Basic concepts in immunology

Evy Sulistyoningrum

Outlines

Introduction
Immune system & components
Immune response
Immunological regulation
Immunity
Immunological memory
Defects in immunity

Introduction
Immunology: the study of the bodys defense
against infection
To protect individual from infectious agents and
damage they cause

History of Immunology
Edward Jenner discovered in 1796 that cowpox, or vaccinia, induced protection
against human smallpox vaccination

The eradication of smallpox by vaccination.

After a period of 3 years in which no cases of
smallpox were recorded, the World Health
Organization was able to announce in 1979
that smallpox had been eradicated.

History of Immunology

Louis Pasteur (18221895) devised a

Robert Koch (18431910) proved

that infectious diseases are

caused by microorganisms

vaccine against cholera in

chickens, and developed a rabies
vaccine that proved a success
upon its first trial in a boy bitten
by a rabid dog

Shibasaburo Kitasato (18921931) in

collaboration with Emil von Behring (1854
1917) discovered specific antitoxin activity
against tetanus and diphtheria in serum

Elie Metchnikoff (1845

1916) :central role of
phagocytes in host
defense.

Immune system
Variety of organs, tissues, cells, molecules that
performed immune response and produce immunity
Cellular components
Immune cells
Lymphoid tissue or organs
Humoral components
Soluble protein: complements, antibody
Physical, mechanical, chemical barriers
Non-immune system inherent component
Performed by other structure not specific to immune
system but acts as first line defense againts pathogen

Immune system: barrier

Cells of the immune system

Origin: Pluripotential hematopoietic stem cells

Located within the bone marrow, fetal liver and yolk
sac of the fetus
Stem cells differentiate into 2 types of committed
stem cells
produce platelets, erythrocytes (red blood cells),
monocytes or granulocytes (myeloid progenitor)
produces cells of the lymphoid line (lymphoid
progenitor)

Myeloid cells

Lymphocytes
3 subsets :
B lymphocytes
T lymphocytes
NK cell

Functions:
B & T cell : adaptive immune response
NK cell : innate immune response

Distributions:
Circulation
Lymphoid organs

T Lymphocytes (T cells)

Derived from stem cells in the bone marrow.

Leave bone marrow and travel to the Thymus to mature
Have T Cell Receptor (CD3)
Can be found in circulation and lymphoid tissues
Approximately 75 to 80% of lymphocytes are T cells
Subsets:

Th : helper
Tc : killer
Tsup : suppressor
Treg: regulator

B lymphocytes (B cells)
Derived from stem cells and become mature in the
Bone marrow in human / Bursa of fabricius in birds
Have BCR (B cell receptor) (CD19/CD20)
Can be found in circulation and lymphoid tissues
Transform into plasma cells and produce
antibodies (immunoglobulins)
Undergo a process called clonal expansion

NK cells

Derived from stem cells in the bone marrow

Circulate in the blood
No TCR and BCR null cell
Large cells, contain cytolytic granules kill cell targets
Important in the defense from certain tumor cell and
from virally infected cells.
Innate immune response
Act without prior activation

Reticuloendothelial System

Tissue and organs of the immune system

Lymphocytes are
produced in bone marrow
Mature in the bone
marrow and thymus
(primary /central
lymphoid organs) =>
mature naive lymphocyte
Congregate in lymphoid
tissues throughout the
body to be exposured by
antigen
(secondary/ peripheral
lymphoid organs)

Tissue and organs of the immune system

Circulation

Primary lymphoid organs: development & maturation

Bone marrow: B cell maturation

Primary lymphoid organs: development & maturation

Thymus: T cell maturation

Secondary lymphoid organs: antigen processing

Lymph node

Circulating lymphocytes encounter antigen in peripheral lymphoid organs

(lymph node, spleen, Mucosal-Associated Lymphoid Tissue)

Secondary lymphoid organs: antigen processing

Spleen

Circulating lymphocytes encounter antigen in peripheral lymphoid organs

(lymph node, spleen, Mucosal-Associated Lymphoid Tissue)

Secondary lymphoid organs: antigen processing

MALT

Circulating lymphocytes encounter antigen in peripheral lymphoid organs

(lymph node, spleen, Mucosal-Associated Lymphoid Tissue)

Humoral component
Plasma soluble protein
Complement system
Protein secreted by cells, complementary effect to antibody
Natural immune response
Acute phase protein
Protein secreted by cells, released due to immune response in early
phase
Natural immune response
Antibody
Secreted by plasma cells, bind to antigen, first known has protective
effect, various mechanism
Adaptive immune response
Cytokine
Soluble protein regulating other cells activity
Natural & Adaptive immune response

