IMMUNOLOGY ML 106

CHAPTER 1: INTRODUCTION TO
IMMUNITY

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 OBJECTIVES

• Define immunity and explain its significance in host defense.

• Differentiate between innate and adaptive immunity
• Identify the major components of the immune system,
including organs, cells, and molecules.
• Compare the mechanisms of innate and adaptive immune
responses.
• Describe the primary and secondary immune responses and
their clinical importance.

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 IMPORTANT TERMS

• Immunology
• the study of the structure of the immune system and its
functions
• Immunity
• the condition of being resistant to infection
• Antigen
• any foreign substance that induces a host response

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• Immune system
• immune tissues and organs, immune cells, immune molecules
• Immune response
• collective and coordinated response to the introduction of foreign
substances
• Antibody
• Protein molecule produced by certain lymphocytes in response to being
exposed to an antigen
• Cluster of Differentiation (CD)
• A classification system for the different antigenic determinants
found on cells.
• Surface molecules of different types of cells that act as markers of
differentiation 4
• Cell-mediated immunity
• Immune response that involves the activation of macrophages and
cytotoxic T cells
• Humoral immunity
• It is an antibody-mediated response that occurs when foreign
materials/antigens are detected in the body
• Antigen Presenting Cell
• A type of immune cell that boots the immune response. It shows
antigen on its surface to other cells of the immune system. E.g.
macrophage
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 THE IMMUNE SYSTEM

• The immune system is a biological structure and processes

within an organism that protects against disease by
identifying and killing pathogens and tumour cells
• It detects a wide variety of agents, from viruses to parasitic
worms and needs to distinguish them from the organism’s
own healthy cells and tissues in order to function properly

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• Structure of the immune system:
• The immune system has a multilayered architecture with defenses
provided at many levels
• It is a complex network security system of chemicals, cells, tissues
and organs that work together to protect the body
• Functions of the immune system
• Without an immune system, a human being would be just as
exposed to the harmful influences of pathogens or other substances
form the outside environment to inside of the body
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 THE MAIN TASKS OF THE BODY’S
IMMUNE SYSTEM

• Classifying ability to distinguish between the body’s own cells (self) and
foreign cells (non-self)
• It provides defenses against pathogens like bacteria, viruses, parasites and
fungi
• Identifying ability to distinguish one pathogen from another
• It removes (scavenges) dead or worn out cells like red blood cells
• It identifies and destroys abnormal cancer cells
• It protects against autoimmune diseases
• It rejects tissue cells with foreign antigens
• Remembering: the ability to remember previously encountered pathogens
• the ability to respond when a pathogen invades 8
• Differentiation between self and non-self substances:
• For protection to be effective, it is important that the immune system
can differentiate between “self-antigens” and “non-self”/foreign
antigens
• Usually, the body should not work against its own healthy cells

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• All cells, as well as some particles such as pollen, display a
unique mix of macromolecules on their surfaces that the immune
system “senses” to determine if they are foreign or not.
• They are known as antigens
• Because foreign cells or particles could potentially enter through
any number of portals, the cells of the immune system constantly
move about the body
• They are searching for potential pathogens
• A process primarily carried out by white blood cells.
• They are able to recognize body cells (self) and differentiate them
from any foreign material in the body, such as microorganisms,
transplanted organs, blood products or tissues, cancer cells 10
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CLASSIFICATION OF
IMMUNITY

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FORMS OF IMMUNITY

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 I N N AT E I M M U N I T Y

• nonspecific immunity - is the natural resistances with

which a person is born.
• It provides resistances through several physical, chemical
and cellular approaches.
• Microbes first encounter the epithelial layers, physical
barriers that line skin and mucous membranes.
• Subsequent general defenses include secreted chemical
signals (cytokines), antimicrobial substances, fever, and
phagocytic activity associated with the inflammatory
responses.
• The phagocytes express cell surface receptors that can
bind and respond to common molecular patterns
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 INNATE IMMUNITY
• Through these approaches, innate immunity can prevent
the colonization, entry and spread of microbes
• A white blood cell engulfs a microbe, then fuses with a
lysosome to destroy the microbe
• There are different types of phagocytic cells:
• Neutrophils engulf and destroy microbes
• Macrophages are part of the lymphatic system and are
found throughout the body
• Eosinophils discharge destructive enzymes
• Dendritic cells stimulate development of acquired 16

immunity
 ACQUIRED IMMUNITY
• Adaptive immunity /Specific
• sub-divided into two major types depending on how the immunity was
introduced:
• Naturally acquired immunity occurs through contact with a disease
causing agent, when the contact was not deliberate
• Artificially acquired immunity develops only through deliberate actions
such as vaccination.
N/B:
• Memory cells are only produced in active immunity.
• Protection for active immunity is permanent whereas in passive immunity it
is only temporary.
• Antigens are only encountered in active immunity.
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• Active immunity takes several weeks to become active but passive is
 NATURAL ACQUIRED IMMUNITY

