A complete syllubus of the Biology bachelor course Immunology (NWI-BB019B). This syllabus was written using notes of the lectures and the book "Cellular and Molecular Immunology".
Chapter 1: Properties and overview of Immune response
Innate and Adaptive immunity
Innate (or natural/native) immunity are
essential for defence against microbes
in the first few hours or days after
infection and is mediate by mechanisms
that are present before infections occur
and allow rapid responses to invaders.
The adaptive (or
specific/acquired) immunity is
stimulated by exposure to infectious
agents and increases in magnitude and
defensive capability with each
exposure. This immunity recognizes a
large number of antigens. Adaptive Figure 1: The innate vs. the adaptive immune response.
responses are stronger and more
specialised than innate responses and therefore pathogens that have grown resistant to the latter
can still be targeted by the former.
The innate immune response provides early danger signals that stimulates the adaptive
immune response. The communication between systems is provided by dendritic cells and cytokines.
Because lymphocytes and other immune cells can circulate among tissues, immunity is
systemic. This means that an immune response initiated at one site, can give protection at distant
sites. This phenomenon is important for vaccination.
Immune responses are also regulated by positive feedback loops and control mechanisms to
prevent inappropriate pathologic reactions. When lymphocytes are activated, they trigger
mechanisms that further increase the response. This is important to allow a small number of
lymphocytes to generate a large response that can eradicate the infection. Regulatory mechanisms
prevent excessive activation of lymphocytes.
The oldest mechanisms of host defence is innate immunity.
Innate immunity: the early defence
The receptors of innate immunity are specific for structures that are common for microbes and these
do not distinguish fine differences between microbes. There are three components in innate
immunity:
1. Physical and chemical barriers such as epithelia and antimicrobial chemicals.
2. Phagocytic cells (neutrophils and macrophages), dendritic cells (DCs), mast cells, natural killer
cells (NK cells) and other innate lymphoid and mast cells.
3. Blood proteins that include components of the complement system and inflammatory
mediators.
Many innate immune cells are always present in most tissues where they ‘keep watch’ for invading
microbes.
The innate immune system fights microbes by recruiting phagocytes and other leukocytes to
the destroy the microbe (inflammation) and by blocking viral replication/killing virally infected host
cells.
Adaptive immunity
Adaptive immunity is mediated by lymphocytes and their products that express highly diverse
receptors capable of recognising a vast number of antigens. These lymphocytes are divided in B and T
lymphocytes.
Cardinal features of Adaptive Immune Responses
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,The fundamental properties of the adaptive immune system reflect the properties of the
lymphocytes that mediate the responses:
- The immune responses are specific for distinct antigens and often for different portions of a
single complex protein, polysaccharide or other macromolecule called determinants or
epitopes. The different specificities of clones of lymphocytes cause clonal selection. Here
lymphocytes antigen-specific clones develop before and independent of exposure to an
antigen. A then introduced antigen can bind an antigen-specific clone and activate it, causing
proliferation of this specific cell in a process called clonal expansion. The diversity of the
lymphocytes is due to the variability in the structures of the antigen-binding sites of the
lymphocyte receptors for antigens. Each clone has a unique antigen receptor and therefore a
singular antigen specificity.
- Responses to a second subsequent exposure to a same antigen (secondary immune
response) are usually more rapid, greater in magnitude and different from the first (primary)
immune response. Immunologic memory is caused by the production of long-lived memory
cells after exposure to an antigen. There are two reasons the secondary response is stronger
than the primary:
1. The memory cells accumulate and become more numerous than the native lymphocytes
specific for an antigen at the initial antigen exposure.
2. Memory cells react more rapidly and vigorously to antigens that native lymphocytes.
Memory allows heightened responses to reoccurring or persistent exposure of certain
antigens.
- Immunological unresponsiveness is also called tolerance and the self-tolerance to the own
individual is one of the most striking features of the immune system. This self-tolerance is
maintained by several mechanisms including eliminating lymphocytes that do express
receptor specificity for self-antigens, inactivating self-reactive lymphocytes or suppressing
these by (regulatory) cells. Abnormalities in the induction or maintenance of self-tolerance
leads to autoimmune diseases.
Overview of Humoral and Cell-Mediated Immunity
There are two types of adaptive immunity called humoral and cell-mediated (cellular) immunity.
Humoral immunity is mediated by antibodies blood and other fluids that are produced by B
lymphocytes. Antibodies neutralize microbes and target them for elimination by macrophages and
the complement system. This immunity is the principal defence for antigens outside the cell.
Cell-mediated/cellular immunity is mediated by T lymphocytes and targets microbes inside
cells by killing these microbes or the infected cells.
Active immunity is the immunity caused by exposure to foreign antigens. Lymphocytes that
have not yet encountered an antigen are called naïve. Although immunity can also be passed on by
transferring antibodies, this is called passive immunity. The enhancement of phagocytosis is called
opsonization.
