BASIC IMMUNOLOGY

Amanah S.Si.,M.Si.Med Immunology and Tropical disease

IMMUNE SYSTEM

Collection of Organs, Tissue, & soluble Factors to
defend against Bacteria, Viruses, & Tumor cells.

Consist of:

Primary (central) Lymphoid Organs in which
Leukocytes develop

Secondary(peripheral)LymphoidOrgans& Tissues in
which Immune Response occur.

Leukocytes in Blood

Mature in Marrow (B cell) or Thymus (T-cell)
IMMUNOLOGY AND THE
IMMUNE SYSTEM

Immunology 
Study system
of the components and function of the immune

Immune System 
Molecules, specific and cells, specific tissues
protection and organs against
which provide non-


Microorganisms 
Microbial toxins 
Tumor cells 
Crucial to human survival
The immune system protects
your body against foreign
pathogens such as bacteria and
viruses. The immune system
has 3 lines of defense against
foreign pathogens:

1. Physical and Chemical Barriers (Innate
Immunity)

2. Nonspecific Resistance (Innate Immunity)

3. Specific Resistance (Acquired Immunity)
First lines of defense

1. Skin acidity - inhibit bacterial growth 2.
Sebum -unsaturated fatty acids provide a
protective film and inhibit growth 3. Lysozyme-
found in perspiration, tears, saliva can
breakdown the cell wall of certain bacterial 4.
Hyaluronic acid - gelatinous substance that
slows the spread of noxious agents 5. Gastric
Juice - strong acid that destroys ingested
microbes and most toxins
Epidermis - provides a physical barrier, periodic shedding
removes microbes
Mucous membranes and mucus - traps microbes and foreign
particles Hair - within the nose filters air containing microbes,
dust, pollutants Cilia - lines the upper respiratory tract traps and
propels inhaled debris to throat
Lacrimal apparatus - produces tears that cleanse the eye
Saliva - dilutes the number of microorganisms and washes the
teeth and mouth
Urine - flush microbes out of the urethra
Defecation and vomiting - expel microorganisms.
Immune System Functions

Scavenge dead, dying body cells

Destroy abnormal (cancerous) Protect from
pathogens & foreign molecules: parasites,

bacteria, viruses
NAIVE LYMPHOCYTES enter blood, are seeded
to the peripheral lymphoid organs and
recirculate

Lymphocyte recirculation
Cells & antigens from a site of infection are
trapped in draining lymphoid tissue. Cells
proliferate and re-enter the RECIRCULATING
LYMPHOCYTE POOL to re-seed the peripheral
lymphoid organs
SPECIFIC RESISTANCE
(IMMUNITY) Responds to threats on an
individualized basis

ACQUIRED IMMUNITY
INNATE IMMUNITY
Produced by prior exposure or antibody
production
Genetically determined
no prior exposure or antibody production
involved
PASSIVE IMMUNITY
ACTIVE IMMUNITY Produced by antibodies that develop in response
to antigens (Immune response)
Produced by transfer
of antibodies from another person
Naturally acquired immunity
Induced passive immunity
Develops after exposure to antigens
in environment
Induced active immunity
Develops after administration of
antigen to prevent disease
Conferred by administration of
antibodies to combat infection
Natural passive immunity
Conferred by transfer of maternal antibodies
across placenta or in breast milk
SISTEM IMUN
NON-SPESIFIK
SPESIFIK
FISIK
LARUT
SELULER
HUMORAL
SELULER
• Kulit
• Selaput lendir
• Silia
Batuk
• Bersin
Biokimia
Lisozim (keringat)
• Sekresi sebaseus
• Asam lambung
• Laktoferin
Asam neuraminik
• Fagosit
Mononuklier - Polimorfonuklier
• Sel NK
• Sel mast
• Basofil
Sel B - IgD - IgM - IgG - IgE
Sel T - Th1 - Th2 - TS - Tdth
Тc
Liga
Humoral
• Komplemen
• Interferon
• CRP
Gambar 1. Sistem imun
Physical and Chemical Barriers
(Innate Immunity)

Physical your body and is invaded.
chemical barriers form the first line of defense when

Physical Barriers 
Your protection
skin has thick layer of dead cells in the epidermis which
provide

Your mucous membranes trap microbes.

Chemical Barriers 
Lysozyme, bacteria)
an enzyme produced in tears, acts as an antibiotic (kills

Gastric juice is highly juice in acidic the stomach (pH 2-
3).
destroys bacteria because the gastric
Nonspecific Resistance
(Innate Immunity)


he second line of defense is nonspecific resistance that destroys invaders in a

generalized way without targeting specific individuals:


Phagocytic cells ingest and destroy all microbes that pass into body tissues. For
example macrophages are cells derived from monocytes (a type of white blood
cell). Macrophages leave the bloodstream and enter body tissues to patrol for
pathogens. When the macrophage encounters a microbe, this is what happens:


The microbe attaches to the phagocyte.



The phagocyte's plasma membrane extends and surrounds the microbe and takes
the microbe into the cell in a vesicle.


The vesicle merges with a lysosome, which contains digestive enzymes.



The digestive enzymes begin to break down the microbe. The phagocyte uses any
nutrients it can and leaves the rest as indigestible material and antigenic fragments
within the vesicle.


The phagocyte makes protein markers, and they enter the vesicle.


The indigestible material is removed by exocytosis.



