Introduc)on

to immunology

Francis Ian L. Salaver, RMT,MD

What is Immunology?

Study of the immune system

What is the Immune system?

Nonmedical students: Composed of

white blood cells
 Immune System
•  Composed of cells, tissues, organs and
soluble substances (antibodies) that
functions to provide IMMUNITY.

–  CELLS – White blood cells

–  TISSUE – Connective tissue below the skin
–  ORGANS – Skin, Stomach, Lacrimal gland
–  SOLUBLE SUBSTANCES – Antibodies, HCl,
Lactic acid in vagina
 Immune System
IMMUNITY is the ability to fight off or resist
an infection.

•  Functions

–  DEFENSE - protection against invading

microorganisms
•  A c t i v a t e d d u r i n g e n t r y o f f o r e i g n
microorganisms or substances in the body
 Immune System
IMMUNITY is the ability to fight off or resist
an infection.

•  Functions

–  SURVEILLANCE – detection of presence of

tumor or malignancies
•  Every cell is constantly checked for presence
of malignant transformation
 Immune System

•  Immunity – ability of the body to

resist infection

– Can Innate of you – PRESENT upon

birth/Natural

– Can be learned upon exposure (part

of adaptation) = ADAPTIVE
 Immunity
•  Can be INNATE or ACQUIRED

•  If innate = Innate immunity

– PRESENT upon birth
– Protects against a wide variety of
microorganisms - nonspecific
– Same magnitude of response upon
re-exposure
 Immunity
•  Can be INNATE or ACQUIRED

•  If acquired = Acquired Immunity

–  Developed only after an exposure
–  Adaptive

–  T and B cells (plasma cells, antibodies)

•  Take note: MEMORY cells – increase
response upon re-exposure
 Acquired Immunity :
B cells and an)bodies
•  Humoral immunity
–  Humor means “substance” = Antibodies
 Acquired Immunity :
T cells
•  Cellular immunity
 Innate or Adap)ve
•  Natural
•  Specific
•  Does not increase magnitude of response
upon re-exposure
•  Present upon birth
•  Acquired
•  Fastest and immediate response
•  Ang kagandahan at kagwapuhan ng
BMLS SPC students
 Checking
•  Lysozyme in tears and saliva destroying
bacterial cell wall
•  Fever
•  Antibodies
•  Virally infected cells destroyed by T
cytotoxic
•  Virally infected cells destroyed by Natural
killer cells
•  Phagocytosis
•  Plasma cells
 Immunity can be also classified as to:

•  Natural Active –
–  Acquired through usual Mode of transmission
and person plays the active role in creating
immune response

•  Artificial Active
–  Antigen is administered into another person
–  Person plays an active role in creating immune
response
 Immunity can be also classified as to:

•  Natural passive –
–  Acquired through usual Mode of transmission
but the person does not play the active role in
creating immune response

•  Artificial Passive
–  Antibodyinjected or transferred to another
person
–  Person does not play an active role in creating
immune response
 Classify the following immune
responses
•  Recovery from german measles
•  Breastfeeding
•  Transplacental transfer of antibody
•  Tetanus toxoid
•  Tetanus immunoglobulin
•  Hepa B vaccination
 Cells of the immune system
•  White blood cells – key players in the
immune system

–  GRANULOCYTES
•  Neutrophils –
•  Basophils – love for basic dye (blue
hematoxylin)
•  Eosinophils – love for eosin (red)

–  AGRANULOCYTES
•  Monocytes
•  Lymphocytes
Neutrophils
•  3-5 nuclear lobes
(Segmenters)

•  Cells having different

nuclear lobe numbers
(Polymorphonuclears)

•  Most abundant
(60-70% of the total
white blood cells)
Neutrophils

•  Lilac pink
secondary granules
containing
enzymes
Neutrophils
•  First cell to migrate
towards the site of
infection
–  Neutrophilia – early
stage of infection/
acute stage

•  Good in phagocytosis
(antibacterial)
–  Neutrophilia – bacterial
infection
Neutrophils
•  Good in killing because
of the digestive enzymes
in its granules +
LYSOSOMES

•  Take note: During

phagocytosis, neutrophils
degranulates and
releases trypsin

–  Trypsin may kill other

bacteria or may damage
surrounding tissue L
Neutrophils
•  Neutrophils undergo
apoptosis after 6-7hrs
of activation
–  PUS

•  REPLACED by
monocytes
 Eosinophils
•  Bilobed nuclei
•  Has affinity to acidic
dye (eosin)

•  Granule content is
Major Basic Protein
(can cause damage to
helminths and larval
stages)
–  Eosinophilia - parasitism
 Eosinophils