• Subdivided into:
• Naturally acquired active immunity: occurs when a person
is exposed to a live pathogen and develops a primary
immune response, which leads to immunological memory.
• This type of immunity is “natural” because it is not
induced by deliberate exposure. Many disorders of
immune system function can affect the formation of
active immunity such as immunodeficiency
• (both acquired and congenital forms) and
immunosuppression. 18
 NATURALLY ACQUIRED PASSIVE
IMMUNITY

• Maternal passive immunity is a type of naturally acquired

passive immunity and refers to antibody-mediated
immunity conveyed to a foetus by its mother during
pregnancy through the placenta.
• IgG is the only antibody isotype that can pass through the
placenta. Passive
• immunity is also provided through the transfer of IgA
antibodies
• found in breast milk that is transferred to the gut of the
infant,
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• protecting against bacterial infections, until the newborn

 ARTIFICIALLY ACQUIRED IMMUNITY

• Artificially acquired active immunity: can be induced by a vaccine, a

substance that contains antigen.
• A vaccine stimulates a primary response against the antigen without
causing symptoms of the disease.
• Artificially acquired passive immunity: is a short-term immunization
induced by the transfer of antibodies, which can be administered in
several forms; such as human or animal blood plasma, in the form of
monoclonal antibodies (MAb).
• Passive transfer is used prophylactically in the case of immunodeficiency
diseases
• It is also used in the treatment of several types of acute infection, and to
treat poisoning. Immunity derived from passive
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• immunization lasts for only a short period of time, and there is also a
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REGULATION OF THE
IMMUNE SYSTEM

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• The immune response is subject to a variety of control mechanisms
which serve to restore the immune system to a resting state when
the response to a given antigen is no longer required
• The nature of the immune response is determined by many factors,
including:
• The form and route of administration of the antigen
• Antigen presenting cells (APC)
• The genetic background of the individual
• Any history of previous exposure to the antigen in question or to a
cross-reacting antigen
• NB: Specific antibodies may also modulate the immune response to
an antigen 23
 REGULATION BY ANTIGEN

• Different antigens elicit different kinds of immune responses

• Polysaccharide capsule antigens of bacteria generally induce
immunoglobulin M responses, and proteins can induce both cell-mediated
and humoral immune responses
• Intracellular organisms induce a cell-mediated immune response, while
soluble proteins induce a humoral response
• Antigen dose: a large dose results in specific tolerance of T and B
cells
• The route of administration of an antigen influences the immune
response
• Administration subcutaneously or intradermally will evoke an immune
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response but administration intravenously, or orally may cause tolerance
 REGULATION BY ANTIGEN
PRESENTING CELLS AND
ANTIBODIES

• Should an antigen be presented to T cells by a non

professional APC that cannot provide stimulation, then
unresponsiveness results, but if an adjuvant is present it may
facilitate an immune response by inducing expression of other
cells
• Can be given to an individual to neutralize a foreign antigen.
• For example, an individual given RhD antibody helps neutralize
foetal RBCs.
• It blocks the interaction between an antigenic determinant and
antibody in the body
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 REGULATION BY CYTOKINE

• Cytokines:
• Small soluble proteins that regulate both innate immunity and
the adaptive response to infection

• Cytokines are induced in response to specific stimuli

• Examples
• Bacterial lipopolysaccharides (LPS)
• Flagellin
• Other bacterial products
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 ROLE OF CYTOKINES

• Cytokines have multiple actions due to:

• Receptors present on many cell types
• Ability to alter expression of numerous genes

• Some cytokines may share properties and receptors

• Some cytokines have overlapping effects

• Cytokines can determine whether the host will be able to mount an

effective defence
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• Their effects work at different ranges
• This can be used to classify them
• Autocrine: Cytokine acts on the cell
that secreted it

• Paracrine: Cytokine acts on nearby

cells

• Endocrine: Cytokine travels through

blood vessels to distant cells
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 MAJOR CYTOKINE FAMILIES

1. Tumor necrosis factors (TNFs)

2. Interferons (IFNs)
3. Chemokines
4. Transforming growth factors (TGFs)
5. Colony-stimulating factors (CSFs)

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 CYTOKINES IN THE INNATE IMMUNE
RESPONSE

• Cytokines that trigger the recruitment of effector cells (cells

that respond to stimulus and make changes, eg plasma cells)

• Interleukin-1 (IL-1)
• Tumor necrosis factor (TNF)-α
• Interleukin-6 (IL-6)
• Chemokines
• Transforming growth factor-β
• Interferons α and β
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 CYTOKINES IN THE INNATE IMMUNE
RESPONSE

• IL-1
• Produced by monocytes and macrophages
• Induces the acute-phase response through its actions on the hypothalamus
• Fever
• Activation of phagocytes
• Production of acute-phase proteins (ex. CRP)

• Induces the production of:

