PH 183 Lecture 3

What is a substance identified or recognized by the host's body as foreign?

Antigen

What antigen originates from outside the body and is not part of the human body?

Foreign antigens/heteroantigens

Foreign antigens are also called as?

Heteroantigens

Foreign antigens can be categorized into what two categories?

1) microbial agents 2) non-microbial agents

What foreign antigens include whole microbes or their parts?

Microbial agents

Give example/s of microbial agents.

capsules, cell walls, flagella, toxins of bacteria, coats of viruses or any surface component of microbes

What foreign antigens arise from animals, plants, and other humans?

Non-microbial agents

Give example/s of non-microbial agents.

Pollen, egg white, serum proteins, blood cells from another individual, and transplanted tissues and organs are

What are antigens that arise from the body's own cells and molecules?

Self antigens/Autoantigens

Self antigens are also called?

Autoantigens

Antibodies bind to the whole antigen.

False; Antibodies do not bind to the whole antigen but bind to epitope.

Antigens are mostly?

Large protein molecules

Immune system does recognize whole pathogen.

False; Immune system does not recognize whole pathogen but their portions or parts called antigens.

Can self-antigens elicit an immune response?

Yes, in cases of autoimmune diseases.

Regions or site of an antigen that are recognized by the immune system, and as a result, they are bound to specific antibodies or T cell receptors?

Epitopes

Epitopes are also known as?

Antigenic determinants

Each antigen can have several epitopes.

TRUE

Why can a single protein antigen produce more than one type of antibody (polyclonal antibody)?

A single protein antigen can contain many different epitopes to which multiple antibody-producing B cells can bind.

What cells of adaptive immunity deals with extracellular pathogens?

B cells

Where are B cells produced and mature?

bone marrow

When B cells are activated, they get differentiated into?

plasma cells and memory cells

What cells of adaptive immunity deals with intracellular pathogens?

T cells

Where are T cells produced?

bone marrow

Where do T cells mature?

thymus

What are the T cell subsets that activated T cells differentiate into?

T cytotoxic cells and T helper cells

What is the ability of a substance to induce either humoral or cellular immune response?

Immunogenicity

What is the ability of a substance to to bind specifically to products of an immune response?

Antigenicity

Are haptens immunogenic or antigenic?

Antigenic

All molecules that are immunogenic are antigenic.

TRUE

All molecules that are antigenic are immunogenic.

FALSE

Cell-mediated immunity involve what immune cell?

T cells

Humoral immunity involve what immune cell?

B cells

It is the ability of a substance to induce an immune response.

Immunogenicity

The ability of a substance to bind specifically to the products of the immune response.

Antigenicity

Any substance that induces an immune response.

Immunogen

Any substance that is capable of binding specifically to the components of the immune system such as to the antibodies.

Antigen

What are the properties determining immunogenicity?

Foreignness, molecular size, chemical complexity, and stability or degradability.

How is foreignness related to its immunogenicity?

More foreign a molecule is, more is its immunigenicity.

How is molecular size related to its immunogenicity?

The larger the substance is, the more immunogenic it is.

What is the immunogenicity of a substance with molecular weight of more than 10,000 Da?

Immunogenic

What is the immunogenicity of a substance with molecular weight of about 100,000 Da?

Highly immunogenic

What is the immunogenicity of a substance with molecular weight of less than 10,000 Da?

Weakly immunogenic

Antigens can be composed of?

carbohydrates, lipids, nucleic acids, or proteins

Immunogenic only if relatively complex polysaccharide structure or when associated with protein carriers.

Carbohydrate Antigens

Give an example of carbohydrate antigen?

blood group antigens

Not immunogenic by themselves, only when they are conjugated to protein carriers.

Lipids and Nucleotide Antigens

Powerful immunogens due to their molecular complexity, size, variety of amino acids, and four level of structures.

Protein Antigens

What is the relationship of molecular complexity and immunogenicity?

Molecules with complex nature are more immunogenic.

What us the relationship of stability or degradability and immunogenicity?

Less soluble and degradable a substance is, the more immunogenic it is.

Adaptive immunity mechanism mediated by T-cell, directed against intracellular pathogens and kill infected cells, tumor cells, etc.

Cell-Mediated Immunity

What immune cells protect extracellular spaces?

B cells

Where do B cells originate and mature?

Bone marrow

After maturation, where do B cells go?

To the blood; recirculate between lymph, blood, and secondary lymphoid tissues.

How do B-cells get activated?

(1) T-dependent activation and (2) T-independent activation

Once activated, what do B cells become?

(1) Effector cells (i.e., Plasma cells) or (2) Memory B cells

Describe the antibody produced by plasma cells.