The antigenic fragments bind to the protein marker and are displayed on the
plasma membrane surface. The macrophage then secretes interleukin-1 which
activates the T cells to secrete interleukin 2, as described below under specific
resistance .


Inflammation is a localized tissue response that occurs when your tissues are
damaged and in response to other stimuli. Inflammation brings more white blood
cells to the site where the microbes have invaded. The inflammatory response
produces swelling, redness, heat, pain


Fever inhibits bacterial growth and increases the rate of tissue repair during an
infection.
 INNATE IMMUNITY Rapid responses to a broad range of
microbes
ACQUIRED IMMUNITY Slower responses to
specific microbes
External defenses
Internal defenses
Skin
Mucous membranes
Phagocytic cells Antimicrobial proteins
Humoral response (antibodies)
Secretions
Invading microbes (pathogens)
Inflammatory response
Natural killer cells
Cell-mediated response (cytotoxic lymphocytes)
Innate Immunity


Innate immunity provides broad defenses against infection 

Present before any exposure to pathogens and is effective from the
time of birth 
Involves nonspecific responses to pathogens 
A encounters on pathogen the body
several that successfully innate cellular breaks and through chemical an
animal’s mechanisms external that defenses
impede its attack


Non-selective and no lag time – immediate response, no previous

exposure required 
Protects against infections, toxins 
Works with specific (acquired) immune response 
Physical barriers, secretion, chemical toxins 
Phagocytosis – molecules
- macrophages neutrophils engulf and digest recognized "foreign" cells


Inflammatory redness, heat, response pain

- localized tissue response to injury producing swelling,


Complement system – activated proteins that destroy pathogen

plasma membranes 
Natural cells and Killer cancer cells cells
– special class of lymphocyte-like cells that destroy virus infected


Interferon - proteins that non-specifically defend against viral infection

PHAGOCYTES
Remove debris and pathogens
Fixed macrophage
Free Neutrophil macrophage
Eosinophil
Monocyte
Innate Immunity /
External Defenses

Epidermis microbes
- provides a physical barrier, periodic shedding removes

Mucous particles
membranes and mucus - traps microbes and foreign

Hair - within the nose filters air containing microbes,
dust, pollutants 
Cilia debris Lacrimal Saliva and Urine Defecation mouth
- - lines - to flush dilutes apparatus throat
the microbes and the upper vomiting number - produces
respiratory out of - tract traps and propels inhaled
of microorganisms tears that cleanse and the washes eye
the teeth
expel the urethra
microorganisms.
interferon
Natural Killer Cells
•

Patrol the body and attack virus-infected

body cells and cancer cells
•

Recognize cell surface markers on foreign

cells
•

Destroy cells with foreign antigens

•

Rotation of the Golgi toward the target

cell and production of perforins
•

Release of perforins by exocytosis

•

Interaction of perforins causing cell lysis+

NK
Infected cell

NK ( Natural Killer )
Cell
A non-phagocytic cell, kills target by direct contact.
Produces perforin (perforates target) and granzyme
(induces apoptosis). Important for defense against
viral infection and tumor. Also pocesses Fc receptor
for Antibody dependent cell cytotoxicity (ADCC)
killing mechanism. Unlike CTL (Cytotoxic T cell), the
process of target killing is HLA independent)
Also called Killer (K) cell or Large granular
lymphocyte (LGL)
Perforin
Granzyme

Lethal hits

Lysis
NK cell
Antigen
Macrophage
Antigen processed
MHC class Il molecule CD4 2 Processed antigen -
CD28 T-cell receptor
Interleukin-1 Helper T cell
3 Costimulation Interleukin-1 receptor
Interleukin-2 Helper T cell
Interleukin-2
receptor Daughter helper T cell
Daughter helper T cell
Helpe
r T cell Helper T cell 6
can
stimulate can be stimulated
B
cells or to divide again
effector T cells
Steps in Immune Defense

During an immune response, cells detect invader/foreign cells,
communicate alarm & recruit immune cells, suppress or destroy
invader

Phagocytosis

Macrophages and neutrophils respond to invasion by foreign
pathogens, engulf and digest recognized "foreign" cells

molecules, remove cellular debris

Monocyte - macrophage system – free and fixed

Macrophages – Neutrophils and eosinophils

Margination – stick to the inner endothelial lining of capillaries
of affected tissue

Move by diapedesis – move through capillary walls, exhibit
chemotaxis

Phagocytes release chemical mediators

Kinins - stimulate complement system (plasma proteins),
chemot0xins, pain

Clotting factors – walling off invasion

Lysosomal enzymes – destroy invaders
Cell immunity


Neutrophils 
Fastest response of all WBC to bacteria and parasites 
Direct actions against bacteria


Release lysozymes which destroy/digest bacteria



Release defensive proteins that act like antibiotics



Release strong oxidants (bleach-like, strong chemicals ) that destroy

bacteria 
Eosinophils 
Leave capillaries to enter tissue fluid


Attack parasitic worms



Phagocytize antibody-antigen complexes 

Monocytes 
Take longer to get to site of infection, but arrive in larger numbers


Become free (roaming) macrophages, once they leave the capillaries



Destroy microbes and clean up dead tissue following an infection

Celluler immunity
(a) Pathogen binds directly to phagocyte receptors.
Pathogen
Membrane
receptor

Phagocyte
(b) Bacteria with capsules must be coated with
antibody before phagocytes can ingest them.
Opsonin molecule

