CHAPTER ONE

Introduction to Immunology
1.0 Learning Objectives
Upon completion of this lecture the student will be able to:

 Define the terms immunity, immunology

 Describe major historical events in the development of

immunology

 Differentiate innate and adaptive immunity in terms of

components and type of immune response.

 Explain the major defenses of innate immunity

 Describe the mechanisms used by the body to defend itself

in an innate response.
1.1 Definition of terms
 Immunology

 The study of immune system or immunity

 The study of the physiological mechanisms which enable

the body to recognize materials as foreign and to neutralize,
metabolize or eliminate them without injury to the host
tissue.

 Immunity

 State of protection from infectious diseases

 Cont…
Immune system
 A remarkably versatile defense system that has evolved to
protect animals from invading pathogenic
microorganisms and cancer.

 It is able to generate an enormous variety of cells and

molecules capable of specifically recognizing and
eliminating an apparently limitless variety of foreign
invaders.
1.2. History of immunology
 Individuals recovering from certain disease rarely
contracted that same disease again.

In 1798, Jenner’s work on vaccination, describing a related,

yet safe procedure.
Noted people, who had cow pox, were spared in small
pox epidemics,
1.2 History Cont
 inoculated boy with pus from milk maid with cow pox,
and

 re-inoculated same boy with infectious pus from a patient

in the active small pox.

 No disease state followed these inoculations, and

experiment was repeated several times with great success!
 Louis Pasteur- demonstrating
that it was possible to attenuate,
or weaken, a
pathogen and administer the
attenuated strain as a vaccine.

In 1885, Pasteur administered his

first vaccine to a human, a
young boy who had been bitten
repeatedly by a rabid dog

Wood engraving of Louis Pasteur watching Joseph Meister receive the rabies vaccine.
[From Harper’s Weekly 29:836; courtesy of the National Library of Medicine.]
1.2 History Cont

 Jenner`s provided first clear evidence that active

immunization could be used safely to prevent an infectious
disease.

 Almost 70 Years later, Pasteur - introduced pasteurization

also

 Recognized and exploited the general principle

underlying vaccination

 At about 1900,

 Role of phagocytes and cellular immunity were elucidated

 1.3. The immune system

Immune System

Innate Adaptive
(Nonspecific) (Specific)

Cellular Humoral Humoral

Cell-Mediated
Components Components (Ab)
 Overview of the Immune System
1.3. The
immune system
1.4 The Innate immunity
Natural immune system (Innate Immunity)
 Non – specific
 First line of defense
 Repeated exposure - no augmentation
 Components
Biochemical
Physical
Cells
 1.4 Innate Immunity
1. Components Lysozymes
a. Biochemical Mucus
 enzymes, C’, etc.
 secretions Cilia: trachea
 pH Sebaceous glands
b. Physical
 skin Skin
 cilia Acid in
c. Cells stomach
 Phagocytes, NK
Commensal
2. Example organisms in
a. Burn response gut & vagina

Spermine in semen
1.4 Innate Immunity
1.4 Innate Immunity
 Overall non-specific reaction of body to injury or
invasion – starts immediately with infection or trauma
 Reactants may initiate, expand, or sustain the response

 Can be acute (short duration) or become chronic

(prolonged duration)

 Has 4 cardinal signs: heat, pain, redness, loss of

function resulting from:
1.4 Innate Immunity
 Increased blood and plasma flow to the area

 Increased capillary permeability by retraction of endothelial

cells

 mediated by vaso active agents such as histamine and

prostaglandins.

 derived from injured cells and later from cells that

infiltrate the area.

 Migration of leucocytes, particularly Neutrophils and

macrophages, from the capillaries to the site of injury is
due to a process called chemotaxis.
1.4 Innate Immunity
 Migration of white cells, especially early migration of
neutraphils then macrophages to the area

 Increased release of mediators such as histamine from

damaged mast cells – furthering capillary dilation

 Increased concentration of acute phase reactants that

can amplify and/or control the response

 Complement – a series of enzymes normally circulating in

an inactive form may be activated resulting in lysis or

enhanced phagocytosis of cells
1.4.1 External Innate Defense Systems
 Prevent entrance:

 Structural barriers– effective with most microorganisms

 Skin - epidermis = layers of tightly packed epithelial cells.

