The Adaptive Immune Response Chapter 16. Strategy of Adaptive Immune Response First response to particular antigen called primary response May take a

The Adaptive Immune Response

Chapter 16

Strategy of Adaptive Immune Response

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

Immune systems remembers pathogen on subsequent exposure Termed secondary response

Adaptive immunity divided into Humoral immunity

Eliminates extracellular pathogens Cellular immunity

Eliminates intracellular pathogens

Strategy of Adaptive Immune Response

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 produces when

antigen bonds B cell receptor

Some B cells produce memory cells

Strategy of Adaptive Immune Response 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

Anatomy of the Lymphoid System

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 removes

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 cell 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


Nature of Antigens

Coined from compounds that elicit antibody production Antibody generator

Includes an enormous variety of materials Today term used to describe any compound that elicits

and immune response Antigen that causes immune response termed

immunogen Proteins and polysaccharides induce swong response

Lipids and nucleic acids often do not Recognition of antigen directed at antigenic determinant

or epitope

Nature of Antibody Structure of the Ab

Basic unit is the monomer Made of four chains of amino acids held together by disulfides

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 regions

Each heavy and light chain has a variable region Variable region is unique to each Ab This region binds to a specific Ag and is know as Fab region

Nature of Antibody

Protective outcomes of antibody-antigen binding Neutralization

Prevents virus or 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 Opsonization

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

Nature of Antibody

Nature of Antibody

Ab divided into five classes Class is based on

constant region of the Ab

Classes include: IgG IgA IgM IgD IgE

Five classes of antibody 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

Nature of Antibody

Five classes of antibody 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 secreations

Breast milk, mucous, tears and saliva

Nature of Antibody

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

Nature of Antibody

Clonal Selection of Lymphocytes

When antigen introduced into body only appropriate antibody bind Initiates multiplication of

specific antibody Process called clonal

selection Repeated cycles of cell

division generates population of copied cells

Termed clonal expansion

Without sustained stimulation cells undergo apoptosis

Lymphocyte characteristics include Naïve

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 speed and effectiveness of

secondary response Remembers antigen on subsequent exposure

Clonal Selection of Lymphocytes

B Lymphocyte and Antibody Response

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 call 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 cell proliferate and differentiate into increasing

numbers of plasma cells as long as antigen in present Net result is slow steady increase in antibody titer Overtime some B cells undergo changes enhancing

immune response including Affinity maturation Class switching Formation of memory cells


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 binds antigen more tightly



Class switching B cells initially programmed to

differentiate into plasma cells Plasma cells secrete IgM

antibodies Helper T cell produce

cytokines Some B cells switch

programming Differentiate to plasma cells

that secrete other classes of antibody

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 eliminating 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

T LymphocytesAntigen Recognition and Response

General characteristics of T cells Have multiple copies of T cell

receptors Receptors have variable site of

antigen bonding Role of T cells different from B

cells T cells never produce antibody T cells armed with effectors that

interact directly with antigen T cell receptor does not react

with free antigen Antigen must be presented

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 class 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 drive 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

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

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

antibodies Allows 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

Lymphocyte Development

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

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

marrow T cell go through process in thymus

Documents

The Adaptive Immune Response Chapter 16. Strategy of Adaptive Immune Response First response to particular antigen called primary response May take a