•  Antibody-dependent
cell cytotoxicity
–  Eosinophils only
degranulate if there is
presence of antibody
on the surface of the
parasite
An)body-dependent cell cytotoxicity
Basophils
•  Bilobed
•  Has affinity to basic
dye – Hematoxylin

•  Main Granule
content: Histamine

•  ALLERGY!!
BLOOD – BASOPHIL
TISSUE – MAST CELL
Basophils
•  Basophil versus Mast cell

•  Some books define Mast

cells as Tissue basophils

•  Basophils leave bone

marrow mature and
stays in the blood

•  Mast cells leave bone

marrow immature and
matures in tissue
Basophils
•  Basophils/Mast cells
have surface
receptors for IgE

•  Crosslinking of at least
2 IgE’s causes the cell
to degranulate and to
release histamine
Monocytes
•  Monocytes

•  Largest white blood

cell
–  Kidney-bean shaped
nucleus
–  Horse-shoe shaped
nucleus

•  Second cell to migrate

towards the site of
infection
Monocytes
•  More efficient
phagocytes than
neutrophils

•  BUT cannot digest

engulfed bacteria
because they lack
cytoplasmic
granules L
Monocytes
•  Instead, these cells act
as antigen presenting
cells

•  PRESENTS ANTIGENS to
T cells

•  T cells, in return
activate B cells to form
plasma cells and to
produce antibodies
 NOTE !!
Parameter Class I MHC Class II MHC

Loca)on All Nucleated Macrophage and

cells in the body B cells

Type of an)gen Viruses Extracellular

presented Intracellular

T cell CD8 CD4

T cytotoxic T helper
CD3 – T CELL RECEPTOR
First Signal for T cell Ac)va)on
•  Antigen-CD3 + Class II MHC-CD4 = T
helper activation

•  Antigen-CD3 + Class I MHC-CD8 = T

cytotoxic activation
 T cell Prolifera)on & Differen)a)on

2 signals for activation

1. MHC-antigen complex
2.Co-stimulatory signal
CD80/CD86/B7 – from APC (B cells,
macrophages)
CD80/86/B7
Of APC Signal 2
Signal 1
CD28
Of T cell
t CYTOTOXIC CELL CAUSES LYSIS OF
TARGET CELLS
•  Perforin –
creates pores
on the target
cell

•  Granzyme-
enters through
the pores and
cause lysis of
the cell
Viruses
EXTRACELLULAR BACTERIA
EXTRACELLULAR BACTERIA
Monocytes versus Macrophages
 Tissue Macrophages
•  Liver : _____________
•  Central nervous system : ____________
•  Kidney/GloMErulus : ________________
•  Bone: ______________________
•  Lungs: ____________________/_______________
•  Skin: ____________________
•  Lymph nodes: ___________________
•  Tissue: _______________________
 Tissue Macrophages
•  Liver : Kupffer cells
•  Central nervous system : Microglia
•  Kidney/GloMErulus : Mesanglial cells
•  Bone: Osteoclast
•  Lungs: Alveolar macrophages/Dust cells
•  Skin: Langerhan cells
•  Lymph nodes: Dendritic cells
Lymphocytes
•  Scanty cytoplasm

•  Nucleus almost
occupies the entire
cells

•  Nucleus has same

size as RBCs
Lymphocytes

•  Small
lymphocytes
– B and T cells

•  Large GRANULAR
lymphocytes
– Natural killer cells
Lymphocytes

•  Small lymphocytes
– B and T cells

•  ADAPTIVE
Immunity
– Cellular – T cells
– Humoral – B cells
Lymphocytes
•  Both T and B cells are
produced in the bone
marrow

•  B cells mature in the bone

marrow

•  T cells leave the bone

marrow and matures in
the Thymus
 Primary versus Secondary Lymphoid
organs
•  Primary lymphoid organs - site of PRODUCTION
AND MATURATION of T and B cells
–  __________________
–  __________________

•  Secondary lymphoid organs – where mature T

and B cells are stored; where they proliferate and
differentiate upon encounter with specific
antigens
–  _________________
–  _________________
–  _________________
–  _________________
 Primary versus Secondary Lymphoid
organs
•  Primary lymphoid organs - site of
PRODUCTION AND MATURATION of T and B
cells
–  Thymus
–  Bone marrow

•  Secondary lymphoid organs – where mature

T and B cells are stored; where they
proliferate and differentiate upon encounter
with specific antigens
–  Spleen
–  Lymph nodes
–  Tonsils
Cardiac defects
Abnormal facies
Thymic
hypoplasia
Cleft palate
Hypocalcaemia
resulting from
22q11 deletions.
Cardiac defects
Abnormal facies
Thymic
hypoplasia
Cleft palate
Hypocalcaemia
resulting from
22q11 deletions.
 DiGeorge Syndrome

