BASIC

IMMUNOLOGY
 Definitions
• Immune system = cells, tissues, and molecules that
mediate resistance to infections (GROWTH OF
MICROORGANISM)
• Immunology = study of structure and function of the
immune system
• Immunity = resistance of a host to pathogens and
their toxic effects
• Immune response = collective and coordinated
response to the introduction of foreign substances in
an individual mediated by the cells and molecules of
the immune system
 Role of the immune system
• Defense against microbes
• Defense against the growth of tumor cells
• kills the growth of tumor cells
• Homeostasis (BALANCE)
• destruction of abnormal or dead cells
(e.g. dead red or white blood cells, antigen-antibody
complex)
 BLOOD CELLS:
- RBC/ ERYTHROCYTES  CONTROLLED BY THE HORMONE ERYTHROPOEITIN
 NO NUCLEUS  ABLE TO TRANSFORM INTO DIFFERENT SHAPE
 HEMOGLOBIN  OXYGEN CARRIER (IRON)
- WBC / LEUOKOCYTES
1. GRANULOCYTE
A. BASOPHIL  ALLERGIC REACTION
B. EOSINOPHIL  PARASITIC INFECTION
C. NEUTROPHIL  FIRST LINE OF DEFENSE; IMMEDIATE RESPONSE
2. LYMPHOCYTE
A. B-LYMPHOCYTE  PRODUCING ANTIBODIES (BONE MARROW)
B. T-LYMPHOCYTE (THYMUS)  T-HELPER CELL (CD4) (HELPS THE B – LYMPHOCYTE
TO MAKE ANTIBODIES) AND CYTOTOXIC T-CELL (CD8) (ATTACKING INFECTED CELLS)
3. MONOCYTE  IRREGULARLY SHAPED WBC CIRCULATING IN THE BLOODSTREAM 
MACROPHAGE (CELL) (PHAGOCYTOSIS  CELL EATING)
- PLATELETS / THROMBOCYTES  BLOOD COAGULATION
-  FRAGMENTS OF CELL
 Immune System

1. Organs
2. Cells
3. Molecules
NON-SPECIFIC / INNATE / NATURAL
1. BARRIERS  1ST LINE (SKIN, STOMACH ACID, MUCOUS MEMBRANE)
2. INFLAMMATION  PHAGOCYTE (MACROPHAGE, NEUTROPHIL) (PUS)
SPECIFIC/ ADAPTIVE  LYMPHOCYTE
1. B – LYMPHOCYTE  HUMORAL RESPONSE (ANTIGEN  BLOOD)
2. T-LYMPHOCYTE  CELL MEDIATED RESPONSE (ANTIGEN  CELL)
MHC II/ ANTIGEN PRESENTER
IMMUNE SYSTEM 
ANTIBODIES
 Immune system:
(1) organs
•Tonsils and adenoids
•Thymus

•Lymph nodes
•Spleen

•Peyer’s patches
•Appendix

•Lymphatic vessels
•Bone marrow
 Immune system:
(2) cells
•Lymphocytes
• T-lymphocytes
• B-Lymphocytes, plasma cells
• natural killer lymphocytes
•Monocytes, Macrophage
•Granulocytes
• neutrophils
• eosinophils
• basophils
 Immune system:
(3) molecules
• Antibodies
• Complement  proteins in our plasma that inhibits or
kills foreign cells
• Cytokines  Secreted proteins and act as signaling
molecule
• Interleukins  signaling molecules expressed by WBC
and are involved in production of more immune cell
(differentiation  CD4, CD8)
• Interferons  group of signaling proteins made and
released by host cell in response to the presence of
virus (VIRAL HEPATITIS)
 Two types of immunity
1. Innate (non-adaptive) / SPECIFIC / NATURAL
• first line of immune response
• relies on mechanisms that exist before infection

