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Learning Unit 2: Components of the immune
system and innate immunity
Work through this learning unit in conjunction with Chapter 33 of your prescribed book.
Learning outcomes
At the end of this learning unit you should be able to:
• Identify the components of the immune system.
• Explain how the components of the immune system detects and respond to infection.
• Identify the connection between innate and adaptive arms of immunity?
• Differentiate between primary and secondary lymphoid organs and tissues in terms of structure
and function.
• Explain the process of phagocytosis.
• Explain the process of inflammation.
2.1 Introduction to components of the immune system
This learning unit is based on Prescott’s Microbiology, Chapter 33, pp. 717 - 550.
We previously begun our discussion with an introduction to the physical and chemical barriers that
microbes face when encountering a host in learning unit 1. To this learning unit, we present the various
cells, tissues, and organs of innate defenses, discussing the mechanism by which they detect and respond
to foreign invaders.
2.2 Cells of the immune system
The immune system is a network of molecules, cells, tissues, and organs, each with a specialized role in
defending the host against extracellular microorganisms, cancer cells, and intracellular parasites. The cells
responsible for both innate defenses and adaptive immunity are the leukocytes (white blood cells). Note
the diagram (figure 33.9) on page 719 of Prescott, Harley and Klein’s Microbiology (2017), show below as
figure 2. This shows that cells (white blood cells) of the immune system originate in the bone marrow
during the process of Hematopoiesis that results in the production of two types of stem cells: the myeloid
stem cells that give rise to cell lines associated with the innate immune system; and the lymphoid stem
cells that give rise to cell lines linked to the acquired immune system. Although most cells of the immune
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system arise from the bone marrow, where many of them develop and mature, some, particularly certain
tissue resident macrophages population ( for example, the microglia of the central nervous system),
originate from the yolk sack or fetal liver during embryonic development. Once mature, immune cells reside
within peripheral tissues, circulate in the bloodstream, or circulate in specialized system of vessels called
the lymphatic system.
Figure 2. Pluripotent hematopoietic stem cells in the bone marrow divide to produce two blood cell lineages, the
common myeloid and the common lymphoid progenitor: (a) the common myeloid progenitor cell gives rise to the
erythroblast that produces erythrocytes (red blood cells), megakaryocytes that produce platelets important in blood
clotting, an unknown precursor that gives rise to mast cells, the granulocytes (eosinophils, basophils, and
neutrophils), monocytes that give rise to dendritic cells (DCs) and macrophages, and a separate lineage of DCs; and
(b) the lymphoid progenitor cell gives rise to innate lymphoid cells that can differentiate into natural killer (NK) cells,
a separate lineage of DCs, B cells, and T (regulatory, helper, and cytotoxic) cells. T and B lymphocytes are
distinguished from other leukocytes by having antigen receptors and from each other by their sites of differentiation-
the thymus and bone marrow, respectively. Note that DCs can arise directly from myeloid and lymphoid progenitor
cells and from nonproliferating monocytes.
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Among the cells derived from the myeloid stem cells are red blood cells together with cells that give rise
to platelets. Note that mast cells are involved in allergic reactions and that granulocytes (cells derived from
the myeloblast line) show some differences regarding function – neutrophils engulf (i.e. take in) and kill
pathogens such as bacteria; basophils are associated with allergies and inflammatory events; while, in
addition to allergy and inflammatory reactions, eosinophils are associated with worm and fungal
infestations. Note that these cells are named according to their uptake of microscopy stains (neutral, basic
or eosin). Under the microscope, monocytes are characterised by bean-shaped nuclei and they give rise
to cells that can engulf cells and foreign matter. Macrophages and dendritic cells are derived from
monocytes and they engulf foreign matter, process it and then present this material to other immune
system cells so as to activate these cells to continue the immune response to the foreign material. These
two cells have the ability to bridge innate resistance and adaptive immunity.
Activity 2.1
Please prepare a table of cell types versus cell characteristics and function for all the above-mentioned
cells. Please transpose the information for each cell type as described in page 719 to 721 of the textbook
onto this table.
