Immunology

AntigensAntigens Some chemical that creates immune responseSome chemical that creates immune response Most are Most are proteinsproteins or large or large polysaccharidespolysaccharides from from

a foreign organism.a foreign organism. MicrobesMicrobes: Capsules, cell walls, toxins, viral capsids, : Capsules, cell walls, toxins, viral capsids,

flagella, etc.flagella, etc. NonmicrobesNonmicrobes: Pollen, egg white , red blood cell : Pollen, egg white , red blood cell

surface molecules, serum proteins, and surface surface molecules, serum proteins, and surface molecules from transplanted tissue. molecules from transplanted tissue.

AntigensAntigensEpitopeEpitope: : Small part of an antigen that interacts Small part of an antigen that interacts

with an antibody. 10-12 amino acidswith an antibody. 10-12 amino acids Any given antigen may have several Any given antigen may have several

epitopes.epitopes. Each epitope is recognized by a different Each epitope is recognized by a different

antibody.antibody.

Epitopes: Antigen Regions that Interact with Antibodies

AntibodiesAntibodies Proteins Proteins that recognize and bind to a particular that recognize and bind to a particular

antigen with very high antigen with very high specificityspecificity.. Made in response to exposure to the antigen.Made in response to exposure to the antigen. One virus or microbe may have several One virus or microbe may have several antigenic antigenic

determinant sitesdeterminant sites, to which different antibodies , to which different antibodies may bind.may bind.

Each antibody has at least two identical sites Each antibody has at least two identical sites that bind antigen: that bind antigen: Antigen binding sitesAntigen binding sites..

Belong to a group of serum proteins called Belong to a group of serum proteins called immunoglobulins (Igs).immunoglobulins (Igs).

Antibody StructureAntibody Structure MonomerMonomer: A flexible Y-shaped molecule with : A flexible Y-shaped molecule with

four protein chains:four protein chains: 2 identical 2 identical lightlight chains chains 2 identical 2 identical heavyheavy chains chains

Variable RegionsVariable Regions: Two sections at the end of : Two sections at the end of Y’s arms. Contain the Y’s arms. Contain the antigen binding sites antigen binding sites (Fab)(Fab). Identical on the same antibody, but vary . Identical on the same antibody, but vary from one antibody to another.from one antibody to another.

Constant RegionsConstant Regions: Stem of monomer and lower : Stem of monomer and lower parts of Y arms.parts of Y arms.

Fc regionFc region: Stem of monomer only. Important : Stem of monomer only. Important because they can bind to complement or cells.because they can bind to complement or cells.

Antibody Structure

How Do B Cells Produce Antibodies?How Do B Cells Produce Antibodies? B cells develop from B cells develop from stem cellsstem cells in the bone in the bone

marrow of adults (liver of fetuses).marrow of adults (liver of fetuses). After maturation B cells migrate to lymphoid After maturation B cells migrate to lymphoid

organs (lymph node or spleen). organs (lymph node or spleen). Clonal SelectionClonal Selection: When a B cell encounters an : When a B cell encounters an

antigen it recognizes, it is stimulated and divides antigen it recognizes, it is stimulated and divides into many clones called into many clones called plasma cellsplasma cells, which , which actively secrete antibodies.actively secrete antibodies.

Each B cell produces antibodies that will Each B cell produces antibodies that will recognize only one antigenic determinant.recognize only one antigenic determinant.

Clonal Selection of B Cells is Caused by Antigenic Stimulation

Humoral ImmunityHumoral ImmunityApoptosisApoptosis Programmed cell death (“Falling away”).Programmed cell death (“Falling away”). Human body makes 100 million lymphocytes Human body makes 100 million lymphocytes

every day. If an equivalent number doesn’t die, every day. If an equivalent number doesn’t die, will develop leukemia.will develop leukemia.

B cells that do not encounter stimulating antigen B cells that do not encounter stimulating antigen will self-destruct and send signals to phagocytes will self-destruct and send signals to phagocytes to dispose of their remains.to dispose of their remains.

Many virus infected cells will undergo apoptosis, Many virus infected cells will undergo apoptosis, to help prevent spread of the infection.to help prevent spread of the infection.

Humoral Immunity (Continued)Humoral Immunity (Continued)Clonal SelectionClonal Selection Clonal SelectionClonal Selection: B cells (and T cells) that : B cells (and T cells) that

encounter stimulating antigen will proliferate into encounter stimulating antigen will proliferate into a large group of cells.a large group of cells.

Why don’t we produce antibodies against our Why don’t we produce antibodies against our own antigens? own antigens?

Clonal DeletionClonal Deletion: B and T cells that react against : B and T cells that react against selfself antigens appear to be destroyed during fetal antigens appear to be destroyed during fetal development. Process is poorly understood.development. Process is poorly understood.

Autoimmune diseases like Lupus, Rheumatic Autoimmune diseases like Lupus, Rheumatic fever, Rheumatoid arthritis occur when fever, Rheumatoid arthritis occur when antibodies attack selfantibodies attack self

Central Role of Helper T Cells

Types of T cells (Continued)Types of T cells (Continued)Cytotoxic T (Tc) Cells: Cytotoxic T (Tc) Cells: Destroy target cells.Destroy target cells.Recognize antigens on the surface of all cells:Recognize antigens on the surface of all cells:

• Kill host cells that are infected with viruses or bacteria.Kill host cells that are infected with viruses or bacteria.• Recognize and kill cancer cells.Recognize and kill cancer cells.• Recognize and destroy transplanted tissue.Recognize and destroy transplanted tissue.

Release protein called Release protein called perforinperforin which forms a pore in which forms a pore in target cell, causing lysis of infected cells.target cell, causing lysis of infected cells.

Undergo Undergo apoptosisapoptosis when stimulating antigen is gone. when stimulating antigen is gone.

Cytotoxic T Cells Lyse Infected Cells

Immunoglobulin Heavy Chain – 110 amino acids longHeavy Chain – 110 amino acids long

100 distinct V segments100 distinct V segments 30 D segments30 D segments 6 J segments6 J segments Enzymes choose one V segment, one D segment and one Enzymes choose one V segment, one D segment and one

J segment and fuse them togetherJ segment and fuse them together 18,000 combinations in encoding antibody molecule18,000 combinations in encoding antibody molecule Splice this variable region to the constant regionSplice this variable region to the constant region

Light Chain – 211 amino acids longLight Chain – 211 amino acids long 10,000 combinations10,000 combinations Total of 180,000,000 distinct B cellsTotal of 180,000,000 distinct B cells

Fusion is sloppy, can create other variantsFusion is sloppy, can create other variants

Relationship Between Cell-Mediated Relationship Between Cell-Mediated and Humoral Immunityand Humoral Immunity

1. Antibody Production1. Antibody ProductionT-Dependent Antigens:T-Dependent Antigens:

Antibody production requires assistance from T helper cells.Antibody production requires assistance from T helper cells. A macrophage cells ingest antigen and presents it to TA macrophage cells ingest antigen and presents it to THH cell. cell. TTHH cell stimulates B cells specific for antigen to become plasma cell stimulates B cells specific for antigen to become plasma

cells.cells. Antigens are mainly proteins on viruses, bacteria, foreign red Antigens are mainly proteins on viruses, bacteria, foreign red

blood cells, and hapten-carrier molecules.blood cells, and hapten-carrier molecules.

Humoral Response to T Dependent Antigens

Overview of the Immune Response

immunoglobulins

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