Cells of Immune System

Prof. Asit Ranjan Ghosh

SBST/VIT/2023
 Immune Cells

• Granulocytes include basophils, eosinophils,

and neutrophils.
• Basophils and eosinophils are important for
host defense against parasites. They also are
involved in allergic reactions.
• Mast cells also are important for defense
against parasites. Mast cells are found in tissues
and can mediate allergic reactions by releasing
inflammatory chemicals like histamine.
 Neutrophils
Neutrophils accumulate within minutes at sites
of local tissue injury.
They then communicate with each other using
lipid and other secreted mediators to form
cellular "swarms."
Their coordinated movement and exchange of
signals then instructs other innate immune cells
called macrophages and monocytes to surround
the neutrophil cluster and form a tight wound
seal.
 Monocytes & Macrophages
• Monocytes, which develop into macrophages, also patrol
and respond to problems. They are found in the
bloodstream and in tissues.
• Macrophages, "big eater" in Greek, are named for their
ability to ingest and degrade bacteria. Upon activation,
monocytes and macrophages coordinate an immune
response by notifying other immune cells of the problem.
• Macrophages also have important non-immune functions,
such as recycling dead cells, like red blood cells, and
clearing away cellular debris. These "housekeeping"
functions occur without activation of an immune response.
 Dendritic cells (DC)
• Dendritic cells (DC) are an important antigen-presenting cell
(APC), and they also can develop from monocytes.
• Antigens are molecules from pathogens, host cells, and
allergens that may be recognized by adaptive immune cells.
• APCs like DCs are responsible for processing large molecules
into "readable" fragments (antigens) recognized by adaptive B
or T cells.
• However, antigens alone cannot activate T cells. They must be
presented with the appropriate major histocompatiblity
complex (MHC) expressed on the APC.
• MHC provides a checkpoint and helps immune cells distinguish
between host and foreign cells.
 Natural killer (NK) cells
• Natural killer (NK) cells have features of both innate and adaptive immunity.
They are important for recognizing and killing virus-infected cells or tumor cells.
• They contain intracellular compartments called granules, which are filled with
proteins that can form holes in the target cell and also cause apoptosis, the
process for programmed cell death.
• It is important to distinguish between apoptosis and other forms of cell death
like necrosis.
• Apoptosis, unlike necrosis, does not release danger signals that can lead to
greater immune activation and inflammation.
• Through apoptosis, immune cells can discreetly remove infected cells and limit
bystander damage.
• Recently, researchers have shown in mouse models that NK cells, like adaptive
cells, can be retained as memory cells and respond to subsequent infections by
the same pathogen.
Adaptive immunity: T-cell and B-cell
activation and function
 Adaptive Cells
B cells
• B cells have two major functions: They present
antigens to T cells, and more importantly, they
produce antibodies to neutralize infectious
microbes. Antibodies coat the surface of a
pathogen and serve three major roles:
neutralization, opsonization, and complement
activation.
Neutralization, opsonization, Complement

• Neutralization occurs when the pathogen,

because it is covered in antibodies, is unable
to bind and infect host cells.
• In opsonization, an antibody-bound pathogen
serves as a red flag to alert immune cells like
neutrophils and macrophages, to engulf and
digest the pathogen.
• Complement is a process for directly
destroying, or lysing, bacteria.
 B-cell receptor (BCR)
• Antibodies are expressed in two ways.
• The B-cell receptor (BCR), which sits on the surface of a
B cell, is actually an antibody.
• B cells also secrete antibodies to diffuse and bind to
pathogens.
• This dual expression is important because the initial
problem, for instance a bacterium, is recognized by a
unique BCR and activates the B cell. The activated B cell
responds by secreting antibodies, essentially the BCR but
in soluble form. This ensures that the response is specific
against the bacterium that started the whole process.
 Overlapping roles of Ig
• Every antibody is unique, but they fall under general
categories: IgM, IgD, IgG, IgA, and IgE. (Ig is short for
immunoglobulin, which is another word for antibody.)
• While they have overlapping roles, IgM generally is
important for complement activation; IgD is involved
in activating basophils; IgG is important for
neutralization, opsonization, and complement
activation; IgA is essential for neutralization in the
gastrointestinal tract; and IgE is necessary for
activating mast cells in parasitic and allergic responses.
 T cells
• T cells have a variety of roles and are classified
by subsets.
• T cells are divided into two broad categories:
CD8+ T cells or CD4+ T cells, based on which
protein is present on the cell's surface.
• T cells carry out multiple functions, including
killing infected cells and activating or
recruiting other immune cells.
 CD8+ T cells
• CD8+ T cells also are called cytotoxic T cells or
cytotoxic lymphocytes (CTLs).
• They are crucial for recognizing and removing
virus-infected cells and cancer cells.
• CTLs have specialized compartments, or
granules, containing cytotoxins that cause
apoptosis, i.e., programmed cell death.
• Because of its potency, the release of granules
is tightly regulated by the immune system.
 CD4+ T-cell subsets
• The four major CD4+ T-cell subsets are TH1, TH2, TH17, and
Treg, with "TH" referring to "T helper cell."
• TH1 cells are critical for coordinating immune responses against
intracellular microbes, especially bacteria. They produce and
secrete molecules that alert and activate other immune cells,
like bacteria-ingesting macrophages.
• TH2 cells are important for coordinating immune responses
against extracellular pathogens, like helminths (parasitic
worms), by alerting B cells, granulocytes, and mast cells.
• TH17 cells are named for their ability to produce interleukin 17
(IL-17), a signaling molecule that activates immune and non-
immune cells. TH17 cells are important for recruiting
neutrophils.
 Regulatory T cells (Tregs)
• Regulatory T cells (Tregs), as the name
suggests, monitor and inhibit the activity of
other T cells.
• They prevent adverse immune activation and
maintain tolerance, or the prevention of
immune responses against the body's own
cells and antigens.
 Communication