Outer layer is dead cells and keratin, waterproofing protein

 Inner layer skin - dermis = blood vessels, hair follicles, sweat

glands, and sebaceous glands that produce an oily secretion
called sebum

 Cilia and cough reflex – helps expel microbe containing mucous

1.4.1 External Innate Defense Systems
 Mucus - conjunctivae, alimentary, respiratory, and urogenital
tracts
• saliva, tears, and mucous secretions wash away invaders
and contain antibacterial or antiviral substances.
• acidity (pH 5.6) of sweat, sebaceous glands, vagina (pH
5) and stomach (pH 1) – unfriendly to many
microorganisms

 enzymes present in the skin and stomach, tears

 Normal flora - out compete pathogens for attachment sites on

the epithelial cell surface and for necessary nutrients.
1.4 Innate Immunity
 Complement – a series of enzymes normally circulating in an
inactive form

 May be activated by the classical or alternate pathways

 Can result in lysis or enhanced phagocytosis of cells

 Lysozyme, a hydrolytic enzyme in mucous secretions and in

tears, can cleave the peptidoglycan layer of bacterial cell wall.

 Interferon, proteins produced by virus-infected cells. Has

many functions including ability to bind to nearby cells and
induce a generalized antiviral state.
1.4 Innate Immunity
 Phagocytosis

 Is a form of endocytosis.

 Important body defense mechanism is process in which

specialized cells engulf and destroy foreign particles such
as microorganisms or damaged cells.

 Macrophages and segmented Neutrophiils are the most

important phagocytic cells.
1.4 Innate Immunity
 Phagocytosis ...
 Adherence – binding of organism to the surface of
phagocytic cell.

 Engulfment:- is the injestion of m/os and formation of

phagosomes.

 Digestion – after the foreign particle or m/os is ingested,

cytoplasm lysosome fuse with phagosome The enzymes of
lysosome then contribute to microbial killing and lysis.
1.4 Innate Immunity
Phagocytosis ...
1.5 Adaptive Immunity
 Specific
 Second line of defense
 Repeated exposure - augmented – memory
 Longer lasting response

Components

Classic Immune System

 Cells (Cell mediated) =CMI
 Soluble Factors (Humoral immunity) = HI
1.5 Adaptive immune system
 Capable of recognizing and selectively eliminating specific
foreign microorganisms and molecules(i.e., foreign
antigens).

 Unlike innate immune responses, adaptive immune

responses are reactions to specific antigenic challenges

 Different populations of lymphocytes and their products are

the major actors together with accessory cells – Antigen
presenting cells (APCs)
 1.5 Adaptive immune system

Cardinal Features of adaptive Immune Responses

 Specificity – specific for distinct antigen, and for

different structural components of a single complex

protein, polysaccharide, or other macromolecules.
 Portions of such antigens recognized by individual
lymphocytes are called determinants or epitopes.

 This fine specificity exists because individual lymphocyte

express membrane receptors able to distinguish subtle
(slight) differences in structure between distinct antigens.
1.5 Adaptive immune system
 Diversity- total number of antigenic specificities of the
lymphocytes in an individual, called the lymphocyte
repertoire, is extremely large.

 estimated mammalian immune system can discriminate

109 to 1011 distinct antigenic date ruminants.

 This property of the lymphocyte repertoire is called

diversity. It is the result of variability in the structures of
antigen- binding sites of lymphocyte receptors for
antigens.
 Memory- Exposure of the immune system to foreign
antigen:

 enhances its ability to respond again to that antigen.

 Responses to second and subsequent exposure to the

same antigen, called secondary immune responses, are
usually more rapid and larger than the first or primary
immune response
Adaptive immune continued
 An effective immune response involves three major
groups of cells: Cellular Immunity (T lymphocytes),
Humoral Immunity (B cells), and Accessory cells
(antigen-presenting cells).

