Lector Tvorko M. S.

 ANTIBODIES (IMMUNOGLOBULINS) Antibodies are globulin proteins (immunoglobulins) that react specifically with the antigen that stim ulated their production. They make up about 20% of the protein in blood plasma.. There are five classes of antibodies: IgG, IgM, IgA, IgD, and IgE.

IMMUNOGLOBULIN STRUCTURE Immunoglobulins are glycoproteins made up of light (L) and heavy (H) polypeptide chains. The terms "light" and heavy" refer to molecular weight; The simplest antibody molecule has a Y shape and consists of four polypeptide chains: two H chains and two L chains. The four chains are linked by disulfide bonds. An individual antibody molecule always consists of identical H chains and identical L chains.

Heavy (H) polypeptide

chains

Class of immunoglobulin

Ig G

Ig M

Ig A

Ig E

Ig D

The Immune system includes 5 classes of Immunoglobulin (Ig)

Ig M - (22)5, (22)5Ig A - (22)n , (22)n,,

Ig E - 22, 22

IgD - 22, 22

Ig G - 22,,22

If an antibody molecule is treated with a proteolytic enzyme such as papain, peptide bonds in the "hinge" region are broken, producing two identical Fab fragments, which carry the antigen-binding sites, and one Fc fragment, which is involved in placenta! transfer, complement fixation, attachment site for various cells, and other biologic activities

IgG. Each IgG molecule consists of two L chains and two H chains linked by disulfide bonds (molecular formula H2L2). Because it has two identical antigen-binding sites, it is said to be divalent.

IgG is the predominant antibody in the secondary-response and constitutes an important defense against bacteria and viruses. IgG is the only antibody to cross the placenta only its Fc portion binds to receptors on the surface of placental cells. It is therefore the most abundant immunoglobulin in newborn. IgG is one of the two immunoglobulins that can activate complement and opsonizes.

IMMUNOGLOBULIN CLASSESIMMUNOGLOBULIN CLASSES

IgM is the main immunoglobulin produced early in the primary response. It is present as a monomer on the surface of virtually all B cells, where it functions as an antigen-binding receptor In serum, it is a pentamer composed of 5 H2L2 units plus one molecule of J (joining) chain. Because the pentamer has 10 antigen-binding sites, it is the most efficient immunoglobulin in agglutination, complement fixation (activation), and other antibody reactions and is important in defense against bacteria and viruses. It can be produced by the fetus in certain infections. It has the highest avidity of the immunoglobulins; its interaction with antigen can involve all 10 of its binding sites.

IgA is the main immunoglobulin in secretions such as colostrum, saliva, tears, and respiratory, intestinal, and genital tract secretions. It prevents attachment of bacteria and viruses to mucous membranes. Each secretory IgA molecule consists of two H2L2 units plus one molecule each of J (joining) chain and secretory component. The secretory component is a polypeptide synthesized by epithelial cells that provides for IgA passage to the mucosal surface. It also prelects IgA from being degraded in the intestinal tract. In serum, some IgA exists as monomericH2L2.

IgE is medically important for two

reasons: (1) it mediates immediate (anaphylactic) hypersensitivity, and (2) it participates in host defenses against certain parasites, eg, helminths (worms). The Fc region of IgE binds to the surface of mast cells and basophils. Although IgE is present in trace amounts in normal serum (approximately 0.004%), persons with allergic reactivity have greatly increased amounts, and IgE may appear in external secretions. IgE does not fix complement and does not cross the placenta.

IgD. This immunoglobulin has no known antibody function but may function as an antigen receptor; it is present on the surface of many

B lymphocytes. It is present in small amounts in serum.

Major Functions of Human ImmunoglobulinsMajor Functions of Human Immunoglobulins• Function IgM Main Ig during Primary Response (Early

antibody).Fixes Complement (most effectively).

• IgG Main Ig during Secondary Response (late antibody).Opsonization.Fixes Complement.Neutralizes Toxins, Viruses.

• IgA Secretory mucosal IgPrevents invasion from gut mucosa.

• IgE Immediate Hypersensitivity.Mast cell and Basophil reactions.Activates Eosinophils in helminth infection

• IgD Function Unknown.Mostly on the Surface of B cells. 