• Immune cells communicate in a number of ways, either

by cell-to-cell contact or through secreted signaling
molecules.
• Receptors and ligands are fundamental for cellular
communication.
• Receptors are protein structures that may be expressed
on the surface of a cell or in intracellular compartments.
• The molecules that activate receptors are called ligands,
which may be free-floating or membrane-bound.
• Ligand-receptor interaction leads to a series of
events inside the cell involving networks of
intracellular molecules that relay the message.
• By altering the expression and density of
various receptors and ligands, immune cells
can dispatch specific instructions tailored to
the situation at hand.
 Cytokines
• Cytokines are small proteins with diverse
functions.
• In immunity, there are several categories of
cytokines important for immune cell growth,
activation, and function.
• Colony-stimulating factors (CSF)are essential for
cell development and differentiation.
• Interferons (IFN) are necessary for immune-cell
activation. Type I interferons mediate antiviral
immune responses, and type II interferon is
important for antibacterial responses.
• Interleukins, which come in over 30 varieties,
provide context-specific instructions, with
activating or inhibitory responses.
• Chemokines are made in specific locations of the
body or at a site of infection to attract immune cells.
Different chemokines will recruit different immune
cells to the site needed.
• The tumor necrosis factor (TNF) family of cytokines
stimulates immune-cell proliferation and activation.
They are critical for activating inflammatory
responses, and as such, TNF blockers are used to
treat a variety of disorders, including some
autoimmune diseases.
 Toll-like receptors (TLRs)
• Toll-like receptors (TLRs) are expressed on innate
immune cells, like macrophages and dendritic
cells.
• They are located on the cell surface or in
intracellular compartments because microbes
may be found in the body or inside infected cells.
• TLRs recognize general microbial patterns, and
they are essential for innate immune-cell
activation and inflammatory responses.
B-cell receptors (BCRs) and T-cell receptors
(TCRs)
• B-cell receptors (BCRs) and T-cell receptors (TCRs) are expressed
on adaptive immune cells.
• They are both found on the cell surface, but BCRs also are
secreted as antibodies to neutralize pathogens.
• The genes for BCRs and TCRs are randomly rearranged at specific
cell-maturation stages, resulting in unique receptors that may
potentially recognize anything.
• Random generation of receptors allows the immune system to
respond to unforeseen problems.
• They also explain why memory B or T cells are highly specific
and, upon re-encountering their specific pathogen, can
immediately induce a neutralizing immune response.
Major histocompatibility complex (MHC)

• Major histocompatibility complex (MHC), or human

leukocyte antigen (HLA), proteins serve two general
roles.
• MHC proteins function as carriers to present antigens
on cell surfaces.
• MHC class I proteins are essential for presenting viral
antigens and are expressed by nearly all cell types,
except red blood cells. Any cell infected by a virus has
the ability to signal the problem through MHC class I
proteins. In response, CD8+ T cells (also called CTLs) will
recognize and kill infected cells.
• MHC class II proteins are generally only
expressed by antigen-presenting cells like
dendritic cells and macrophages. MHC class II
proteins are important for presenting antigens
to CD4+ T cells. MHC class II antigens are
varied and include both pathogen- and host-
derived molecules.
• MHC proteins also signal whether a cell is a host cell or a foreign cell.
• They are very diverse, and every person has a unique set of MHC
proteins inherited from his or her parents. As such, there are
similarities in MHC proteins between family members.
• Immune cells use MHC to determine whether or not a cell is friendly.
• In organ transplantation, the MHC or HLA proteins of donors and
recipients are matched to lower the risk of transplant rejection,
which occurs when the recipient's immune system attacks the donor
tissue or organ.
• In stem cell or bone marrow transplantation, improper MHC or HLA
matching can result in graft-versus-host disease, which occurs when
the donor cells attack the recipient’s body.
 Complement
• Complement refers to a unique process that clears away
pathogens or dying cells and also activates immune cells.
• Complement consists of a series of proteins found in the blood
that form a membrane-attack complex.
• Complement proteins are only activated by enzymes when a
problem, like an infection, occurs.
• Activated complement proteins stick to a pathogen, recruiting
and activating additional complement proteins, which assemble
in a specific order to form a round pore or hole.
• Complement literally punches small holes into the pathogen,
creating leaks that lead to cell death.
• Complement proteins also serve as signaling molecules that
alert immune cells and recruit them to the problem area.