9. antibodies

2 branches of adaptive immune response

1. humoral response: antibody production by plasma cells

2. cell-mediated response (aka T cell mediated immunity): cytokine secretion & killing of altered self-cells

**note: B cells need to interact with T cells to produce most antibodies

antibodies belong to which category of globulins?

gamma globulins

what are antibodies?

antigen-specific products of B cells

• only secreted antigen-specific product

characteristics of antibodies

• highly effective when pathogen is outside the cell

• can function at sites distant from site of production

• high binding specificity → can distinguish between a single amino acid

• high binding versatility (collectively) → ~10⁷ diff specificities

• biological activity → have effector functions on their own

Fab

fragment antigen binding → two identical fragments able to bind antigen

Fc

fragment crystallizable → effector functions

general antibody structure

symmetric core structure

• 2 identical light chains

• 2 identical heavy chains

• constant region

• variable region

how are the antibody chains held together?

disulfide bonds (covalent linkage)

constant region

• consistent among antibodies of the same class

• towards carboxy terminal end

• effector functions (includes Fc region)

  • complement binding

  • Fc binding for phagocytosis, NK cells

variable region

• differs between different Ab

• concentrated at amino terminal end

• antigen-binding site formed by both light and heavy chains

complementarity-determining regions (CDRs)

• hypervariable regions of the light and heavy chains

• 3 per variable region of each light and heavy chain

• 6 CDRs together form one antigen-binding site

how are isotypes (antibody classes) determined?

based on differences in the structure of the constant region of their heavy chain → determine effector function

general characteristics of IgG

• predominant Ig of blood

• found in all body fluids

• monomer; smallest Ig

• longest half-life

• passive transfer

IgG functions

• neutralization

• agglutination

• opsonization

• complement activation → need >1 binding relatively close to each other to activate due to small size

hinge region (IgG)

increases flexibility for arms to move around

general characteristics of IgM

• macroglobulin

• intravascular → (difficulty moving from circulation into tissues)

• major Ig of primary immune response (first dose of antigen)

  • detecting IgM > IgG indicates recent, new infection

IgM structure

• no hinge region

• 4 heavy chain constant domains (C_H)

  • compared to 3 in IgG

• 1 unit → membrane receptor on surface of naive B cell

• 5 units → secreted

  • J chain helps hold structure together

IgM functions

• agglutination

• complement activation → better at activating; only need 1 to activate due to large size

serum IgA

• found as dimer in blood

  • J chain

• cannot activate complement → Fc portion not as exposed

• extremely small concentrations in blood

secretory IgA

• major secretory Ig in non-ruminants (external secretions)

  • mucosal secretions (GI, respiratory, urogenital)

  • glandular secretions (milk, saliva, tears & sweat)

• dimer with a J chain

• secretory component produced by epithelial cells

IgA functions

mucosal immunity

• prevents attachment & penetration of microbes

• neutralization of toxins and viruses

how does IgA acquire its secretory component?

plasma cells in sub-epithelial mucosa/glands secrete dimer IgA → IgA attaches to poly-Ig receptor → receptor mediated endocytosis → enzymatic cleavage of poly-Ig receptor → part of poly-Ig receptor remains on IgA, becoming the secretory component

what is the function of the secretory component?

helps resist proteloytic digestion (ex. in the GI tract)

IgE

• 1 unit (monomer) produced by plasma cells in submucosal surface

• extra C_H domain binds IgE-specific receptors on basophils and mast cells → induces degranulation and release of granule contents

IgE functions

• parasitic immunity

• also involved in type I hypersensitivity

  • allergic responses (ex. feline allergic asthma)

IgD

• 1 unit (monomer)

• not in all species

• long hinge region

• found as membrane receptor on early B cells

(not really important for this class)