Kotebe University of Education

College of Science and Mathematics Education

Department of Biology
Introduction to Immunology ((Biol 4062) )
 1. INTRODUCTION
• Although there are high tech developments nowadays, human kind
has been through and still in challenges of health problems due to
both infectious and non-infectious disease.
• Immunology continues to fascinate and frustrate researchers all
over the world eg. tumor immunology, autoimmunity and
responses to immunization
• The power of immune defense against disease is a gift of nature.
• You will learn more about the architecture and mechanism of
immune response from the course.
• Had it not been there the immune system what could happen to
you?
• Immunology is primarly for whom?
-Biology students, medical students, researchers on health, and its
general concept for all.
 Intro. Cont’d
1.1. Basic concepts in Immunology
• Immunology - the scientific study of the way in which the body defends itself
against invading organisms or internal invaders (tumors).
• Immune system - a remarkably versatile defense system that has evolved to
protect animals from pathogens or cancer like a defense force of a country
who protects the country from both internal and external enemies.
- It is clearly 'a good thing', but like mercenary armies, it can turn to bite the hand
that feeds it, and cause damage to the host e.g. autoimmune diseases, transplant
rejection
- generate an enormous variety of molecules and cells that are capable of
specifically recognizing and eliminating an apparently limitless variety of
foreign invaders.
- Immune response - the coordinated reaction of immune system against
infections (and other foreign substances). Immunological responses serve
three broad functions:
Recognition – foreign from self • Defence against micro
Immune response organisms
• Homeostasis; removal of
Response – intimate reaction damaged or effete cells
• Surveillance; recognition and
against ther ecognized foreigners
 Intro. Cont’d
- Once a foreign organism has been recognized, the immune system
recruits a variety of cells and molecules to mount an appropriate
response (effector response) for elimination or neutralization of
foreign invaders.
- Later exposure to the same foreign organism induces a memory
response, characterized by a more rapid and heightened immune
reaction that serves to eliminate the pathogen and prevents the
disease.
- In some instances the immune system fails to act as a protector
because of some deficiency in its components. In other times it
becomes an aggressor and turns its power against its own host.
- The great historian of the Peloponnesian War (Thucydides) in 430
BC describes a plague in Athens and wrote that only those who had
recovered from the plague could nurse the sick because they would
not contract the disease a second time without the knowledge of
immune system.
- The first recorded attempts to induce immunity deliberately were
performed by the Chinese and Turks in the fifteenth century.
 Intro. Cont’d
Edward Jenner in 1798 showed inoculation of fluid from a cowpox
pustule into people might protect humans from smallpox.

Edward Jenner (1749-1823) Louis Pasteur (1822-1895)

Louis Pasteur - induction of immunity to cholera was the next major

advance in immunology. He succeeded in growing the bacterium
thought that cause fowl cholera by culturing and then had shown that
 Intro. Cont’d
- injected some chickens with an old culture and the chickens
became ill, but, to Pasteur’s surprise, they recovered.
- Due to shortage of chickens he used the previously injected and
recovered chicken. To his surprise the chicken were protected.
- the attenuated bacterial strain was called vaccine (from the Latin
vacca, meaning “cow”), in honor of Jenner’s work with cowpox
inoculation.
- Extended this findings to other diseases and described that the
attenuated or weakened pathogen as vaccine.
- In 1881, Pasteur vaccinated one group of sheep with heat-
attenuated anthrax bacillus (Bacillus anthracis); then challenged
the vaccinated sheep and some unvaccinated sheep with a virulent
culture of the bacillus. vaccinated sheep lived, and all the
unvaccinated ones died. The beginning of immunology.
 Intro. Cont’d
In1885, Pasteur administered his first vaccine (attenuated rabies virus) to a human
and had been repeatedly bitten a young boy (Joseph Meister) by a rabid dog. The
boy lived and later became a custodian at the Pasteur Institute.

Fig. Administration of the first vaccine to human being (Joseph Meister)

- Emil von Behring and Shibasaburo Kitasato in 1890 gave the first insights into
the mechanism of immunity or the how question; earning von Behring the Nobel
Prize in medicine in 1901.
- Behring and Kitasato demonstrated that serum from animals previously immunized to
diphtheria could transfer the immune state to unimmunized animals.
 Intro. Cont’d
- active component from immune serum (antitoxin, precipitin,
and agglutinin) could neutralize toxins, precipitate toxins, and
agglutinate (clump) bacteria, respectively.
- In 1930, gamma-globulin (now immunoglobulin) was thought
to be the immune serum component and the active molecules in
the immunoglobulin fraction as antibodies.
- The immunity mediated by antibodies was called as humoral
immunity.
- before the discovery that a serum component could transfer immunity, Elide
Metchnikoff in 1883 demonstrated (cell mediated immunity) that cells also contribute to
the immune state of an animal.
- both are correct and immunity requires both cellular and humoral responses.
- The active phagocytic cells (white blood cells) identified by Metchnikoff were likely
blood monocytes and neutrophils.
- in 1940s, Merrill Chase succeeded in transferring immunity against tuberculosis
organism by transferring white blood cells between guinea pigs.