Pathogen
Polysaccharide capsule
Opsonin receptor
Phagocyte
Phagocytosis Mechanisms

Chemotaxis- released phagocytes at the to attraction
injury
site of damage, to certain chemotaxins chemical
mediators,
induce

Opsonization- mediators, most identify important
(mark) opsonins
pathogen, coated with chemical

Toll-like plasma markers, and distinguish receptors
membrane recognition from (TLR’s)- receptor self-
cells
function phagocytic proteins, - allows cells
phagocytes bind studded with pathogen
to with
“see”
Phagocytosis
Recognition receptors ( for recognizing
the pathogen-associated molecular
patterns ) Toll like receptor (TLR) : TLR 2 :
receptor for Gram- pos
bacteria
(peptidoglycan) TLR 4 : receptor for Gram-
neg. bacteria (LPS) dsRNA-activated
kinase : receptor for ds RNA virus
Mannose receptor Fc and complement
receptors (opsonized microbes)
Specific Resistance (Acquired
Immunity)


he found third in line foreign of defense microbes.

is specific resistance. This system relies on antigens, which are specific substances


Response specific to individual Antigen (Ag) 

SELF TOLERANCE: 
Absence of tissue immune Antigens.
response to one’s own


Necessary to prevent auto-immune diseases 

Most comes antigens from ANTI-body are proteins GENerating that serve substances.
as the stimulus to produce an immune response. The term "antigen"


Here are the steps in an immune response: 

When T-cells immunity. an to become antigen The body is activated. detected contains
millions The by a activation macrophage of different of T-cells T-cells, (as describe by
each a specific able above to antigen under respond is phagocytosis), called to one cell-
mediated
specific this antigen.
causes the


The T-cells secrete interleukin 2. Interleukin 2 causes the proliferation of certain

cytotoxic T cells and B cells. 
From here, the immune response follows 2 paths: one path uses cytotoxic T cells and the
other uses B cells.
Acquired (Adaptive) Immune
Response

Depends on B and T lymphocytes

Specific immune response directed attack against
pathogens (antigen)

Lag time

Previous Antigen exposure required

Protects against pathogens and cancer cells

Types

Antibody-mediated: B cells

Cell-mediated: T cells
Adaptive (Acquired) Immune
Response

Adaptive (Acquired) Immune Response - 3rd
line of defense Depends on B and T
lymphocytes - specific immune response
directed attack against pathogens (antigen) Lag
time ~ two weeks, previous Antigen exposure
required Protects against pathogens and cancer
cells
Two 
Antibody-mediated: Components:
B cells

Cell-mediated: T cells
Properties of Acquired
Immunity

Specificity – activated by and responds to a
specific antigen Versatility – is ready to
confront any antigen at any time Memory –
“remembers” any antigen it has encountered
Tolerance – responds to foreign substances but
ignores normal tissues
Lymphocytes 
- B and T cells originate in red
bone marrow, move to lymphatic tissue from
processing sites and continually circulate

Primary lymphatic organs - lymphocytes mature
into functional cells (red bone marrow B cells
and thymus T cells) Secondary lymphatic
organs site of immune response – lymph nodes
T CELLS
3 Memory
1 Helper
4 Suppressor
Cytotoxic
5 Natural Killer
There are 3 major types of T
cells:

1. destruction protein membrane. Cytotoxic that of
creates The T cells: the holes pathogen's These holes
cause cells in the the DNA secrete pathogens
pathogen or perforin cytotoxin to plasma
which lyse which (rupture).
is a
triggers

2. stimulates these Helper cells T cell cells:These
recruit division even cells of more T cells secrete
cells and to interleukin B help cells. fight In other 2
the (I-2) pathogen.
words, which

3. exposure again, to pathogen
Memory convert even to themselves T an
cells:These if it antigen. is years into later, cells If
the cytotoxic remain the same memory dormant
antigen T cells cells and presents after are help the
stimulated
fight itself
initial
the
T Cells Only Recognize Antigen Associated with MHC
Molecules on Cell Surfaces
Types of T cells:

T Helper (TH) Cells - Primary role in immune
response. - Most are CD4 (identifier - acts as an
accessory molecule, forming part of larger structures
such as the T-cell receptor) - Recognize antigen on
the surface of antigen presenting cells (e.g.:
macrophage). - Secrete Interleukin II (T-cell growth
factor), interferon and cytokines which stimulate B-
cells and natural killer cells
- Activate macrophages - Induce formation of
cytotoxic T cells - Stimulate B cells to produce
antibodies.
Major types of T cells

- Cytotoxic T cells (TC) – attack foreign cells -
Helper T cells (TH) – activate other T cells and
B cells - Suppressor T cells (TS) – inhibit the
activation of T and B cells - Memory T cells –
function during a second exposure to antigen
 T-cell receptor Class II MHC molecule
Antigen Bacterium
fragment
TH cell
Tc cell
Cell-mediated immunity (attack on infected cells)
Interleukin-2 and other cytokines activate Th cells, B cells, and T cells.
B cell
Humoral immunity (secretion of antibodies by plasma cells)
APC (macrophage)
Interleukin-1 activates Th cells.
©1999 Addison Wesley Longman, Inc.
Cytotoxic T (Tc) Cells:
Destroy target cells

- Killer Ts or CD8
- Recognize antigens on the surface of all cells:
kill host cells that are infected with viruses or
bacteria. Also recognize and kill cancer cells,
and transplanted tissue.
- Release protein called perforin which forms a
pore in target cell, causing lysis of infected
cells.
- Produce cytokines, which promote
phagocytosis and inflammation - Undergo
apoptosis when stimulating antigen is gone.
Memory T-Cells