 The two major populations of lymphocytes—B

lymphocytes (B cells) of Humoral immunity and T
lymphocytes (T cells) of Cellular Immunity provide us
with our specific adaptive immunity
Adaptive immune continued
 Specialization –the immune system responds in distinct and
special ways to different microbes, maximizing the efficiency
of antimicrobial defense mechanisms.

 Self –limitation- All normal immune responses returning the

immune system to its resting or basal state with time after
antigen stimulations, process called homeostasis.
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
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
 CHAPTER 2

Cells and organs of immune system

Learning Objectives
Upon completion of this lesson the student will be able to:

 Describe cells and organs of immune system

 Describe lymphoid tissue by primary or secondary, locations

of specialized cells produced and key role in immunity.

 Describe the morphology, source and role of macrophages,

natural killer cells, cytotoxic, helper, suppressor or B
lymphocytes and plasma cells.

 Discuss the role of surface markers in cells involved with

immunity, referring to specific markers used to differentiate T
and B lymphocytes.
2.1. Organs of the immune system

 The immune system consists of many different organs and

tissues that are found throughout the body.

 These organs can be classified functionally into two main

groups.

 The primary lymphoid organs provide appropriate

microenvironments for the development and maturation
of lymphocytes. This includes Thymus, Bone marrow,
Fetal liver
 Organs of the immune system cont..
 The secondary lymphoid organs trap antigen from defined
tissues or vascular spaces and are sites where mature
lymphocytes can interact effectively with that antigen.
 These are
 Lymph nodes, Spleen,
 Mucosa Associated Lymph tissue (MALT)
 Tonsils, Peyers patches, lamina propria (largest amount of
lymphs), appendix collectively known Gut associated
lymhoid tissue (GALT)
 Bronchial associated lymphoid tissue (BALT)
Organs of the Immune System Continued
tertiary lymphoid tissues

 which normally contain fewer lymphoid cells than secondary

lymphoid organs,

 Can import lymphoid cells during an inflammatory response.

 Most prominent of these are

 cutaneous-associated lymphoid Tissues (CALT).

Organs of the Immune System Continued
 Once mature lymphocytes have been generated in the
primary lymphoid organs,

 they circulate in the blood and lymphatic system, a network

of vessels that collect fluid that has escaped into the tissues
from capillaries of the circulatory system and ultimately return
it to the blood.
2.2.1 Lymphoid System
Classification-Residence
1. Primary lymphoid tissue
primary diff/maturation
1. Thymus
2. Bone marrow
3. Fetal liver
2. Secondary Lymphoid tissue -
Ag exposure and final
differentiation
1. Lymph nodes, Spleen
2. Mucosa Associated Lymph tissue
(MALT)
Organs of the Immune System continued

THYMUS
 the site of T-cell development and maturation.
 flat, bilobed organ situated above the heart.
 each lobe is surrounded by a capsule and is divided into
lobules.
 each lobule is organized into two compartments:
 the outer compartment, or cortex, is densely packed with
immature T cells, called thymocytes.
 the inner compartment, or medulla, is sparsely populated with
thymocytes.
Organs of the Immune System continued
Organs of the Immune System continued
 Both the cortex and medulla are crisscrossed by a
three-dimensional stromal-cell network composed of
 epithelial cells,

 dendritic cells, and

 macrophages, which make up the framework of the organ

and contribute to the growth and maturation of thymocytes
(T cells)
Organs of the Immune System Continued
BONE MARROW

 the site of B-cell origin and development.