Specific antibodies recognized by the B cells.

These are glycoproteins shaped like a Y, having two antigen-binding sites, and a stalk called the Fc region.

Antibodies

Why are antibodies called "immunoglobulins?"

Because they belong to a group of GLYCOPROTEINS called GLOBULINS.

True or False. The basic structure of all antibodies and the structure of BCRs is similar.

TRUE

BCR vs Antibody

BCRs are membrane-bound immunoglobulin; Antibodies are secreted immunoglobulins

All antibodies have the same core structure. Enumerate.

(1) Four polypeptide chains, composed of two identical H chains, and two identical L chains, (2) disulfide bonds, and (3) the hinge region

In an antibody structure, where are the NH3- located?

Tip end

In an antibody structure, where are the COO- located?

Base of polypeptide chain

Hinge region purpose

Adjust to varying spatial arrangements of antigens/epitopes; it allows the Ab to rotate and bend

To each heavy polypeptide chain, ______ are attached.

short carbohydrate chains

Function of carbohydrate chains in an antibody?

Increasing the solubility of immunoglobulins.

What attaches the light chain to a heavy chain?

Disulfide bond

How many S-S bonds connect two heavy chains?

Two S-S bonds

These are the two shorter subunits of a basic antibody molecule.

Light Chains

How much do L chains weigh?

About 25 kDa

How many polypeptides are in each light chain?

~220 amino acids

In humans, there are two types of light chains. What are those?

Kappa chains and Lambda chain

Kappa chain vs lambda chain [light chain]

Kappa chain is encoded in Chromosome 2, while Lambda chain is encoded in Chromosome 22.

True or False. Each antibody produced by a B-cell should have both kappa or lambda light chains because these are important in antigen recognition via epitope.

False. Either kappa or lambda, never both.

The human body has how many percentages of kappa and lambda light chains?

Kappa light chains = 60%; Lambda chains = 40%

These are the longer subunits of the antibody structure.

Heavy Chains

What is the molecular weight of heavy chains?

~50-70 kDa

How many amino acids comprise each heavy chain?

~440 amino acids

In humans, there are five types of heavy chains. On what chromosome are they encoded?

Chromosome 14

What are the five classes of heavy chains?

α (IgA), δ (IgD), ε(IgE), γ(IgG) and μ

Each antibody has two distinct regions. What are those?

Variable Regions and Constant Regions

These regions have the first 110 or so amino acids of the N-terminal region of both light and heavy chains.

Variable Regions

Why is it called variable region?

Because the amino acids in these sequences have great variability

The antigen-binding sites are formed by?

Variable Light Chains and Variable Heavy Chains

Variability of amino acids in variable regions are precisely organized. What do we call these areas?

Hypervariable regions or Complementarity Determining Regions (CDRs)

What is the importance of Complementarity Determining Regions?

These regions form a complementary structure to the specific antigen bound by the antibody.

In the variable region, how many complementarity determining regions are there?

Three, designated as CDR1, CDR2, and CDR3

What do we call the intervening sequences between CDRs?

Framework Residues

When are CDRs brought together?

When the antibody molecule folds to its native conformation

What do we call the regions beyond the region of both heavy and light chains?

Constant Regions

Why do we call it "constant" region?

Because the amino acid sequence in this region shows little variation among antibodies.

Constant regions in heavy chains are ____.

3-4

What is the basis of antibody classification?

Heavy chain constant region

Each variable and constant region in an antibody molecule has at least one disulfide bond. What do you call these S-S bonds?

Internal Disulfide Bonds

What werethe key experiments that revealed the antibody structure?

(1) Proteolytic treatment of immunoglobulin with enzymes papain and pepsin and (2) chemical treatment of immunoglobulin with mercaptoethanol.

Who were the scientists who shared the 1972 Nobel Prize in Physiology or Medicine for determining chemical structure of antibody?

Gerald M. Edelman and Rodney R. Porter

What will happen if antibody is treated with papain?

It cuts the antibody molecularbefore the 2 disulfide bonds link the two heavy chains, thus, splitting the antibody into 3 fragments (2 light chains (Fab), 1 heavy chain(Fc)) of about equal size,

What will happen if antibody is treated with mercaptoethanol?

It breaks disulfide bonds resulting to the splitting of antibody into 2 light chains (22 kDa each) and 2 heavy chains (53 kDa each).

What will happen if antibody is treated with pepsin?

It cleaves the antibody at the C terminal resulting to the splitting into 2 fragments — F(ab')2 and pieces of Fc fragments.

Antigen binding fragments that containd variable region at the first constant region of n-terminal side.

Fab