IMMUNITY

Immunity: Ability of an organism to recognize and

defend itself against specific pathogens or antigens.

Immune Response: Third line of defense. Involves

production of antibodies and generation of
specialized lymphocytes against specific antigens.
 History of Medicine
The Nobel Prize in
Physiology or Medicine
1908

•Pioneer in using dyes

•Distinguished types of WBC
using stains.
•Red cell changes in various
diseases
•Laid foundations of cyto
chemistry, chemotherapy
Father of Immunology immunology
HUMORAL IMMUNITY •Coined the term Complement
system
 History of Medicine
FATHER OF NATURAL IMMUNITY

The Nobel Prize in Physiology

or Medicine 1908

•Described Phagocytosis
•Diapedesis
•Theory of cellular immunity
Elie Metchnikov
1845 - 1916. Russian biologist
The Immune System is the Third Line of
Defense Against Infection

DISEASE
Neutrophil
Marcophages
 IMMUNITY

Innate Acquired

Passive Active

Passive Natural Passive Artificial Active

IgG antibodies – Serum with Active
via placenta to antibodies
Natural
Clinical disease Artificial
fetus Injection of Vaccines
activated Sub clinical
Antibodies thro Toxoids
lymphocytes infection
colostrum
 Protects body from all
types of disease causing
Innate Immunity organisms

• Inherent & Non specific, present in all the subject ,from birth
• Physical barrier – skin, cilia
• Chemical barrier- sweat, sebum, wax, lysozymes
• Reflex mechanisms – cough, sneeze
• Secretions – Saliva, gastric juice, intestinal juices
• GIT flora
• Microphages and Macrophages
• Natural killer cells- by directly attacking them
• Complement complexes – facilitate phagocytosis
NATURAL KILLER CELLS

•Large granular Non T, Non B

lymphocyte cells.

•NK cells releases lethal

substances into the infected
target cell and leads to death of
the cell

•Prevents multiplication of
virus in the cell
Acquired Immunity
Immunity that an organism develops during lifetime.
• Not genetically determined.
• May be acquired naturally or artificially.
• Development of immunity to measles in response to
infection or vaccination.
Types of Acquired Immunity

Naturally Acquired Immunity:

Obtained in the course of daily life

Artificially Acquired Immunity:

Obtained by receiving a vaccine or immune serum.
 Types of Naturally Acquired Immunity
Naturally Acqd Active Immunity

• Antigens or pathogens enter

body naturally
• Body generates an immune
response to antigens
Immunity may be
• lifelong (chickenpox or
mumps)
• temporary (influenza or
intestinal infections)
 Types of Naturally Acquired Immunity
Naturally Acquired Passive immunity:

• Antibodies pass from mother to fetus

via placenta or breast feeding
(colostrum)
• No immune response to antigens
• Immunity is usually short-lived (weeks
to months)
• Protection until child’s immune system
develops
 Types of Artificially Acquired Immunity
Artificially Acquired Active Immunity:

• Antigens are introduced in

vaccines (immunization)
• Body generates an immune
response to antigens
Immunity can be
• lifelong (oral polio vaccine)
• temporary (tetanus toxoid)
 Types of Artificially Acquired Immunity
Artificially Acquired Passive Immunity

▪ Preformed antibodies (antiserum)

are introduced into body by
injection
▪ Snake antivenom injection from
horses or rabbits

• Immunity is short lived (half life

three weeks)
• Host immune system does not
respond to antigens
 Development of acquired immunity
• some lymphocyte
• During fetal life stage precursors –remain in BM
• some lymphocyte or reach spleen & liver
precursors –reach ---
thymus –where they
processed in to ‘’T ‘’ • Where they processed in to
Lymphocytes----’’CELL ‘’B ‘’ Lymphocytes----
MEDIATED IMMUNITY’’ ’’HUMORAL MEDIATED
IMMUNITY’’
 Types of Naturally Acquired Immunity

• Cellular Immunity or Cell mediated

immunity: by T cells
• 70% of Lymphocytes

• Humoral Immunity: by B cells through

antibodies
• 25-30% of Lymphocytes
 Antigens
Most are proteins or large polysaccharides from a
foreign organism.
• Microbes: Capsules, cell walls, toxins, viral
capsids, flagella, etc.
• Nonmicrobes: Pollen, egg white , RBC surface
molecules, serum proteins & surface molecules
from transplanted tissue
Lipids & nucleic acids are only antigenic when
combined with proteins or polysaccharides.
Molecular weight of 10,000 or higher.
 Hapten & Epitope
Hapten
➢ Small foreign molecule that is not antigenic
➢ Must be coupled to a carrier molecule to be
antigenic
➢Once antibodies are formed they will
recognize hapten
Epitope
➢Small part of an antigen that interacts with
an antibody
➢Any given antigen may have several
epitopes
➢Each epitope is recognized by a different
antibody.
Epitopes: Antigen Regions that Interact with
Antibodies
 Antibodies
Proteins that recognize and bind to a particular
antigen with very high specificity
Made in response to exposure to the antigen