- Can survive a long time and give lifelong
immunity from infection
- Can stimulate memory B-cells to produce
antibodies - Can trigger production of killer T
cells - Thymosin - hormone important in T cell
lineage, enhances capabilities of existing T cells
and the proliferation of new T cells in lymphoid
tissues - decreases after age 30-40
Activation T cell
Cell-Mediated Immunity –
T Cells

Antigens that stimulate this response are mainly
intracellular (cell to cell). - Requires constant
presence of antigen to remain effective - Involves
cytokines: Chemical messengers of immune cells. -
Over 100 have been identified. - Stimulate and/or
regulate immune responses.

Interleukins: Communication between WBCs.

Interferons: Protect against viral infections.

Chemotaxins: Attract WBCs to infected areas.
Cell-Mediated Immunity –
T Cells
 -T cell-surface - histocompatibility - fragments called -
the - different - cytotoxic transplants MHC Infected A
Depending Antigen cells nearby cell’s molecules antigen
bind classes surface
activates T cells and T cells proteins to cell on small
produce presentation then that their of can are complex
MHC effector fragments are called lyse then source
encoded transported MHC molecules
virus-infected detect MHC T peptide cells molecules of
by molecules
antigens the and a family to antigens antigen cells,
produces the which that cell of tumor genes fragment are
surface bind are memory handled cells, bound called to
antigen in displayed and a T to the process by
cells tissue
normal
major
and on
IMMUNE RESPONSE
▶
Major Histocompatibility Complex (MHC)
▶
In Humans the MHC called HLA ▶
Genes immune that encode response.
proteins that regulate the
▶
Class Platelets 1: located (HLA –A, on HLA-
B, surface HLA-C)
of all Nucleated cells +
▶

Associated with Cytotoxic T cell ▶

Class 11: located on Langerhan cells &
activated Macrophages (HLA-DR, HLA-DQ)
Associated with Th & TDTH cells
IMMUNE RESPONSE
▶
Class 111 encode Complement
proteins
▶
Associated with C2 & Factor B ▶
Not related rejection
to Transplant acceptance or
▶
HLA diseases: ▶
Arthritis (HLA DR4) ▶
Sjogren’s syndrome (HLA DR3) ▶
IDDM (HLA DR3 & 4)
Antigen Recognition

Lymphocytes respond to antigens bound to
either class I or class II MHC proteins - T cell
membranes contain CD markers - CD3 markers
present on all T cells - CD8 markers on
cytotoxic and suppressor T cells - CD4 markers
on helper T cells
Major Histocompatibility
Complex

- T cell activation involves recognition of
antigens combined with major
histocompatability (MHC) glycoproteins on the
surface of cells. - Class I molecules display
antigens on surface of nucleated cells, resulting
in destruction of cells - Class II molecules
display antigens on surface of antigen-
presenting cells, resulting in activation of
immune cells
Major Histocompatibility
Complex
Class I MCH molecules are
found on almost all nucleated
cells of the body display peptide
antigens to cytotoxic T cells.
Class II MHC molecules are located mainly on dendritic
cells, macrophages, and B cells display antigens to helper
T cells.
1. 
A fragment of foreign protein (antigen)
inside the cell associates with an MHC molecule
and is transported to the cell surface.

2. The combination of MHC molecule and
antigen is recognized by a T cell, alerting it to
the infection.
Antigen 
Presenting Cells

- Macrophages & Dendritic Cells engulf foreign antigens
by phagocytosis, proteins broken down into peptides -
Peptides go to ER and Golgi where they are attached to
new MHC self antigen molecules - New self antigen and
its antigen fragment are added to the cell membrane and
presented to lymphocytes
Bone marrow – origin of
blood cells

Thymus – site of maturing T Lymphocytes

Lymph nodes – Exchange Lymphocyte w/
lymph (remove, store, produce, add). Resident
macrophages remove microbes and debris from
lymph. Lymphocytes produce antibodies and
sensitized T cells released in lymph

Spleen – Exchange Lymphocytes with blood,
residents produce antibodies and sensitized T
cells released in blood, (worn RBCs)
Lymphatic
vessel Adenoid -Tonsil
Blood -Lymph nodes capillary
Thoracic duct, entering vein Thymus
-Tissue cells Interstitial fluid

Right lymphatic - duct, entering vein

-Lymphatic capillary
(b)
Spleen
Thoracic duct Peyer's patch (small intestine)
Masses of
lymphocytes and macrophages
Appendix
Bone marrow
Lymphatic vessels
(a)
©1999 Addison Wesley Longman Inc.
Antigens

- An antigen is any foreign molecule that is
specifically recognized by lymphocytes and
elicits a response from them - A lymphocyte
actually recognizes and binds to just a small,
accessible portion of the antigen called an
epitope or antigenic determinant

Antigenic determinants - Specific regions of a given
antigen recognized by a lymphocyte

Antigenic receptors -Surface of lymphocyte that
combines with antigenic determinant
Antibody-Mediated (Humoral)
Immunity


Involves production of antibodies against foreign antigens.



- Antibodies are produced by a subset of lymphocytes called B cells.



- Mature in Bone marrow - lymphatic tissue, especially spleen and

lymph nodes


- B cells that are stimulated will actively secrete antibodies and are
called plasma cells.