•  Thymic hypoplasia leading to variable immunodeficiency

•  The result of common 22q11.2 dele)on is a
developmental field defect involving the third and
fourth pharyngeal pouches leading to defec)ve
migra)on of the neural crest cells during the fourth
week of embryogenesis.
•  Por)ons of the heart, head and neck, thymus, and
parathyroids derive from these pouches.
3 and 4 pharyngeal pouches
rd th
Cardiac defects
Abnormal facies
Thymic
hypoplasia
Cleft palate
Hypocalcaemia
resulting from
22q11 deletions.
 Case Study
•  You were given
a cell culture in
the lab and the
d o c t o r
requested that
you identify the
cells as T cells or
B cells.

•  What will you

do?
Electron microscope
B cell
•  Hairy
appearance
because of the
surface
immunoglobulins

•  T cells dont
appear hairy
under EM
 Stages of B cell development
•  Pro – B cell – no significant marker
 Stages of B cell development
•  Pre – B cell – mu heavy chain in cytoplasm
 Stages of B cell development
•  Immature B cell – surface IgM
 Immature B cell = IgM
Mature B cell = IgM and IgD
•  Mature B cell
Bruton tyrosine kinase
X-linked Agammaglobulinemia

• Low levels of all types of

an)bodies
• Recurrent bacterial infec)ons
• Symptoms at 9 mo. to 2 yr of age
• Treat with intravenous
immunoglobulin (IVIG)
Immunoglobulin Levels vs. Age
 CD markers of B cells
•  CD 19
•  CD 20
•  CD 21 - receptor for Epstein Barr virus
What is the results of the following test in
Brutons X-linked Agammaglobulinemia?

•  Electron microscope?
•  CD 19, CD 20 and CD 21 marker?
•  An)body level in the serum?
 Common Variable
Immunodeficiency

•  Failure of the mature B cells to respond

to T cells thus they cannot differen)ate
into plasma cells
What is the results of the following test in
CVID?

•  Electron microscope?
•  CD 19, CD 20 and CD 21 marker?
•  An)body level in the serum?
 T Cell markers
Cluster of Differen)a)on
•  CD2
– Pan-T cell marker (present in all T cells
irregardless of type
–  Form rosette formation with sheep red
cells
–  CELLS plus Sheep red cells = (+)
Agglutination = T cells
–  CELLS plus Sheep red cells = No
agglutination = B cells
 T Cell markers
Cluster of Differen)a)on

•  CD3
– New Pan-T cell marker
–  Involved in the activation of T cells
 T Cell markers
Cluster of Differen)a)on
•  CD4
–  Recognizes Class II MHC
–  T helper and T delayed hypersensitivity

•  CD8
–  Recognizes Class I MHC
–  T cytotoxic
 T cell subsets
•  T helper cells
•  T cytotoxic cells
•  T suppresor
•  T delayed hypersensitivity
 T cell subsets
•  T helper cells – Activates B cells to form plasma
cells and produce antibodies

•  T suppressor – Regulates the function of the other

T cells

•  T cytotoxic cells – kills virally infected cell and

tumor cell upon contact

•  T delayed hypersensitivity – activates and recruits

T cells and macrophage (IFN-gamma) into the
site of infection
 T cell subsets
•  T helper cells – Activates B cells to form plasma
cells and produce antibodies CD2 CD3 CD4

•  T suppressor – Regulates the function of the other

T cells CD2 CD3 CD8

•  T cytotoxic cells – kills virally infected cell and

tumor cell upon contact CD2 CD3 CD8

•  T delayed hypersensitivity – activates and recruits

T cells and macrophage into the site of infection
CD2 CD3 CD4
 Updates!
•  T suppressor was later found out to be CD4 T
cell, and not CD8

•  Thus its name was changed

 New T Cell Subsets
•  T helper 1 -

•  T helper 2 –

•  T helper 3 –

•  T cytotoxic
 New T Cell Subsets
•  T helper 1 - former TdH
–  CD2 CD3 CD4

•  T helper 2 – former Thelper

–  CD2 CD3 CD4

•  T helper 3 – former T Tsuppressor; also known

as T regulatory
–  CD2 CD3 CD4

•  T cytotoxic
Lymphocytes
•  Large Granular
lymphocytes

•  Non-T and Non-B

lymphocytes

•  CD markers: CD16
and CD56
Lymphocytes

•  Provides
nonspecific
immune response
against viruses

•  Kills virally infected

cells upon contact
•  Natural killer
cell will also
destroy virally
infected cell or
tumor cell using
perforin and
granzyme
 Lines of dEfenses
•  First line of defense = prevents entry of
microorganisms