2. Acquired (adaptive)
• Second line of response (if innate fails)
• relies on mechanisms that adapt after infection
• handled by T- and B- lymphocytes
• one cell determines one antigenic determinant
 Innate immunity:
first line of defense
• Based on genetic make-up
• Relies on already formed components
• Rapid response: within minutes of infection
• Non-specific
• same molecules / cells respond to a range of
pathogens
• Has no memory
• same response after repeated exposure
• Does not lead to clonal expansion
 Innate immunity:
mechanisms
• Mechanical barriers / surface secretion
• skin, acidic pH in stomach, cilia
• Humoral mechanisms
• lysozymes, basic proteins, complement, interferons
• Cellular defense mechanisms
• natural killer cells, neutrophils, macrophages, mast cells,
basophils, eosinophils

NK Cell Eosinophils Basophils & Mast Monocyte

Neutrophil
cells Macrophage
 Adaptive Immunity:
second line of response
• Based upon resistance acquired throughout life
• Relies on genetic events and cellular growth
• Responds more slowly, over few days
• Is specific
• each cell responds to a single epitope on an
antigen
• Has anamnestic memory
• repeated exposure leads to faster, stronger
response
• Leads to clonal expansion
 Immunity
Active immunity – you make the antibodies
Passive immunity – you are given with the antibodies

Natural – you get the antibodies naturally

Artificial – antibodies are artificially introduced to the
body.
 Immunity
Natural Active – acquire disease
Natural Passive – from placenta

Artificial Active – vaccine containing antigens

Artificial Passive – vaccine containing antibodies
 Adaptive Immunity:
active and passive

Active Immunity Passive Immunity

via breast milk
clinical, sub-clinical
Natural (COLOSTRUM) ,
infection
placenta

Vaccination:
Artificial immune serum, immune
Live, killed, purified cells
antigen vaccine
Adaptive Immunity: mechanisms

• Cell-mediated immune response (CMIR)

• T-lymphocytes
• eliminate intracellular microbes that survive within
phagocytes or other infected cells
• Humoral immune response (HIR)
• B-lymphocytes
• mediated by antibodies
• eliminate extra-cellular
microbes and their toxins Plasma cell
(Derived from B-
lymphocyte, produces
antibodies)
 Humoral immune response
1. B lymphocytes recognize
specific antigens
• proliferate and
differentiate into
antibody-secreting
plasma cells
2. Antibodies bind to specific
antigens on microbes;
destroy microbes via
specific mechanisms
3. Some B lymphocytes
evolve into the resting state
- memory cells
Cell-mediated immune response
1. T-cell
• recognizes peptide
antigen on macrophage
in association with major
histo-compatibility
complex (MHC) class
• identifies molecules on
cell surfaces
• helps body distinguish
non-self materials
2. T-cell goes into effectors
cells stage that is able to kill
infected cells
 T lymphocytes
2 types
• helper T- lymphocytes (CD4+)
• CD4+ T cells activate phagocytes to kill microbes
• Cytolytic/CYTOTOXIC T-lymphocyte (CD8+)
• CD8+ T cells destroy infected cells containing
microbes or microbial proteins
Cell mediated immune response
Primary response
• production of specific clones of effector T cells and
memory clones
• develops in several days
• does not limit the infection
Secondary response
• more pronounced, faster
• more effective at limiting the infection
Example - cytotoxic reactions against intracellular parasites, delayed
hypersensitivity (e.g., Tuberculin test) and allograft rejection
Antibodies (immunoglobulins)
•Belongto the gamma-globulin fraction of
serum proteins
•Y-shaped or T-shaped polypeptides
• 2 identical heavy chains
• 2 identical light chains
•Five kinds of antibodies (GAMED)
• IgG, IgM, IgA, IgD, IgE
 Antibodies
3. Structure:
a. All immunoglobulin molecules are made up of a
basic four-chain polypeptide unit that consists of
two large chains, called heavy or H chains, and two
smaller chains, named light or L chains.
b. These chains are held together by noncovalent
forces in addition to disulfide interchain bridges.
 Antibodies
c. Antigen Recognition Unit: The amino-terminal ends
of both light and heavy chains are unique to a
specific antibody molecule, and these serves as the
antigen recognition unit. (PARATOPE)