- Antibodies (immunoglobulins, Ig) are found in extracellular fluids

(blood plasma, lymph, mucus, etc.) and the surface of B cells.


- Defense against bacteria, bacterial toxins, and viruses that circulate

freely in body fluids, before they enter cells.


- Also cause certain reactions against transplanted tissue.



- 1000s of different B cells, each recognizes a different antigen on the

surface of a macrophage.


- Each antigen stimulates production of a single specific antibody B cells

(along with T cells) come in contact with antigen.


- They are stimulated (by T cells) to produce many clones, plasma cells,
which make antibodies.


- Memory B cells – secondary response = faster, more sensitive

flesh
wound
bacteria
antibodies B cell
Antibody Structure

- Antibodies or Immunoglobulins (Ig)

- Classes: IgG, IgM, IgA, IgE, IgD

- Structure: Variable region - combines with
antigenic determinant of antigen Constant
region -responsible for activities
Antibodies (immunoglobulins, Ig) are
proteins that recognize specific antigens
and bind to them. They are found in
extracellular fluids (blood plasma,
lymph, mucus, etc.) and the surface of B
cells.
Defense 
against bacteria, bacterial toxins, and
viruses that circulate freely in body fluids,
before they enter cells. Also cause certain
reactions against transplanted tissue.

Antigenic determinants - specific regions of a
given antigen recognized by a lymphocyte
Antigenic receptors are found on surface of
lymphocyte that combines with antigenic
determinant to form Antigen-Antibody Complex

Antibodies affinity: A measure of binding
strength.
Consequences of Antibody
Binding

- Agglutination: Antibodies cause antigens (microbes) to
clump together.
- Hemagglutination: Agglutination of red blood cells.
Used to determine ABO blood types - like Antibodies &
antigens will agglutinate.
- Opsonization - Phagocytosis - Activates Complement
System/Inflammatory Response - Antigen-Specific
Responses Activate T lymphocytes: direct attack Activate
B lymphocytes to become: memory cells: secondary
immune response to that antigen, plasma cells that
produce more antibodies to attack that antigen
 Copyright @ The McGraw-Hill Companies, Inc. Permission
required for reproduction or display (a) Inactivates (b) Binds

(c)
Activates the the antigen. antigens
complement together.
casc
ade. Antigen
Complement
cascad
e activated Antibody
I
nflammation (d) Initiates the release of
Che
motaxis Lysis inflammatory chemicals.
(e) Facilitates
phagocytosis.
Chemicals
Inflammation Mast cell or
basophil
Macrophage
Agglutination
PROTECTIVE MECHANISM OF BINDING ANTIBODIES
TO ANTIGENS
Activation of complement Cell lysis
Complement
Enhances phagocytosis and reduces
number of infectious units to be dealt with
....
....

Bacterium
Lysis
Bacteria Opsonization
Coating antigen with antibody
enhances phagocytosis
Phagocyte
Inflammation
Disruption of Blood vessel
cell by complement/ reactive protein attracts phagocytic
and other defensive Tafecting Macro- immune system cells .cell p
hage
..
Neutralization
Virus
Blocks adhesion
 of bacteria and viruses
Blocks active site of toxin
Antibody-dependent cell-mediated cytotoxicity
Antibodies attached to target cell cause destruction by non-specific
immune system cells
to mucosa
Bacterium
Toxin
O BENJAMINICUMMINGS

Antigen-Specific Responses - Activate T
lymphocytes: direct attack - Activate B lymphocytes
to become: Memory cells: secondary immune
response to that antigen Plasma cells: antibodies –
attack that antigen
Classes of
Immunoglobulins


IgG Percentage Enhances phagocytosis, serum antibodies: neutralizes 80%, toxins

location: and Blood, viruses, lymph, protects intestine
fetus and
newborn. 
IgM Percentage First antibodies serum produced antibodies: during 5-10%, an infection.
location: Effective Blood, lymph, against B microbes cell surface and (monomer)
a
gglutinating antigens. 
IgA Percentage Localized protection serum antibodies: of mucosal 10-15%, surfaces.
location: Provides Secretions immunity (tears, to infant saliva, digestive intestine, tract.
milk), blood and lymph.


IgD Percentage In serum function serum is antibodies: unknown. On 0.2%, B cell

location: surface, B-cell initiate surface, immune blood, response
and lymph


IgE Percentage body. Allergic Blood.

reactions. serum Possibly antibodies: lysis of 0.002%, worms.
location: Bound to mast cells and basophils throughout
B Cell Antibody
Production

B cells develop from stem cells in the bone
marrow of adults (liver of fetuses). - After
maturation B cells migrate to lymphoid organs
(lymph node or spleen). - Clonal Selection:
When a B cell encounters an antigen it
recognizes, it is stimulated and divides into
many clones called plasma cells, which actively
secrete antibodies. - Each B cell produces
antibodies that will recognize only one antigenic
determinant.
Antigen receptor
Antigens
Variety of B cells
Cell proliferation
Clone of plasma cells
Clone of memory cells
- Antibodies secreted
into circulation
1999 Addison Wesley Longan, Inc
Immunological Memory:

Primary Response - After initial exposure to
antigen, no antibodies are found in serum for
several days. A gradual increase number of Abs,
first of IgM and then of IgG is observed. Most B
cells become plasma cells, but some B cells
become long living memory cells. Gradual
decline of antibodies follows.

