antigen and antibodies

Antigen or Immunogen

– molecule that generates an immune response; foreign molecular structures

Antigenicity

– ability of a molecule to be recognized by an antibody or lymphocyte

microbial antifen

• bacterial antigen

• viral antigen

• other microbial antigen

Bacterial Antigens

• The major components of bacterial surface are cell wall, capsule (K antigens), pili (F or K antigens), fimbriae and flagella (H antigens)

• Cell wall of gram-positive organisms is largely composed of peptidoglycan but in gram-negative organisms, the layer of peptidoglycan is thin covered by an outer membrane consisting of lipopolysaccharides

• The lipopolysaccharides in these organisms are mostly associated to the antigenicity of gram-negative bacteria

• Bacterial lipopolysaccharides in gram-negative bacteria are also called endotoxins

• Other bacterial antigens include:

  • i. Porins

    2. heat-shock proteins

    3. exotoxins – highly immunogenic proteins and stimulate the production of antibodies called antitoxins; when treated with formaldehyde. It will lose its toxicity but retains its antigenicity and thus it will modified and called toxoids
       

other bacterial antigen include

• porin

• heat shock protein

• exotoxin

exotoxin

highly immunogenic proteins and stimulate the production of antibodies called antitoxins; when treated with formaldehyde.

It will lose its toxicity but retains its antigenicity and thus it will modified and called toxoids

toxoid

It will lose its toxicity but retains its antigenicity and thus it will modified

endotoxin

• Bacterial lipopolysaccharides in gram-negative bacteria are also

K antigen

capsule

F or K antigen

pili

H antigen

fimbriae and flagella

• gram-positive organisms

• largely composed of peptidoglycan

• gram-negative organisms

• ayer of peptidoglycan is thin covered by an outer membrane consisting of lipopolysaccharides

viral protein

• Can grow only inside living cells, thus, are “obligate”, intracellular parasites

• Capsid proteins are good antigens and are highly capable of provoking antibody formation

• Proteins in the virions act as antigens and trigger acquired immune response

• Viral nucleic acid can be integrated into a cell’s genome. The viral genes code for new proteins, some of which are carried to the surface of infected cells and are then considered foreign and can provoke strong immune responses

capsid protein

• good antigens and are highly capable of provoking antibody formation

Non-microbial Antigens

Some food may contain foreign molecules which may trigger an immune response and cause allergic reaction.

Inhaled dusts can contain fungal spores or pollen grains and enter the respiratory system. Snake bite or mosquito bite may inject foreign molecule

factors that signidicantly influence the antigenicity of a molecule

• ✓  Size

• ✓  Complexity

• ✓  Dose

• ✓  Route of administration

• ✓  Host genetics

• ✓  Chemical stability

• ✓  Foreignness

waht makes a good antigen

foreignness

• however, not all foreign molecules can stimulate immune

  response. (e.g. steel bone pins and plastic heart valves)

• This is due to the molecular uniformity and inertness. These polymers cannot be degraded and processed by cells

Epitopes or antigenic determinants

• These are sites on the surface of an antigen that stimulates a specific immune response

• Many different epitopes may be recognized by the immune system, but some are much more immunogenic than others

Haptens

• Small molecule that cannot initiate an immune response unless it is bound to an immunogenic carrier molecule

• The antigenic molecule to which the haptens are attached is called the ‘carrier’

example of hapten

o Antibiotic penicillin (small nonimmunogenic molecule) → forms “penicilloyl” group when degraded in the body→bind to serum proteins such as albumin→penicilloyl-albumin complex→penicilloyl hapten→recognized as foreign epitope in some individuals → antibodies response and cause allergic reaction

o Resin of poison ivy plant called urushiol → binds to protein it comes in contact (e.g. skin proteins of person who rubs against the plant) → modified skin proteins→regarded as foreign→attacked my lymphocytes →allergic contact dermatitis

cross reactivity

• There are instances that identical or similar epitopes can be found on apparently unrelated molecules.

• Antibodies directed against one antigen may react unexpectedly with an unrelated antigen

• Antibodies directed against a protein in one species may also react in a detectable manner with homologous or similar protein in another species

antibodies

• Once B cell response is triggered, the receptors are shed into the surrounding fluid, where they act as antibodies

• They bind to specific antigens and facilitates removal by phagocytes, activate complement and neutralize the activity of the antigen

• They are glycoproteins called Immunoglobulins

• Consists of two pairs of protein: the heavy and light chain linked together by disulfide bond

• Antibodies monomers have a Y shape with an antigen-binding site at the end of each arm of the Y. The tail of the Y is the Fc region.

