The TH1 Response

These cells are recombinant receptors that have been developed specifically for this purpose. These CARs are usually composed of an extracellular antigen recognition receptor that is attached by a spacer to a transmembrane domain. Around these transmembrane domains could be additional domains that function as co-stimulator to produce a further immune response. In a normal t-cell, there is a requirement of an MHC molecule to bind and recognize the antigen, however, the CAR T-cells are capable of overcoming the limitation. So CAR T-cells are able to bind directly and independent of this system allowing the cell to read a much diverse pool.

Cytotoxic T cells have receptors that allow them to connect with specific antigens and kill them to prevent an immune response to a virus. T helper cells have a surface protein called CD4 which aids in cell interaction and the secretion of cytokines.

a. This function is mediated by T cells and B cells (memory cells) in our body via adaptive immunity. The adaptive immune system evolved in early vertebrates and allows for a stronger immune response as well as immunological memory, where each pathogen is “remembered” by a signature antigen. The adaptive immune response is antigen-specific and requires the recognition of specific “non-self” antigens during a process called antigen presentation. Antigen specificity allows for the generation of responses that are tailored to specific pathogens or pathogen-infected cells. The ability to mount these tailored responses is maintained in the body by memory cells. Should a pathogen infect the body more than once, these specific memory cells are used to quickly eliminate it. So basically killer T cells will identify antigens present on foreign cells. These antigens are not found in any of the cells inside our body. Therefore, T cells will identify them and kill them.

At the DN3 stage – also in the subcapsular cortex, the thymocytes begin their development as αβ or γδ T-cells is made. This decision is made by the successful completion of the rearrangement of the β TCR gene. If a cell chooses to become a γδ T-cell, it finishes development here and enters the periphery. Once this lineage choice has been made, the expression of CD25 is halted and the pre-TCR is expressed on the cell surface.

this occurs in a series of steps, the first of which is incorporation of unidentified antigens by APCs in the epidermis and dermis. This process involves binding of the antigens to the MHC on the APC surface and the APC migrates to the lymph nodes. There, the APC binds reversibly and briefly with naïve or resting T cells through interactions between surface molecules located on both cells. Next, the MHC presents the antigen to a T lymphocyte receptor to begin activation of the T lymphocyte. The second signal for T lymphocyte activation is a non-antigen/ cell-cell interaction known as costimulation. If costimulation does not occur, the T lymphocyte will either undergo apoptosis or become unresponsive. Costimulation involves pairing of receptor with ligand on the T cell; these pairs include (LFA)-3 interacting with CD2, B7 interacting with CD28, and ICAM-1 interacting with LFA-1 (Lebwohl, 2003).

Within the immune system, the thymus receives immature T cells from the bone marrow and turns them to mature T cells so that they can detect foreign substances. Antigens from epithelial cells are presented to the immature T cells. The T cells that recognize the antigens of the foreign cells continue to be tested and shown native cells from the body. If the T cells bind to the native cell, they are labeled autoimmune and destroyed, but those that

When a particular pathogen reinfected the body, it is met by an expansion of clonally selected cells, which has an antigen-specific memory toward the pathogen. This allows it to undergo much more rapid differentiation into effector cells when compared to the first antigen encounter. This result in a stronger and faster secondary immune response that eliminates the pathogen before it affects the body.

The major innate immune cell is the dendritic cell and the major adaptive immune cell is the T-cell. An innate cell is a cell that is always active and is not specific to an antigen. An adaptive cell circulates in the body in a naïve form until it is stimulated by a specific antigen. When the naïve cell becomes stimulated it turns into an effector cell that is specific to the antigen that stimulated it. Each of these cells have a specific function in the immune system and in graft rejection. The dendritic cell is important in recognizing MHC because it is a professional antigen presenting cell. This means that it will take up a part of the foreign MHC and display it within its own MHC. It is able to do this because there are two types of MHC. MHC class I displays proteins that are created within the cell, while MHC class II can display proteins from other cells that are phagocytosed (engulfed) by an antigen presenting cell. When a dendritic cell phagocytoses part of the foreign MHC and displays it on its own MHC class II it travels to a lymph node in the body and shows it to a T-cell’s receptor (TCR). This is the 1st signal required to stimulate a T-cell. The second signal occurs when CD28 on the T-cell binds to B7 on the antigen presenting cell. A dendritic cell is a professional antigen presenting cell because when it travels to the lymph node with the foreign antigen it increases the amount of

