Adaptive immunity

Goal of the lecture

Pathogens

Innate First lines of defence

Immunity Second lines of defence

Antigen presenting
Adaptive cells

MHC molecules
Immunity
B cells
Protection T cells
Concept of adaptive immune response
Also called acquired immune response because it
is initiated after the exposure to a certain
pathogens or their antigens

It is triggered only if microbes or their antigens pass

through epithelial barriers and are delivered to
lymphoid organs where they can be recognized by
lymphocytes.
An immune response to an introduced foreign
substances(Ag) which is mediated by cells and
molecules of the immune system
 Comparison between
Innate and Adaptive Immunity

Attribute Innate Immunity Adaptive Immunity

Activation Active prior to exposure Activated by exposure to
to any microbe or antigen microbes or antigens
Lag phase Absent Present
Response is immediate Response takes few days
Specificity Limited High
Targets all pathogens Targets specific pathogen
Memory Absent Present
Same response in 1st and Amplified response in
subsequent exposure subsequent exposure
 Adaptive Immunity
Adaptive immune system has two arms
Adaptive Immunity
Humoral Immunity Cell mediated Immunity

1-Provided by B lymphocytes • 1.Provided by T lymphocytes •

2-Can recognize protein, • 2.Can recognize only protein •
polysaccharide, phospholipid and antigens
nucleic acid antigens 3.Recognizes antigens presented •
3-Can act against soluble or free by APCs with Class I or Class II
antigens by class II MHC molecules MHC molecule
4-Provides immunity to • 4.Provides immunity to •
extracellular bacteria, viruses and intracellular bacteria, viruses, fungi
toxins and protozoa
5-Causes Type I, II & III • 5.Causes Type IV hypersensitivity •
hypersensitivity Causes acute graft rejection •
Adaptive immunity

Adaptive immunity response mediated by :

1- antibody to eliminate extra cellular pathogen

(humeral immunity).

2- cell-mediated immunity for intracellular

pathogen which required T-cell .
Types of intracellular microbes combated by T cell-mediated immunity
Adaptive immunity

Adaptive immunity acquired by two ways:

A- passive : Transmitted by antibody or T-cell pre-
formed in another host .

B- active : induced after contact with Ag (clinical and

sub clinical infection , immunization with live or
killed microbes or microbial product ).
Different types of antigen-presenting cells

Name Location Present to

Dendritic cells Lymph nodes T cells
Mucous Membranes B cells
Blood
Langerhans’ cells Skin T cells

Macrophages Various tissues T cells

B cells (BCR( Lymphoid tissues T cells

 Features of Antigen Presenting Cells

• Strategic location
- Skin (SALT(
- Mucous membranes (GALT, NALT, BALT(
- Lymphoid organs (Lymph nodes, spleen(
- Blood circulation (plasmacytoid and myeloid DC(

• Pathogen capture
-Phagocytosis (whole microbe(
-Macropinocytosis (soluble particles(cell drinking

• Diversity in pathogen sensors (PRRs(toll like R

- Extracellular pathogens (bacteria(
- Intracellular pathogens (viruses(
 MHC Restriction
T cells (CD4 helper) recognize antigen in association
with class II MHC proteins, whereas (CD8 cytotoxic T
cells) recognize antigen in association with class I MHC
proteins. This is called MHC restriction; {Rule of8}
 Antigen processing and presentation pathways

Endogenous Exogenous
pathway Pathway
(All cells) (APCs)
 Antigen capture , processing and
presentation :
 Endogenous antigens within cells (like intracellular
viral antigen, tumor OR even self Ag ) are presented
in association with MHC class I .

 Exogenous antigens (extra cellular organisms toxins

,soluble proteins ) are presented by APC in
association with MHC class II .


Major Histocompatibility Complex (MHC(
or Human Leukocyte Antigen (HLA(

Class I molecules
Found on all nucleated
cells

Class II molecules Pr. Jean Dausset

Found on dendritic cells, Nobel prize1980
macrophages, B cells
 15
Clinical problems with MHC molecules

• Major causes for organ transplant rejection

- HLA molecules mismatch between donor and
recipient (Allograft(
- Graft-Versus-Host reaction (GVH(

• HLA association and autoimmune disease

- Ankylosing spondylitis
• HLA-B27 -> 90% of patients
- Insulin-Dependent Diabetes Mellitus
• HLADQ2 -> 50-75% of patients
 Lymphocytes :
1. Thymus derived cells : (T – cell).
Originate from stem cell in Bone Marrow but mature
in thymus

2. Bone marrow – derived cell : (B cell).

Originate & mature in bone marrow

3. Natural killer cells originated in bone marrow

 1.T lymphocyte:
T-cell maturation
The main two process of maturation involved :
A- positive selection :

 T-cell that recognize foreign antigen via MHC will

survive.

B- Negative selection (Deletion)

- T-cells with receptor recognize self antigen with

high affinity deleted .
T-cell express either CD4 or CD8 Surface marker
which can be used to define the major sub population
of T-cell:
1. CD4 characterize the helper T-cell population and
produce cytokine and coordinate of immune
response.it is called helper because it help B cells and
other T cells to multiply & differentiated in to
effector cells.

