Adaptive Immunity

What You Have To Know

• The components of the adaptive immunity

• Attributes of the adaptive immune responses

• Interactions between innate and adaptive immune responses

• The structure and function of the major histocompatibility

complex (MHC) gene products

• How antigens are processed, presented, and recognized

• The properties and biological functions of cytokines

•The subclasses of T-helper (Th) cells and their functions

 ADAPTIVE (ACQUIRED) IMMUNITY
• B-cells (along with T-cell help) synthesize proteins called antibodies that mediate
humoral immunity and T-cells are major players in cell-mediated immunity.

• An individual lymphocyte expresses receptors of a single and unique antigen-

binding specificity. Antigens are substances that can trigger an immune response.

• It is stimulated by exposure to infectious agents and increases in magnitude and

defensive capability with each successive exposure to a particular pathogen.

• It is mediated by B and T-lymphocytes that recognize different types of antigens.

B-cell receptors bind whole unprocessed molecules and intact pathogens, whereas
T-cell receptors only interact with pathogen-derived processed peptides bound to
proteins of the major histocompatibility complex (MHC).

• IMMUNOLOGICAL MEMORY – Both B cells and T cells of the adaptive

immune system “remember” each encounter with a pathogen or foreign antigen,
so that subsequent encounters stimulate increasingly more effective defense
mechanisms.
 ADAPTIVE (ACQUIRED) IMMUNITY
• Acquired immunity develops during a host’s lifetime.
• Six major characteristics of acquired immunity

Acquired immunity: (1) requires

time (4 days-3 weeks) for induction,
(2) variant (a unique response to each
foreign substance), (3) highly
specific, and (4) Second and
subsequent encounters with same
foreign material produces larger, more
rapid response (basis for vaccination)
 ACQUIRED (ADAPTIVE) IMMUNITY

Immune cells Macrophages, Dendritic cells, B cells,

T helper (Th) cells, T cytotoxic (Tc)
cells
Chemical Antibodies, cytokines
mediators
Response Slow, specificity, diversity, long-term
characteristics immunological memory
Innate and Adaptive Immunity
ACQUIRED IMMUNITY
Type of Adaptive Immunity
HUMORAL IMMUNITY
HUMORAL IMMUNITY

Clonal Selection and Expansion

HUMORAL IMMUNITY

IgG
IgA
Low antigenic affinity High antigenic affinity IgE
IgM

Memory B cells

Somatic mutations
Class-switching

Anamnestic response
 Antibodies

Proteins secreted by differentiated B

cells called Plasma cells. Antibodies
possess various functions. Among them
are neutralization and opsonization.
CELL-MEDIATED IMMUNITY
CELL-MEDIATED IMMUNITY
CYTOTOXIC T-LYMPHOCYTES

CD95L

Target CD95

Death
 ACQUIRED IMMUNITY
Macrophage
IL-12
NK cell IFN-
IL-1
Th0 IFN-
Naive
Delayed type-
Th2 Th1
hypersensitivity
(DTH)
Th1
IL-10,13
IL-4,5,6
CD45RA
Th2
Naive
Naive CTL Target
Cell-mediated
Humoral Immunity (CMI)
Immunity (HI)

Effector CD45RO Effector

Antigen Recognition in Adaptive Immunity
Cytotoxic
Helper

CD8+
CD8+
CD4+

CD8+ CD4+

(APC)
1. Dendritic cells
2. Macrophages
3. B cells
MHC class I vs MHC class II
Antigen Presenting Cells (APC)
 Target cell Antigen Presenting Cell

CD8+ cytotoxic T-cell CD4+ helper T-cell

MHC class I vs MHC class II
MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)

HLA –DR, DQ, DP HLA –A, B, C

Processing of Endogenous Antigens

Tap 1
and 2

Proteosome
Processing of Exogenous Antigens
Cytokines
Properties
Cytokines of the Adaptive Response
Cytokine Secreted by Targets and effects
IL-2 T-cells T- and B-cell proliferation; growth factor
IL-4 TH2 cells; Dendritic cells; Promotes TH2 differentiation; isotype switch to IgE;
mast cells inhibits the formation of TH1 cells
IL-5 TH2 cells Promotes B cell differentiation; isotype switch to IgA;
promotes Eosinophils differentiation
IL-6 Macrophages; TH2 Induces acute phase proteins; influences humoral immunity