Immune response
Response against pathogen infection
Distinguish self vs non-self
Resulted in immunity (an immune condition)
Classification :
Innate immune response
Adaptive immune response

Immune response
4 main tasks:

Immunological recognition
Immune effector function
Immune regulation
Immunological memory only in adaptive immune response

Innate vs Adaptive
Innate/Natural/Native

Adaptive /Acquired

Time

Immediate (0-4 hours)

Delayed (>96 hours)

Specificity

Non-specific : Certain
structure of all pathogens

Specific : Specific parts of

the specific pathogen
(antigen)

Diversity

Limited

Large range

Memory

(-)

(+)

Cellular &
chemical barriers

Skin, mucosal epithelia,

Antimicrobial chemicals

Lymphocytes in epithelia,
antibodies in epithelial
surfaces

Humoral

Complements, acute phase

protein, cytokines

Antibodies , cytokines

Cellular

Phagocytes, NK cell

Lymphocytes (B & T)

Characteristics

Components

Innate & adaptive immune response

Innate immunity

May prevent
establishment of
infection?

Immunological recognition
Innate
PAMPS (Pathogenassociated molecular
patterns)
Certain sugar residue
Anionic polymers
LPS

PRR (Pattern recognition

receptors)
MBL
Macrophage mannose receptor
TLRs, etc

Adaptive
Antigen: specific part of the
specific pathogen with
epitope (special site that
can bound to its specific
receptor)
Antigen receptors
T cell receptor
MHC molecules

B cell receptor

Examples of PRR: TLRs

Antigen recognition by lymphocytes

Immunological effector phase

Actions of immune system to combat pathogen
elimination of pathogen
Innate effector actions
Phagocytosis or other killing mechanisms
Inflammatory reactions
Cytokines release

Adaptive effector actions

T cell : Cellular-mediated mechanism
B cell :Antibody-mediated mechanism humoral
Cytokines release

Immunological regulation
Ability of immune system to self regulate
Mantain adequate response to dangerous agent & prevent
excessive response that can damage the body
Failure in regultion: autoimmunity, allergy
T reg: regulatory T cell
Produce cytokines that regulate development & activity of
other cells

Immunological regulation

Immunological regulation

Immunological memory
Specific feature of adaptive immune response
Protective immunity against reinfection against the same
pathogen
Memory cells
Memory-associated immune response classification:
Primary immune response
Secondary immune response

Immunological memory

Application of Immunological
Memory
Immunization
Introduction of a pathogen, which allows are
body to do its primary immune response without
the risk of actual sickness
Active immunization
Passive immunization
Result in immunity of an immune person

Interaction between innate &

adaptive immune response
Infectious pathogen
Mechanical barriers
Tissue resident cells pathogen
Elimination of pathogen
Inflammatory reaction
Chemokine & cytokine
Complement system
Inflammatory cells

Induction adaptive immune response

Activation of adaptive immune response
Effector phase of adaptive immune response

Recognition by innate
immune system
PAMPs - PRRs
Activation of cells in innate
immunne response
Pathogen killing
Release of cytokine &
chemokine
Inflammatory process

Activation of complement
system
Release of Acute Phase
Protein

Phagocytosis
Engulfing activity digestion
Large particles, ex: bacteria
Performed by phagocytes
Macrophage
Neutrophil, eosinophil (little effect)

Receptor Ligand
Engulfing phagosome formation fuse with lysosome
Digestion mechanism:
O2 dependent
O2 independent

Opsonization by opsonins

Phagocytes

Phagocytosis

NK cell killing
Killing mechanism performed by NK cell
Viruses, tumor cell, intracellular bacteria
Recognition by NK cell
Activating (NKARs) & inhibitory receptors (NKIRs)

Release granules that kills pathogen

Perforin
Granzymes
Granulysin

(= Tcytotoxic cell)
Induce apoptosis of cell targets
ADCC

NK cell

NK cell

Inflammatory process

Inflammation
Cardinal signs of inflammation
Rubor
Kalor
Tumor
Dolor
Functiolaesa
Organ + -itis

