IMMUNOLOGY

By Tamba Edmond

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 Outline
• Introduction, general properties and components

• Innate immunity and adaptive immunity

• Types of Adaptive immunity

• Properties of adaptive immune responses

• Cells of the immune system

• Tissues of the immune system

• Overview of immune response to microbes

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 Introduction
• Immunology (from immunis, Latin for "exempt") is the study of the cells,
organs, and chemical components of the immune system.

• Immunity describes a state of having sufficient biological defenses to avoid

infectious disease, or other unwanted biological invasion.

• Immunity involves both specific and non-specific components.

• The non-specific components act either as barriers or as eliminators of

pathogens to stop infection by micro-organisms before they can cause
disease. 3
 Introduction
• The collection of cells, tissues, and molecules that mediate resistance to
infections is called the immune system, and the coordinated reaction of these
cells and molecules to infectious microbes comprises an immune response.

• Immunology is the study of the immune system, including its responses to

microbial pathogens and damaged tissues and its role in disease.

• The most important physiologic function of the immune system is to prevent or

eradicate infections

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 The role of the immune system
1. Defense against infection:
• Deficiency in immunity leads to susceptibility to infections
• Vaccination boosts immune defenses and protects against infection
2. Defense against tumours:
• It prevents the growth of some tumors, and some cancers can be treated by
stimulating immune responses ( e.g NK cells) against tumor cells
3. Can injure cells and induce pathology
• Allergies, autoimmune and other inflammatory diseases
4. Recognizes and responds well to tissue grafts and newly induced proteins:
• Immune responses are barriers to transplantation and gene therapy

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 The role of the immune system cont.
5. Clearance of dead cells and in initiating tissue repair

6. Products of immune cells can also be of great practical use:

• Antibodies are used in clinical laboratory testing and in research as highly
specific reagents for detecting a wide variety of molecules in the circulation
and in cells and tissues
• Antibodies designed to block or eliminate potentially harmful molecules and
cells are used widely for the treatment of immunologic diseases, cancers, and
other types of disorders
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 Innate and Adaptive Immunity
• Host defenses are grouped under innate immunity, which provides immediate
protection against microbial invasion, and adaptive immunity, which develops
more slowly and provides more specialized defense against infections

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 Innate and adaptive immunity
Innate immunity/ natural immunity/ native immunity:

• Always present in healthy individuals (hence the term innate),

• Prepared to block the entry of microbes and to rapidly eliminate microbes that do
succeed in entering host tissues.

Adaptive immunity/ specific immunity/ acquired immunity:

• Requires expansion and differentiation of lymphocytes in response to microbes

before it can provide effective defense; that is, it adapts to the presence of
microbial invaders.
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 Innate immunity
• The first line of defense is provided by epithelial barriers of the skin and
mucosal tissues and by cells and natural antibiotics present in epithelia, all of
which function to block the entry of microbes.

• If microbes do breach epithelia and enter the tissues or circulation, they are
attacked by phagocytes, specialized lymphocytes called innate lymphoid cells,
which include natural killer cells, and several plasma proteins, including the
proteins of the complement system.

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 Innate immunity cont.
• All these mechanisms of innate immunity specifically recognize and react against
microbes.

• In addition to providing early defense against infections, innate immune

responses enhance adaptive immune responses against the infectious agents.

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 COMPONENTS OF THE INNATE IMMUNE SYSTEM

1. Mechanical barriers.
• These barriers prevent the attachment and penetration of infectious pathogens to
the host body these are; Intact skin, mucus, beating of cilia, coughing and
sneezing, flushing actions, urine, saliva, tears, vomiting, and diarrhea.

1. Chemical and biochemical inhibitors of infection

• Numerous substances found in body secretions provide a natural defense
against microorganisms that invade the body.