 Immature B cells proliferate and differentiate within the bone

marrow, and stromal cells within the bone marrow interact
directly with the B cells and secrete various cytokines that are
required for development.

 selection process within the bone marrow eliminates B cells

with self-reactive antibody receptors.
Organs of the Immune System Continued
LYMPH NODES
 These are sites where immune responses are mounted
to antigens in lymph.
 are encapsulated bean shaped structures containing a
reticular network packed with
 lymphocytes,
 macrophages, and
 dendritic cells
Organs of the Immune System Continued
LYMPH NODES

 the first organized lymphoid structure to encounter antigens

that enter the tissue spaces.
 Morphology
lymph node can be divided into three
 the cortex
 The outermost layer,,
 Contains lymphocytes (mostly B cells), macro-phages, and
follicular dendritic cells arranged in primary follicles.
 After antigenic challenge, the primary follicles enlarge into
secondary follicles, each containing a germinal center.
Organs of the Immune System Continued
 the paracortex
 Beneath the cortex.
 populated largely by T lymphocytes and
 contains interdigitating dendritic cells
 These interdigitating dendritic cells express high levels of
class II MHC molecules, which function as APC .
 the medulla
 The innermost layer .
 more sparsely populated with lymphoid-lineage cells; of
those present, many are plasma cells actively secreting
antibody molecules.
Organs of the Immune System Continued

B cells

T cells

Lymph Node
Organs of the Immune System
SPLEEN
 plays a major role in mounting immune responses to antigens
in the blood stream.
 large, ovoid situated high in the left abdominal cavity.
 specializes in filtering blood and trapping blood-borne
antigens;
 can respond to systemic infections.
 two compartments
 the red pulp populated by MØs, RBCs and few
lymphocytes
 A site where old and defective RBCs are
destroyed and removed
 white pulp, is primarily populated by T cells and B cells
Organs of the Immune System Continued

Structure of SPLEEN
Organs of the Immune System Continued

Cutaneous-Associated Lymphoid Tissue

 The skin is barrier to the external environment.

 important in nonspecific defenses.

 epithelial cells the outer layer of the skin

(keratinocytes) secrete a number of cytokines that
may function to induce a local inflammatory reaction.
Organs of the Immune System Continued
 keratinocytes can be induced to express class II MHC
molecules and may function as APC.

 The Langerhans cells migrate from the epidermis to regional

lymph nodes, where they differentiate into interdigitating
dendritic cells.

 These cells express high levels of class II MHC molecules and

function as potent activators of naive TH cell
Summary
 The cells that participate in the immune response are white
blood cells.

 The lymphocyte is the only cell to possess the immunologic

attributes of specificity, diversity, memory, and self/non self
recognition

 The primary lymphoid organs provide sites where

lymphocytes mature and become antigenically committed

 Secondary lymphoid organs capture antigens and provide sites

where lymphocytes become activated by interaction with
antigens.
 Development of Immune cells
Hematopoiesis

 All blood cells arise from a type of cell called the

hematopoietic stem cell (HSC).

 Stem cells are cells that can differentiate into other cell types;
they are self-renewing-they maintain their population level by
cell division.

 In humans, hematopoiesis, the formation and development of

red and WBCs, begins in the embryonic yolk sac during the
first weeks of development.
Cells of the immune system
Cells of the immune system

Polymorphonuclear
Neutrophilic
Leukocytes, a.k.a.,
PMNs. They are
shorter lived than
macrophages but
have greater killing
power.
Cells of the immune system
Cells of the immune system

These are Cells of

the adaptive
immune system
2.1. Cells of the immune system
 Lymphocytes: (B cells and T cells)
Lymphocytes are the central cells of the immune system,
responsible for adaptive immunity and the immunologic
attributes of diversity, specificity, memory, and self/non-self
recognition.
 The other types of white blood cells play important roles,
engulfing and destroying microorganisms, presenting
antigens, and secreting cytokines such as Natural Killer cells
(NKs), Nutrophils, Macrophage, Eosinophils, Basophilis,
Mast cells and Dendritic cells.
 Cells of Innate Immunity
Natural Killer Cells

 Natural killer cells (NKs), described in 1970s, were shown to

be a small population of large, granular lymphocytes that
display cytotoxic activity against a wide range of tumor cells
in the absence of any previous immunization with the tumor.

 NK cells play an important role in host defense both against

tumor cells and against cells infected with some though not all,

viruses.
Cells of Innate Immunity

Natural Killer Cells Continued

 do not express the membrane molecules and receptors that

distinguish T- and B-cell lineages.

