Immune System and its Components

This assignment delves into the complexities of the human immune system. It examines various components, including T cells (regulatory and invariant gamma delta), B cells (differentiation, function, and memory), and dendritic cells. The role of metabolism in T cell regulation is also discussed, along with the functions of B cells in immunity and tolerance. The assignment emphasizes the intricate interplay between these cellular players in maintaining a healthy immune response.

Running head: IMMUNOLOGY
Immunology
Name of the Student
Name of the University
Author note

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An immune system is responsible for producing responses to pathogens depending upon
the keen choreographed interactions among the diverse cells of the immune system (Parham
2014). Two types of immunity: innate and acquired are produces immune response to fight
against pathogens. For this, immune cells play the most important role providing the immunity
and line of defence for the body. Immune cells of innate immunity provide the first line of
defence against pathogens where antigen-presenting cells (APCs) communicate the pathogen to
lymphoid cells coordinating to form adaptive response generating memory cells preventing
future infections (Mauri and Bosma 2012). This coordination is mediated by immune system
organized throughout the body in time and space. Specialized cells like mature red blood cells,
macrophages, granulocytes, lymphocytes and dendritic cells are the immune cells that play the
major role in the immune system action. Therefore, the following discussion involves the
development and functioning of immune system cells (myeloid and lymphoid lineage) united to
perform functions as a whole.
The specialized cells that function to perform immune activity arise from single cell type,
hematopoietic stem cells (HSCs) via differentiation to form maturing blood cells by the process
of haematopoiesis. In this process, self-renewing HSCs give rise to myeloid and lymphoid
progenitors forming mature immune cells in the bone marrow and them migrating to peripheral
organs via blood (Owen et al. 2013). Macrophages and mast cells also undergo maturation, but
outside bone marrow. B cells develop to maturity in bone marrow and T cells in the thymus. An
HSC is induced for haematopoiesis or differentiation losing its self-renewal capacity and break
down into two broad lineage and commitment choices. Common myeloid-erythroid progenitor
(CMP) gives rise to all the RBCs (erythroid lineage) monocytes, neutrophils, granulocytes and
macrophages (myeloid) or into common lymphoid progenitor (CLP) giving rise to B

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lymphocytes, T lymphocytes and Natural Killer (NK) cells. Lymphocytes are a part of adaptive
immune response and generation of refined antigen-specific immune response and immune
memory. NK cells and myeloid cells are the part of innate immune system providing the first line
of defence towards pathogens or infections (Sompayrac 2015).
HSCs progress towards chosen lineages; they lose the capacity to contribute to the other
lineages. Both myeloid and lymphoid lineages give rise to APCs, dendritic cells with diverse
features, functions playing an important role in the initiation of adaptive immune responses.
Myeloid progenitors give rise to phagocytic cells (macrophages, monocytes and dendritic cells)
performing professional APCs. They perform the cellular bridging function between innate and
adaptive immunity by making a contact with pathogen at the infection site and communicating
this encounter to T lymphocytes to lymph node making “antigen presentation” (Owen et al.
2013). Lymphoid lineage progenitors give rise to lymphocytes being the principle players in the
adaptive immune response. It is again broadly divided into three major populations based on
function and phenotypic differentiation giving rise to T lymphocytes (T cells), B-lymphocytes (B
cells) and NK cells. B cells (APC) is involved in humoral immunity that present antigen and
secrete cytokines and T cells are involved in cell-mediated immunity. Therefore, the subsequent
sections involve the development, activation and function of both B and T cells.

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Figure 1- Haematopoiesis (Owen et al. 2013)