The neutrophils and macrophages are phagocytic leukocytes that are present in large numbers and are evident within hours at the site of inflammation. The neutrophil is the primary phagocyte that arrives early at the site of inflammation, usually within 90 minutes of injury, and is often referred to as PMN’s (polymorphonuclear neutrophils or segmented neutrophils (segs). The neutrophil count in the blood often increases greatly during an inflammatory process, especially with bacterial infections (Porth, p. 379). Neutrophils have a lifespan of only about 10 hours, and as a result, the circulating WBC count is increased, causing leukocytosis. With excessive demand for phagocytes, immature forms of neutrophils are released from the bone marrow. These immature cells are called bands. Within 24 hours, mononuclear cells arrive at the inflammatory site, and by 48 hours, monocytes and macrophages are the predominant cell

The immune system is constituted by two major subdivisions: the innate or non-specific immune system and the adaptive or specific immune system. Both major subdivisions of the immune system possess cellular and humoral characteristics by which they carry out their protective task. Even though these two arms of the immune system have distinct functions, they interact between each other (i.e., components of the innate immune system influence the adaptive immune system and vice versa) (Cruvinel et al., 2010; http://www.microbiologybook.org/ghaffar/innate.htm).

Immunology basically involves understanding the immune system and how it responds to various disease conditions. the immune system consists of a number of components. Traditionally, it is divided into humoral and cellular immune responses. It can also be distinguished into innate and adaptive immunity. The innate immunity can discriminate between normal tissues , self and newly encountered non-self-proteins while the adaptive immunity is the more complex system aimed at the eradication of intracellular pathogens. To do this, antigen derived from such pathogens that are often new to the host organism, need to be recognised by receptor-bearing specialised immune cells which respond to a complex system of stimulatory and costimulatory signals. Better understanding of the human immune system has led to the identification of a number of tumor-associated antigens in the 1980s and the development of various immunotherapeutic approaches. In recent years, identification of the specific antigenic MHC class I epitopes, advancements in genetic engineering, gene delivery, and cell-based therapeutic approaches allowed development of the novel immunotherapeutics.

Inflammatory response Diseased organisms trigger the inflammatory response off in the affected tissues. It is a non-specific defence which attacks invading organisms. Blood flow increases and neutrophil cells ingest and destroy organisms. The invading organisms damage the tissues so they release prostaglandins and histamine.

royed • Lysosome fuses with phagosome to form phagolysosome • Foreign materials trapped within phagolysosme is digested by enzymes Adaptive immunity • Initiate immune response →present antigens after digestion of foreign material • Antigen (protein on the surface of a pathogen) stimulates T lymphocytes • Antigen on macrophage’s membrane displayed with attachment of MHC II → not recognized as pathogen • Stimulates production of antibodies that attach to pathogen’s antigens →easier for macrophage to attach with cell membrane and undergo phagocytosis Wound Healing • Two days after wound injury polymorphonuclear neutrophils replaced • Platelets and other cells releasing growth factors attract macrophage to wound • Monocytes (matures to become macrophages) passes through blood vessel walls to arrive at wound • Phagocytose foreign material • Repair tissue by producing →platelet derived growth factor →fibroblast growth factor →transforming growth factor beta • Vascular endothelial growth factor stimulated and produced →endothelial cell growth →create granulation tissue →new extracellular matrix generated Macrophage activities • M1 (classically activated)→”killer” →inhibit cell proliferation and damage tissue →activated by natural killer cells and interferon gamma • M2 (alternatively activated)→ “repair” →wound healing and tissue repair →activated by eosinophils and basophils Summary • Effector cell →

Initial injury causing release of inflammatory mediators (e.g. histamine, serotonin, leukotriene, SAS-A, lysosomes enzymes and prostaglandins).

when a B-cell encounters a pathogen it triggers the humoral immune response where they secret antibodies that are made specifically for that antigen. B lymphocytes are activated in the lymph nodes. CD4 cells that become helper T cells help to activate B cells (Marieb & Hoehn, 2016), with the help of IL4 and MHC II proteins. They transform into plasma cells that make antibodies that bind to antigens. Humoral immunity is found in the red bone marrow and its primary targets are pathogens found in the extracellular such as bacteria and viruses. B-cells become plasma effector cells and forms memory