 Although NK cells do not have T-cell receptors or

immunoglobulin incorporated in their plasma membranes,
they can recognize potential target cells in two different ways:
 Natural Killer Cells Continued
 NK cells may employ receptors that distinguish abnormalities,
notably a reduction in class I MHC molecules and the unusual
profile of surface antigens displayed by some tumor cells and
cells infected by some viruses.

 NK cells recognize potential target cells depends upon the fact

that 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
their surfaces
Cells of Innate Immunity
 Mononuclear Phagocytes
 The mononuclear phagocytic system consists of:

 Monocytes

 Macrophages all sorts

 Polymorphonuclear phagocytic cells (PMNs)

 PMNs are capable of ingesting and digesting

exogenous antigens, such as whole microorganisms
and insoluble particles, and endogenous matter.
Dendritic cells (DCs)
 Derived from myeloid progenitor (some lymphoid)
Immature DCs:
 migrate from blood to reside in tissues and are both phagocytic
and micropinocytic (ingest large amount of the surrounding
ECF)
 continuously migrate from the tissues bearing self Ags and
induce tolerance as they lack co-stimulatory molecules
 Upon encountering a pathogen, they readily mature, express
co-stimulatory molecules, and migrate to lymph nodes
Dendritic cells (DCs) cont’d
Mature DCs:

 specialized to take up Ag, process it, and display it for

recognition by T Lymphocytes i.e., act as APCs to T cells
initiating adaptive IR (express co-stimulatory molecules
when encountering pathogen)

 classified by location as follows:

 langerhans cells (epidermis/skin and mucous membranes)

 interstitial DCs (organs: heart, lungs, liver, kidney, GIT)

Cells of Innate Immunity
Cells of Innate Immunity
Lymphocyte Recirculation

 Lymphocytes are capable of recirculation, continually moving

through the blood and lymph to the various lymphoid organs

 Lymphocytes migrate from the blood into lymph nodes

through specialized areas in post-capillary venules called high-

endothelial venules (HEVs).

Lymphocyte recirculation
Neutrophil Extravasation
 Neutrophils first bind to inflamed endothelium and
extravasate into the tissues.

 Neutrophils recognize the inflamed endothelium and adhere .

 so that they are not swept away by the flowing blood.

 The bound neutrophils then penetrate the endothelial layer and

migrate into the underlying tissue.

 Monocytes and eosinophils extravasate by a similar process,

Neutrophil Extravasation
Neutrophil Extravasation
 Neutrophil extravasation has four sequential steps:
 rolling,

 activation by chemoattractant stimulus,

 arrest and adhesion, and

 trans endothelial migration.

Neutrophil Extravasation
The Inflammatory Process
 Is a physiologic response to a variety of stimuli
 such as infections and tissue injury.

 An acute inflammatory response

 has a rapid onset

 lasts a short and

 accompanied by a systemic reaction known as the acute-

phase response, which is

-characterized by a rapid alteration in the levels of several

plasma proteins.
The Inflammatory Process continued
 chronic inflammation results in,

- persistent immune activation

- pathologic consequences

- lead to formation of a granuloma

 The accumulation and activation of macrophages is the

hallmark of chronic inflammation.

The Inflammatory Process continued
 Two cytokines in particular, IFN- and TNF-, play a
central role in the development of chronic
inflammation.

 TH1 cells,NK cells, and TC cells release IFN- ,

while activated macrophages secrete TNF-.
The Inflammatory Process continued
 Inflammatory Responses May Be Localized or
Systemic

 The hallmarks of a localized acute inflammatory

response, are
 swelling (tumor)
 redness(rubor)
 heat (calor)
 pain (dolor), and loss of function
The Inflammatory Process continued
 The local inflammatory response is accompanied by a
systemic response known as the acute-phase
response , marked by
 the induction of fever,

 increased synthesis of hormones such as hydrocortisone,

 increased production of white blood cell (leukocytosis),

 production of a large number of acute-phase proteins (C-

reactive protein) in the liver.
The Inflammatory Process
continued

 Many systemic acute-phase effects are due to the combined

action of IL-1, TNF- and IL-6.
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