Elie Metchnikoff Merrill Chase

 Intro. Cont’d
- in 1950s, lymphocyte was identified as the cell responsible for
both cellular and humoral immunity.
- Bruce Glick at Mississippi State University indicated that
there were two types of lymphocytes: T lymphocytes derived
from the thymus mediated cellular immunity, and B
lymphocytes from the bursa of Fabricius (an outgrowth of the
cloaca in birds) were involved in humoral immunity.
1.2 Components of the immune system (IS)
- you are probably aware that inside your chest you have an organ called a
"heart". Who doesn’t know to have a heart, lung, kidney? But you might
not be aware of thymus. It is there near your heart and one component of
the IS.
 Antibodies  Hormones
 Bone marrow  Spleen
 Complement system  Thymus
 1.3. Principles of Innate and Adaptive Immunity
The state of protection from infectious disease

Innate immunity Adaptive immunity

 Less specific - more of specific
 Provides the first line of defense - second line of defense
 present before the onset of infection - after the onset of infection
 Includes barriers like - lymphocytes and the antibodies
Phagocytic, anatomic, physiologic and and other molecules they produce.
inflammatory - provides increased protection
against
subsequent re-infection (memory
response)
- Immediate action - Delayed
 Immune System

Innate Adaptive
(Nonspecific) (Specific)

Cellular Humoral Humoral

Cell-Mediated
Components Components (Ab)
 Summary of innate and adaptive immunity

Comparison of Innate and Adaptive Immunity

Innate Immunity Adaptive Immunity

• No time lag • A lag period

• Not antigen specific • Antigen specific

• No memory • Development
of memory
 Summary of innate and adaptive immunity

Adaptive and Innate - Interactions

Infectious Innate Immunity No
Exposure holds Disease

Innate Immunity
Fails
Adaptive Immunity
Specific memory

Disease

Adaptive Second Infectious

Recovery Exposure
Immune system
Same organism
 1.4 Hematopoiesis
• is the formation and development of blood cells from hematopoietic stem cells (HSC)
• Self renewing HSC gives rise to lymphoid and myeloid progenitor.
1.5 Cells and organs of the immune system
1.5.1 Cells of the immune system
1.5.1.1 Lymphoid cells
Lymphocytes – cells of the immune system that play a key role in the
control and regulation of immune responses as well as in the
recognition of infected or heterologous cells
• responsible for adaptive immunity and the immunologic attributes of
diversity, specificity, memory, and self/non-self recognition.
• engulf and destroy microorganisms, present antigens and secret
cytokines.
• constitute 20%–40% of the body’s white blood cells and 99% of these
cells are found in the lymph.
• continually circulate in the blood and lymph and are capable of
migrating into the tissue spaces and lymphoid organs
• broadly subdivided into three populations as B cells, T cells, and
natural killer cells
 Intro. Cont’d
Table 1.1 lymphocytes and their amount at different sites of the body
Approximate % of lymphocytes

T-lymphocytes B-lymphocytes Natural killer cells (NK-Cells)

Peripheral 70-80 % 10-15 % 10-15 %

blood

Bone marrow 5-10 % 80-90 % 5-10 %

Thymus 99 % <1% <1%

Lymph node 70-80 % 20-30 % <1%

Spleen 30-40 % 50-60 % 1-5 %

 Intro. Cont’d
B Lymphocytes
- bursa of Fabricius in birds
- When they leave their maturation site express unique
antigen binding receptor
- mature B cells are distinguished from other
lymphocytes by their synthesis and display of
membrane-bound immunoglobulin (antibody)
molecules, which serve as receptors for antigen.
- function in the humoral immunity component by
secreting antibodies.
 Intro. Cont’d
- Antibodies are glycoproteins consisting two identical heavy
polypeptide chains and two identical light polypeptide chains
(Figure 1.2)