T helper( CD4) recognize Ag associated with MHC II

molecules which processed and presented by APC ,
after Ag recognition CD4 activated
and further subdivided in to TH1,TH2,TH17 and T reg
cell based on their cytokines and functional activity.
 Phases of T cell responses

There are three phases of T cell activation

- Antigen recognition phase
- Activation and differentiation phase
- Effector phase
Steps in the activation of T lymphocytes:
Naive T cells recognize major histocompatibility
complex (MHC)-associated peptide
antigens displayed on antigen-presenting cells
(APCs) and other signals . The T cells respond by
producing cytokines, such as IL-2, and expressing
receptors for these cytokines, leading to an autocrine
pathway of cell proliferation. The result is clonal
expansion of the T cells.
Some of the progeny differentiate into (1) effector
cells, which serve various functions in cell-mediated
immunity, and (2) memory cells, which survive for
long periods.
The role of costimulation in T cell activation (A)
Ligand-receptor pairs involved in T cell activation
ROLE OF COSTIMULATION IN T CELL ACTIVATION, 2ND SIGNAL

The best-defined costimulators for T cells are two related

proteins called B7-1 (CD80) and B7-2 (CD86), both of which are
expressed on APCs and whose expression is greatly increased
when the APCs encounter microbes. These B7 proteins are
recognized by a receptor called CD28, which is expressed on
virtually all T cells. Signals from CD28 on T cells binding to B7
on APCs work together with signals generated by binding of the
TCR and coreceptor to peptide-MHC complexes on the same
APCs.
CD28-mediated signaling is essential for initiating the
responses of naive T cells; in the absence of CD28-B7
interactions, engagement of the TCR alone is unable to
activate the T cells. The requirement for
costimulation ensures that naive T lymphocytes are activated
fully by microbial antigens, and not by harmless foreign
substances, because, as stated previously, microbes stimulate
ROLE OF COSTIMULATION IN T CELL ACTIVATION, 2ND
SIGNAL
The biochemical signals triggered in T cells by
antigen recognition and co-stimulation result in the
activation of various transcription factors that stimulate
the expression of
1-genes encoding cytokines: Activated T cells can
produce cytokines (IL-2, 4, 5, 10,13,17 etc.) and

2-cytokine receptors: express cytokine receptors, that

promote T cells to proliferate and differentiate

3-Adhesion molecule: ex:[lymphocyte function adhesion]

(LFA-1)

.
 Effector functions of activated T cells

1) CD4+ T cells
Th1: secrete IFN-, etc.
Activate macrophages
express CD40L
effect on lymphocytes: IL-2
effect on neutrophil: TNF-,
Th2: IL4,5 Which promote B cell growth and
Ig production.
The development of TH1, TH2, and TH17 subsets is not a
random process but is regulated by the stimuli that naive
CD4+ T cells receive when they encounter microbial antigens.
Cytokines that induce TH1 development include IL-12 (and IL-
18), which are produced by microbe-activated antigen-
presenting cells (APCs), such as dendritic cells and
macrophages.
Interferon-(IFN- ) made by natural killer (NK) cells or by the
responding T cells themselves also is critical for TH1
development.
TH2 cells are induced by IL-4, which may be produced by the
T cells themselves and by other cells, such as mast cells.
TH17 differentiation is triggered by TGF- which can be
made by many cell types, in the presence of inflammatory
cytokines such as IL-6, IL-1, and IL-23, which may be
produced by APCs also induce Th17 differentiation of T-cell.
 2-CD8+ T cells
Cytotoxicity: kill target cells
a. necrosis: perforin and granzyme
b. apoptosis: FasL-Fas

Characteristics of CD8+ T cell cytotoxicity

a. Specificity
b. MHC I restriction
c. High efficiency
Generation of memory T cells
1) Migrant(TRAVELLING)
2) Long-lived memory to specific antigen
3) Mediate faster, stronger and more effective immune
response
Inhibition of T-cell activation
1-After T-cells have served their function and
infection is resolved a cytotoxic T-lymphocyte
antigen-4 (CTLA-4) appear on the T-cell surface
displacing CD28 and interact with B7 lead to
inhibition of T-cell activation by blocking IL-2
synthesis.
2-Programmed cell death-1(PD-1): is another
inhibitory protein on T-cells interact with its
ligand on APCs (like Dendritic cells and
macrophage lead to inhibition immune response
Inhibition of T-cell activation
B lymphocyte:

Mature B cells(plasma cell) synthesize

immunoglobulin molecules that are found
within the cells to be secreted on need or
displayed on their surface(IgM monemer).

On the surface they function as B cell epitope-

specific receptor(BCR)
What are differences between TCR & BCR?
 Immune functions of Antibodies

IgG IgA
1-Ab-dependent phagocytosis Mucosal Immunity
2-Complement activation by Prevent adhesion
3-Neonatal Immunity
4-Toxin/virus neutralization IgM
5-ADCC 1-Monemer: as BCR
IgE 2-Pentamer: may
1-mmunity against helminths achieves neutralization,
2-Mast cell degranulation Complement activation
(allergies(
Amrani 04-11-13
Characteristics of the antibody response
(adaptive immunity)