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When T cells interact with T cell receptors, the initiation of adaptive immune response is
generated and MHC peptides on APCs exposed to pathogens. T-cells development and
generation occurs in thymus where differentiation of T cells is directed by thymic
microenvironment through positive and negative selection. HSCs develop lymphoid progenitors
in bone marrow that migrate for the completion of antigen-independent maturation to become
functional t cells. In the thymus, there are specific T cell markers like CD3, CD8, CD4, TCR and
CD2 where they undergo thymic selection via positive and negative selection. In thymus, T cell
precursors enter the sub capsular spaces in the cortical areas encountering network of thymic
stroma or cortical epithelial cells and undergo proliferation (Roberts et al. 2012). After the
differentiation, they move to medulla from cortex of the thymus and direct T cell development.
Majority of cells die before completing the steps by apoptosis to become a mature naive T cell.
The binding of double positive T cells to cortical epithelial cells that expresses Class I or II
MHCs and self-peptides with high affinity survives called positive selection. The binding of
double positive T cells to bone marrow derived APCs like dendritic cells, macrophages
expressing Class I and II MHC and self peptides with high affinity receiving apoptotic signal
called negative selection. Concisely, it can be said that this selection occurs when self-peptides
are in thymus and MHC presents its self-peptides in the pathogen absence (Owen et al. 2013).
Activation of T lymphocytes is an antigen-dependent process that leads to proliferation
and differentiation of naive T cells. Co activating and primary signals trigger cascade of
intracellular signal transduction and new genetic expression. When T cell receptor (TCR) binds
to foreign antigen on cell surface of an APC or target cell and T cell co-receptor binding to MHC
on target cell, it is called signal 1. Signal 2 occurs when binding takes place between co-
activating molecules on T cell to co-stimulatory molecules on target cell or APC where B7 is the

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most important protein. The binding of B7 by T cell co-stimulatory molecules result in T cell
activation, on the other hand, lack of binding can result in apoptosis. However, many naive T
cells do not possess B7 protein; there is prevention of T cells from reacting to own proteins of
the host. This combination of signal 1 and 2 is the determining factor for the T cell response too
an Ag. Activation of cytotoxic T cells (CD8) via MHC Type I binding results in direct target cell
lysis. The activation of helper T cells (CD4) via binding of MHC II causes multiple down
streaming effects that includes pro-inflammatory molecules synthesis (cytokines) like tumour
necrosis factor (TNF), enhanced B cell antibody secretion and killing by CD8 cells (MacIver,
Michalek and Rathmell 2013).
CD4 T cells have a large number of immune responses and critical for immune
functioning in the body. For example, when CD4 cells are less or become dysfunctional, it
indicates that host is immunocompromised and susceptible to opportunistic infections. On the
contrary, overactivity of CD4 cells may lead to over secretion of inflammatory cytokines and
eventually, inflammatory diseases.
The function of T cells is that it recognizes and invades viruses and bacteria responsible
for cell-mediated immunity. Helper T cells help in the direction of immune system where it
releases cytokines. It stimulates B cells forming plasma cells that in turn form antibodies
stimulating T cells types’ production; cytotoxic T cells and suppressor cells. Cytotoxic T cells
release chemicals that break open in killing invading pathogens. Memory T cells follows this
process helping immune system responding quickly to the same pathogen when the body again
encounter it. Suppressor T cells suppress the immune response in order to save the normal cells
after the job is done (Josefowicz, Lu and Rudensky 2012).

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The development of B cell takes place in the fetal liver and continues in bone marrow for
the rest of our lives. When a B cell is able to express both μ and L chains on it membranes
surface, it is a naive B cell. Lymphoid progenitors receive signals from the stromal cells in bone
marrow and begin B cell development. Cytokines induce recombinase and TdT (RAG 1 and 2)
for the synthesis in CD34+ lymphoid progenitors. D-J joining in cells takes place on H
chromosome and become early pro-B cells beginning to express CD45 or (B220) and MHC II
Figure 2- T cell development (Owen et al. 2013)