Immunity is measured by measuring certain specific products such as antibodies. Individuals
that have previously encountered an antigen are said to be sensitized to the antigen and the reaction
is a measure of sensitivity.
Initiation and Development of Adaptive Immune Responses
Most antigens enter through the epithelial barrier, the adaptive immune response to this develops in
the peripheral (secondary) lymphoid organs. Initiation of the response requires capture and display
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,of the antigen by antigen-presenting cells
(APCs) such as dendritic cells (DCs). DCs
capture microbial antigens and transport
them to the lymphoid organs to present
them to naïve T lymphocytes.
Activation of naïve lymphocytes
leads to proliferation of this specific
lymphocyte clone in a process called clonal
expansion. This expansion is followed by
differentiation of the activated
lymphocytes into cells that can eliminate
antigens, effector cells, and memory cells.
Antigen elimination often requires
nonlymphoid cells such as macrophages or
neutrophils as well. The activation of a
lymphocyte often takes a few days.
After the response is eradicated, the
Figure 2: Overview of the components involved in humoral and cellular
effector cells die but the memory cells immunity.
remain.
The interactions of the cells in the immune response is mediated by cytokines, which are a
large group of proteins that regulate and coordinate cells in the innate and adaptive immune
response. Cytokines promote growth and differentiation, activate effector functions of lymphocytes
and phagocytes, and stimulate directed movement of immune cells from blood to tissue.
Chemokines are a subset of cytokines that direct movement and regulate cell migration.
Humoral Immunity
B lymphocytes that recognize antigens proliferate and differentiate into plasma cells that secrete
different classes of antibodies with distinct functions. The B lymphocytes contain receptors that are
bound versions of antibodies. The response of B cells to protein antigens requires activating signals
from CD4+ T cells (T helper cells) but can respond to non-protein antigens without activation.
Plasma cells secrete antibodies with the same antigen binding region as the B cell receptor.
Polysaccharides and lipids stimulate the secretion of IgM antibodies, whereas protein antigens
induce release of IgG, IgA and IgE. T helper cells also stimulate production of antibodies with
increased affinity for the antigen. This is called affinity maturation.
Antibody mediated neutralisation is the only type of adaptive immunity that stops an infection
before it actually occurs. IgG antibodies target microbes for phagocytosis. And IgM and IgG activate
the complement system.
Cell-Mediated Immunity
T lymphocytes recognize antigens of cell-associated antigens and different types of T cells help
phagocytes to destroy the microbes or infected cells.
T cells recognize peptide derived from foreign proteins bound in the major histocompatibility
complex (MHC) expressed on the surface of the cell. Helper T cells function by secreting cytokines,
whereas cytotoxic T lymphocytes (CTLs) produce molecules that kill cells. Regulatory T cells inhibit
immune responses.
Activation of T cells occurs in secondary lymphoid organs where naïve T cells differentiate into
effector cells. When these effector T cells again encounter the target antigen, they perform their
function to eliminate the antigen. CD4+ helper T cells secrete cytokines to recruit leukocytes and
stimulate production of microbicidal substances in phagocytes. CD4+ helper T cells can also produce
cytokines to help B cells to produce IgE and activate eosinophils, which can kill large microbes.
CD8+ CTLs kill infected cells and tumor cells that express antigens that are recognized as
foreign.
3
, Chapter 2: Cells and Tissues of the Immune System
The immune system faces several
challenges to generate effective
immune responses:
1. The immune system must
be able to respond rapidly
to small numbers of many
different microbes at any
site in the body.
2. In the adaptive immune
response very few naïve
lymphocytes specifically
recognize and respond to
one antigen.
3. The effector mechanism of
the adaptive immune
system (antibodies,
effector T cells) may have
to locate and destroy
microbes at sites that are
distant form the initiation
site.
Cells of the immune system
The cells that play a role in innate
and adaptive immunity are almost
all derived from hematopoietic
stem cells (HSCs) in the bone
marrow. Based on common Figure 3: The different cells involved in the immune response.
precursors, immune cells are
classified as:
- Myeloid cells (phagocytes and most DCs)
- Lymphoid cells (all lymphocytes)
Most of these cells are located in the blood, although responses of lymphocytes to antigens occur in
lymphoid tissue and change in blood concentration of these cells is therefore not a measure of their
activity.
The expression of membrane proteins is used to distinguish different populations of immune
cells. Most helper T cells express a surface protein called CD4 and most CTLs a different protein
called CD8. The most common way of testing whether if a particular marker protein is present on an
immune cell is to test if antibodies specific for the marker bind the cell.
CD molecules have important functions in immune responses and are often the target of
therapeutic antibodies in the treatment of inflammatory diseases and cancer.
Phagocytes
Phagocytes such as neutrophils and macrophages primarily ingest and destroy microbes and remove
damaged tissues. Response of phagocytes in defence goes as follows:
- Recruitment of the cells to the sites of infection
- Recognition of microbes and activation by microbes
- Ingestion of microbes via phagocytosis
- Destruction of ingested microbes
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