cell wall and kill the pathogens.
B-CELLS or B Lymphocytes
- A type of white blood cell and, specifically, a type of lymphocyte.
- Many B cells mature into what are called plasma cells that produce antibodies (proteins) necessary to fight off infections while other B cells mature into memory B cells.
- B cell activation occurs in the secondary lymphoid organs, such as the spleen and lymph nodes.
- The maturation of B cells takes place in birds in an organ called the bursa of Fabricus. B cells in mammals mature largely in the bone marrow.
How B cells works
- With the help of T-cells, B-cells make special Y-shaped proteins called antibodies. Antibodies stick to antigens on the surface of germs, stopping them in their tracks, creating clumps that alert your body to the presence of intruders. Your body then starts to make toxic substances to fight them. Patrolling defender cells called phagocytes engulf and destroy antibody-covered intruders.
Activation of B-Cells
- Activation of B cells occurs through different mechanisms depending on the molecular class of the antigen. Activation of a B cell by a protein antigen requires the B cell to function as an APC, presenting the protein epitopes with MHC II to helper T cells. Because of their dependence on T cells for activation of B cells, protein antigens are classified as T-dependent antigens.
- In contrast, polysaccharides, lipopolysaccharides, and other nonprotein antigens are considered T-independent antigens because they can activate B cells without antigen processing and presentation to T cells.
T Cell-Independent Activation of B cells
- A T Cell-Independent Activation of B cells is activation of B cells without the cooperation of helper T cells is referred to as T cell-independent activation and occurs when BCRs interact with T-independent antigens(e.g., polysaccharide capsules, lipopolysaccharide).
- Once a B cell is activated, it undergoes clonal proliferation and daughter cells differentiate into plasma cells. Plasma cells are antibody factories that secrete large quantities of antibodies.
- The T cell-independent response is short-lived and does not result in the production of memory B cells. Thus it will not result in a secondary response to subsequent exposures to T-independent antigens.
T cell-dependent activation
- Antigens that activate B cells with the help of T-cell are known as T cell-dependent (TD) antigens and include foreign proteins.
- Once a BCR binds a TD antigen, the antigen is taken up into the B cell through receptor-mediated endocytosis, degraded, and presented to T cells as peptide pieces in complex with MHC-II molecules on the cell membrane. T helper (TH) cells, typically follicular T helper (TFH) cells recognize and bind these MHC-II-peptide complexes through their T cell receptor (TCR).
- Now activated, B cells participate in a two-step differentiation process that yields both short-lived plasma blasts for immediate protection and long-lived plasma cells and memory B cells for persistent protection. The first step, known as the extrafollicular response, occurs outside lymphoid follicles but still in the SLO. During this step activated B cells proliferate, may undergo immunoglobulin class switching, and differentiate into plasma blasts that produce early, weak antibodies mostly of class IgM.
- The second step consists of activated B cells entering a lymphoid follicle and forming a germinal center (GC), which is a specialized microenvironment where B cells undergo extensive proliferation. These processes are facilitated by TFH cells within the GC and generate both high-affinity memory B cells and long-lived plasma cells.
- Resultant plasma cells secrete large amounts of antibody and either stay within the SLO or, more preferentially, migrate to bone marrow
Natural killing cells
- Natural killer cells (also known as NK cells, K cells, and killer cells) are a type of lymphocyte (a white blood cell) and a component of innate immune system.
- NK cells play a major role in the host-rejection of both tumours and virally infected cells.
- NK cells are cytotoxic; small granules in their cytoplasm contain special proteins such as perforin and proteases known as granzymes.
- Upon release in close proximity to a cell slated for killing, perforin forms pores in the cell membrane of the target cell through which the granzymes and associated molecules can enter, inducing apoptosis.
- NK cells are activated in response to interferons or macrophage-derived cytokines.
- They serve to contain viral infections while the adaptive immune response is generating antigen-specific cytotoxic T cells that can clear the infection
- Patients deficient in NK cells prove to be highly susceptible to early phases of herpes virus infection.
How do natural killer cells works?
- All of our cells have specific set of proteins on their surface that identifies them as ‘self’(MHC class I).
- Natural killer cells recognize cells that have too few of the self proteins on their surface and therefore may be infected.
- When an infected cells is recognized, the natural cell releases a mixture of proteins that enter infected cell and lead to cell death(apoptosis).
- Dendritic cells(DCs) are antigen-presenting cells(also known as accessory cells) of the mammalian immune system.
- Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system.
- They act as messengers between the innate and the adaptive immune systems.
Functions of dendritic cells
- Maintain immune memory in tandem with B cells.
- Antigen presentation and activation of T-cells.
- Inducing and maintaining immune tolerance.
- To process antigen material and present it on to T-cells, thus functioning as antigen-presenting cells.
Monocytes and Macrophages
- A monocyte is a type of white blood cell and a type of phagocyte.
- A type of immune cell that is made in the bone marrow and travels through the blood to tissues in the body where it becomes a macrophage.
- Macrophages surround and kill microorganisms, ingest foreign material, remove dead cells, and boost immune responses
Functions of monocytes
- Monocytes and their macrophage and dendritic cell progeny serve three main functions in the immune system. These are phagocytosis, antigen presentation, and cytokine production.
- Phagocytosis is the process of uptake of microbes and particles followed by digestion and destruction of this material.
- Monocytes can perform phagocytosis using intermediary proteins such as antibodies or complement that coat the pathogen, as well as by binding to the microbe directly via pattern-recognition receptors that recognize pathogens.
- Monocytes are also capable of killing infected host cells via antibody-dependent cell-mediated cytotoxicity.
Functions of macrophages
- They assume a defensive role exhibited by their ability to carry on phagocytosis of parasites and microbes.
- They regulate lymphocyte activation and proliferation and they are essential in the activation process of T- and B-lymphocytes by antigens and allogenic cells.
- The removal of dying cells is, to a greater extent, handled by fixed macrophages