Immunoglobulins

• Antibody-mediated mechanisms of antigen disposalBinding of antibodies to antigens

inactivates antigens by

Viral neutralization(blocks binding to host)

and opsonization (increasesphagocytosis)

Agglutination ofantigen-bearing particles,

such as microbesPrecipitation ofsoluble antigens

Activation of complement systemand pore formation

Bacterium

Virus Bacteria

Solubleantigens Foreign cell

Complementproteins

MAC

Pore

Enhances

Phagocytosis

Leads to

Cell lysis

Macrophage

• Class II MHC molecules, located mainly on dendritic cells, macrophages, and B cells– Display antigens to helper T cells

1

2

Microbe Antigen-presentingcell

Antigenfragment

Class II MHCmolecule

T cellreceptor

Helper T cell

A fragment offoreign protein(antigen) inside thecell associates withan MHC moleculeand is transportedto the cell surface.

1

The combination ofMHC molecule andantigen is recognizedby a T cell, alerting itto the infection.

2

(b)

Infected cell

Antigenfragment

Class I MHCmolecule

T cellreceptor

(a) Cytotoxic T cell

A fragment offoreign protein(antigen) inside thecell associates withan MHC moleculeand is transportedto the cell surface.

1

The combination ofMHC molecule andantigen is recognizedby a T cell, alerting itto the infection.

2

1

2

• Class I MHC molecules, found on almost all nucleated cells of the body– Display peptide antigens to cytotoxic T cells

• The role of helper T cells in acquired immunity

After a dendritic cell engulfs and degrades a bacterium, it displays bacterial antigen fragments (peptides) complexed with a class II MHC molecule on the cell surface. A specific helper T cell binds to the displayed complex via its TCR with the aid of CD4. This interaction promotes secretion of cytokines by the dendritic cell.

Proliferation of the T cell, stimulatedby cytokines from both the dendritic cell and the T cell itself, gives rise toa clone of activated helper T cells(not shown), all with receptors for thesame MHC–antigen complex.

The cells in this clonesecrete other cytokines that help activate B cellsand cytotoxic T cells.

Cell-mediatedimmunity(attack on

infected cells)

Humoralimmunity

(secretion ofantibodies byplasma cells)

Dendriticcell

DendriticcellBacterium

Peptide antigenClass II MHC

molecule

TCR

CD4

Helper T cell

Cytokines

Cytotoxic T cell

B cell

1

2 3

1

2 3

21

3

B cell

Bacterium

Peptide antigen

Class II MHCmolecule

TCR

Helper T cell

CD4

Activated helper T cell Clone of memory

B cells

Cytokines

Clone of plasma cellsSecreted antibodymolecules

Endoplasmicreticulum of plasma cell

Macrophage

After a macrophage engulfs and degradesa bacterium, it displays a peptide antigencomplexed with a class II MHC molecule.A helper T cell that recognizes the displayed complex is activated with the aid of cytokines secreted from the macrophage, forming a clone of activated helper T cells (not shown).

1 A B cell that has taken up and degraded the same bacterium displays class II MHC–peptide antigen complexes. An activated helper T cellbearing receptors specific for the displayedantigen binds to the B cell. This interaction,with the aid of cytokines from the T cell,activates the B cell.

2 The activated B cell proliferatesand differentiates into memoryB cells and antibody-secreting plasma cells. The secreted antibodies are specific for the same bacterial antigen that initiated the response.

3

Humoral Immune response

Cytotoxic T cell

Perforin

Granzymes

CD8TCRClass I MHCmolecule

Targetcell Peptide

antigen

Pore

ReleasedcytotoxicT cell

Apoptotictarget cell

Cancercell

CytotoxicT cell

A specific cytotoxic T cell binds to a class I MHC–antigen complex on a target cell via its TCR with the aid of CD8. This interaction, along with cytokines from helper T cells, leads to the activation of the cytotoxic cell.

1 The activated T cell releases perforin molecules, which form pores in the target cell membrane, and proteolytic enzymes (granzymes), which enter the target cell by endocytosis.

2 The granzymes initiate apoptosis within the target cells, leading to fragmentation of thenucleus, release of small apoptotic bodies, and eventual cell death. The released cytotoxic T cell can attack other target cells.

3

12

3

• The activated cytotoxic T cell– Secretes proteins that destroy the infected target

cell

Immune synapsis