Figure 1.2 structure of antibodies

 Intro. Cont’d
- present antigen to T cells and also secrete cytokines.
- express B cell receptors (BCRs) on their cell membrane that
allow the B cell to bind a specific antigen, against which it
will initiate an antibody response.
- All clonal progeny from a given B cell secrete antibody
molecules with the same antigen-binding specificity.
Plasma cells - are antibody-secreting effector cells of B
lymphocyte with a characteristic cytoplasm that contains
abundant endoplasmic reticulum and Golgi vesicles.
• effector cells of T-cell lineage include the cytokine-secreting
TH and TC cells.
• Some of the progeny of B and T lymphoblasts differentiate
into memory cells.
 Intro. Cont’d
T Lymphocytes
• derive their name from their site of maturation –
thymus
• Like B lymphocytes, they have also membrane receptors for
antigen (TCR). But TCR is structurally distinict from IG.
• Unlike the membrane-bounded antibody on B cells, the TCR
does not recognize free antigen.
• TCR recognizes only antigen that is bound to particular
classes of self-molecules called major histocompatiblity
complex (MHC).
• All T-cell subpopulations express the T-cell receptor, a
complex of polypeptides that includes CD3; but most can be
distinguished by the presence of one or the other of two
membrane molecules, CD4 and CD8.
 Intro. Cont’d
• T cells that express the membrane glycoprotein molecule CD4
are restricted to recognizing antigen bound to class II MHC
molecules, whereas T cells expressing CD8, a dimeric
membrane glycoprotein, are restricted to recognition of
antigen bound to class I MHC molecules.
• CD4_T cells generally function as T helper (TH) cells and are
class-II restricted; CD8_ T cells generally function as T
cytotoxic (TC) cells and are class-I restricted.
• TH cells are activated by recognition of an antigen–class II
MHC complex on an antigen-presenting cell. After activation,
the TH cell begins to divide and gives rise to a clone of
effector cells, each specific for the same antigen–class II MHC
complex. These TH cells secrete various cytokines, which play
a central role in the activation of B cells, T cells, and other
cells that participate in the immune response.
 Intro. Cont’d
• TH1 response produces a cytokine profile that supports
inflammation and activates mainly certain T cells and
macrophages.
• TH2 response activates mainly B cells and immune responses
that depend upon antibodies.
• TC cells are activated when they interact with an antigen–class
I MHC complex on the surface of an altered self-cell
• most CTLs secrete few cytokines. Instead, CTLs acquire the
ability to recognize and eliminate altered self-cells.
• some T cells help to suppress (TS) the humoral and the cell-
mediated branches of the immune system.
• B and T lymphocytes that have not interacted with antigen are
referred to as naive or unprimed.
 Intro. Cont’d
Natural killer cells (NK cells) – first described in 1976
- are large, granular lymphocytes that do not express surface
markers unlike typical B or T cells.

- play an important role against tumor cells and cells infected

with some viruses.
• recognize potential target cells in two different ways.
1. reduction in the display of class I MHC molecules and the unusual profile of surface
antigens displayed by some tumor cells and cells infected by some viruses.
2. Some tumor cells and cells infected by certain viruses display antigens against which
the immune system has made an antibody response, so that antitumor or antiviral
antibodies are bound to NK surfaces which express CD16
 Intro. Cont’d
1.5.1.2. Phagocytic cells
• Are cells of the immune system that includes monocytes,
macrophages, neutrophils, eosinophils, basophils and
denderitic cells

monocytes macrophages neutrophils

denderitic cell

eosinophils basophils
 Intro. Cont’d
• Monocytes, macrophages and granulocytes are able to ingest particulate matter
serving as phagocytic functions.
• phagocytic activity is greater in macrophages.
• monocyte is a leukocyte in transit through the blood and when fixed
in a tissue it becomes a macrophage.
neutrophils
• granulocytes eosinophils cellular morph. + cyto. staining
basophils
neutrophils eosinophils basophils
multilobed nucleus or polymorphonuclear bilobed nucleus (PMN a lobed nucleus
leukocytes (PMN leucocyte)
leucocyte)
their granules stain poorly with stains with the acid dye granules stain a dark purplish blue with the
both acidic and basic dyes eosin red basic dye methylene blue
Ingest and destroy microbes. Against allergic reactions release histamine, leukotrienes, and
and parasitic infections. prostaglandins, chemicals that promote
inflammation.
phagocytic Phagocytic not
constitute 50%–70% of the 1%–3%) 1%
circulating WBC
 Intro. Cont’d
Mast cells: - formed in the bone marrow by hematopoiesis and
released into the blood as undifferentiated cells until they enter
tissues (skin, connective tissues of various organs, mucosal
epithelial tissue of the respiratory, genitourinary, and digestive
tracts).
- Like basophils have large number of granules that contain
histamine.
- play an important role in the development of allergies and
protect mucosal surfaces againist pathogens
Dendritic cells (DC): acquired its name because it is covered
with long membrane extensions that resemble the dendrites of
nerve cells.
- Presents antigen to TH cell as its main function.
 Intro. Cont’d
1.5.2 Organs of the Immune System
● can be distinguished by function as the primary and secondary lymphoid
organs.
primary (or central) lymphoid organs:
- The site where maturation of lymphocytes takes place
- Includes thymus and bone marrow
Secondary (or peripheral) lymphoid organs:
- Includes lymph nodes, spleen, and various mucosal associated
lymphoid tissues (MALT) such as gut-associated lymphoid tissue (GALT) ,
NALT and BALT
- Trap antigen and provide sites for mature lymphocytes to interact with that
antigen.
Tertiary lymphoid tissues:
- normally contain fewer lymphoid cells than secondary lymphoid organs
- can import lymphoid cells during an inflammatory response.