One virus or microbe may have several antigenic

determinant sites, to which different antibodies may
bind

Each antibody has at least two identical sites that

bind antigen: Antigen binding sites
Belong to a group of serum proteins (20% of plasma
proteins) – glycoproteins called globulins called
immunoglobulins (Igs)
 Antibody Structure
• Y shaped proteins
• 2 heavy chains, 2 light chains- joined by S-S bridges
• Fab: antigen-binding fragment
• Fc: constant fragment, determines “class”
Antibody Classes
• IgG - 75%, Secondary response
Based on heavy chains
• IgM - Primary antibody response antibodies are classified
into 5 different types
• IgA - Secretory: saliva, tears

• IgD - Cell-surface receptor on B lymphocytes GENERAL

IS MADE
• IgE - Allergic responses
 Both heavy & light chains are divided into 2
regions • 2. variable region :
• This region enables antibody
• 1. constant region : to recognize the specific
• Identification & functions of antigen & to bind itself with
different types of the antigen –”antigen binding
immunoglobulins depends on region” - Fab
constant region

• This region has complement &

macrophage binding sites
 Immunoglobulin Classes - G, M, A, D,E
I. IgG II. IgM III. IgA
Structure: Monomer Structure: Pentamer Structure: Dimer
% serum antibodies: 80% % serum antibodies:5-
10% Percentage serum
Location: Blood, lymph, antibodies: 10-15%
intestine (except CSF) Location: Blood, lymph,
B cell surface
Functions: Enhances (monomer) Location: Secretions
phagocytosis, neutralizes (tears, saliva, intestine,
toxins and viruses, Functions: First
antibodies produced milk), blood and lymph.
protects fetus and
newborn. during an infection.
Blood group A& B Functions: Localized
Protects body from viral & protection of mucosal
bacterial infection antibodies belong to
this group surfaces. Provides
‘’Watch guard for all body immunity to infant GI
fluids’’ ‘’Protector of blood
stream’’ tract.
 Immunoglobulin Classes
IV. IgD
V. IgE
Structure: Monomer Structure: Monomer

Percentage serum antibodies: Percentage serum

0.2% antibodies: 0.002%
Location: B-cell surface, blood, Location: Bound to mast
and lymph
cells and basophils.(cause
Known Functions: In serum release of histamine &
function is unknown. On B cell heparin, SRS-A etc)
surface, initiate immune
response. (help them in
recognizing – antigen) Known Functions: Allergic
reactions. Possibly lysis of
 • 1. Macrophage
• Antibodies bound to the
antigen on microbial • 2. complement system
surface do not directly kill • 3. NK cells
the microbe but
Connect the microbe to the
killing mechanism
• Via these 3 mechanism –
antibody destroy invading
foreign microbes
How Do B Cells Produce Antibodies?
• B cells develop from stem cells in the bone marrow of adults
(liver of fetus).
• 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.
Clonal Selection of B Cells is Caused by
Antigenic Stimulation
 Link to step
through of this
diagram

An activated B cell proliferatesafter stimulation by cytokines released by helper T cells. The B cell’s clone enlarges.
Some cells of the clone give rise to anti-body-secreting plasma cells and others to dormant memory cells.
 HUMORAL IMMUNITY
• Relating to body fluids
• Acting against extracellular pathogens which are
present in the body fluids

• Mediated by antibodies
• Antibody mediated immunity
• Antibodies are produced by plasma cells (derived
from B lymphocyte)
Mechanism of activation of B lymphocyte
• Take place in lymph node or • 1. bacterial antigen – direct
spleen effect
• When bacteria reach these • 2. activated ‘T’ helper cells
places – TH2 cells
• B lymphocyte interacts with • 3. macrophage(Act as APC)
3 structures with processed antigen
• 4. IL- Produced by
macrophage
Antigen processing & presentation
Mechanism of humoral immunity
Activation of humoral immunity
 Macrophage acting as an APC
Presents to processed antigen –complexed with MHC-2
proteins
Secretes IL-1

