Adaptive Immunity

Adaptive immunity:
second line of response
 Based upon resistance acquired during life
 comes into action after innate immunity fails to get
rid of
microbe
 Relies on genetic events and cellular growth
 Responds more slowly, over few days

Three major functions

 Recognize nonself
 Respond to nonself
 Remember nonself
 Four Characteristics of Adaptive
(Specific) Immunity
• Discrimination between self and non-self
 usually responds selectively to non-self, producing
specific responses against the stimulus
• Diversity
 generates enormous diversity of molecules
• Specificity
 can be directed against one specific pathogen or
foreign
substance among trillions
• Memory
 response to a second exposure to a pathogen is so
fast that there is no noticeable pathogenesis
 Adaptive Immunity
The resistance that an
individual acquires
during life

Active Immunity Passive Immunity

Resistance developed as a Resistance transmitted
result of antigenic stimulus passively in ready made form

Artificial
Natural acquired
active Artificial Natural
active passive
immunity passive
immunity
immunity immunity
Type of specific Preformed
(vaccination Transfer of antibodies or
immunity a host antibodies,
) lymphocytes
develops after e.g., mother
exposure to Intentional produced by
to fetus one host are
foreign exposure to a
foreign across introduced
substance
material into another
host
 Adaptive Immunity
Active immunity Passive immunity
Produced actively by host Immunoglobulins received
immune system passively

Induced by Acquired by-

 clinical, sub-clinical  Mother to fetus IgG
Infection (natural) transfer, breast milk,
 Vaccination (artificial) (natural)
Live, killed, purified  Readymade antibody
antigen vaccine transfer immune serum,
immune cells (artificial)

Long lasting Lasts for short time

Types of Adaptive(Acquired )
 Adaptive immunity: mechanisms
▶ Cell-mediated immune response (CMIR)
 Mediated by T cells via:
 Direct lysis of target (infected) cells
 Production of cytokines that activate infected cells to kill
pathogens
• Eliminate intracellular microbes that survive
within phagocytes or other infected cells
▶ Humoral immune response (HIR)
• Mediated by antibodies produced by B cells
 Antibodies bind to whole or fractions of antigens outside
cells
• Eliminate extra-cellular microbes and
their toxins
Lymphocyte
Formation
 Spleen

 From arteriol
central blood vessels
smaller e
fan
out, eventual
terminating lyin a
specialized --
zone
perifollicular zone
(PFZ),

 Cells and antigen then

pass into the white
spaces
pulp th
through open
in
blood-filled e
perifollicular zone
.
Lymph
Node

@ Janeway's
Lymphocytes in the blood enter lymphoid tissue

CCR
7

▶ Lymphocytes in the blood enter lymphoid tissue by crossing the walls of high
endothelial
venules.
▶ Binding of L-selectin on the lymphocyte to sulfated carbohydrates of
GlyCAM-1 and CD34 on the HEV.
▶ Local chemokines such as CCL21 bound to a proteoglycan matrix on the HEV
surface
stimulate chemokine receptors on the T cell, leading to the activation of LFA-1.
Cell-mediated immune response
T-cell
 recognizes peptide antigen on
(macrophage)APC in
association with major histo-
compatibility complex (MHC)
class
 distinguish self from non-self
 antigens
T cells with CD4 molecule
are restricted to
antigen bound recognizing to
MHC molecules, class II
T cells expressing CD8
are restricted to recognition
of antigen bound to class I MHC
molecules.

T-cell goes into effectors cells

stage that is able to kill
infected cells
Once a TCR
engages MHC-peptide on the Schematic of T-cell receptor
surface of an APC, the signaling.
co-receptor CD4 or
CD8 steps in
to stabilize interaction
 The tyrosine kinases Lck
and ZAP-70 initiate
 TCR signaling
 And
phosphorylate(ITAMs)
CD3 tail as well as
adapter molecules LAT
and SLP-76.