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class. The joining of V segment to D-JH is the completion of late pro-B cell stage (Bendall et al.
2014).
Pro-B cells starts becoming pre-B cells when they start expressing membrane μ chains
along with surrogate light chains in pre-B receptor where surrogate L chains resemble the actual
L chains and present on every pre-B cell. Ig heavy chains’ cytoplasmic tails are too short and
could not enter cytoplasm cytoplasm and hence, transmit antigen-binding signal. When antigen-
TCR binding takes place, ITAMs (Immunoreceptor Tyrosine Activation Motifs) become
phosphorylated present on Ig α Ig β signal transduction molecules. This phosphorylation gives
rise to cascade of cytoplasmic signalling where halting of H chain recombination takes place and
clone of B cell proliferation that produces same μ chain. Diving cells are larger than resting cells
and large pre-B cells stage occur (McHeyzer-Williams et al. 2012). After the proliferation, small
pre-B cells do not divide and undergo V-L joining on one of the L chain chromosome. After this,
L chain expresses itself with μ chain on the cell membrane and forming immature B cell. These
cells are sensitive to Ag binding and without it; they die in the bone marrow. B cells that do not
bind to self-antigen δ chain and membrane IgD with IgM leave the bone marrow and become
mature naive B cells. Positive selection occurs when developing B cells are positively selected
when binding takes place between pre-B cell with the ligand. It shows the ability for binding to
MHC and its peptides. The binding to receptor resulting in cell death is negative selection where
immature T and B cell are negatively selected that binding self-antigen (Corfe and Paige 2012).
Activation of B cell takes place when IgD and IgM surface receptors bind to specific
antigen. It serves two roles in the B cell activation; firstly, there is delivering of biochemical
signals by Ag-induced receptor clustering to B cells initiating process of activation. Secondly,
receptor binding to protein antigen and internalization into endosomal vesicles with further

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processing and presentation to helper T cells at MHC II molecule surface (Pieper, Grimbacher
and Eibel 2013).
B cell antigen receptor delivers activating signals to cells when receptor molecules cross-
link or brought together by multivalent antigens. Igα and Igβ, the two membrane proteins are
linked together with disulphide bonds covalently to each other linking membrane Ig that
transduces the signals generated by surface receptor clustering. The two molecules when linked
together with surface Ig, B lymphocyte antigen receptor complex is formed and ultimately
activation of transcription factors take place inducing genes expression producing products that
are required for functional B cell activation (Kil et al. 2012).
B cell function in humoral immunity as a part of adaptive immune system secretes
antibodies. Antibodies are formed by B cells with the help of T cells that stick to foreign
pathogen and create clumps. After this, body releases toxic substances and by the process of
phagocytosis, destroy the foreign pathogens. In addition, they present antigen known as APCs
and secretion of cytokines. B cells bind the intact Ag present in the form of soluble molecules in
extracellular matrix and intact molecules when B cells pull from APCs surface like dendritic
cells and macrophages. Through receptor-mediated endocytosis, bound antigen molecules are
engulfed by B cell and digested into fragments. Helper T cells binding to B cell, secrete
lymphokines and stimulating B cells to enter divide by repeated mitosis and identical BCRs
through clonal selection (Poe and Tedder 2012).

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Macrophages are a form of WBCs that plays an important role in adaptive immunity.
Monocytes move through bloodstream and mature to macrophages, living, patrolling and
keeping cells clean. It plays an important role in phagocytosis where engulfs the pathogen in a
pocket called phagosome around it. Enzymes are released into phagosome within macrophage
called lysosome digests the pathogen and remaining debris exit macrophages absorbed back to
body. In the adaptive immunity, along with DCs, it presents antigens that play a vital role in
immune response. Macrophages play a crucial role in inflammation development producing
monokines, complement proteins and interleukin-1 (regulatory factor). It also carries receptors
Figure 3- B cell activation and function (Owen et al. 2013)

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for lymphokines allowing them to become activated into tumour cells and microbes (Guilliams et
al. 2014).
Dendritic cells are APCs performing the main function of processing of antigen material
and presenting it on cell surface to T cells. DCs act as messengers between adaptive and innate
immune systems. These cells have the capacity to induce primary immune response in naive T
lymphocytes, capturing Ag from invading, process, present on APC surface along with co-
stimulatory molecules. They produce cytokines promoting B cell activation and differentiation.
After the antibody response, DCs found in germinal centre of lymph node contribute to B cell
memory through Ag-Ab complex. This forms the main source of B cells Ag presentation to T
cells. Once DCs are activated, they move to lymph nodes interacting with B or T cells shaping
adaptive immune response (Merad et al. 2013).
Figure 4- Macrophages (Owen et al. 2013)

