First response to particular antigen called primary response› May take a week or more to develop

Immune system remembers pathogen on subsequent exposure› Termed secondary response

Adaptive immunity divided into› Humoral immunity

Eliminates extracellular pathogens

› Cellular immunity Eliminates intracellular pathogens

Overview of humoral immunity› Mediated by B lymphocytes

a.k.a B cells

› Develops in bone marrow› B cells may be triggered to proliferate into

plasma cells Plasma cells produce antibodies

Antibodies produce when antigen bonds B cell receptor

› Some B cells produce memory cells

Overview of cellular immunity

› Mediated by T lymphocytes a.k.a T cells

› Matures in thymus› Divided into 2 subsets

Cytotoxic T cells Helper T cells

T cell receptors help with antigen recognition

Lymphoid system collection of tissues and organs designed to bring B and T cells in contact with antigens› In order for body to mount appropriate

response, immune cells must encounter antigen

Lymphoid system includes› Lymphatic vessels› Secondary lymphoid organs› Primary lymphoid organs

Lymphatic vessels› Carry lymph to body tissues

Lymph formed as result of body’s circulatory system

› Lymph travels through vessels to lymph nodes Material such as protein is removed

Fluid portion empties back into blood stream

Secondary lymphoid organs› Sites where lymphocytes gather to

encounter antigens; organs include Lymph nodes Spleen Tonsils Adenoids Appendix

› Organs situated strategically Allows for initiation of immune response

from nearly any place in body

Primary lymphoid organs› Bone marrow and thymus are primary

lymphoid organs Location where stem cells destined to

become B and T cells mature B cells mature in bone marrow T cells mature in thymus

Once mature, cells leave primary lymphoid organs and migrate to secondary lymphoid organs

Coined from compounds that elicit antibody production› Antibody generator

Includes an enormous variety of materials Today, term used to describe any

compound that elicits an immune response› Antigen that causes immune response termed

immunogen Proteins and polysaccharides induce

string response› Lipids and nucleic acids often do not

Recognition of antigen directed at antigenic determinant or epitope

Structure of the Antibody (Ab)› Basic Y-shaped structure› Made of four chains of amino acids held together by disulfide

bonds Two chains are heavy Two chains are light

› Each heavy and light chain has a constant region The constant region is known as Fc region

› Each heavy and light chain has a variable region Variable region is unique to each Ab This region binds to a specific Antigen and is known as “Fab”

region

Protective outcomes of antibody-antigen binding› Neutralization

Prevents toxin from interacting with cell

› Immobilization and prevention of adherence Antibody bonding to cellular

structures to interfere with function

› Agglutination and precipitation Clumping of bacterial cells by

specific antibody Bacteria more easily

phagocytized

Protective outcomes of antibody-antigen binding› Opsinization

Coating of bacteria with antibody to enhance phagocytosis

› Complement activation Antibody bonding triggers

classical pathway

› Antibody-dependent cellular cytotoxicity Multiple antibodies bind a cell

which becomes target for certain cells

Five classes of Ab› IgM

First Ab to respond to infection 5 – 13% of Ab in circulation Structure: pentamer

Five monomer units joined together at the constant region

Found on the surface of B lymphocytes as a monomer

Only Ab that can be formed by the fetus

Five classes of Ab› IgG

Dominant Ab in circulation 80 – 85% Ab in circulation

Structure = monomer Only Ab that can cross the placenta The antibody of memory!!!!!

› IgA Found in secretions 10 - 13 % of Ab in circulation Structure

Monomer in serum Dimer in secretions

Breast milk, mucus, tears and saliva

Five classes of Ab› IgD

<1% of total Ab in circulation Structure = monomer Maturation of antibody response

› IgE Barely detectable in circulation Structure = monomer Active in allergic reaction

When antigen introduces into body, only appropriate antibody bonds› Initiates multiplication of

specific antigen Process called clonal

selection Repeated cycles of cell

division generates population of copied antibodies Termed clonal expansion

Without sustained stimulation, cells undergo apoptosis

Lymphocyte characteristics include› Immature

Antigen specific receptors not fully developed› Naive

Have antigen receptor but have not encountered antigen

› Activated Able to proliferate Have bound antigen

› Effectors Descendents of activated lymphocytes Able to produce specific cytokines Plasma cells, T helper and cytotoxic T cells effector

cells› Memory lymphocytes

Long-lived descendents of activated lymphocytes Memory cells responsible for seed and effectiveness

of secondary response Remembers antigen on subsequent exposure

Antigen binds to B cell receptor› Poises B cell to respond

In many cases B cell needs conformation from helper T cells

Ag enters the body and is phagocytized and processed by macrophages› These macrophages destroy Ag and present a portion on the

surface of the macrophage next to self Ag Macrophages are called antigen-presenting cells (APC)