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i. Chemicals found in body secretions provide natural defense against pathogens,
such as, hydrolytic enzymes in saliva, lysozyme in tears inhibit growth of gram-
positive bacteria, sialic acid in mucus, low pH in sebaceous gland secretions
(organic acids), fatty acids interfere with the function of the cell membranes, A
pH dependent polyamine found in sperm and seminal fluid, which inhibit growth
of gram negative bacteria, and etc.….
ii. Acid pH found in almost all physiologic secretions, e.g., urine and vaginal
secretions, as well as HCl in the stomach.
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1. Phagocytosis. It is a process by which particulate e.g., such as
bacteria are ingested and digested by the phagocytic cells.
Phagocytosis requires energy, which is generated through glucose
metabolism. It is one form of the endocytosis; the other form is
pinocytosis, which is the internalization of the fluid and solutes with
synthesis of new cell membrane and an active cytoplasmic contractile
protein system.

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1. . Phagocytic cells include:
• - Neutrophils (polymorphonuclear leukocytes, PMNs) are
granulocytes that circulate in the blood and migrate quickly in
response to local invasion by microorganisms.
• - Monocytes, it differentiated into macrophages, when they migrate
into tissues, which reside in all body tissues. For example:
• (1) Kupffer cells of the liver are macrophages.
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• (2) Histiocytes in connective tissues are macrophages.
•(3) Microglial cells are the nervous system macrophages.

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• 4. Opsonization. Opsonin are substances that bind to particles
and make them more susceptible to phagocytosis. Phagocytosis
can occur in a very simple system. For example, if neutrophils,
saline, and bacteria are combined, phagocytosis will occur. It can
also be remarkably enhanced in the presence of serum or plasma,
however, because the blood constituent contains opsonin.
• 5. Humoral factors contributing to nonspecific immunity.
• a. Antibody-mediated complement activation in bacteriolysis
• Normal serum can kill and lyse gram-negative bacteria.

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• Bacteriolysis begins with the lytic action of antibody-activated
complement on the outer lipopolysaccharide layer of the cell wall.
•- A bacterial cell wall contains two layers: an outer membrane
layer of lipoproteins and lipopolysaccharide and inner layer of
mucopeptide (peptidoglycan).
•- The antibody and complement disrupt the lipopolysaccharide
layer of the cell wall. Complement becomes an esterase which
provides for the majority of this enzymatic activity.

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• b. Non-antibody humoral factors contributing to nonspecific
immunity.
•- Chemotactic factors attract phagocytes; the chemotaxis C5a is
an extremely important split product of C5 generated during
complement activation.
•- Interferons are proteins produced, usually, by virally infected
cells, and they protect other cells in the area. (Although there are
other triggers for interferon release, virus infection is the most
common and natural one).

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 Adaptive immunity
• The adaptive immune system consists of lymphocytes and their products, such as
antibodies.

• Adaptive immune responses are especially important for defense against

infectious microbes that are pathogenic for humans and may have evolved to
resist innate immunity.

• Whereas the mechanisms of innate immunity recognize structures shared by

classes of microbes, the cells of adaptive immunity (lymphocytes) express
receptors that specifically recognize a much wider variety of molecules produced
by microbes as well as noninfectious substances. 19
• Adaptive immunity is found exclusively in vertebrates.
• The adaptive immune response is a more highly developed system
than the innate immune system

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 Adaptive immunity cont.
• Any substance that is specifically recognized by lymphocytes or antibodies is
called an antigen.

• Adaptive immune responses often use the cells and molecules of the innate
immune system to eliminate microbes, and adaptive immunity functions to
greatly enhance these antimicrobial mechanisms of innate immunity.

• For example, antibodies (a component of adaptive immunity) bind to microbes,

and these coated microbes avidly bind to and activate phagocytes (a
component of innate immunity), which ingest and destroy the microbes.
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1. IMMUNE RESPONSE
• When an individual exposed to non-self-substance either by injection
or infection, a complex series of events are created:
• a. An antigen-presenting cell (usually a macrophage) processes
the antigen and presents it to the lymphoid cells of the immune
system.
• i. For a successful immune response to occur, the processed
antigen (specifically, its epitope) must be presented to lymphocytes in
association with a glycoprotein encoded by genes of the major
histocompatibility complex (MHC).
• ii. This requirement for effective cell interaction is called MHC
restriction.
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• b. The lymphoid cells recognize that particular epitope and
acquire the ability to react with it.
• c. The result of these consequences of events is the activation of
antigen-specific B and T cells, causing them to proliferate and mature.