30
Fig. The functional organization of lymphoid tissue.
Stem cells (SC) arising in the bone marrow differentiate into imunocompetent T- and B-cells in
the primary lymphoid organs and then colonize the secondary lymphoid tissues where immune
responses are organized. The mucosal-associated lymphoid tissue (MALT) produces antibodies
for mucosal secretions. 31
 Intro. Cont’d
A. Primary Lymphoid Organs
a) THYMUS
- is a flat, bilobed organ situated above the heart.
- the site of T-cell development and maturation.
- the outer compartment (cortex), is densely packed with immature T
cells, called thymocytes, whereas the inner compartment (medulla), is
sparsely populated with thymocytes.
- Important to generate and select a repertoire of T cells that will protect
the body from infection.
- Induces the death of those T cells that cannot recognize antigen-MHC
complexes and those that react with self-antigen–MHC and pose a
danger of causing autoimmune disease.
- More than 95% of all thymocytes (T cell precursor) die by apoptosis in
the thymus without ever reaching maturity.
Q. What will be the expected consequences if the thymus is removed from
your body?
32
 Intro. Cont’d
b) BONE MARROW
- is the site of B-cell origin and development (not in all species).
• In birds, a lymphoid organ called the bursa of Fabricius, a lymphoid
tissue associated with the gut, is the primary site of B-cell maturation.
• In mammals such as primates and rodents, there is no bursa and no
single counterpart to it as a primary lymphoid organ.
• In cattle and sheep, the primary lymphoid tissue hosting the
maturation, proliferation, and diversification of B cells early in
gestation is the fetal spleen.
• In gestation, this function is assumed by a patch of tissue embedded
in the wall of the intestine called the ileal Peyer’s patch, which
contains a large number of B cells.
• The rabbit, too, uses gut-associated tissues such as the appendix as
primary lymphoid tissue for important steps in the proliferation and
diversification of B cells.
33
 Intro. Cont’d
 Lymphatic System
• thoracic duct - the largest lymphatic vessel.
• captures fluid lost from the blood and returns it to the blood
ensuring steady-state levels of fluid within the circulatory
system.
• The heart does not pump the lymph through the lymphatic
system; instead the flow of lymph is achieved as the lymph
vessels are squeezed by movements of the body’s muscles.
• lymph flows only in one direction.
• lymph nodes trap foreign antigen circulating in the lymph
B. Secondary Lymphoid Organs
• Lymph nodes and the spleen are the most highly organized
secondary lymphoid organs.
• Less-organized lymphoid tissue, collectively called mucosal-
associated lymphoid tissue (MALT),
34
 Intro. Cont’d
• MALT is found in various body sites including Peyer’s
patches (in the small intestine), the tonsils, and the appendix,
as well as numerous lymphoid follicles within the lamina
propria of the intestines and in the mucous membranes lining
the upper airways, bronchi, and genital tract.
a) LYMPH NODES
• are encapsulated bean shaped structures containing a reticular
network packed with lymphocytes, macrophages, and
dendritic cells.
• are the sites where immune responses are mounted to antigens
in lymph.
• can be divided into cortex, paracortex and the medulla,

35
Structure of a lymph node 36
37
 Intro. Cont’d
b) Spleen
• A large encapsulated bean shaped organ with a
spongy interior situated on the left side of the
body below the diaphragm.
• Contains T and B lymphocytes as well as many
phagocytes.
• Protect the body against blood born infections
and it is particularly important for B cell
responses to polysaccharide antigens.

38
39
40
Fig.The distribution of major lymphoid organs and tissues throughout
41
the body.