Note the brief description of the origin, activation and replication of lymphocytes provided on page 722 of
the textbook. Lymphocytes are derived from lymphoid stem cells are divided into three populations: T cells,
B cells, and Natural killer cells. T cells and B cells are major cells of the adaptive immune response,
whereas the Natural killer cells are part of the innate immune response. The T cells (processed in the
thymus) effectively control the immune system while the B cells (initially noted to be processed in the avian
bursa of Fabricius) secrete antibodies. These cells are relatively long-lived cells and one of the reasons
for this is that once the lymphoid cells leave the bone marrow they do not immediately start dividing. This
stasis is maintained after they differentiate into T or B cells and only after these cells are activated following
interaction with foreign material do they start dividing. This division leads to a group of cells that is specific
in its interaction with that foreign material. As previously mentioned, activated T cells control the immune
system by producing cytokines that are molecules that affect the activity of other cells in the immune
system. Activated B cells are called plasma cells, and these cells produce and secrete antibodies specific
for foreign material. These features of T and B cells are shown in Figure 33.11 on page 722 of Prescott,
Harley and Klein’s Microbiology (2017), show below as figure 3.
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Figure 3. B cells and T cells arise from the same cell lineage but diverge into two different functional types.
Immature B cells and T cells are indistinguishable by histological staining. However, they express different proteins
on their surfaces that can be detected by immunohistochemistry. Additionally, the final secreted products of mature
B and T cells can be used to identify the cell type.
Activity 2.2
After a Mycobacterium tuberculosis cell enters the body, it may encounter a macrophage that engulfs it
and breaks it down. Thereafter, bacterial antigens appear on the surface of the macrophage and these are
complexed to major histocompatibility complex class II proteins (MHC class II proteins). In this way,
bacterial antigen is presented to antigen specific receptors on the surface of helper T lymphocytes (TH
cells). The TH cells increase in number and mediate a response to the Mycobacterium tuberculosis. The
resulting formation of granuloma tissue around the Mycobacterium tuberculosis separates it from the
rest of the lung tissue. Answer the following questions
1. Compare this defence mechanism to that involving an intracellular pathogen such as the
influenza virus.
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2.3 Organs and tissues of the immune system
Lymphocytes circulate in the blood and the lymph and are also found in large numbers in Lymphoid tissues
or Lymphoid organs. Based on function, the organs and tissues of the immune system can be divided into
central or primary lymphoid organs, where immature lymphocytes mature and differentiate into antigen
sensitive B and T cells, and the peripheral or secondary lymphoid organs, where lymphocytes may
encounter and bind antigen, which triggers their proliferation and differentiation into fully active, antigen-
specific effector cells. The diagram (figure 33.14) on page 724 of the textbook, shown as figure 4 below
indicates that the thymus is the site of T cell development while bone marrow is the site of B cell
development. These are, thus, primary lymphoid organs. Secondary lymphoid organs and tissue include
the spleen, as well as lymph nodes and mucosal- and gut associated lymphoid tissue (MALT and GALT).
These are sites where foreign material is broken down (mainly in cells that are associated with innate
immunity) before the degraded foreign material (now known as antigen) is presented to T and B cells to
cause their activation. The now activated T and B cells are primed to interact with the intact foreign material
that originally caused the T and B-cell activation.
Figure 4. Anatomy of the lymphoid system. (a)The thymus is the site for T cell development while the (b) bone
marrow is the site for B cell development. Lymph is distributed through a system of lymphatic vessels, passing
through many (c) lymph nodes.
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Central to activation of the T and B cells is the breaking down of foreign material into simpler compounds.
Before the T and B cells can be activated, foreign material is ingested by phagocytes within the secondary
lymphoid tissue, a process called phagocytosis, a process that will be discussed below. These simpler
compounds (or antigens) are then presented on the surface of the phagocyte. T and B cells come into
contact with these phagocytes and the surface-bound antigens are recognised by T and B cells that are
then activated.
Refer to page 725-726 To have a detailed explanation of the primary and secondary lymphoid
organs and tissues.
Activity 2.3
Features of infection with HIV include reduction in numbers of specific T cells and lymphadenopathy -the
swelling and tenderness of lymph nodes. Indicate which cells are targeted by HIV and also indicate where
immune cell contact takes place.