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• b) The consequences of the initial interaction between
lymphocytes and their homologous epitopes are far-reaching.
•- A subsequent exposure to antigen will induce some B
lymphocytes (memory B cells) to proliferate and differentiate into
antibody-secreting plasma cells.
• i. These active plasma cells secrete their specific antibody in large
amounts when they contact antigen a second time, a phenomenon
known as anamnesis.

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• ii. The secreted antibodies react specifically with the antigen that
originally induced the B cell to proliferate. The potential exists to
produce an extremely large (> 100,000) variety of different,
specifically reactive, antibodies.
•- Some T lymphocytes (memory T cells) are induced to
differentiate and proliferate to form mature progeny that will be
triggered to release biologically active metabolites when they contact
antigen a second time.

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• c) The immune response is under highly complex genetic control.
Most of the genes that code for chain segments of the
immunoglobulin molecule or the T cell receptor are polycistronic
(present in the cell in many forms). The process of DNA re-
arrangement and deletion, followed by RNA splicing, selects alleles
that code for a particular immunologic specificity.

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 Types of Adaptive Immunity
• There are two types of adaptive immunity: humoral immunity and cell-
mediated immunity.

• They are mediated by different cells and molecules and provide defense against
extracellular microbes (by B-cells)and intracellular microbes(by T-cells),
respectively.

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 Humoral immunity
• Humoral immunity is mediated by proteins (antibodies), which are produced by cells (B
lymphocytes).

• Secreted antibodies enter the circulation and mucosal fluids, and they neutralize and
eliminate microbes and microbial toxins that are present outside host cells; in the blood,
extracellular fluid derived from plasma, and in the lumens of mucosal organs such as the
gastrointestinal and respiratory tracts.

• One of the most important functions of antibodies is to stop microbes that are present at
mucosal surfaces and in the blood from gaining access to and colonizing host cells and
connective tissues. In this way, antibodies prevent infections from ever being established.
Antibodies cannot gain access to microbes that live and divide inside infected cells. 31
 Cell-mediated immunity
• Defense against intracellular microbes is called cell-mediated immunity because
it is mediated by cells, which are called T lymphocytes.

• Some T lymphocytes activate phagocytes to destroy microbes that have been

ingested by the phagocytes into intracellular vesicles (helper T cells).

• Other T lymphocytes kill any type of host cells that are harboring infectious
microbes in the cytoplasm (cytotoxic T cells).

• In both cases, the T cells recognize microbial antigens that are displayed on host
cell surfaces, which indicates there is a microbe inside the cell.
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 Active vs Passive immunity
• Immunity may be induced in an individual by infection or vaccination (active
immunity) or conferred on an individual by transfer of antibodies or lymphocytes
from an actively immunized individual (passive immunity)

• Active immunity: an individual exposed to the antigens of a microbe mounts an

active response to eradicate the infection and develops resistance to later
infection by that microbe. Such an individual is said to be immune to that
microbe, in contrast with a naive individual, not previously exposed to that
microbe’s antigens.
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 Active vs Passive immunity cont.
• Passive immunity: a naive individual receives antibodies or cells (e.g.,
lymphocytes, feasible only in animal experiments) from another individual
already immune to an infection.

• The recipient acquires the ability to combat the infection for as long as the
transferred antibodies or cells last.

• Passive immunity is therefore useful for rapidly conferring immunity even before
the individual is able to mount an active response, but it does not induce long-
lived resistance to the infection.
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 Active vs Passive immunity cont.
• The only physiologic example of passive immunity is seen in newborns, whose
immune systems are not mature enough to respond to many pathogens but who
are protected against infections by acquiring antibodies from their mothers
through the placenta and breast milk.