Leucocyte migration to infection site: role of

chemokine & cellular adhesion molecules

Cell lysis by complement system

MAC = Membrane attack complex
Formation of a hole in the membrane cell lysis

Complement-Mediated Lysis of E. coli

Adaptive immune response

Feature

Functional significance

Specificity

Ensures distinct antigens elicit specific

response

Diversity

Enables immune system to respond to a large

variety of antigens

Memory

Lead to enhanced responses to repeated

exposures to same antigens

Clonal expansion

Increases number of antigen-specific

lymphocytes

Specialization

General responses that are optimal for defense

against different pathogens

Contraction and
homeostasis

Allows immune system to respond to newly

encountered antigens

Adaptive immune response

APC: Process & presents antigen to lymphocytes in
secondary lymphoid organs
T cell activation
B cell activation
Proliferation Differentiation into effector cell
Cellular mechanism
Humoral mechanism

Immunological memory

Induction of adaptive response

Activation of specialized
antigen-presenting cells
(APC) is a necessary first
step for induction of
adaptive immunity

Induction of adaptive response

Antigen recognition
Antigen: substances that specificly bound to lymphocytes
Recognized by:
Antibody/B cell receptor
T cell receptor
Major histocompatibility Complex (MHC)

T cell & B cell activation

Proliferation & Differentiation of T

cell & B cell
Active lymphocyte Lymphoblast
T cell differentiation effector T cell
Th cell ( CD4+)
Tc cell : CTLs (CD8+)

Proliferate in T cell region of 2nd lymphoid organs

B cell differentiation
Naive B cell plasma cell (producing antibody)

B cell proliferation:
B cell region of 2nd lymphoid organs

Effector B & T cell exits from 2nd lymphoid organs

Effector mechanism of adaptive

components
Humoral
B cell antibody producing plasma cell
Neutralization
Opsonization
Complement activation
ADCC
Cellular
T cell
T cytotoxic/cytolitic : Destroy target cells
T helper:
Activate macrophages
Induce formation of cytotoxic T cells
Stimulate B cells to produce antibodies.

Summary
Innate immunity
Pathogen recognition non specific effector &
inflammation elimination of pathogen

Antigen Presenting Cells (APC)

Antigen processing and presentation

Adaptive immunity
Antigen recognition activation of T & B cell specific
effector cells elimination of pathogen memory

Stop press

Active immunity vs passive immunity

Active Immunity
Body produce antibodies after
exposed to the antigen in the
past either through:
- Exposure to the actual
disease
- Planned exposure to a
form of the antigen that
has been killed or
weakened
(immunization/vaccinatio
n)

How long does active immunity

last?
Depends on the antigen
Some pathogen develop
new forms of antigen body
doesnt recognize annual
immunization
Some pathogen only induce
low level of immunity
booster/repeated
immunization
Last for a lifetime

Passive Immunity
Body doesnt produce
the antibodies
A mother will pass
immunities on to her baby
during pregnancy
Antibodies will protect the
baby for a short period of
time
Lasts until antibodies die
Why doesnt the mother just
pass on the WBCs that
remember the antigens?

Stop press 2
CD molecules

CD (cluster of differentiation/cluster designation)

molecules

Surface markers
Indicate: functional properties, maturation stage, and
lineage identity
Detected by panel of monoclonal antibodies:
well documented: CD1 CD247
examples:
- CD4+: TH; CD8+: CTL (cytolytic T lymphocyte)
- CD19+: B cell
- CD56+: NK cell; CD16+ Fcg receptor on NK cell
- CD14+: macrophage

CD molecules on B cell

CD molecules on T cell

Defects in immune system

Immune Disorders
~Hipersensitivites or Allergies~
- Immune system mistakenly
recognizes harmless foreign
particles as serious threats
- Launches immune response,
which causes allergic
symptoms
- Anti-histamines block effect of
histamines and bring relief to
allergy sufferers

Aquired Immune Deficiency Syndrome

Caused by the Human
Immunodeficiency Virus
Specifically targets and kills Tcells
- The HIV virus lowered immune
system
- With immune system shutted
down, common diseases that
immune system normally could
defeat become life-threatening
- No symptoms for several
months all the way up to 10
years

AIDS
Transmitted
by sexual
contact, blood
transfusions,
contaminated
needles
As of 2007, it
affects an
estimated 33.2
million people

Thank you very much.

References

Murphy K, Travers P, Walport M, Janeways

Immunobiology, 7th ed
Abbas AK dan Lichtman AH, Pillai S, Cellular &
Molecular Immnunology, 6th ed
Roitt, IM., Delves, PJ, Roitts Essential Immunology
Burmester, Colour Atlas of Immunology