Adaptive Immunity

• Purposes:
• Destruction of infectious microorganisms that are
resistant to inflammation
• Long‐term highly effective protection against future
exposure to the same microorganism
• Inducible
• Specific
• End products
• Immunoglobulins
• Lymphocytes (T cells, B cells)
 Adaptive Immunity (cont’d)
• Components:
• Humoral—immunoglobulins (antibodies)
• Bind to antigens on bacteria and viruses
• Cellular—T cells
• Subpopulations (effector T cells)
• Kill target directly
• Stimulate other leukocytes
• Both produce memory cells
• Interact
 Adaptive Immunity (cont’d)
• Active immunity
• Exposure to antigen
• Immunization
• Passive immunity
• Preformed antibodies or T cells are administered
 Antibodies
• Also called immunoglobulins
• Produced by plasma cells
• Classes of antibody
• IgG, IgA, IgM, IgE, and IgD
• Characterized by antigenic, structural, and
functional differences
Antibodies (cont’d)
 Antibody Structure
• Antigen‐binding fragment (Fab)
• Recognition sites (receptors)
for antigenic determinants
• Crystalline fragment (Fc)
• Responsible for biologic
function
• Polypeptide chains (4)
• Light chains (2) and heavy
chains (2)
 Antibody Structure (cont’d)
• Hinge region
• Constant and variable regions:
• Complementary‐determining
regions (CDRs)
• Framework regions (FRs)
Direct and Indirect Functions of Antibodies
Immunologic Mechanisms of Inflammation
 Immunoglobulin A (IgA)

• Two classes:
• IgA1 molecules are found predominantly in
the blood
• IgA2 molecules are found predominantly in
normal body secretions
 Immunoglobulin A (IgA) (cont’d)

• IgAs found in body secretions are dimers

anchored by a J chain and a “secretory”
piece
• Secretory piece may function to protect
IgAs against enzyme degradation
 Immunoglobulin D (IgD)

• Low concentration in the blood

• Located primarily on the surface of developing
B lymphocytes
• Function as one type of B cell antigen receptor
 Immunoglobulin E (IgE)

• Least concentrated of the immunoglobulin

classes in the circulation
• Mediator of many common allergic responses
• Defender against parasites
 IgE Function

• Provides protection from large parasites

• Initiates an inflammatory reaction to attract
eosinophils
• When produced against innocuous environmental
antigens, they are a common cause of allergies
• Fc portions of IgEs are bound to mast cells
IgE Function (cont’d)
 Immunoglobulin G (IgG)

• Most abundant class (80%‐85%)

• Accounts for most of the protective
activity against infections
• Transported across the placenta
• Four classes:
• IgG1
• IgG2
• IgG3
• IgG4
 Immunoglobulin M (IgM)

• Largest of the immunoglobulins

• Pentamer stabilized by a J chain
• First antibody produced during the primary
response to an antigen
• Synthesized during fetal life
 Secretory (Mucosal) Immune System

• Lymphoid tissues that protect the

external surfaces of the body
• Antibodies present in tears, sweat,
saliva, mucus, and breast milk
• IgA is the dominant immunoglobulin
• Small numbers of IgG and IgM are
present
 Cellular Immunity

• T lymphocytes:
• T Cytotoxic (Tc) cells
• T Helper (Th) cells
• Memory cells
 Adaptive Immunity

• Clonal diversity
• Production of T and B lymphocytes
• Antigen recognition
• Lymphocyte specificity
• Clonal selection
• Antigen processing and presentation
• Complex cellular interactions
 Generation of Clonal Diversity

• All necessary receptor specificities are produced

• Takes place in the primary (central) lymphoid organs
(thymus, bone marrow)
• Results in immature but immunocompetent T and B
cells
• Primarily occurs in the fetus
 Clonal Diversity

• B Cell Development:
• Production, proliferation, differentiation in
bone marrow
• Travel to lymphoid tissue and reside there as
immunocompetent cells
• Each cell responds to only one specific antigen
 Clonal Diversity (cont’d)

• T Cell Development:
• The thymus is the central lymphoid organ of T cell
development
• Development of antigen‐specific T cell receptors
(TCRs)
• Leave thymus, travel to and reside in lymphoid
tissue as mature immunocompetent cells
 Clonal Selection: Antigen Processing and
Presentation