• Clinically, passive immunity is limited to treatment of some immunodeficiency

diseases with antibodies pooled from multiple donors, and for emergency
treatment of some viral infections and snakebites using serum from immunized
donors.
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 Properties of adaptive immune responses
• Several properties of adaptive immune responses are crucial for the effectiveness
of these responses in combating infections
Feature Functional significance
Specificity Ensures that distinct antigens elicit specific responses

Diversity Enables immune system to respond to a large variety of

antigens
Memory Leads to enhanced responses to repeated exposures to the same
antigen
Clonal expansion Increases the number of antigen specific lymphocytes from a
small number of naïve lymphocytes
Specialization Generates responses that are optimal for defense against
different types of microbes
Contraction and Allows immune system to respond to newly encountered
homeostasis antigens
Non-reactivity to self Prevents injury to the host during response to foreign antigens
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Specificity and diversity:

• The adaptive immune system is capable of distinguishing among millions of different

antigens or portions of antigens.

• Specificity is the ability to distinguish between many different antigens.

• Hence, the total collection of lymphocyte specificities (the lymphocyte repertoire) is

extremely diverse.

• The basis for this remarkable specificity and diversity is that lymphocytes express clonally
distributed receptors for antigens, meaning that the total population of lymphocytes
consists of many different clones (each made up of one cell and its progeny), and each
clone expresses an antigen receptor that is different from the receptors of all other clones
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• The clonal selection hypothesis, formulated in the 1950s, correctly predicted
that clones of lymphocytes specific for different antigens develop before an
encounter with these antigens, and each antigen elicits an immune response by
selecting and activating the lymphocytes of a specific clone.

• The diversity of the lymphocyte repertoire, enables the immune system to

respond to a vast number and variety of antigens.

• Very few cells, perhaps as few as 1 in 100,000 or 1 in 1,000,000 lymphocytes,

are specific for any one antigen. Thus, the total number of naive (unactivated)
lymphocytes that can recognize and react against any one antigen ranges from
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about 1000 to 10,000 cells.
• To mount an effective defense against microbes, these few cells have to give rise
to a large number of lymphocytes capable of destroying the microbes.

• The remarkable effectiveness of immune responses is attributable to several

features of adaptive immunity, including the marked expansion of the pool of
lymphocytes specific for any antigen upon exposure to that antigen, and selection
mechanisms that preserve the most useful lymphocytes.

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Clonal selection 40
Memory:
• The adaptive immune system mounts larger and more effective responses to
repeated exposures to the same antigen.

• Implying that the immune system remembers exposure to antigen, therefore called
immunologic memory.

• The response to the first exposure to antigen (the primary immune response), is
initiated by naive lymphocytes that are seeing antigen for the first time.

• Subsequent encounters with the same antigen lead to the secondary immune
responses that usually are more rapid, larger, and better able to eliminate the
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antigen than primary responses.
• Secondary responses are the result of the activation of memory lymphocytes( by IL 2
and IL4), which are long-lived cells that were induced during the primary immune
response.

• The term memory arose because of the realization that these cells must remember
previous encounter with antigen since they respond better upon subsequent encounters.

• Immunologic memory optimizes the ability of the immune system to combat

persistent and recurrent infections, because each exposure to a microbe generates
more memory cells and activates previously generated memory cells.

• Memory also is one of the reasons why vaccines confer long-lasting protection against
infections.
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Primary and secondary immune responses
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Clonal expansion:

• When lymphocytes are activated by antigens, they undergo proliferation,

generating many thousands of clonal progeny cells, all with the same antigen
specificity.

• This process, called clonal expansion, rapidly increases the number of cells
specific for the antigen encountered and ensures that adaptive immunity keeps pace
with rapidly proliferating microbes.

Specialization:

• Immune responses are specialized, and different responses are designed to defend
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best against different classes of microbes.
Self limiting:

• All immune responses are self-limited and decline as the infection is eliminated,
allowing the system to return to a resting state, prepared to respond to another infection.

Immunological tolerance:

• The immune system is able to react against an enormous number and variety of
microbes and other foreign antigens, but it normally does not react against the host’s
own potentially antigenic substances (self antigens).

• This unresponsiveness to self is called immunological tolerance, referring to the

ability of the immune system to coexist with (tolerate) potentially antigenic self
molecules, cells, and tissues. 45
 Cells of the Immune System
• The cells of the immune system are located in different tissues and serve
different roles in host defense

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• Lymphocytes: circulate through lymphoid organs and non-lymphoid tissues.
They recognize foreign antigens and initiate adaptive immune responses.