IL-10 TH2 cells Suppresses the production of macrophage-cytokines;

inhibits the formation of TH1 cells; down-regulates the
expression of MHC class I molecules
IL-12 Macrophages; Dendritic cells Activates NK cells; promotes TH1 subsets
IFN- TH1 cells; Tc cells; NK cells Activates macrophages; increases expression of MHC class
I and II molecules; promotes isotype switch to IgG
subclasses; inhibits the formation of TH2 cells
TNF- TH1 cells; Tc cells Cytotoxic activity to tumors
TGF-  TH3 (Treg); macrophages; Inhibits macrophage, B- and T-cell proliferation; promotes
mast cells isotype switch to IgA
 Chemokines
Chemokines Chemokine Chemokines
family receptors
C XCR1 Lymphotactin
CC CCR2 MCP-1
CCR5 MIP-1α, MIP-1β, RANTES
CCR8 I-309
CXC CXCR3 IP-10, MIG
CXCR4 SDF-1
CXC3C CX3CR1 Fractalkine
Phases of Adaptive Immune Responses
Characteristic Innate Immunity Adaptive Immunity
Synonyms Nonspecific, natural Specific, acquired
Mode of activation Present at birth Acquired response to antigens
Inducible No Yes
Immunological Memory No Yes
Response time Rapid 0-6 hours Slow initiation, rapid thereafter
Phagocytosis Yes No
Leukocytes included Neutrophils, Macrophages, Macrophages, Dendritic cells,
Eosinophils, NK cells B cells, T cells
Specific antibodies No Yes
Complement components Yes Yes
Anatomical barriers Yes No
Cytokines Yes Yes
Lysozyme in secretions Yes No
Induces fever Yes No
Causes inflammation Yes Yes
Memory is the hallmark of adaptive immunity
– Primary response is initiated upon first exposure to an
antigen
• Memory lymphocytes are left
behind after antigen is cleared
– A second exposure to the
same antigen re-stimulates
memory lymphocytes
• Reactivation yields faster,
more significant, better response
– Memory is NOT present in
innate immunity
 Summary
•The adaptive immunity is divided into humoral and cell-mediated immunity
and it consists of T and B lymphocytes and antigen-presenting cells (APC).

• The humoral immunity is mediated by antibodies synthesized by B-cells and

secreted by plasma cells and it is the major defense mechanism against
extracellular microbes and toxins.

•The cell-mediated immunity protects against intracellular pathogens.

•Antigen-presenting cells include B-cells, Macrophages, and Dendritic cells.

•Adaptive immune responses are specific, diverse, self-limiting, capable of self

versus non-self recognition, and display memory.

•Immunologic memory is generated as pathogens are eliminated by the immune

response. Long-lived memory B- and T-cells are generated and recirculate
through the body in surveillance for the antigen.

•The secondary response (anamnestic response) is more rapid, larger, has higher
affinity, and requires less antigenic stimulation than the primary response.
 Summary
• Class I MHC molecules are two chain structures: the alpha chain and beta2-
microglobulin. These molecules are expressed on all nucleated cells of the body in
a codominant fashion.

•Class II MHC molecules are two chain structures: alpha and beta chains. These
molecules are expressed only on antigen-presenting cells in a codominant fashion.

•APCs uptake peptides and partially digest them. Digested peptides are loaded
into the groove of class II MHC molecules by the exogenous pathway.

•APCs migrate to the secondary lymphoid organs, where they present this
processed antigen to recirculating naïve lymphocytes.

•The binding of the TCR to the peptide/MHC class II complex provides the first
signal in T-cell activation.

•Activated T-helper (Th) cells act as the orchestrators of the effector mechanisms
of the immune response such as antibody synthesis, macrophage activation,
cytotoxic T-cell (CTL) and NK cell killing.
 Summary
• The cytokines produced by Th subsets (Th1, Th2, and Th3): IFN-g produced
by Th1 cells activates cell-mediated immunity and inhibit Th2 cells; IL-4 and
IL-10 produced by Th2 cells activates humoral immunity and inhibit Th1 cells;
TGF-beta produced by Th3 cells inhibit both Th1 and Th2 cells.

•Macrophages kill intracellularly in response to TNF-a, TNF-b, and IFN-g.

•NK cells are stimulated by IFN-a, IFN-b, and IL-12, and kill targets lacking
MHC class I molecules. They kill tumor and virus-infected cells using
granzymes and perforin.

•Cytotoxic T-lymphocytes (CTL) are stimulated by IL-2, and kill targets

expressing MHC class I molecules. They kill tumor and virus-infected cells
using granzymes, perforin, and Fas ligand.

•The innate and adaptive immunity interact with and augment each other
through soluble substances such as antibodies, complement, and cytokines.