• Initiated when T and B cells interact with an

antigen
• Must first be processed and then presented by
antigen‐processing (antigen‐presenting) cells
(APCs)
• Results:
• Differentiation of B cells into active antibody‐ 
producing cells (plasma cells)
• Differentiation of T cells into effector cells,
such as Cytotoxic cells
Clonal Selection: Antigen Processing
and Presentation (cont’d)

• For processing and presentation to occur, the

antigen must be of the appropriate type, the
lymphocytes must be prepared to recognize the
presented antigen, and the antigen must be
presented appropriately
 B Cell Clonal Selection

• B cell Activation:
• When an immunocompetent B cell encounters an
antigen for the first time, B cells with specific BCRs
are stimulated to differentiate and proliferate
• A differentiated B cell becomes a plasma cell
• A plasma cell is a factory for antibody production
• Single class or subclass of antibody
B Cell Clonal Selection (cont’d)
 T Cell Clonal Selection (cont’d)

• T cell activation
• Binding antigen to specific T cell receptors
• Allows:
• Direct killing of foreign or abnormal cells
• Assistance or activation of other cells
• T regulatory cells (Tregs)
• Regulate the immune response to avoid
attacking “self”
• Memory T cells
Antigen Processing and Presentation
Antigen Processing and Presentation
(cont’d)
 Antigen Presentation

• Major histocompatibility complex (MHC)

• Glycoproteins on the surface of all human cells
(except RBCs)
• Also referred to as human leukocyte antigens
(HLAs)
 Primary and Secondary Responses

• Primary response
• Initial exposure
• Latent period or lag phase
• B cell differentiation is occurring
• After 5 to 7 days, an IgM antibody for a
specific antigen is detected
• An IgG response equal or slightly less follows
the IgM response
 Primary and Secondary Responses (cont’d)

• Secondary response
• More rapid
• Larger amounts of antibody are produced
• Rapidity is caused by the presence of memory cells
that do not have to differentiate
• IgM is produced in similar quantities to the primary
response, but IgG is produced in considerably greater
numbers
 Recognition and Response

• Required for a successful immune response

• Clusters of differentiation (CD)
• Originally used to describe proteins found on the
surface of lymphocytes
• Now it is a labeling system used to identify a
family of proteins on many cells
 Helper T‐Lymphocytes

• “Help” the antigen‐driven maturation of B

and T cells
• Facilitate and magnify the interaction
between APCs and immunocompetent
lymphocytes
 Helper T‐Lymphocytes (cont’d)

• Steps
• Th interacts through antigen‐specific and
antigen‐ independent mechanisms
• Undergoes differentiation
• Mature Th interacts with plasma or T‐effector
cells
 Helper T‐Lymphocytes (cont’d)

• Subsets
• Th1 cells provide help in developing
cell‐mediated immunity
• Th2 cells provide help in developing
humoral immunity
• Differences based on cytokine production
 Superantigens (SAGs)

• Bind the variable portion of the TCR and the MHC class
II molecules outside of their antigen‐ presentation sites
• Activates a large population of T‐lymphocytes
regardless of antigen specificity

SAGs induce an excessive production of cytokines

- Causes fever, low blood pressure, and potentially
shock
 T‐Cytotoxic (Tc) Cells

• Destroy cancer cells or cells infected with

virus
• Perforin, granzymes, or direct receptor
interactions
Cell‐Killing Mechanisms
 Other Cells

• Natural killer (NK) cells

• Complement Tc cell mechanisms
• Regulatory T cells (Treg)
• Provide peripheral tolerance
• Affect recognition of antigen and suppress
proliferative steps of antigen recognition
 Pediatric Immunity

• Fetus has sufficient IgM but deficient IgG, IgA responses

• Maternal antibodies provide protection within the fetal
circulation and during the first months of life
• Immunologically immature when born with deficiencies in
antibody production, phagocytic activity, and complement
activity
Fetal and Neonatal Immunity
 Aging and Immune Function

• Decreased T cell activity

• Thymic size is 15% of its maximum size
• Thymic hormone production drops, as does the
organ's ability to mediate T cell differentiation
• Decreased antibody response to antigens
• Increase in circulating antigen‐antibody complexes
• Increase in circulating autoantibodies
• Decrease in circulating memory B cells
Thank you