Introduction to Immunology

Immunology: The study of all aspects of the

immune system including its structure and
function, disorders of the immune system, blood
banking, immunization and organ transplantation.

•The study of immunology is a broad field

encompassing both basic research and clinical
applications
• deals with host defense reactions to foreign
(non self) entities known as antigens, antigen
recognition molecules, and cell-mediated host
defense functions, especially as they relate to
immunity to disease, hypersensitivity
(including allergy), autoimmunity,
immunodeficiency, and transplantation
 Immunity
• The word “Immuis” means free from burden and
“immunitas” means exemption from:

– government taxes

– civic duties
This concept provided the English terminology Immunity.

Immunity: is a protective or defense mechanism of our body,

which leads us to a healthy life.
Historically -Immunity refers to protection from disease
• Early observers noticed that survivors of certain diseases were resistant to
re-infection

Some examples:

Ancient Chinese practiced “Variolation”

• Variolation—the deliberate infection with smallpox.

Dried smallpox scabs (from Smallpox (Variola) lesions) were blown into the

nose of an individual who then contracted a mild form of the disease.

Upon recovery, the individual was immune to smallpox.

Person with small pox
• Edward Jenner(1749-1823) noted that milkmaids who
had Cowpox (from vaccinia virus) lesions did not get Small
pox (Variola virus)- cross protected
• Inject 8year old boy with Cowpox - got Cowpox
• 2 months later injected with Smallpox did not get Smallpox
• Cowpox = Vaccinia (Latin - cows)
* Therefore the word “Vaccine” emerged
• Louis Pasteur(1880) accidentally discovers “attenuation” Culture
of Chicken Cholera left on bench at room temperature for
several weeks
- Injected chickens with old culture– did not get sick
- Injected with fresh culture - did get sick
• Attenuation: the alteration/decreasing the virulence of a
pathogenic microorganism
• Louis Pasteur (1881 )grows attenuated Anthrax at higher
temperatures (42-43Oc ) (attenuated)
• 1885 Louis Pasteur discovers Rabies
vaccine(attenuated)
• 1888 Richet & Herricourt discovered that serum
from vaccinated animals will agglutinate the bacteria
in test tube (passive immunity) while serum from
Non-immune animal did not cause agglutination
• 1970s attenuated vaccine for Hepatitis B
• 1980s vaccine developed for Haemophilus influenzae

• Late 1980s recombinant vaccine for Hepatitis B

• 1990s vaccines developed for Hepatitis A

• 1920s-1950s – many vaccines developed for humans

mostly bacteria such as Diphtheria, Tetanus, Pertusssis,

etc.
 Organs of the Immune system

1.Primary/Central lymphoid organs

Thymus and bone marrow:
where lymphocytes B and T cells originate
- Thymus = T-cells
- Bone marrow = B-cells
• Thymus is the site for maturation of T cells
Thymus: maturation of T cells
• Bone marrow and fetal liver are the sites for maturation of B cells
Bone marrow, fetal liver: maturation of B cells
Hematopoiesis
 2.Secondary/Peripheral lymphoid organs
1.Lymph node
– Site where immune response is initiated
– Swollen lymph node denotes stimulation of immunity and cell growth.
– Dendritic cells and antigen from the periphery enter through the afferent lymphatic
vessel into the medulla where the T cells reside.
– B cells wait in follicles for T cell activation, and antigenically stimulated B cells are in the
germinal centers within the follicles. B cells: located in germinal centers
2.Spleen
– Site of immune responses to antigens in blood
– Filter for dead erythrocytes and microbial particulates, especially encapsulated bacteria
3.Mucosa-associated lymphoid tissue (MALT)
– Intestine
• Gut-associated lymphoid tissue (GALT)
– M cell in mucosal epithelium is the door keeper to Peyer patch. M cell: "door keeper" to Peyer patches
– Peyer patch is a mini lymph node.
– Intraepithelial lymphocytes patrol mucosal lining.
– Tonsils and adenoids
• Highly populated by B cells
Figure 1-8 part 1 of 2
Figure 1-7
 Immune System
Immune System Has two branches:
I. The Innate Immune system
- a general response to anything other than recognized “self cells”
- Present at birth
- considered as first line of defense
II. The Adaptive Immune System
– a specific counter-attack against a “known foreign” invader
[previously recognized]
– Not present at birth but becomes part of our immune system
as the lymphoid system develops
 I. The Innate Immunity Characteristics

• In born and non specific

• Consistent within species

• Signals stimulated by common structures of microbes

• Lacks ability to distinguish fine differences between

foreign substances

• Generic response to all substances

• Precedes Adaptive immunity so is faster

 The Innate Immunity
It includes:
1. The Integumentary System/Physical barriers - the
1st line of defense
– Skin
– Mucous membranes
– Mucous
– Normal flora-biological

provides a physical barrier preventing microbial access

2. Physiological barriers
– pH of our environment, HCl in stomach, lactic acid in
vagina ,acidity of urine
– temperature of our body
3. Chemical barriers
– tears, saliva, (enzymes lysozyme), vaginal secretions, sweat
(lysozyme, toxic lipids)
4. Humoral components
– Complement can be activated by microbial surfaces
– Coagulation system
– Cytokines
5. Innate immune cells
– Neutrophils
– Monocytes/macrophages
– Dendritic cells
– Natural killer cells(NK cells)
– Eosinophils
– Mast cells
– Basophils
Innate Immunity
Granulocytes

