Cells & Organs of The Immune System, Cellular Immunity
Cells & Organs of The Immune System, Cellular Immunity
Cell-Mediated Immunity
B cells: the earliest cells which develop are called B1 cells; they express CD5 cell-surface
molecule and are the source of "natural antibodies", which are IgM antibodies and are
frequently polyreactive (recognize different antigens, pathogens and autoantigens). Natural
antibodies have a relative low affinity. Most B cells lack the CD5 molecule, they develop
later and are called B2 cells. Mature B2 cells coexpress IgM and IgD antibodies on their cell
surface. The genes encoding B-cell receptors undergo a process of somatic hypermutation;
the final stages of differentiation of B2 cells into antibody secreting plasma cells occurs
within the germinal centres of secondary lymphoid tissues.
• To elicit a strong antibody response, B cells require:
• Antigen
• T cells for direct contact (usually TH2 cells)
• Soluble cytokines (e.g. IL4 + IL13, INF-γ or IL10)
• Certain adhesion molecules
• The primary function of the antibody is to bind the antigen; the antibody
directs specificity towards the antigen. By doing do, it also arms the killer
cells and activates complement, processes that eliminate foreign organisms,
which the antibody by itself cannot do. Of the different classes of antibodies,
two will be discussed briefly:
• IgM class: is the predominant antibody (it is the first to appear) in primary
immune responses and is associated with the immune responses to
antigenically complex, blood -borne agents. Once bound to the antigen, it is a
powerful activator of the classical pathway complement: a single molecule of
bound IgM is able to initiate the cascade because of the adjacent positioning
of the Fc regions.
• IgG class: is the most important class of immunoglobulin in secondary
immune responses
• The exposure to foreign antigen yields a biphasic response. The first phase is
associated with production of IgM, followed by production of IgG. The second
phase is characterized by a reduction of IgM followed by an increase of IgG.
The antigen will select and expand a clone of effector B cells which will
develop into plasma cells and produce antibodies.
• Complement system
• The complement system consists of about 20+
serum molecules (some of them being
proteases) constituting nearly 10% of the
total serum proteins and forming
one of the major defence systems of the
body. The complement system is
activated by the Ag-Ab complex. The
principle functions are the initiation of:
• chemotactic factors: polymorphs and macrophages have
specific receptors for small complement fragments
generated during complement activation. The fragments
diffuse away from the site of activation and stimulate
chemotaxis, the way chemokines do.
• vasodilation factors: some of the protein fragments of the
complement system (C5a) causes degranulation of mast cells
and basophils with release of histamine and other vasoactive
mediators. Consequently, there are indirect effects on blood
vessels, vasodilation and increased permeability of
capillaries.
• factors that increase phagocytosis: phagocytic cells carrying
receptors for the complement components are then able to
bind to the foreign particle (opsonization), and this triggers
phagocytosis and cell activation.
• membrane attack complex: the final step in complement
activation brings about the assembly of a membrane
attack complex, which can insert itself into lipid bilayers,
causing the lysis of the foreign body.
• The basic unit composed of B zones and T zones
are located within the cortex of the LN and the
white pulp of the spleen. Some MALTs, such
as tonsils and Peyer's patches
(PPs), are clusters of follicles
associated with T zones in the
interfollicular area.
• In addition to follicles, a significant proportion of
splenic B cells is located in 'marginal zones'
(MZs), which surround lymphoid follicles and
T- cell areas in spleen. MZs are
absent in peripheral lymph
nodes and Peyer's patches.
• B cells are primarily clustered in structures called
lymphoid follicles, whereas T cells are found
mainly in the paracortex.
• within the lymph node due to the
compartmentalization of the lymph nodes. The T
lymphocytes are present within the paracortex
lobules, and B lymphocytes are situated within
the cortex lobule.
•
• majority of T cells in the human body are likely
found within lymphoid tissues (bone marrow, spleen,
tonsils, and an estimated 500-700 lymph nodes) with
large numbers also present in mucosal sites (lungs, small
and large intestines) and skin, with estimates of 2–3% of
the total T cell complement found in human peripheral
blood
• B lymphocytes can be found in primary lymphoid tissues,
such as the bone marrow and ileal Peyer's patches (a
primary lymphoid tissue in some species because it is the
site of B lymphocyte development, rather than the bone
marrow), and in secondary lymphoid tissues, such as the
spleen, lymph nodes, tonsils, and Peyer's ...
• B lymphocytes can be found in primary lymphoid tissues, such as the bone
marrow and ileal Peyer's patches (a primary lymphoid tissue in some
species because it is the site of B lymphocyte development, rather than
the bone marrow), and in secondary lymphoid
tissues, such as the spleen, lymph nodes, tonsils, and Peyer's patches.
Within secondary lymphoid tissues, B
lymphocytes are aggregated in the form of distinct lymphoid
follicles, which on activation expand to form prominent pale regions
called germinal centers (Fig. 5-9). This anatomic localization, similar
to T lymphocytes in the PALS and paracortex, is
the result of elaboration of chemokines for which the B lymphocyte has
receptors. The antigen receptor of the B lymphocyte is the
membrane-bound immunoglobulin. After the
antigen-independent phase of development, B lymphocytes
express IgM and IgD on their surface, which signifies a mature B
lymphocyte. In the antigen-dependent phase, antigen-activated mature
B lymphocytes differentiate into IgM-secreting
plasma cells or switch to another antibody isotype.