Act on both B cells & T helper cells (TH2) --& Activate them

T helper cells – multiply in numbers & secrete – IL -2,4,&5

IL -2,4,&5 –Causes proliferation & differentiation of –B cells
IL -2 – act on itself & enhance its multiplication
IL-1 from APC & 4,&5 from T helper cells (TH2) act as co
stimulants for B cells
B cells – multiply & increase in numbers – some of them
transformed into
Plasma cells – start producing specific antibodies
Some become memory cells – respond faster to an antigen that appears @
future time
• Plasma cell: • Memory cell:
• Present in BM & medullary cord • Respond rapidly when the
of lymphoid tissue antigen reappears at a
• Life span – 2- 3 days future time
• Produce specific antibodies
against invading organisms • Initiates production of
antibodies without wasting
time
• Memory cells survive for
longer periods–
responsible for permanent
immunity
Primary Response
• Antibody production on 1st
exposure ---very much less
& short lived

• Slow rise in antibody titre

• IgM & IgG followed by
gradual decline
secondary Response
• Subsequent exposure will
produce an amplified &
long lasting response

• Antibody produced have a

higher time & have more
affinity to the antigen &
last longer
• ‘’Principle for booster
doses’’
 Consequences of Antigen-Antibody Binding
Attack phase

Direct Actions Indirect actions – by activation of

complement
Agglutination Opsonization & Phagocytosis

Precipitation Lysis by perforins

Neutralization Chemotaxis

Lysis Activation of mast cell, basophils

Inflammation
 Consequences of Antigen-Antibody Binding

Antigen-Antibody Complex: Formed

when an antibody binds to an antigen it
recognizes.

➢Agglutination: Antibodies cause  phagocytosis &

antigens to clump together.  the no. of infectious units

➢ Opsonization: Antigen is covered

with antibodies that enhances its
ingestion and lysis by phagocytic cells.

Coating Ag with Ab  phagocytosis

Consequences of Antigen-Antibody Binding

➢Neutralization: Binding to the surface and

neutralize toxins by blocking their active sites.

➢Complement Activation: Both IgG and IgM

trigger the complement system which results
in cell lysis and inflammation.

➢ Antibody-dependent cell-mediated
cytotoxicity:
Target organism is coated with antibodies
and bombarded with chemicals from
nonspecific immune cells. [Used to destroy
large organisms (e.g.: worms)]
Consequences of Antibody Binding
 COMPLEMENT SYSTEM

• 20 proteins present in blood – • 11 proteins

that constitute complement • C1 to c9
system
• 3 form – C1q, C1r, C1s,
• (Complement the effect of
antibodies in destroying antigen)
• Other factor B,D,P (
PROPERDIN)
• H&I
• Complement system consist of 3 units

• C1 q,r,s ---comprise the Recognition unit

• C2,3,4 ---- activation unit
• C5 –C9 –forms---- membrane attack complex
(MAC)
Complement pathways:

•Classical Pathway – gets

activated by antigen- antibody
complex

•Alternate Pathway – gets

activated by endotoxin etc

•Once activated the terminal

components helps in host
defense mechanism
 • Function
• Activates B cell –facilitates –
• Lectin pathway : humoral immunity
• Initiated by binding of • By activating B cells –
mannose binding lectin to a complement system serve
polysaccharide on the as link B/W innate &
surface of pathogen acquired immunity
• Following apoptosis , helps
• Activates C2 –C9 in disposing the debris
 Cell Mediated Immunity
- T Lymphocytes

Defense against:
•Bacteria & viruses that are
inside host cells & are
inaccessible to antibodies.
•Fungi, protozoa & helminths
•Cancer cells
•Transplanted tissue
 Types of T cells

• Helper T cells (TH) (CD4)

• Cytotoxic T cells (TC) (T Killer- CD8)
• Memory T cells
• T suppressor cells (CD8)

• CD --- Cluster differentiation glycoprotein

Located on ---membrane of the
“T’ cell
 Major histocompatibility
complex:
• CD4 + T LYMPHOCYTE • 2 Types of MHC
• CD8 + T LYMPHOCYTE • MHC –I ---Presents antigen to CD8
(Tc) + T LYMPHOCYTE
• MHC –I – present in all the cells
(except RBC)
MHC restriction
Tc binds to antigens complexes • MHC –II Presents antigen to CD4
with class I MHC (TH) + T LYMPHOCYTE
TH binds to antigens complexes
• MHC –II – present in IMMUNE
with class II MHC SYSTEM (APC , eg: Dendritic cell)
 Activation of helper T cell (CD4) Or T4 cells
• T helper cells ----activated --- lymph
node / spleen • B cell can also –act as an
APC to “T” helper
• Macrophage –acting as APC • Entire antigen is not
• Activates ‘’T’’ helper in 2 ways presented, only –fragments
of antigen
• 1. by presenting the antigen
complexed with MHC class II
protein
• 2.Stimulus by secreting IL-1
Mechanism of response of T
helper cells to an antigen
Antigenic part complexed with MHC C-II
protein