•  Second line of defense = fights off

microorganisms that have evaded the
first line of defense

•  Third line of defense = involves the

activities of T cells and B cells
 First Line of Defense
•  Anatomical
–  Skin
–  Sweat and sebaceous glands
–  Lacrimal glands

•  Chemical
–  HCl in stomach
–  Lactic acid in vagina
–  Lysozymes in tears (can breakdown cell wall)
–  Mucus
–  High salt content of sweat
 First Line of Defense

•  Mechanical
–  Sneezing
–  Coughing
–  Vomiting
–  Urination
–  Defecation
Second line of Defense
Inflamma)on
 Inflamma)on
•  Second line
of defense

•  Localizes
infection to
prevent
spread to
deeper
tissues
 Explana)on
•  Damaged cells synthesize histamine and
prostaglandin
•  In the presence of injury, these chemical
mediators are released into the surrounding
tissue

•  EFFECTS:
–  VASOdilation -> Increased blood flow -> Redness on
the area and heat (RUBOR AND CALOR)
–  Histamine acts on Nerves – PAIN (DOLOR)
–  Increased vascular permeability – LEAKAGE -
>Swelling/ TUMOR
Inflamma)on
Increased blood flow = Increased
blood = Heat and Redness
Increased vascular permeability =
Leakage of fluid = swelling
Histamine on nerves = PaIN
Chemotaxis and Phagocytosis
CHEMOTAXIS – MIGRATION OF WHITE BLOOD CELLS
TOWARDS THE SITE OF INFECTION
Chemotaxis
•  Migration of the white
blood cells from the
blood vessels to the
site of infection

•  4 stages
–  Margination
–  Rolling
–  Adhesion
–  Transmigration/
Diapedesis
Chemotaxis
Chemotaxis
•  Low level of chemotac)c
s)muli (early stage of
infec)on)

1.  WBC marginates

2.  WBC expresses L-
selec)n
3.  Endothelium expresses
E/P-Selec)n

•  L and E selec)n binding is

weak = ROLLING
Chemotaxis
•  Higher levels of
chemotac)c s)muli

1.  WBC expresses

integrin

2.  Endothelium
expresses ICAM
Phagocytosis
Neutrophils die ager 6-7 hours oa
ac)va)on
 Leukocyte Adhesion defect
•  Absence of Integrin (type 1)
•  Absence of L-Selec)n (type 2)
Phagocytosis
Steps in phagocytosis
 Chediak-Higashi Syndrome
•  Absence of LYST protein (lysosomal trafficking
proteins) which aid in the fusion of lysosome and
phagosome to form phagolysosome.

•  LYST protein is also important in transfer of melanin

from melanocytes to kera)nocytes = albinism
Chediak Higashi
Trivia: What is the bacteria ingested
were Aerobic???
Aerobic bacteria killing
 CGD
•  is a diverse group of hereditary diseases in
which certain cells of the immune
system have difficulty forming the
reac)ve oxygen compounds
•  most importantly the superoxide radical due
to defec)ve phagocyte NADPH oxidase used
to kill certain ingested pathogens
 What is PAMP?

•  Pathogen-Associated Molecular Pakern

•  – substances present in bacteria but not
present in human hosts
•  -detected by phagocytes to iden)fy self from
nonself

•  cell wall, capsule, lipopolysaccharide

Phagocytosis
 Opsoniza)on
•  Process of coating an antigen to facilitate
phagocytosis
–  OPSONINS
•  IgG
•  C3b
•  C- reactive protein
Interferon
 Interferons and types
•  Interferon – alpha - produced by
white blood cells
•  Interferon – beta – produced by
fiBroBlasts

•  Both interferon- alpha and beta are

called type 1 interferons
–  Have antiviral activities
 Interferons and types
•  Interferon – gamma – produced by T
delayed hypersensitivity cells which
recruits other T cells and macrophages

•  Interferon gamma is type 2 interferon

–  No antiviral activities
Fever
Fever (IL-1, IL-6 and TNF)
 Acute phase reactants
•  Proteins produced by the liver in acute
stages of infection
•  In response to IL-1 IL-6 and TNF

•  Examples
–  Lactoferrin – transports iron away from
bacteria
–  Alpha-1 antitrypsin
–  Ceruloplasmin – transports copper
–  CRP - opsonin
 Characteristics of Specific
immunity
1. SPECIFICITY – targets
specific antigens
2. Diversity – for every
antigen, there is a
corresponding
specific T and B cells
3. Memory –
remembers
encountered antigen
4. Can recognize self
from nonself
Primary versus Secondary Immune
response
Primary versus Secondary Immune
response
 Primary versus Secondary
•  Longer lag period?
•  Higher antibody level?
•  Mediated by memory cells
•  More of IgG than IgM