Secondary Response - Subsequent exposure to
the same antigen displays a faster/more intense
response due to the existence of memory cells,
which rapidly produce plasma cells upon
antigen stimulation
Copyright The MoGrow-Hill Companies, Ino. Permission requred for reproduction or display.

Memory
More B cells
memory B cells
Secondary
immune response to antigen A
Fewer plasma cells
Second exposure
to antigen A. first exposure to antigen B
Memory B cells
103
More plasma cells
First exposure to antigen A
Fewer antibodies
More
antibodies
(b)
Antibody concentration
(arbitrary units)
Primary immune response to antigen A
Primary immune response
to antigen B

Secondary response
101

| First
exposure
Second exposure
Antibodies
to A
Antibodies
to B
Primary response
100+

o
;
14
21
28
35
42
49
56
Longer response time
Shorter response time
Time (days)
Copyright
The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Processed antigen Class II

MHC molecule ?
T-cell receptor
B-cell receptor Unprocessed
B cell
H
elper antigen
T cell
Interleukins trigger B cell division
Daughter
B cell
Daughter
B cell
Daughter cells continue to divide and produce antibodies
Clonal Selection:

.B cells (and T cells) that encounter stimulating
antigen will proliferate into a large group of cells. -
Why don’t we produce antibodies against our own
antigens? We have developed tolerance to them. -
Tolerance: To prevent the immune system from
responding to self-antigens - Clonal Deletion: B and
T cells that react against self antigens are normally
destroyed during fetal development - Preventing
activation of lymphocytes – activate suppressor T
cells, control the immune system when the antigen /
pathogen has been destroyed
Apoptosis- programmed cell
death (“Falling away”).

- Human body makes 100 million lymphocytes
every day. If an equivalent number doesn’t die,
will develop leukemia. - B cells that do not
encounter stimulating antigen will self-destruct
and send signals to phagocytes to dispose of
their remains. - Many virus infected cells will
undergo apoptosis, to help prevent spread of the
infection.
Autoimmune Diseases:
Failure of “Self- Tolerance”

- Some diabetes mellitus – attack beta cells
- Multiple sclerosis – attack on myelin nerve
sheath - Rheumatoid arthritis – attack joint
cartilage - Myasthenia gravis – ACh-receptors at
endplate attacked
Allergic Response -
Inflammation Reaction to
Non-pathogen

- First exposure: sensitization and activation
clone B cells that form antibodies and memory
cells
- Re-exposure: many antibodies produced,
activated Ts intensify inflammatory response
Allergen
.
First exposure
Allergen ingested and processed by antigen-presenting cell

MCH-11
activates
Antigen-presenting cell activates helper T cell
B lymphocyte
Helper T cell
becomes
-- Plasma cell
Memory B and T cells
retain memory of exposure to allergen
secretes
Antibodies
Reexposure
Activated T
cells

-IgE
-I9G
Mast cell

Degranulation
Cytokines Activation of complement proteins
Cytokines
Vasodilation Bronchoconstriction - Intlammation - + Vascular permeability
Cytotoxic T Cell Pathway

The cytotoxic T cells are capable of recognizing
antigens on the surface of infected body cells.

The cytotoxic T cells bind to the infected cells
and secrete cytotoxins that induce apoptosis
(cell suicide) in the infected cell and perforins
that cause perforations in the infected cells.

Both of these mechanisms destroys the pathogen
in the infected body cell.
T Cell Pathway

T-cells can either directly destroy the microbes or
use chemical secretions to destroy them.

At the same time, T cells stimulate B cells to divide,
forming plasma cells that are able to produce
antibodies and memory B cells.

If the same antigen enters the body later, the
memory B cells divide to make more plasma cells
and memory cells that can protect against future
attacks by the same antigen.

When the T cells activate (stimulate) the B cells to
divide into plasma cells, this is called antibody-
mediated immunity.
Antibodies

Antibodies proteins specific antigens, that (also
circulate called thereby through immunoglobulins
attacking the blood microbes.
or stream Ig's) are and Y-shaped
bind to

The lymph antibodies to the pathogen are
transported invasion through site.
the blood and the

The respond body to contains one specific millions
antigen.
of different B cells, each able to

There least common): are 4 classes IgG. of
antibodies IgM. IgA. (listed IgE. IgD
from most common to

Each heavy identical each region. molecule site.Each
antibody other. chains The to antibody while
constant each Each and is the made other contains 2
has variable light region 2 and of antigen-binding
chains. four a forms regions both constant
polypeptide Both light the forms heavy main chains
region sites.
the part (protein) chains are and antigen-binding of
identical a the are
variable chains: to
2
IMMUNE RESPONSE
▶
Antigen: bind to an any Antibody
substance or T cell that receptor.
can specifically
▶

Examples: act as Ab epitope)

Proteins LPSDNA Lipid Haptens (small
molecules
▶
Immunogen: response.
that which induces an immune
▶
Epitope (Antigenic Determinant)
▶
Specific where Ab site binds
on Ag that is recognized by the immune system,
▶
Antibody: able to bind to epitopes
IMMUNE RESPONSE
▶
ANTIBODIES (Ab) ▶
Act on Ag-specific receptors on B cells
▶
Secreted responses by (Antibodies Plasma
cells in blood)
and mediate Humoral
▶
20% of plasma proteins ▶
Ag → B cell → Ab ▶
Bind Epitopes on Ag ▶
Activate Complement ▶
Binds Fc receptors on other Lymphoid
cells
IMMUNE RESPONSE
▶
ANTIBODIES (cont) ▶
Structure: ▶
4 Heavy), polypeptide bound chains by
disulfite (2 identical bonds
Light + 2 identical
▶
Have (responsible Hypervariable for Ag-
binding)
regions at Amino acid end
▶
Have Constant regions at Carboxyl end
▶
Light chains 2 types: kappa & lamda
IMMUNE RESPONSE