Antigen-Presenting Cells
1. Macrophage
2. Dendritic cells
3. B cells
Important Cells of cell-mediated immunity
• Important cells of cell-mediated immunity
1. Macrophages,
– Phagocytosis bacteria & Present the antigen to T cells;
2. Helper T cells,
– Participate in antigen recognition and in regulation
(helper and suppressor) functions
3. Natural killer (NK) cells
– Kill virus-infected cells and cancer cells & Produce
gamma interferon that activates
macrophages to kill ingested bacteria
4. cytotoxic T cells
– Kill virus-infected & tumor cells with or without
antibody.
• Functions:
1. Phagocytosis
• Lysosomes contain a variety of degradative enzymes which have bactericidal
action.
• Important for innate host defenses, & severe bacterial infections occur in low in
number (neutropenia) or are deficient in function, as in chronic
granulomatous disease.
2. Opsonization:
• Neutrophils have receptors for IgG on their surface, so IgG is the only
immunoglobulin that opsonizes, i.e., makes bacteria more easily
phagocytosed.
3. Tissue damage:
• The positive edge of the sword of neutrophil is their powerful microbicidal activity,
but the negative edge is the tissue damage caused by the release of
degradative enzymes. An excellent example of the latter is the
damage to the glomeruli in acute poststreptococcal
glomerulonephritis. The damage is caused by enzymes released
•
Eosinophils
Eosinophils are WBC with cytoplasmic granules stained red in Wright stain.
• The growth and differentiation of eosinophils is stimulated by interleukin-5.
• Role of eosinophils in types of diseases:
1. Parasitic diseases
– Eosinophil count elevated by nematodes. Important defense against migratory larvae
of nematodes, Strongyloides & Trichinella. They attach to the surface of the
larvae and discharge the contents of their granules, which in
turn damages the cuticle of the larvae. Attachment to
the larvae is mediated by receptors on the eosinophil surface for
the Fc portion of the heavy chain of IgG and IgE.
– Diseases caused by protozoa are typically not characterized by eosinophilia.
2. Hypersensitivity diseases
– Eosinophil count elevated in allergic conditions, such as, asthma and serum sickness.
– Causes immediate hypersensitivity reactions because the granules of eosinophils
contain histaminase, an enzyme that degrades histamine.
– The granules of the eosinophils also contain leukotrienes and peroxidases, which can
damage tissue and cause inflammation.
– The granules also contain major basic protein that damages respiratory epithelium and
contributes to the pathogenesis of asthma.
3. Phagocytose bacteria: Weakly & not sufficient to protect against pyogenic bacterial
infections in neutropenic patients.
Basophils
• Basophils are WBC with cytoplasmic granules stain blue
in Wright stain.
• Basophils circulate in the bloodstream
• Functions:
– Antigen-presenting cells
• Express class II MHC proteins & present antigen to CD4-positive Th cells.
– Main inducers of the primary antibody response.
Follicular Dendritic Cells (FDCs)
• Similar appearance but different from dendritic cells
in their location & function.
• located in the B-cell–containing germinal centers of
the follicles in the spleen and lymph nodes.
• Do not present antigen to helper T cells because they
do not produce class II MHC proteins.
• Capture antigen–antibody complexes via Fc receptors
located on their surface. The antigen–antibody
complexes are then detected by activated B cells. The
antibody produced by these B cells undergoes affinity
maturation. (Affinity maturation is the improvement
in the affinity of an antibody for the antigen that
occurs upon repeated exposure to the antigen.)
• FDCs produce chemokines that attract B cells to
the follicles in the spleen and lymph nodes.
Natural Killer Cells
• Nature of NK Cells
– Large granular lymphocytes
– Thymus is not required for development
– Lack T-cell receptor, CD3 proteins, and surface IgM and IgD
– Normal numbers in severe combined immunodeficiency disease (SCID)
patients
– Activity not enhanced by prior exposure
– involved in both innate and adaptive immunity, active all the time, & travel
around our bodies looking for infection or disease that it needs to
fight.
• Function of NK Cells
– Kill virus-infected cells & cancer cells
– Killing is nonspecific & is not dependent on foreign antigen presentation by
class I or II MHC proteins
– Produce gamma interferon that activates macrophages to kill ingested
bacteria
T Cells
• T-cell subpopulations are characterized by certain surface
glycoproteins
– CD3
– CD4
– CD8
• Mature T cells have either CD4 or CD8 proteins but not both.
T Cells
• The regulatory functions are mediated primarily by helper
(CD4-positive) T cells & Suppressor T cells
– Function of helper (CD4-positive) T cells produce interleukins
• Interleukin-4 (IL-4) and IL-5, which help B cells produce antibodies
• IL-2, which activates CD4 and CD8 cells
• Gamma interferon, activates macrophages, the main mediators of
delayed hypersensitivity against intracellular
organisms such as Mycobacterium tuberculosis.
• A subset of CD4 cells called Th-17 cells play an important role
in
mucosal immunity
– Function of Suppressor T cells
• Downregulate the immune response
Left: Virus released by an infected cell interacts with the antigen receptor (IgM
monomer) specific for that virus located on the surface of a B cell. The virus is
internalized, and the viral proteins are broken down into small peptides. B cells (as well as
macrophages) can present viral epitopes in association with class II MHC proteins and
activate CD4 cells. The CD4-positive helper cell produces IL-4 and IL-5, which induce
the B cell to differentiate into a plasma cell that produces antibody specifically against
this virus.