1.Neutrophils (polymorphonuclear leukocytes): phagocytic; first line of

cellular defense Neutrophils die and make pus.
-Strongly phagocytic cells important in controlling bacterial
infections
-Normally are first cells to arrive at site of infection and have a short
life span and rapid turnover (apoptosis)
2. Eosinophils: allergic reactions; destroys intestinal worms.
Weakly phagocytic
Main role in allergic reactions and destruction of parasites
3.Basophils and mast cells : release histamine
-Non phagocytic granulocytes that possess cell surface receptors for
immunoglobulin E (IgE)
-Mediate allergic and antiparasitic responses due to release of
histamine and other mediators following activation
 Monocytes are released from the bone marrow,
circulate in the blood, and enter tissues where they
mature into dendritic cells or macrophages.
1.Dendritic cells (DCs) DCs initiate, direct and control
the T cell response through interactions and
cytokines.
– Found in various tissues (e.g., Langerhans cells of the
skin), peripheral blood, and lymph Langerhans cells: DCs
of skin; process antigens
– Have long arm-like processes
– Required to initiate an immune response and very
efficient at presenting antigen to both CD4 TH and CD8 TC
cells
– Secrete cytokines that direct the nature of the T cell
response (e.g., IL-12 for TH1)
2.Macrophages: follow neutrophils in inflammation;
phagocytose; process antigen
– Help to initiate early innate immune response
– Secrete numerous cytokines that promote immune responses
– Secrete antibacterial substances, inflammatory mediators,
and complement
– Phagocytose and inactivate microbes
– Present antigen associated with class II MHC molecules to
CD4 TH cells
3.Activated ("angry") macrophages: larger and exhibit
enhanced antibacterial, inflammatory, and antigen-presenting
activity Macrophages eat (phagocytize) and secrete (cytokines)
but must be angry to kill.
– Activation is initiated by phagocytosis of particulate antigens
and enhanced by interferon-γ produced by T cells and natural
killer cells. Asplenic individuals are prone to infections with
encapsulated bacteria.
 Major Cells of the Immune System
CELL TYPE MORPHOLOGY SURFACE MARKERS PRIMARY FUNCTIONS
Granulocytes

Neutrophils (PMNs) Multilobed nucleus, small granules, band form IgG receptors Phagocytose and kill bacteria nonspecifically
(immature) IgM receptors Mediate ADCC of Ab-coated bacteria
C3b receptors

Eosinophils Bilobed nucleus, numerous granules with core of IgE receptors Involved in allergic reactions
major basic protein Mediate ADCC of parasites

Basophils, mast cells Irregular nucleus, relatively few large granules IgE receptors Release histamine and other mediators of
allergic and anaphylactic responses

Myeloid Cells

Macrophages* Large, granular mononuclear phagocytes present Class II MHC Phagocytose and digest bacteria, dead host cells,
in tissues IgG receptors and cellular debris
IgM receptors Mediate ADCC of Ab-coated bacteria
C' receptors Process and present Ag to CD4 TH cells
Toll-like receptors Secrete cytokines that promote acute phase and
T cell responses

Dendritic cells Granular, mononuclear phagocytes with long High levels of class II MHC, B7 coreceptors Process and present Ag to T cells
processes; found in skin (Langerhans cells), Toll-like receptors Secrete cytokines that promote and direct T cell
lymph nodes, spleen response
Required to initiate T cell response
Lymphocytes

B cells Large nucleus, scant cytoplasm, agranular Membrane Ig Process and present Ag to class II MHC-restricted
Class II MHC T cells
C3d receptor (CR2 or CD21) On activation, generate memory B cells and
plasma cells

Plasma cells Small nucleus, abundant cytoplasm   Synthesize and secrete Ab

Helper T cells (TH cells) Large nucleus, scant cytoplasm CD4 Recognize Ag associated with class II MHC
TCR complex molecules
CD2, CD3, CD5 On activation, generate memory TH cells and
cytokine-secreting effector cells

Cytotoxic T (TC) cells) Large nucleus, scant cytoplasm CD8 Recognize Ag associated with class I MHC
TCR complex molecules
CD2, CD3, CD5 On activation, generate memory TC cells and
effector cells (CTLs) that destroy virus-infected,
tumor, and foreign graft cells

Memory B or T cells Large nucleus, scant cytoplasm CD45RO Generated during primary response to an Ag and
Usual B or T cell markers mediate more rapid secondary response on
subsequent exposure to same Ag