ANTIBODIES (cont)

Heavy Chains:

IgG – gamma heavy chain

IgA – alpha heavy chain

IgM – mn heavy chain

IgE – epsilon heavy chain

IgD – delta heavy chain
IMMUNE RESPONSE
▶
ANTIBODY-BINDING SITES ▶
Found end of at Heavy Variable & Light
Region chains
at Amino acid terminal
▶
Variability binding of specificity
Amino acid sequence gives Ag-
▶
Different bound different by Abs
structurally same Ag-binding related Ags site
on can cross- react &
&
▶
Important related & cross in Rheumatic
react with Fever Myosin.
– Strep Ags structurally
IMMUNE RESPONSE
▶
IDIOTYPE responsible = areas for Ag on
Specificity
the Variable Region
▶
ISOTYPE by Heavy unique chain =
subclass Constant gene
of Igs that are Regions distinguished
encoded by
▶
ALLOTYPE detected species
as = protein an Ag product by another of
an member Allele that of the may same be
▶
It Constant involves Region different of
the Alleles Heavy at chain.
a specific site on the
IMMUNE RESPONSE
▶
IMMUNE SERUM contain a mixed
population of Abs with varying affinity
for Ags
▶
MONOCLONAL ANTIBODIES
▶
Specific for a Single Epitope
▶
Produces in Lab by Hybridomas
(fusion of
activated B cells to Plasma cell)
IMMUNE RESPONSE

PROPERTIES OF
IMMUNOGLOBULINS

IgG:

Major defense against Bacterie & Toxins

Only Ig to cross the human placenta,
protecting newborn for 4 – 6 months.

Associated with Opsonization

Associated with Complement activation

Important in Secondary immune response to Ag
→ provides Long-lasting immunity
IMMUNE RESPONSE

IgM: (only Ig produced by the Fetus)

Primary respone to Antigens

First Ab detected in serum post Viral infection

Rheumatoid factor & Heterophile Abs are IgM

Found on B cell membranes

Very efficient activator of Complement
IMMUNE RESPONSE
(cont)
▶
IgA: ▶
Important surfaces
barrier function on mucosal
▶
Function in secretory immune response
▶
Secretory Saliva, Colostrum, IgA (sIgA)
Breast found Milk)
in Tears,
▶
Produced by Plasma cells in GIT & URT
IMMUNE RESPONSE
▶
IgD: (very low concentration in serum)
▶
Cell surface Ag receptor on naive B cells
▶
Primary receptor for Ag on B cells
▶
Stimulate B cell proliferation
▶
IgE: (very very low concentration in
serum)
▶
Allergic & immediate Hypersensitivity
▶
Fc region of IgE binds to surface of Basophils &
Mast cells → Histamine, LT, ECF, Heparin →
Immediate
Hypersensitivity reaction
Antibodies work in different ways: 
1. antibody function. a viral Neutralizing antigen This
complex. is an from how Antigen. This toxins binding forms
from The to a a antibody bacteria shield body around cell can
can thereby be bind the neutralized antigen, to preventing an
antigen, preventing or how infection.
forming a cell its normal
an can antigen-
prevent


2. liver series cluster membrane.This chemotaxis cells

Activating that at of together the reactions normally site and
Complement:Complement of lyses to inflammation,
invasion.
are that form (ruptures) inactive activates a pore in the both
or these the channel cell. of body. proteins. which Other is a
that An group increase complement antigen-antibody inserts
Some of plasma into of the the a number proteins microbe's
activated proteins complex of can white made plasma
proteins cause
triggers blood
by can the a


3. to easier the to phagocytic Precipitating cross-link clump

antigens for together phagocytic them. cells within
AntigensSometimes to This in the ingest a cells causes
process cells them to walls ingest the called by of antigen
phagocytosis.
the them the agglutination, antibodies bacteria by to
precipitate phagocytosis can can again cross-link, bind out
(as making to of describe solution, the causes same it easier
the making above). free bacteria
for
antigen
it
Also,


4. attack. phagocytosis.
Facilitating The complex Phagocytosis also binds :The to
antigen-antibody the surface of macrophages complex
signals to further phagocytic facilitate
cells to
Inflammatory Response

Effects of inflammation include: temporary
repair of injury, slowing the spread of
pathogens, mobilization of local, regional, and
systemic defenses
Macrophages, Mast Cells
release histamine

- Localized vasodilation

Capillary permeability - increased gaps in capillaries
bring more WBC's & plasma proteins

Swelling, redness, heat and pain are incidental

- Phagocytes release chemical mediators

Kinins - stimulate complement system (plasma
proteins), chemotaxinsClotting factors – walling off
invasion

Remove pathogens, debris
inflamation
Antimicrobial Proteins -
Complement System

System blood and of inactive on cell membranes
proteins produced by liver circulating in

Cascade antibodies of or plasma antigens
complement causing cascade proteins of (C)
chemical activated reactions
by