• The antibody monomer is composed of two identical heavy chains and two identical light chains; each chain forms several domains. The variable region contains the antigen binding site; the constant region encompasses the entire Fc region as well as part of the Fab regions.

• two pairs of protein:

• the heavy and light chain linked together by disulfide bond

• Antibodies monomers

• have a Y shape with an antigen-binding site at the end of each arm of the Y.

Fc region

• The tail of the Y

immunoglobulin

they are glycoprotein

antibodies

• function

o Primary: bind to antigen
o Neutralize bacterial toxin
o Prevent viral attachments to cells by forming bridge between phagocyte and invader

immunoglobulin classes

• IgG

• IgM

• IgA

• IgE

• IgD

immunoglobulin variation

1. allotypes

2. idiotypes

Immunoglobulin G (IgG)

• Highest concentrations in serum

• Made and secreted by plasma cells in the spleen, lymph nodes, and bone

  marrow

• Plays the major role in antibody-mediated defense mechanisms

• Consists of two identical light chains and two gamma heavy chains

• Smallest antibody (can escape from the blood vessels more easily)

• Major antibody of secondary immune response

Immunoglobulin M (IgM)

• Also produced by plasma cells in the spleen, lymph nodes and bone marrow

• Second highest concentration in serum

• The major antibody produced during a primary immune response although it is also produced during secondary immune response

• Considerably more efficient than IgG at complement activation, opsonization, neutralization of viruses and agglutination

• Due to very large size, they rarely enter tissue fluids at sites of inflammation

Immunoglobulin A (IgA)

• Secreted by plasma cells located under body surfaces (e.g. in the walls of intestine, respiratory tract, urinary system, skin and mammary gland

• Main antibody on the mucosal surfaces of the body

• Either pass through epithelial cells into external secretions or diffuse into the bloodstream

• Prevents antigens adhering to body surfaces (important in protecting the intestinal, respiratory, and urogenital tracts, mammary gland and the eyes against microbial invasion

• Does not opsonize antigens and does not activate the classical complement pathway

• Secreted in milk of lactating dams

Immunoglobulin E (IgE)

• Also produced beneath body surfaces

• Typical Y-shaped, four-chain immunoglobulin with four constant domains in its

heavy chains

• Present in extremely low concentrations in serum

• Cannot simply bind and coat antigens but triggers acute inflammation by acting

as a signal transducing molecule (signaling molecule) and are found on the

surface of mast cell and basophil

• Has the shortest half-life (2-3 days)

• An important immune response to parasites

Immunoglobulin D (IgD)

• Unique because it has not been detected in all mammals

• It is present in primates, rodents, cattle, sheep, pigs and dogs

• Absent in horses, rabbits and chickens

• Present only in trace amounts

• Can be destroyed by mild heat treatment like IgE

Allotypes

• The inherited sequence variations in heavy chain genes of the immunoglobulin

• Thus, immunoglobulins of one individual may differ from those of another

  individual of the same species

Idiotypes

• Results from the variations in the amino acid sequences within the variable domains on light and heavy chains

• Differences associated with the antigen-binding region of an antibody

Monoclonal Antibodies

– antibodies specific for one antigen; produced by hybridoma (cell line derived by the fusion of a single normal B cell and an immortal B cell tumor line); widely use in research

Polyclonal Antibodies

– collection of antibodies from different B cells that recognize multiple epitopes on the same antigen

Affinity

- a measure of the binding strength between an antigenic determinant (epitope) and an antibody binding site (paratope)

Avidity

the total strength of all the interactions in an antibody-antigen complex which may have more than on bonding site; it is influenced by affinity as well as structural arrangements of epitope and variable regions of antibody

Antigen binding site

– part of an antibody that binds antigen

Anti-serum

– serum that contains a detectable number of antibody molecules that bind to a particular antigen

Diversity

– presence of large numbers of antibodies that bind different specificities

Domain

– a region found in molecules coded for by members of the immunoglobulin supergene family, which comprises approximately 110 amino acids

Fab (Fragment antigen binding)

– part of an antibody which contains the antigen binding site of the molecule composed of the variable regions of one light chain and one heavy chain

Fc (Fragment crystallizable)

– fragment of an antibody molecule lacking the antigen binding sites caused by papain digestion. It contains the constant regions of both the heavy chains from the hinge region to the carboxyl terminus of the molecules

Paratope

– part of an antibody molecule which makes contact with the antigenic determinant

Serum

– residual fluid when blood forms clot and is where antibodies can be found