 Phosphorylation generates
docking sites for the
assembly and organization
of signaling molecules,
 which lead to the
activation of
transcription
factors.
Activation of a naïve T cell in the secondary lymphoid tissues
results in the generation of effector and memory T cells
 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
 T lymphocytes
 Once T cells activated they proliferate into effector
cells and memory cells
 2 types cells
 Helper T- lymphocytes (CD4+)
 Cytotoxic T-lymphocyte (CD8+)
 Helper T- lymphocytes (CD4+)
 CD4 T cells differentiate into several subsets of effector T cells
with a
variety of different functions.
 Main functional classes
 TH1
 TH2,
 TH17,
 TH9
 TH22
 T follicular helper cell(T )
 T Helper Cells
• TH1 cells
 promote cytotoxic T cell activity and activate
macrophages
 mediate inflammation and delayed
hypersensitivity by producing a specific set of
cytokines
 IL-2, IFN-γ, tumor necrosis factor (TNF)-β

• TH2 cells
 stimulate antibody responses and defend
against helminth parasites
 involved in promoting allergic reactions
 produce a specific set of cytokines 2
6
 T Helper Cells
TH9cells
 Protects against extracellular
pathogensInvolved in mucosal
autoimmunity
 Producing a specific set of cytokines--- IL-9

TH17cells
• Protects against fungal and extracellular
bacterial infections
• Contributes to inflammation, autoimmunity
• produce a specific set of cytokines--IL-17A,IL-
17F 2
6
TH 22cells
T Helper Cells
 Protects against extracellular
pathogens
 Involved in inflammatory skin
disease
 produce a specific set of
cytokines---IL22
T follicular helper cell(TFH)Cells
 TFH cells contribute to humoral immunity
by stimulating the production of antibodies
by B cells and inducing class switching,
 can produce cytokines characteristic of
either TH1
or TH2 cells 2
6
 Regulatory T Cells
• Treg cells
 Has an inhibitory manner to suppress immune responses
and inflammation.
 Suppress T-cell activity and help prevent the development
of autoimmunity during immune responses
 IL-10 induces regulatory function by inhibiting T helper
cell
function.
 Activates transcription factor Foxp3
 Foxp3 upregulated CD25 and CTLA-4
 CTLA-4 binds to B7 on APCs, blocking the 2nd signal
required for lymphocyte activation
 Tregs also suppress/regulate functions by secretion of
IL-9 and TGF-β
2
0
• Regulatory T-cell immunotherapy has recently become a reality
in clinical trials.
 Treg effectiveness in preventing graft-versus-host disease
(GvHD) after bone marrow transplantation
 Cytotoxic T Cells (TCs)
▶ T cells that express CD8 molecule on their surface
▶ 30% of T cells in the periphery
▶ Destroy cells infected by intracellular pathogens and
cancer cells Class I MHC molecules (nucleated body
cells) expose foreign proteins
▶ Releases perforin and granzymes, proteins that form
pores in the target cell membrane; causing cell
lysis and/or apoptosis
 Superantigens
 Bacterial and viral proteins
 staphylococcal enterotoxin B
 the toxin that causes toxic shock syndrome
 mouse tumor virus superantigen
 putative proteins from Epstein-Barr and rabies
viruses
 Stimulate stronger immune response than normal
antigens by “tricking” T cells into activation
although they have not been triggered by a specific
antigen
 Stimulate T cells to proliferate nonspecifically
 Contribute to microbial pathogenicity
 stimulate release of massive quantities of cytokines
from T cells
 may result in circulatory shock and multiorgan
failure
Superantigens Are a Special Class of
T-Cell Activators
Humoral immune response
▶ Mediated by B cells B cell
▶ Mature in bone marrow
▶ Contain B cell receptors (BCRs) that bind to
antigens.

 B lymphocytes recognize specific antigens

 proliferate and differentiate into antibody-
secreting plasma
cells
 Antibodies bind to specific antigens on
microbes; destroy microbes via specific
mechanisms
 Some B lymphocytes evolve into the resting state -
memory
cells
B-Cell
Receptor