d. Hinge Region: It is the segment of the heavy chain

located between the CH1 and CH2.
 3. Heavy chain

5. Antigen 1. Fab region

binding
site
(paratope)
2. Fc region

4. Light chain
6. Hinge regions.
Immunoglobulin
 IMMUNOGLOBLULIN
IgG GAHAMAN
 MOST PREDOMINANT
IgA ALAT
 BODY SECRETIONS (SWEAT, SALIVA)
IgM MALAKI
 BIGGEST
IgE ELLERGY, EPAL
 LEAST PREDOMINANT
IgD DITAK
 2ND LEAST ABUNDANT
 IgG
• 70-75% of total immunoglobulin  MOST
PREDOMINANT
• Secreted in high quantities in secondary exposures
• Cross the placenta • 4-fold rise or fall
• Major functions / applications indicates active
• neutralize microbes and toxins
infection
• A single positive
• opsonize antigens for phagocytosis
sample indicates past
• activate the complement exposure
• protect the newborn
• participate in agglutination (CLUMPING OF THE ANTIGEN) and
precipitation reactions
 IgM
• Secreted initially during primary infection
• Major functions / applications
• secreted first during primary • Presence in newborn
exposure means infection
• Single positive sample
• activates the complement in serum or CSF
• used as a marker of recent indicates recent or
active infection
infection
• Used to detect early
phase of infection
 IgA
• Monomeric in serum (IgA1)
• Dimeric with secretory component in the lumen of the
gastro-intestinal tract and in the respiratory tract
(IgA2)
• Sero-diagnosis of
• Major function / application tuberculosis
• neutralizes microbes and toxins • Synthicial respiratory
virus tests
 IgD
• Monomeric
• Extremely scarce (<0.2% of total immunoglobulin)
• Major functions / applications
• present on the surface of B lymphocytes
• functions as membrane receptor
• role unclear
• has a role in antigen stimulated lymphocyte
differentiation
 IgE
• Mediates type I hypersensitivity
• Monomeric
• Major functions / applications
• associated with anaphylaxis (REDNESS,
VASOCONSTRICTION, DIFFICULTY IN BREATHING)
• plays a role in immunity
Serodiagnosis of infectious and
to helminthic parasites non-infectious allergies
(e.g., allergic
bronchopulmonary
aspergillosis, parasitic
diseases)
 Monomer
IgD, IgE, IgG

Pentamer
Dimer
IgM
IgA
 Sequential IgM-IgG humoral
response
•IgM
• produced as a first response to many antigens
• levels remain high transiently
•IgG
• produced after IgM
• higher levels persist in small amounts throughout life
• produced in large amounts during secondary
response
• persistence of antigen sensitive ‘memory cells’
after primary response
 IgM – IgG sequential response
Anamnestic
response
Antibody titer

IgG

IgM

Time

First stimulus Second stimulus

 Immunoglobulin
IgG IgM IgA IgD IgE
Most Biggest Ig Secretory Ab Found in Allergic Ab
predominant surface of B
cells

Longest half-life 1st Ab produced Found in tears, Present during

in initial saliva, mucus, hypersensitivity
infections milk reactions

Crosses Effective in Binds to mast

placental agglutinating cells and
barrier; protects microorganisms basophils
newborn

Enhances
phagocytosis

Neutralize
toxins
 Antigens and immunogens
• An antigen
• A substance that reacts with antibody molecules and
antigen receptors on lymphocytes
• An immunogen
• An antigen that is recognized by the body as non-self
and stimulates an adaptive immune response
 Antigens and immunogens
• For simplicity, both antigens and immunogens are
usually referred to as antigens
• To be immunogenic, an antigen must possess three
characteristics:
a. high molecular weight
b. chemical complexity, and
c. foreignness (recognized as non-self by the body)
 Antigens and immunogens:
chemical nature
• Chemically, antigens are large molecular weight
proteins and polysaccharides
• including conjugated proteins such as glycoproteins,
lipoproteins, and nucleoproteins, and
• including lipopolysaccharide
 Antigens and immunogens:
epitopes
• Epitopes (or antigenic determinants)
• the actual portions or fragments of an antigen that
react with receptors on B-lymphocytes and T-
lymphocytes, as well as with free antibody molecules
• Composed of polysaccharides or proteins
 Antigens and immunogens:
recognition
• The body recognizes an antigen as ”foreign” when
epitopes of that antigen binds to B-lymphocytes and
T-lymphocytes
• By means of epitope-specific receptor
Antigens and immunogens: haptens