Direct membranes
effect is lysis of microorganisms by destroying
target cell

Indirect inflammation: effects recruit include:
phagocytes, chemotaxis, B & opsonization,
T lymphocytes
Reaction of complement
complement

Complement system –System of inactive
proteins produced by liver circulating in blood
and on cell membranes, activated by antibodies
or antigens causing cascade of chemical
reactions, direct effect is lysis of
microorganisms via membrane attack complex
that destroy pathogen plasma membranes

Indirect effects include:
- Chemotaxis - Opsonization - Inflammation:
recruit phagocytes, B & T lymphocytes
Classical pathway of complement
Bacteria enter extracellular fluid from outside
Skin or mucous membrane
External environment
ECF
lyses
Bacteria
Membrane attack complex

Opsonins
activate
make

ingest and
disable
present antigens to

Complement
proteins
- activate
Mast cells
secrete
Phagocytes
Th cells
Acute phase
proteins
Chemotaxins

Histamine
secrete

Antibodies
increases permeability
B lymphocytes
act as

Capillary
Plasma proteins
Circulating leukocytes
attract -
Interferon

proteins produced uninfected viral replication
that by cells, non-specifically virus-infected triggers
production cells, defend binds of against to chemicals
membranes viral infection,
that of interfere adjacent,
with

Enhances activity
macrophage, natural killer, and cytotoxic T cell & B cell

Slows cell division and suppresses tumor growth

Three major types of interferons are: 
Alpha– Beta– Gamma activity
secreted produced – secreted by by fibroblasts by leukocytes
T cells causing and and NK attract/stimulate cells slow
stimulate inflammation
macrophage NK cells
Summary

- Body defends itself with barriers, chemicals &
immune responses - WBCs and relatives conduct
direct cellular attack: phagocytosis, activated NK &
cytotoxic T cells and produce attack proteins (i.e.
antibodies, complement, & membrane attack
complex) - Cytokines, communicate cell activation,
recruitment, swelling, pain, & fever in the
inflammation response - Defense against bacteria is
mostly innate while viral defense relies more on
acquired immune responses

- Autoimmune diseases are a failure of self-tolerance
Copyright © The McGraw-Hill Companies, Inc. Permission requied for reproduction or display

Helper T cell proliferates Cytokines and antibodies

and secretes cytokines enhance inflammation and
Helper T cell
phagocytosis can activate
Helper T cell a B cell
Helper Helper
can activate
a T cell T cell T cell
B cell
T cell

B cell proliferates and differentiates

T cell proliferates and differentiates
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Innate

Antigen Immunity
Interferons
General
Mechanical Neutrophils, Chemical prevent response
viral + mechanisms macrophages, mediators that does not "
infections basophils, improve with
and subsequent
eosinophils exposure
Inflammation and phagocytosis
cause destruction Adaptive
of the antigen Immunity
Specific
Macrophage
Macrophage response
presents that improves
processed with
antigen to subsequent
helper T cell Helper T cell exposure Begins
with a macrophage
Helper T cell Cytokines and presenting an
proliferates antibodies enhance antigen to a
and secretes inflammation helper T cell
cytokines and phagocytosis
Plasma cell Memory B cell
Memory T cell
Effector T cell
Direct effects against antigen
Antibodies Responsible for Lysis of cells Cytokines
adaptive immunity expressing antigen Antibody-
mediated Cell-mediated immunity immunity
Effector T cells act against antigens
Antibodies act against bound to MHC molecules on the antigens in
solution or on surface of cells; effective against the surfaces of
extracellular intracellular microorganisms, tumors, microorganisms.
and transplanted cells.
PRIMARY RESPONSE
SECONDARY RESPONSE

Antibody
Antibody concentration
in plasma
Antibody concentration
in plasma
Antibody
23 -Time (weeks)
Time (weeks)
First exposure to antigen
Clonal expansion
Memory cells are Second exposure long-lived, continue to antigen to reproduce
Stronger and more rapid response

O
-O O-00-30
O
O
O
*070 - 0 Õ
Antigen
Effector cells carry out immediate response; short-lived

Primary response
Secondary response
First exposure to a pathogen's antigens
Natural exposure to virulent, antigenic pathogen
Exposure to nonvirulent, antigenic pathogen through vaccination
Virulent portion
Antigenic portion
Combat
No virulence
Disease
Specific B cell clone
Specific B cell clone
No disease
Plasma cells
Plasma cells
Memory cells
(long-term. immunity)
Memory cells
(long-term immunity)
Antibodies
(slow, weak primary response)
Antibodies (not needed)
Subsequent exposure to same virulent pathogen
(a)
(b)
Plasma cells
Plasma cells
Combat
Combat
Antibodies (swift, strong secondary response)
Antibodies (swift, strong secondary response)
D= Primary response
= Long-term immunity
No disease
O FIGURE 12-15 Means of acquiring long-term immunity Long-term immunity against
a pathogen can be acquired through having the disease or being vaccinated against it. (a)
Exposure to a virulent (disease-producing) pathogen. (b) Vaccination with a modified
pathogen that is no longer virulent (that is, can no longer produce disease) but is still
antigenic. In both cases, long-term memory cells are produced that mount a swift,
secondary response that prevents or miniinizes symptoms on a subsequent natural
exposure to the same virulent pathogen.
IMMUNE RESPONSE TO THE BACTERIA
105
IMMUNE RESPONSE TO
VIRUS
106
THE FOUR KINGDOMS