 BCR is unique the receptors

 Surface-bound immunoglobulin functions as the epitope-specific
BCR.
 All BCRs expressed by a single B cell have identical epitope
specificity.
 B- cells
 Activation of naive B cells is triggered by antigen.
 leads to generation of plasma cells and memory B
cells.
 In the absence of antigen-induced activation
 Naive B cells in the periphery have a short life span,
dying within a few weeks by apoptosis
 Depending on the nature of the antigen, B-cell
activation proceeds by two different routes
 one dependent upon TH cells and other not.
 The B-cell response to thymus-dependent (TD)
antigens
 requires direct contact with TH cells, not simply
exposure to TH -derived cytokines.
 Antigens that can activate B cells in the absence of
direct participation by TH cells are known as thymus
independent (TI) antigens.
a) TD antigens bind to the Ig receptor of B cells. Some of the antigen is
processed and presented to helper T cells.
 After binding to T cell , secretes cytokines such as IL-2 and IL-
4, which are recognized by receptors on the B cell surface.
 Cytokines deliver differentiation, proliferation, and survival signals to
the B cells.
b) T-independent-type 1 (TI-1) antigens bind to B cells through both Ig and
innate immune receptors.
• For example, LPS from gram-negative organisms binds to B
cells via both membrane-bound immunoglobulin (mIg) and TLR4,
resulting in signaling from both receptors.
(c) T-independent-type 2 (TI-2) antigens are frequently bound by C3d
complement components and cross-link both mIg and CD21 receptors on
B cell signaling
B cells that
differ in Antigen
Antigen
antigen receptor
specificity

Antibody

Memory cells Plasma cells

 Activation of B Cells
▶Activation of B cells formed Plasma
cells in response to cytokines.
▶ Plasma cell produce antibody molecules
▶ Antibodies
are versatile effector
molecules that, through a variety of
mechanisms,
▶ play direct roles in protecting us from
▶pathogens
▶pathogen-derived toxins,
▶and cells that have become dangerous
through
infection or malignant transformation

© 2011 Pearson Education, Inc.

 Two identical light (L) chain
molecular weight about
25000 Da
 two identical heavy (H)
chain of larger polypeptide
of about 50000 Da or
more.

• All immunoglobulins are not antibodies

• Five kinds of antibodies based on constant
region of heavy chain
• IgG, IgM, IgA, IgD, IgE
Antibody-mediated effector function
▶ Antibodies contribute to immunity in
following ways
▶ Neutralization

▶ Opsonization

▶ Antibody-dependent cell-mediated
cytotoxicity
(ADCC)

▶ Activation of classical complement pathway.

 Neutralization
▶ Antibodies bind to viral surface proteins preventing
infection of a host cell
▶ Antibodies may also bind to toxins in body fluids and
prevent them from entering body cells
▶ Neutralizing antibodies are usually of the lgG and
lgA isotypes.

Antibody

Viru
s
 Opsonization
▶ Antibodies bind to antigens on bacteria creating a
target for macrophages or neutrophils, triggering
phagocytosis
▶ As macrophages, dendritic cells, and neutrophils bear
surface receptors (FcR) for the Fe portion of bound
immunoglobulin.
Antibody-dependent cell-mediated
cytotoxicity (ADCC)
Antibody bound to target
cells (virus infected cells
of the host) with the Fc
receptors of a number of
cell types, particularly
natural killer (NK) cells
• can direct the
activities cytotoxic
cell against
of the
thetarget
cell.
effector
 FcRs on NK cells and
eosinophils are lgG-,
lgE-
,and lgA-specific.
Complement
activation

▶ The classical pathway of

complement is activated by
conformational changes that
occur in the Fc portion of
 Function of Antibody
Isotypes
Antibod Isotype –specific Effector function
y
Isotype
s
IgG • Opsonization of antigens for phagocytosis by macrophages and
neutrophils (IgG1 and IgG3)
• Activation of the classical pathways of Complements. IgG3 is the
most effective complement activator, followed by IgG1; IgG2 is less
efficient, and IgG4 is not able to activate complement at all.
• Antibody dependent cell mediated cytotoxicity mediated by
natural killer cells
• Neonatal immunity: transfer of maternal antibody across placenta
(IgG1, IgG3, and IgG4 )
• Feedback inhibition of B-cell activation

IgM • first immunoglobulin produced in a primary response to an antigen

• Activation of the classical pathway of complements
• Antigen receptor of naïve B lymphocytes
• Endocytosis, phagocytosis
IgA • Mucosal immunity : secretion of IgA into lumens of the GI and
Respiratory tracts
• Antibody-dependent cell-mediated cytotoxicity
IgE • Mast cell degranulation(immediate hypersensitivity reaction
• Antibody-dependent cell-mediated cytotoxicity
IgD • Antigen receptor of naïve B lymphocytes
Immunological Memory (memory B cell)
▶ Immunological memory is responsible for long-
term protections against diseases, due to either a
prior infection or vaccination

▶ The first exposure to a specific antigen represents

the
primary immune response

▶ During this time, selected B and T cells give rise to

their
effector forms

▶ In the secondary immune response, memory

cells facilitate a faster, more efficient response
© 2011 Pearson Education, Inc.
 Primary immune response Secondary immune response to
to antigen A produces antigen A produces antibodies to A;
antibodies to A. primary immune response to antigen
B produces antibodies to B.