• A hapten
• small molecule that by itself is not immunogenic
• act as an antigen when it binds to a larger protein
molecule
Failure of immune response

• Immune response helps individuals defend against

• microbes
• some cancers
• Immune response can fail
• hypersensitivity reactions
• immunodeficiency
 Hypersensitivity reactions
• Cause cell damage through excessive immune
response to antigens
• Hypersensitivity
• overreaction to infectious agents
• Allergy
• overreaction to environmental substances
• POISON IVY
• Autoimmunity / AUTOIMMUNE/ CYTOTOXIC DISEASE
• overreaction to self
 Hypersensitivity reactions
• Types
• Type 1 – Anaphylaxis (IMMEDIATE) (ASTHMA)
• Type 2 – Cytotoxic (AUTOIMMUNE DISEASE)
(RHEUMATOID ARTHRITIS)
• Type 3 – Immune Complex (ANTIBODY IS LESSER
THAN THE ANTIGEN)
• Type 4 – Delayed (NOT IMMEDIATE, 2-3 DAYS
REACTION) (TUBERCULIN SKIN TEST/ PURIFIED
PROTEIN DERIVATIVE TEST/ MANTOUX TEST)
 Immunodeficiency
• Loss or inadequate function of various components of
the immune system
• Can occur in any part or state of the immune system
• physical barrier, phagocytes, B lymphocytes, T
lymphocytes, complement, natural killer cells
• The immuno-compromised host
• has an impaired function of immune system
• is at high risk of infection  IMMUNOSUPRESSANT
(PREVENT REJECTION OF ORGAN IN ORGAN
TRANSPLANT)
 Immunodeficiency
• Congenital (primary) immunodeficiency
• genetic abnormality
• defect in lymphocyte maturation

• Acquired (secondary) immunodeficiency

• results from infections, nutritional deficiencies or
treatments
• AIDS, chronic leukemia
 Altered immunity: immuno-compromised
Disorder Compromised function
Altered Mucus membrane Reduction in IgA Microbe binding
anatomic
barrier Gastro-intestinal Elevated pH Bacteria killing
tract
Change in flora Colonization resistance

Immune Innate immunity Reduction of complement Activates phagocytosis

system
Opsonization of bacteria
Membrane attack complex

Neutropenia Phagocytosis
Monocytopenia Bacteria killing

Adaptive immunity Reduction of T cells Activation of macrophages

Activation of B lymphocytes

Hypo-gammaglobulinemia Neutralizes pathogens and

toxins, opsonization,
complement activation
 Summary (1)
• Innate immunity
• relies on mechanisms already existing before microbe
infects host
• is the first line of defense
• has no memory for subsequent exposure
• relies on non specific mechanisms
 Summary (2)
• Adaptive immunity
• develops following entry of microbe into the host
• comes into action after innate immunity fails to get rid
of microbe
• has memory to deal with subsequent exposure
• happens through specific cells
• T cells (cell mediated)
• B cells (antibody mediated)
 Summary (3)
• Primary immune response
• short lasting
• smaller in magnitude
• Secondary immune response
• longer in duration
• larger in magnitude
• develop ‘memory cells’ following primary response
• Failure of immune response can result in:
• hypersensitivity
• immunodeficiency
Investigation strategies and methods

Developed by the Department of Epidemic and Pandemic Alert and

Response of the World Health Organization with assistance from:

European Program for Intervention Epidemiology Training

Canadian Field Epidemiology Program

Thailand Ministry of Health

Institut Pasteur