Presented –to – T helper cell

T helper cell recognize MHC C-II protein
& gets activated
Activated T cells ---secrete IL-2--- Autocrine
effect --- stimulate its own multiplication
2 classes of helper T cells are formed – TH1 &
TH2
TH1 – Secretes IL-2, Interferon gamma & TNF
–Beta
Participate in cellular immunity, these factor +
multiplication
 & activity of cytotoxic T cells & T
suppressor cells
++++ activity of NK cells & macrophages

, Interferon gamma – directly kills antigen bearing cells ( viral

infected cells & cancer cells)

Role of TH2 cells – 1. concerned with proliferation,

activation, & maturation of B lymphocytes

++++ multiplication of plasma cells & production

of antibodies by plasma cells
T Cells Only Recognize Antigen Associated with MHC
Molecules on Cell Surfaces
Mechanism of activation of MECHANISM OF ACTIVATION OF CYTOTOXIC
cytotoxic cells
CELLS (CD8)
All nucleated cells –bearing MHC C-I protein –
on their plasma membranes can act as APC
Virus infected cells, cancerous cells & foreign
graft cells ---produce—abnormal proteins --
which act as an antigens
Peptide fragments of these antigens
complexed with MHC C –I protein
Cytotoxic T cells (CD 8) -- recognize this
complex & get activated

Activation of cytotoxic T cells also requires IL-

2 produced by T helper cells
 FUNCTION OF CYTOTOXIC T CELLS: (TC)

Activated CYTOTOXIC T CELLS – release –perforin & Lymphotoxin --- they destroy ---virus
infected cells, cancerous cells, & foreign grafted cells

Perforin: forms –holes in plasma membrane of the target cell

Which allow –ECF– to flow in & the cell dies

Lymphotoxin --- activates –damaging enzymes with in target cell

Destroy – DNA ----Cell dies

They also release gamma interferon & They also Destroy –
macrophage migration inhibition factor –which bacteria directly by
attract the macrophages --- increase phagocytic releasing cytotoxic
activity substances
Cytotoxic T Cells Lyse Infected Cells
Activation of cellular
immunity
 • 3. prevent autoimmunity
T SUPPRESSOR CELL • 4. promote immune tolerance
• 5. suppress antibody
• Activation of T SUPPRESSOR production by B cell
CELLS is very similar to Cytotoxic • 6. supress cytotoxic & helper T
cell activity
T cells
• When cytotoxic T cell over
activated they cant
differentiate normal & foreign
• FUNCTIONS: cells , so they start killing
normal cells also
• 1. Inhibit proliferation of B & T
cells
• To prevent that --- suppressor T
• 2. Dampen the immune cells are activated it will
response by producing cytokines suppress the activity of
cytotoxic T CELL
Forms 15% of total lymphatic population

Present in spleen, lymph nodes, bonemarrow, & blood

Participate in non specific immunity

NK cells – activated by IL-2, & Interferon Gamma,

secreted by T helper cells
FUNCTIONS: NK cells attack virus infected cells,
tumour cells & other abnormal & foreign cells &
destroy them
Destroy protozoa & bacteria

Role in haemopoiesis through cytokines released by

them
• Delayed Hypersensitivity T (TD) Cells:

• Mostly T helper and a few cytotoxic T cells that are involved

in some allergic reactions and rejection of transplanted
tissue.
 IMMUNE DISORDERS
• B LYMPHOCYTE DEFICIENCY – HUMOURAL IMMUNITY DEFICIENT
• MENINGITIS, RTI, PNEUMONIA

• B LYMPHOCYTE PROLIFERATION – MULTIPLE MYELOMA, INCREASE

–PLASMA CELLS

• T LYMPHOCYTE DEFICIENCY –CELL MEDIATED IMMUNITY DEFICIENT

• DIGEORGES SYNDROME
• AIDS
• AUTOIMMUNE DISEASES

• MYASTHENIA GRAVIS
• RHEUMATIC FEVER
• RHEUMATOID ARTHRITIS
• GRAVES DISEASE
• MULTIPLE SCLEROSIS
• GLOMERULONEPHRITIS
• PERINICIOUS ANEMIA
• IMMUNO INFLAMMATORY DISEASE- HYPERSENSITIVE
REACTIONS –BA, HAY FEVER, ALLERGIC RHINITIS

• SEVERE COMBIND IMMUNODEFICIENCY DISEASE – B & T

• PHAGOCYTIC DISORDER
• APPLICATIONS

• DIAGNOSIS –PREGNANCY
• HORMONAL ASSAY
• VACCINES – IMMUNIZE A PERSON AGAINST SPECIFIC PATHOGEN

• TISSUE GRAFTING & TRANSPLANTATION