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From the above discussion, it can be concluded that immune system is plays the most
vital role in fighting with foreign invaders or pathogens. They are primarily the immune cells
that produce immune response in fighting with the pathogens and in protecting from diseases and
foreign invasion. Two types of immunity are present in the body; innate and adaptive immunity.
Among all cells, WBCs plays the most important role in immunity called leukocytes comprising
of macrophages and B cells, dendritic cells, T cells being APCs. Every cell has their own
development, maturation and function. It plays a crucial role in the neutralization of pathogens
by recognizing and removing them from the body. B cells development and maturation takes
place in bone marrow and T cells in thymus and therefore, they are named as B and T cells.
Similarly, macrophages and DCs are also important for Ag presentation, inflammation process
Figure 5- Dendritic cells (Owen et al. 2013)

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and phagocytosis. Therefore, proper immune system development and functioning is vital for
fighting against pathogens and protecting the body from diseases and infections.

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References
Bendall, S.C., Davis, K.L., Amir, E.A.D., Tadmor, M.D., Simonds, E.F., Chen, T.J., Shenfeld,
D.K., Nolan, G.P. and Pe’er, D., 2014. Single-cell trajectory detection uncovers progression and
regulatory coordination in human B cell development. Cell, 157(3), pp.714-725.
Corfe, S.A. and Paige, C.J., 2012, June. The many roles of IL-7 in B cell development; mediator
of survival, proliferation and differentiation. In Seminars in immunology (Vol. 24, No. 3, pp.
198-208). Academic Press.
Guilliams, M., Bruhns, P., Saeys, Y., Hammad, H. and Lambrecht, B.N., 2014. The function of
Fc [gamma] receptors in dendritic cells and macrophages. Nature Reviews Immunology, 14(2),
pp.94-108.
Josefowicz, S.Z., Lu, L.F. and Rudensky, A.Y., 2012. Regulatory T cells: mechanisms of
differentiation and function. Annual review of immunology, 30, pp.531-564.
Kil, L.P., de Bruijn, M.J., van Nimwegen, M., Corneth, O.B., van Hamburg, J.P., Dingjan, G.M.,
Thaiss, F., Rimmelzwaan, G.F., Elewaut, D., Delsing, D. and van Loo, P.F., 2012. Btk levels set
the threshold for B-cell activation and negative selection of autoreactive B cells in
mice. Blood, 119(16), pp.3744-3756.
MacIver, N.J., Michalek, R.D. and Rathmell, J.C., 2013. Metabolic regulation of T
lymphocytes. Annual review of immunology, 31, pp.259-283.
Mauri, C. and Bosma, A., 2012. Immune regulatory function of B cells. Annual review of
immunology, 30, pp.221-241.

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McHeyzer-Williams, M., Okitsu, S., Wang, N. and McHeyzer-Williams, L., 2012. Molecular
programming of B cell memory. Nature reviews Immunology, 12(1), pp.24-34.
Merad, M., Sathe, P., Helft, J., Miller, J. and Mortha, A., 2013. The dendritic cell lineage:
ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed
setting. Annual review of immunology, 31, pp.563-604.
Owen, J.A., Punt, J., Stranford, S.A. and Jones, P.P., 2013. Kuby immunology. 7th. New York:
WH Freeman, 27(692), p.28-48.
Parham, P., 2014. The immune system. Garland Science, pp.1-4.
Pieper, K., Grimbacher, B. and Eibel, H., 2013. B-cell biology and development. Journal of
Allergy and Clinical Immunology, 131(4), pp.959-971.
Poe, J.C. and Tedder, T.F., 2012. CD22 and Siglec-G in B cell function and tolerance. Trends in
immunology, 33(8), pp.413-420.
Roberts, N.A., White, A.J., Jenkinson, W.E., Turchinovich, G., Nakamura, K., Withers, D.R.,
McConnell, F.M., Desanti, G.E., Benezech, C., Parnell, S.M. and Cunningham, A.F., 2012. Rank
signaling links the development of invariant γδ T cell progenitors and Aire+ medullary
epithelium. Immunity, 36(3), pp.427-437.
Sompayrac, L.M., 2015. How the immune system works. John Wiley & Sons, pp.13-24.