Processed Ag combines with specific TH with the appropriate receptor

APC releases substances to activate TH cell

TH cell activates B cells to divide and differentiate

› Produce plasma cells and memory B cells

Characteristic of primary response› Lag period of 10 to 12 days occurs before

antibody detection in blood Activated B cells proliferate and differentiate into increasing

numbers of plasma cells as long as antigen is present

› Net result is slow steady increase in antibody titer

Over time, some B cells undergo changes enhancing immune response including

Affinity maturation Class switching Formation of memory cell

Affinity maturation› Form of natural selection

Occurs among proliferating B cells

› Fine tunes quality of response with respect to specificity B cell receptors more and more specific to

antigen Antibody bonds antigen more tightly

Class switching› B cells initially programmed to differentiate into plasma

cells Plasma cells secrete IgM antibodies

› Helper T cells produce cytokines Some B cells switch programming

Differentiate to plasma cells that secrete other classes of antibodies Commonly IgG

Formation of memory› B cells that have undergone class

switching Produce IgG antibody

IgG is antibody of memory

IgG antibody can circulate in body for years allowing protection against specific antigens

Characteristics of secondary response› Memory cells responsible for swift effective

reaction of secondary response Often eliminate invaders before noticeable

harm is done› Vaccine exploits phenomenon of

immunologic memory› Some memory B cells will differentiate into

plasma cells Results in rapid production of antibodies

T-independent antigens› Can stimulate antibody

response Activate B cells without

helper T cells Few antigens are T-

independent› B cell receptors bind

antigen simultaneously Leads to B cell activation

› Some polysaccharides and lipopolysaccharides act as T-independent antigens

General characteristics of T cells› Have multiple copies of T cell

receptors Receptors have variable sites of

antigen bonding› Role of T cells different from B cells

T cells never produce antibodies T cells armed with effectors that

interact directly with antigen T cell receptor does not react with

free antigen Antigen must be present by APC

General Characteristics› During antigen presentation, antigen

cradled in grove of major histocompatability complex molecule (MHC molecule) Two types MHC

MHC class I Bind endogenous antigen

MHC class II Bind exogenous antigen

General characteristics› Two major function T cell populations

Cytotoxic T cells Proliferate and differentiate to destroy infected or

cancerous “self” cells Have CD8 marker Recognize MHC class I

Helper T cells Multiply and develop into cells that activate B cells

and macrophages Stimulate other T cells; orchestrate immune

response Have CD4 marker Recognize antigen display by MHC class II

Functions of Tc (CD8) cells› Induce apoptosis in “self” cells

Cells infected with virus or intracellular microbe

Destroys cancerous “self” cells

› Nucleated cells degrade portion of proteins Load peptides into groove of MHC class I

molecule MHC class I molecule recognized by

circulating Tc cell Cell destroyed by lethal effector function of

Tc cell Tc cells releases pre-formed cytokines to

destroy cell

Functions of TH (CD4) cells› Orchestrate immune response

Recognize antigen presented by MHC class II molecules MHC class II molecules found only on APC

If TH cell recognizes antigen, cytokines are delivered Cytokines activate APC to destroy antigen

Role of TH cells in B cell activation

› If TH cell encounters B cell bearing peptide: MHC calls II complex TH cell responds by producing cytokines

› B cell is activated in response to cytokine stimulation B cell proliferates and undergoes class

switching Also drives formation of B memory cells

Role of TH cells in macrophage activation› Macrophages routinely engulf

invading microbes resistant to lysosomal killing

› TH cells recognize macrophage with engulfed microbes resistant to killing

› TH cells activate macrophages by delivering cytokines that induce more potent destructive mechanisms

Natural killer cells descend from lymphoid stem cells› They lack antigen specificity

No antigen receptors Recognize antigens by means of Fc portion of IgG

antibodies Allow NK cells to attach to antibody-coated cells

Actions augment adaptive immune response› Important in process of antibody dependent

cellular toxicity Enable killing of host cells with foreign protein in

membrane

Natural killer cells recognize destroyed host cells with no MHC class I surface molecules› Important in viral infection

During lymphocyte development, B and T cells acquire ability to recognize distinct epitopes› Once committed to specific antigen, cells

“checked out” to ensure proper function› B cells undergo developmental stages in bone

marrow› T cells go through process in thymus