• Vascular cell-adhesion molecules
• Chemokines
• IL-6
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 CYTOKINES IN THE INNATE IMMUNE
RESPONSE

• TNF-α
• Is most prominent of TNF family
• Exists in membrane-bound and soluble forms
• Secreted by activated monocytes and macrophages
• Causes vasodilation and increased vasopermeability
• Is triggered by presence of LPS (found in gram-neg bacteria)
• Central mediator of pathological processes in rheumatoid arthritis and
other inflammatory illnesses, such as Crohn’s disease
• Can activate T cells through its ability to induce expression of MHC class
II molecules, vascular adhesion molecules, and chemokines, in a similar
manner to IL-1 32
 CYTOKINES IN THE INNATE IMMUNE
RESPONSE

• IL-6
• Produced by both lymphoid and nonlymphoid cells
• Part of the cytokine cascade released in response to LPS
• Induces CD4+ T cells to produce greater quantities of both
pro- and anti-inflammatory cytokines
• Pleiotropic: also plays a role in acute-phase reactions
• Triggered by IL-1
• Stimulates B cell proliferation and differentiation

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 CYTOKINES IN THE INNATE IMMUNE
RESPONSE

• Chemokines
• Involved in the initiation and development of inflammatory
responses in numerous disease processes
• Enhance motility and promote migration of many types of
WBCs toward the source of the chemokine (chemotaxis)
• Facilitate the extravasation of leukocytes into the tissues in
areas of inflammation

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 CYTOKINES IN THE INNATE IMMUNE
RESPONSE

• TGF-β
• Regulates cell growth, differentiation, apoptosis, migration, and
the inflammatory response
• Helps down-regulate the inflammatory response when no
longer needed
• Inhibits activation of macrophages and the growth of different
somatic cell types
• Functions as an anti-inflammatory factor for mature T cells
• Inhibits proliferation of activated B cells
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 CYTOKINES IN THE INNATE IMMUNE
RESPONSE

• Type I IFNs
• Produced by dendritic cells
• Induce production of proteins and pathways that interfere with
viral replication and cell division
• Activate natural killer cells
• Enhance the expression of MHC class I proteins
• Also active against certain malignancies and other
inflammatory processes

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 CYTOKINES IN THE ADAPTIVE
IMMUNE RESPONSE

• Secreted by T cells, especially T helper (Th) cells

• Affect T cell and B cell function more directly than
cytokines involved in the innate immune response
• Three main subclasses of CD4+ T cells:
1. Th1 (T helper 1)
2. Th2 (T helper 2)
3. T regulatory cells (Tregs)
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 CYTOKINES IN THE ADAPTIVE
IMMUNE RESPONSE

• When the T-cell receptor (TCR) on a CD4+ T

helper cell captures antigen, clonal expansion
of that T cell occurs
• Differentiation into Th1, Th2, or Treg cell
lineages is influenced by the spectrum of
cytokines expressed in the initial response

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 CYTOKINES IN THE ADAPTIVE
IMMUNE RESPONSE

• Th1 cytokines
• Interferon γ
• Stimulates antigen presentation by class I and class II
MHC molecules
• Activates macrophages to stimulate phagocytic and
cytotoxic abilities
• Regulates action of CD4+ Th cells, CD8+ cytotoxic
lymphocytes, NK cells
• IL-2
• Known as the T-cell growth factor
• Drives the growth and differentiation of T and B cells 39
 CYTOKINES IN THE ADAPTIVE
IMMUNE RESPONSE

• Th2 cytokines
• IL-4
• Helps drive antibody responses in various diseases:
• Allergies
• Autoimmune diseases
• Parasitic infections
• IL-4 Receptor is expressed on lymphocytes and
various nonhematopoietic cell types

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 CYTOKINES IN THE ADAPTIVE
IMMUNE RESPONSE

• T regulatory cytokines
• TGF-β
• Suppresses other T cells
• TGF-β down-regulates APC function and blocks
proliferation and cytokine production by CD4+ T
cells
• Help establish peripheral tolerance to various self-
antigens, allergens, tumor antigens, transplant
antigens, and infectious agents
• The immune response is down-regulated, and 41

chronic inflammation is prevented

 COLONY-STIMULATING FACTORS
(CSFS)

• CSFs stimulate growth of hematopoietic cells in the bone marrow in

response to inflammatory cytokines such as IL-1
• Include:
• IL-3
• Granulocyte (G-CSF)
• Macrophage (M-CSF)
• Granulocyte-macrophage (GM-CSF)
• Erythropoietin (EPO)
• Primarily produced in the kidneys
• Regulates RBC production in the bone marrow 42
 REVIEW QUESTIONS

• Define immunology and the state of being immune

• What are the differences between innate immunity and
acquired immunity
• What role do cytokines play in the immune system
• List the cytokine families
• How do natural and artificial acquired immunity differ?
• Describe the three ways in which cytokines can be
classified
• Innate immunity is said to be functional at birth, where
does the newborn get this type of immunity from? 43