Natural killer cells Large granular lymphocytes IgG receptors Kill virus-infected and tumor cells by perforin or
KIRs, CD16 Fas-mediated, MHC-independent mechanism
None of usual B or T cell markers Kill Ab-coated cells by ADCC
Macrophages and other antigen presenting cells such as dendritic cells, participate
in both the innate arm and acquired arm of the immune system. They are in effect
a bridge between the two arms. As part of the innate arm they ingest and kill
various microbes. They also present antigens to helper T cells which is the essential
first step in the activation of the acquired arm.
 Important components of innate immunity
Factors that limit entry of microorganisms into the body

Factor Mode Of Action

-Keratin layer of intact skin -Acts as mechanical barrier

-Lysozyme in tears and other secretions -Degrades peptidoglycan in bacteria
-Respiratory cilia
-Low pH in stomach and vagina;
fatty acids in skin
-Surface phagocytes
(eg. alveolar macrophages)
-Defensins (cationic peptides)
-Normal flora of throat, colon
and vagina
cell wall
-Elevate mucus containing trapped organisms
-Retards growth of microbes
-Ingest and destroy microbes
-Create pores in microbial membrane
-Occupy receptors which prevent
colonization by pathogens
 Important components of innate immunity
Factors that limit growth of microorganisms within the body

• Natural killer cells • Kill virus infected cells

• Neutrophils • Ingest and destroy microbes
• Macrophages and dendritic • Ingest and destroy microbes, and present
cells antigen to helper T-cells
• Interferons • Inhibit viral replication
• Complement • C3b is an opsonin, membrane attack
complex creates holes in bacterial
membranes
• Transferrin and lactoferrin • Sequester iron required for bacterial
growth
• Fever • Elevated temperature retards bacterial
growth
• Inflammatory response • Limits spread of microbes
 Principles of innate immunity

•The macrophages and neutrophils of the innate immune

System provide a second line of defense.
•They can not always eliminate infectious microorganisms
•The lymphocytes of adaptive immune system provide a more
versatile means of defense and also against subsequent re-
infection with the same pathogen.
•However, the cells of the innate immune system play a crucial
part in the initiation and subsequent direction of the adaptive
immune response as well as participating in the removal of
pathogens.
•Since the adaptive immune response is initiated after 4-7 days
of infection, the innate immune response is crucial during this
period.
•Most infectious agents induce inflammatory response by
activating innate immunity.
• Microorganisms penetrate epithelial surface taken up by
cells and molecules of the innate immune response
 
• Phagocytic macrophages conduct the defense by means of
surface receptors that are able to recognize and bind
common constituents of many bacterial surfaces and
facilitate phagocytosis and also induce secretion of
biologically active molecules. 
• Activated macrophages secret cytokines, which are
proteins released by cells that affect the behavior of other
cells that bear receptors for them.
• They also release proteins called chemokines that
attract cells with specific chemokine receptors such as
neutrophils and monocytes from the bloodstream.
• The cytokines and chemokines released by
macrophages in response to pathogen initiate
inflammation.
• Local inflammation and the phagocytosis of invading
bacterial may also be triggered as a result of the
activation of complement on the bacterial cell surface.
 Inflammation
• Inflammation is traditionally defined by four
conditions: heat, pain, redness and swelling
• All of which reflect the effects of cytokines and
other inflammatory mediators on the local
blood vessels.
• Dilation and increased permeability of blood
vessels lead to increased local blood flow and
the leakage of fluid, and account for the heat,
redness, and swelling.
• The main cell types seen in an inflammatory
response in its initial phase are neutrophils;
shortly followed by monocytes. So neutrophils
and macrophages are also called inflammatory
cells. Inflammatory responses later in an
infection also involve lymphocytes following
antigen stimulation through DC cells.
• Pathogen recognition and tissue damage initiate an
inflammatory response
– Injury & infection
– Monocytes slip between cells to arrive and become macrophages.
– Cytokine chemicals attract other “troops” [chemotaxis] histamine
chemicals dilate blood vessels for easier access to injury [vasodilation].
• Mast cells/basophils release histamine that dilates blood vessels
causes redness [erythremal, swelling [edema], and heat
[fever].
• Phagocytic cells – able to ingest small foreign invaders
– Neutrophils
– Monocyte
• They release cytokines that enhance the immune response
 Inflammation
• Triggered by tissue
damage
• First responders are
tissue macrophages
• Recruit cells and
proteins to infection
site
• Contain pathogen
• Alert adaptive
response

(redness&heat) (Pain)
Injury and Mediator Release
Fluid and Phagocytes Enter
Edema and Pus Formation
Repair
 Inflammation has many beneficial functions including:
• Dilutes and removes toxins
• Limits spread of bacteria
• Facilitates influx of neutrophils, complement,
opsonins and antibodies
• Provides a supply of inflammatory mediators
• Ensures an increased supply of nutrients for cells
• Promotes initiation of the immune response
• Initiates the healing process.