• Cells resident in tissues detect the presence of microbes and react against them.
These cells include:

• Macrophages: whose function is to ingest and destroy foreign substances;

• Dendritic cells: which capture microbes and display them to lymphocytes to

initiate immune responses, and are therefore called antigen-presenting cells; and

• Mast cells: which help to recruit other leukocytes to destroy microbes.

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• Phagocytes that normally circulate in the blood, including neutrophils and
monocytes, are rapidly recruited to sites of infection in the process called
inflammation.

• These leukocytes (white blood cells) ingest and destroy microbes and then start
the process of repairing damaged tissues. Because these phagocytes, as well as
some T lymphocytes, are responsible for the effect of the immune response,
which is to destroy microbes, they are sometimes called effector cells.

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 Tissues of the Immune System
• The tissues of the immune system consist of the generative lymphoid organs, in
which T and B lymphocytes mature and become competent to respond to
antigens, and the peripheral lymphoid organs, in which adaptive immune
responses to microbes are initiated.

• Most of the lymphocytes in a healthy human are found in lymphoid organs and
other tissues.

• However, lymphocytes are unique among the cells of the body because of their
ability to circulate among tissues.
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 Peripheral Lymphoid Organs
• The peripheral lymphoid organs, which consist of the lymph nodes, the spleen,
and the mucosal and cutaneous immune systems, are organized in a way that
promotes the development of adaptive immune responses.

• T and B lymphocytes must locate microbes that enter at any site in the body, then
respond to these microbes and eliminate them.

• In addition, in the normal immune system, very few of these lymphocytes are
specific for any one antigen. It is not possible for the few lymphocytes specific
for any antigen to patrol all possible sites of antigen entry.
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• This organization is complemented by a remarkable ability of lymphocytes to circulate throughout
the body in such a way that naive lymphocytes preferentially go to the specialized organs in which
antigen is concentrated, and effector cells go to sites of infection where microbes must be
eliminated.

• Furthermore, different types of lymphocytes often need to communicate to generate effective

immune responses.

• For example, helper T cells specific for an antigen interact with and help B lymphocytes specific
for the same antigen, resulting in antibody production.

• An important function of lymphoid organs is to bring these rare cells together after stimulation by
antigen so they interact.

• The major peripheral lymphoid organs share many characteristics but also have some unique
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features.
• Based upon the functional development of the lymphatic cells the lymphoid
organs are classified into 2 groups:

• 1. Primary Lymphoid Organs / central/ generative organs

• 2. Secondary Lymphoid Organs /perpheral

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 BONE MARROW

• Bone marrow is the primary lymphoid organ. It is a soft tissue within the cavity of bones.
Bone marrow is divisible into 2 :

1.vascular region 2, haemtopoietic region.

Vascular region is the circulatory system that supplies nutrient and removes waste from
actively growing blood vessels.

• Red marrow is actively involved in haemtopoiesis.

• Red marrow contains titipoent cells called stem cells.

• The development of blood cells from stem cells is called Haematopoies.

• Haematopoiesis forms RBC,WBC- granulocytes, lymphocytes, monocytes and platelets.

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• All the cells of the immune system are initially derived from the bone marrow
through a process called hematopoiesis

• In human bone marrow is the site for B- cell origin.

• It is also the site for B-cell maturation.

• Immature B cells arise from lymphoid progenitors, proliferate and differentiate

within the bone marrow

• The stromal cells in the bone marrow interact with B cells and secrete cytokines
and help in the maturation of b-cells .
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• Majority of lymphoid progenitors develop into B lymphocytes in the bone
marrow.

• Some of lymphoid progenitors migrate into the thymus , where they develop into
the T-lymphocytes.

• During secondary immune response large number of plasma cells are produced
in the bone marrow.

• They secrete large amount of abs. So bone marrow is a source of ab synthesis.

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 THYMUS

• Thymus is the site of T cell differentiation and maturation.

• It is a bilobed gland, situated above heart in the thorax region each lobe is encapsulated
and it is divided into lobules which are separated by strands of connective tissue –
called trabeculae.