2.4 Phagocytosis
To recap: Secondary lymphoid organs and tissue are distributed at sites throughout the body and contact
between phagocytes and foreign material takes place within this tissue. Before T and B cells are activated,
however, the foreign material needs to be presented to the T and B cells in a form that can be recognised
by the T and B cells. To achieve this, processing of the foreign material occurs in the phagocytes following
ingestion of the foreign material (phagocytosis) and its biochemical breakdown within the phagocyte.
Phagocytes (macrophages, dendritic cells, and neutrophils) are important early defenders of invading
microorganisms. Phagocytes ingest and kill cellular microbes by the process called phagocytosis and
intracellular pathogens by the process of autophagocytosis (or autophagy), but only phagocytosis will be
detailed in this learning unit. Phagocytes use two basic molecular mechanisms to recognize an invading
microorganism: (1) opsonin-independent (nonopsonic) recognition and (2) opsonin-dependent (opsonic)
recognition. The process of phagocytosis is shown on page 730 (figure 33.19), also show below as figure
5 and that of autophagy is shown on page 731 (figure 33.20) of the textbook.
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Figure 5. (a) Receptors on a phagocytic cell (e.g., a macrophage) and the corresponding MAMPs participating in
phagocytosis. The process of phagocytosis includes (b) ingestion, (c) participation of granules, and O2-dependent
killing events, (d) intracellular digestion, and (e) exocytosis. As with autophagy, digested fragments can also enter
the endoplasmic reticulum to be processed for antigen presentation. MHC proteins will be discussed later. LPS
receptor: lipopolysaccharide receptor; TLRs: toll-like receptors; MHC-I: class I major histocompatibility protein; MHC-
II: class II major histocompatibility protein; MAMPs: microbe-associated molecular patterns.
The processed foreign material is then presented to the T and B cells on the surface of the phagocyte. We
will study the details of antigen presentation on the surface of the phagocyte and specific recognition of
the antigen by T or B cells in a special topic later on in this course.
As shown in figure 5 (a) above, note that the phagocyte has protein receptor molecules on its surface
including TLRs (toll-like receptors), mannose receptors and lipopolysaccharide receptors. Note, also, that
PAMPs are described on the surface of the bacteria and that the pattern recognition receptors (PPRs) on
the phagocyte (that bind to PAMPs) are indicated in the diagram as TLRs.
The processes of phagocytosis:
1 Recognition of foreigness
2 The internalisation of foreign material within a phagosome.
3 This phagosome is then linked to a lysosome to form a structure called the
phagolysosome.
4 This contains the foreign material and various enzymes and reactive compounds that
degrade foreign material.
The last stage in phagocytosis involves the expelling of degraded material from the phagocyte. This is
essentially the reverse of ingestion and involves the fusion of the phagolysosome membrane with the cell
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membrane and the voiding of debris from what was previously the phagolysosome. Antigen presentation
is a second possible outcome, and this is critical in activation of lymphocytes. This process involves the
transfer of antigen generated in the phagolysosome to the surface of the phagocyte linked to major
histocompatibility complex (MHC) proteins. The combination of MHC protein and antigen can then be
recognized by passing T cells and it is this recognition process that activates the T cell. We will discuss
this activation process in more detail in study unit 3.
As this learning unit deals with mechanism by which humans detect and respond to foreign invaders. It is
of paramount importance to discuss the process of inflammation in this learning unit.
2.5 Inflammation
Inflammation may be acute or chronic. Acute inflammation is an immediate and short-lived response to
injury or cell death, while chronic inflammation is a slow process associated with the build-up of connective
tissue, usually associated with permanent tissue damage.
Before we tackle inflammation, I think we should first understand process that led to inflammation. To
recall: Pattern Recognition Receptors (PRR) are well described during the process of phagocytosis.
Activation of these PRRs on innate immune cells such as macrophages and neutrophils can directly induce
effector function such as phagocytosis and degradation of an invading pathogen. These innate immune
cells can also serve to amplify immune response by the production of inflammatory mediators. These
inflammatory mediators are cytokines and chemokines which act by conveying important signals to other
immune cells.
Inflammation is the immune response to a wound. In this case, there is a coordinated response linking
most of the components of innate immunity in an attempt to neutralise pathogens that might have been
introduced into the body. Gross features of inflammation are swelling, warmth, pain and redness around
the site of the wound. The main events in inflammation revolve around attracting mast and phagocytic
cells from the bloodstream into the tissue at the site of the wound. Basically, chemical attractants are
released by damaged cells and by cells at the site of the wound and these attractants cause leukocytes to
leak out of blood vessels into the tissue around the wound. These cells then destroy any pathogens in the
wound.