104

103
(arbitrary units)
concentration Antibodies
to A
Antibody
102 Antibodies
to B

101

100
0 7 14 21 28 35 49 56
42
Exposure Exposure to
to antigen A antigens A and B
Time (days)
Stages in adaptive immune
response
Attribu Innate Adaptive
te immunity immunity

Response Minutes/ Day

time hours s
Specificit Specific for molecules and Highly specific; discriminates
y molecular patterns between even minor
associated with differences in molecular
pathogens and molecules structure of microbial or non
produced by dead microbial molecules
/damaged cells Highly diverse; a very large
Diversit
A limited number of number of receptors arising
y
conserved, germ line– from genetic recombination of
encoded receptors receptor genes in each
Some (observed in individual
Memory invertebrate innate Persistent memory, with
respons responses and faster response of greater
es mouse/human NK cells) magnitude on subsequent
Self/nonself Very good; no microbe- exposure
Very good; occasional failures of
discriminatio specific discrimination result in
n self/non self patterns in autoimmune disease
Major host
Phagocytes , natural killer T cells, B cells, antigen-
cell (NK) cells, other leukocytes, presenting cells
types epithelial and endothelial
cells
 Herd immunity
▶ Herd immunity is defined as the overall
immunity of a community (or herd) towards
a pathogen.
▶ Elements that contribute to create a
strong herd
immunity are-
o Occurrence of clinical and subclinical
cases in the herd
o On-going immunization programme
o Herd structure i.e. type of population
involved
o Type of pathogen-Herd immunity may not
be strong in a community against all the
pathogens.
 Herd immunity
▶ Herd immunity develops following
effective vaccination against some diseases
like:
o Diphtheria and Pertussis vaccine
o Measles, Mumps and Rubella (MMR)
vaccine
o Polio (Oral polio vaccine)
o Smallpox vaccine

o “Herd immunity against COVID-19 should be achieved

by protecting people through vaccination, not by
exposing them to the pathogen that causes the
disease.” Director-General’s 12 October media
briefing speech from WHO.
 Failure of immune response
o Immune response helps individuals defend
against
o microbes and some cancers
o Immune response can fail in
o hypersensitivity reactions
o immunodeficiency

Hypersensitivity Reaction
 Cause cell damage through excessive immune
response to antigens
 Hypersensitivity
 overreaction to infectious agents
 Allergy
 overreaction to environmental substances
 Autoimmunity
 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
Types of Immunodeficiency
o Congenital (primary) immunodeficiency
o genetic abnormality
o defect in lymphocyte maturation
o Acquired (secondary) immunodeficiency
o results from infections, nutritional deficiencies or
treatments
o AIDS, chronic leukemia
Altered immunity: immuno-compromised
Disorder Compromised
function
Immun Adaptive Reduction of T cells Activation of macrophages
e immunity
system Activation of B
lymphocytes

Hypo-gammaglobulinemia Neutralizes pathogens and

toxins, opsonization,
complement activation
 Summary
• Evolutionary need for adaptive immunity:
 Self/non-self discrimination, specificity, amplification, regulation,
duration and memory
• T and B cells are mediators of adaptive immunity
 T cells: cell-mediated immunity
 B cells: humoral immunity
 Cells of innate immunity also participate (DCs, Macrophages)
• Activation of T and B cells are different:
 T cells: specific recognition of peptide/MHC complex (signal 1)
and costimulatory signals by APC (Signal 2)
 B cells: recognize native proteins (signal 1). May/may not require
signal 2 from CD4+ Th cells (TD and TI antigens)
• Immunological memory: an important hallmark
 Faster and rapid response on a second antigen encounter
• Innate immune response shapes the adaptive immunity
Overview ofImmune System Responses
Thank
you