• Each lobule contains – lymphocytes & each lobule organized into 2 compartments:
1.Outer cortex
2.Inner medulla

• Relative Size Greatest in Newborn

• Absolute Size Greatest at Puberty 59

• The cortex contains mostly immature & proliferating thymocytes, Medulla is sparsely
populated with thymocytes.

• In medulla they learn to discriminate between self and non-self during fetal development
and for a short time after birth.

• T cells leave the medulla to enter the peripheral blood circulation, through which they are
transported to the secondary lymphoid organs About 95% of all T cells die in the thymus.

• Besides lymphoid cells it is composed of 1.Epithelial cells (cortical and medullary) 2.

Macrophages 3. Dendritic cells 4. Nurse cells 5. Hassall’s corpuscles Lymphocytes in the
thymus are called thymocytes
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• Through clonal selection mechanism, thymus cause the death of those T- cells
that cannot recognize Ag- MHC- complexes and those that react with self Ag-
MHC & stop danger of causing autoimmune diseases.

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 Secondary lymphoid organs
• Primary follicle
Inactivated lymphoid follicle

• Secondary follicle
Follicle that is activated by antigen
Ring of B cells that surround germinal center
Proliferating B cells and T helper cells

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 Lymphatic system
• Interstitial fluid (the portion that doesn’t enter venous system) is returned to
circulatory system by lymphatic vessels

• Largest lymphatic vessel – thoracic duct

• Enters left subclavian vein ○

• Lymph from right arm and right side of head enters through right lymphatic duct, drains
into right subclavian

• Antigen is carried by lymph to lymph nodes

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ANTIBODIES
•• They are also known as immunoglobulins and are produced by
plasma cells in response to the presence of antigens.
•• The immunoglobulins form 20% of the total plasma proteins.
Though produced by B-lymphocytes, the antibodies are found in
almost all the tissues of the body.

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Classes of antibodies
• Fives class exists namely;
• IgA (Ig alpha) accounts for (15-20%) of antibodies in the body
takes part in localized defense mechanism in external secretions like
tears, urogenital, and mucus secretion. It is dimeric and does not fix
complement.
• IgD (Ig delta) (<1%): found on surface of B lymphocytes and
function as B cell Ag receptor; is important in ADCC (antibody
dependent cell-mediated cytotoxicity). It is monomeric.

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•• Ig E (Ig epsilon) (<0.1%): found on the surface of mastocytes
and basophils. Accounts for anaphylactic shock and allergic diseases
like asthma. Protects against parasitic worm.
•• Ig G (Ig gamma) (70-75%): major antibody class in blood. They
are responsible for secondary response; can cross placenta and confer
immunity to fetus. It is a monomer and is found in other fluids like
lymph.
•• Ig M(Ig mu)(5-10%): this is a major antibody class in primary
response; 5 times heavier than Ig G. cannot cross placenta . causes
agglutination and lysis of microbes.

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3.Autoimmunity disorders
• Sometimes the immune system fails to distinguish self from non-
self. producing antibodies, called autoantibodies, and cytotoxic T cells
that attack and damage the body's tissues and organs. This attack
against self is called autoimmunity

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4.Transplantation and Tissues
rejection
• Transplanted tissues and organs include corneas, kidneys, lungs,
pancreases, bone marrow, pieces of skin, livers, and hearts.
• The danger the immune system poses to transplanted tissue is that
the recipient's cells may recognize the donor's tissues as foreign and
attempt to destroy the transplanted tissue. Such a response is called a
tissue rejection reaction.
• Tissue rejection resembles the cellular immune response against a
foreign antigen. The greater the antigenic difference between the cell
surface molecules (MHC: major histocompatibility) of the recipient
tissues and the donor tissues, the more rapid and severe the rejection
reaction
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•• The four major varieties of grafts (transplant tissue) include
• Isograft. Tissue is taken from a genetically identical twin.
• Autograft. Tissue is taken from elsewhere in a person's body.
(Technically, this is not a transplant because it occurs within an
individual.)
• Allograft. Tissue comes from an individual who is not
genetically identical to the recipient, but of the same species.
• Xenograft. Tissue comes from a different species, such as pigs and
baboo

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THANK YOU

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