As indicated, chronic inflammation is a persistent condition associated with a slow onset and usually leads
to the formation of new connective tissue resulting in permanent tissue damage. Chronic inflammation is
associated with infections involving pathogens that are relatively resistant to phagocytosis and intracellular
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killing. These pathogens include bacteria such as Mycobacterium tuberculosis (whose cells have a wall
with a high lipid and wax content), as well as Listeria and Brucella, fungi such as Histoplasma capsulatum,
worms such as Schistosoma as well as protozoa such as Leishmania. We will see that large antibody-
antigen complexes are also associated with conditions such as rheumatoid arthritis. The immune response
to such infections involves the infiltration of lymphocytes and macrophages into the area of the infection
and if they cannot remove the pathogens, they attempt to seal off the area by forming a granuloma around
the pathogens and surrounding damaged tissue.
Refer to page 732-734 To have a detailed explanation of the inflammation process.
Activities
1.4 Define primary and secondary lymphoid organs.
1.5 Discuss differences and similarities between cells of the immune system.
1.6 How do macrophages and dendritic cells become antigen-presenting cells?
1.7 Distinguish acute and chronic inflammation in terms of the host responses involved in each.
1.8 How does chronic inflammation differ from acute inflammation?
More readings on this topic
Refer to your prescribed textbook, Prescott’s Microbiology, Chapter 33, pp. 717 - 734.
Discussion forum on this topic
The following questions must be discussed on the myUnisa site. Please present your answers in the
discussion forum:
• From an evolutionary perspective, do you consider the inflammatory response to be an
ancient defence mechanism? In terms of HIV infection, where do you expect inflammatory
involvement?
• What major events occur during an inflammatory reaction, and how do they contribute to
pathogen destruction?
• Injury to the spleen can lead to its removal. What impact would this have on host defenses?
Self-assessment questions
1. Matching: Classify the following as lymphoid or myeloid in origin:
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A Eosinophils
B B cells
C Neutrophils
D NK cells
E Mast cells
F Macrophages
G Red blood cells
2. Multiple Choice: The immunologist’s dirty little secret involves the addition of microbial constituents in
order to stimulate a strong immune response against the desired protein antigen of interest. Which of the
following is not a receptor or receptor family that can recognize microbial products in order to achieve a
potent immune response?
A Toll-like receptors (TLRs)
B T-cell antigen receptors (TCR)
C NOD-like receptors (NLRs)
D Pattern Recognition receptors (PRRs)
3. True or False: Toll-like receptors (TLRs) recognise intracellular bacteria, while NOD-like receptors
(NLRs) recognize extracellular bacteria
4. Matching: Classify each of the following as a central/primary or peripheral/secondary lymphoid organ:
A Bone marrow
B Lymph node
C Spleen
D Thymus
E Appendix
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5. Multiple Choice: Which of the following events do not occur during inflammation?
A Cytokine secretion
B Chemokine secretion
C Recruitment of innate immune cells
D Constriction of blood vessels
2.6 Conclusion
In this learning unit we dealt with the components of the immune system, in particular, various cells of the
immune system and discussed the mechanisms by which they detect and respond to foreign invaders.
Mechanism such as phagocytosis and inflammation were well described. These cells are found in different
tissues as well as in primary and secondary lymphoid organs. An injury to some of these organs, more
especially the spleen will have an impact on the host response to an invading pathogen. Pathogen
recognition receptors that are found on the surface of host immune cells plays a pivotal role in initiating an
immune attack.
Sources consulted for this unit
Joanne M. Willey, Linda M. Sherwood, & Christopher J. Woolverton. 2017. Prescott’s Microbiology.
Tenth edition. Mcgraw-Hill Education. ISBN: 978-1-259-28159-4, MHID: 1-259-28159-0. New York.
(Prescribed book)
Kenneth Murphy & Casey Weaver. 2017. Janeway’s Immunology. 9th edition. Garland Science, Taylor &
Francis Group, LLC. ISBN: 978-0-8153-4505-3.USA and UK.
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