Functions of Immunoglobulins (humoral immunity II) Flashcards
Antibody function is related to _______!
Structure
*structural differences between the antibody isotypes allow them to confer different functions.
What factors are influenced by the sequence difference between immunoglobulin heavy chains?
1) The number of constant domains
2) Number and location of oligosaccharide groups
3) Number and location of interchain disulphide bonds
4) Length of the hinge region
*these differences can confer distinct functions for each immunoglobulin isotype.
1) What is a unique feature of IgM and IgA?
2) What role does the J chain play, and how does it impact IgM and IgA?
1) IgM and IgA contain a tailpiece of 18 amino acids that contains a CYSTEINE residue for POLYMERIZATION.
2) An additional polypeptide called the J chain promotes POLYMERIZATION by linking the cysteine residues together. IgM becomes a pentamer and IgA becomes a dimer.
1) What advantages does the pentameric structure of IgM provide?
2) What is the function of the dimeric IgA?
1) IgM are generally low affinity BUT they can form PENTAMERS that have 10 antigen-binding sites. This confers overall HIGHER AVIDITY when binding to multivalent antigens.
2) IgA can form DIMERS that function mainly in epithelial surfaces of intestinal and respiratory tracts—and functions largely as a neutralizing antibody (mucous secretions).
Which one of the statements is true?
1) Due to the large pentameric size, IgM is generally found in the intercellular spaces within tissues.
2) The J chain segment should not be confused with the J gene segment in immunoglobulins.
2!
For 1) Due to the large pentameric size, IgM is generally found in the BLOODSTEAM (or to a lesser extent in the lymph) RATHER THAN INTERCELLULAR spaces within tissues.
1) Which immunoglobulin isotype is predominant in secretions and epithelium lining?
2) Which immunoglobulin isotypes are smaller than IgM? What does this allow for?
3) What does IgE bind to?
1) IgA is a major isotype in secretions and epithelium lining.
2) IgG, IgA, and IgE are smaller and can DIFFUSE OUT OF BLOOD AND INTO TISSUES.
3) IgE binds avidly to receptors on MAST cells that are found beneath the skin/mucosa/connective tissues.
Maternal ___ is transported across the placenta directly into the bloodstream of the fetus. Babies at birth already have ___ levels of this isotype, with the ____ range of antigen specificity as the mother.
___ antibodies are secreted in breast milk and are transported across the ____ _______ of newborns where they protect against infectious agents.
IgG; high; same
IgA; gut epithelium
Newborns have high levels of circulating IgG antibodies derived from the mother during gestation, enabling the baby to benefit the broad immune experience of the mother.
What happens to this passive protection as the baby ages?
The passive protection falls at about 6 months as the baby’s own immune response takes over.
Total antibody concentrations are low from 6 months to 1 year after birth (increased susceptibility to disease).
Signals from the bound antigen to the BCR and from the helper T cell induce the B cell to proliferate and differentiate into plasma cells that secrete antibodies.
What are the three mechanisms used by the antibodies to protect the host?
1) Neutralization
2) Opsonization (& phagocytosis)
3) Complement activation
Fill in the blanks regarding the different antibody isotypes:
1) ____ are present on mature B cells with an elusive role in B cell activation.
2) _____ and ____ are key for the neturalization function.
3) ___ important for complement activation.
4) ___ critical for mast cell degranulation (allergy).
1) IgD
2) IgG & IgA
3) IgM
4) IgE
Why do we need neutralizing antibodies?
Pathogens can cause damage to host by producing toxins or by directly infecting cells.
Antibodies against pathogens and toxins can PREVENT BINDING of these agents to HOST cellular receptors.
These types of antibodies inhibit or neutralize the infectivity of microbes and toxins and are referred to as “neutralizing antibodies.”
*IgG and IgA possess neutralization functions.
Briefly describe the mechanism of action of toxins and the defensive role of antibodies against them.
Man bacteria (and some insects and snakes) cause their damaging effects by producing toxic proteins, which are often composed of several distinct moieties.
Often, one part of the toxin binds to a cellular receptor which enables the molecule to be internalized. Another part of the toxin enters the cytoplasm and poisons cells.
Antibodies INHIBIT toxin BINDING and can prevent (neutralize) the toxic effects.
Apart from toxins, what other entities can antibodies neutralize?
Antibodies can neutralize various pathogens, including viruses and bacteria, by binding to them and preventing their harmful effects.
VIRUSES must bind to the host cell’s surface receptor for replication (to get genes inside the cell). Antibodies disrupt this process by binding to viral surface proteins, preventing the virus from attaching or entering the target cell.
BACTERIAL infections require an interaction between the bacteria and cell-surface receptors on the target cell. Antibodies inhibit the adhesion of bacteria to cell surfaces, blocking colonization/uptake.
What is the mucosal immune system composed of?
The mucosal immune system is continuously exposed to antigens entering from the environment. Which isotype plays an important role in neutralizing these antigens?
The mucosal immune system compromises the internal body surfaces that are linked by a MUCUS-SECRETING EPITHELIUM.
It also includes the EXOCRINE GLANDS associated with these organs such as lachrymal, salivary and mammary glands.
IgA plays an important role as a neutralizing antibody in the mucosal tissues.
What is the lamina propria?
It is a thin layer of connective tissue that lies beneath the epithelium.
*in mucosal tissues of the human body, the arrangement follows the order of the mucus layer, epithelial cells and the lamina propria.
