Cell Functions:
-> Autolysis

- degradative reactions in cells caused by indigenous intracellular enzymes – usually occurs after cell death
- Irreversible (along with Coagulative necrosis or infarcts) – reversible: fatty degeneration, & hydropic degeneration

-> Autolysin:
•    Ab causing cellular lysis in the presence of complement
•    Autolytic enzymes produced by the organism degrade the cell’s own cell wall structures

-> In the presence of cephalosporins & penicillins, growing bacterial cells lyse
•    W/o functional cell wall structures, the bacterial cell bursts

-> Heterolysis: cellular degradation by enzymes derived from sources extrinsic to the cell (e.g., bacteria)

-> Necrosis: sum of intracellular degradative reactions occurring after individual cell death w/in a living organism

STRUCTURE AND SOME PROPERTIES OF IG CLASSES AND SUBCLASSES

A.  IgG

1. Structure

 All IgG’s are monomers (7S immunoglobulin). The subclasses differ in the number of disulfide bonds and length of the hinge region.

2. Properties

IgG is the most versatile immunoglobulin because it is capable of carrying out all of the functions of immunoglobulin molecules.

a) IgG is the major Ig in serum – 75% of serum Ig is IgG

b) IgG is the major Ig in extra vascular spaces

c) Placental transfer – IgG is the only class of Ig that crosses the placenta. Transfer is mediated by a receptor on placental cells for the Fc region of IgG. Not all subclasses cross equally well; IgG2 does not cross well.

d) Fixes complement – Not all subclasses fix equally well; IgG4 does not fix complement

e) Binding to cells – Macrophages, monocytes and neutrophils and some lymphocytes have Fc receptors for the Fc region of IgG.  A consequence of binding to the Fc receptors on such cells  is that the cells can now internalize the antigen better. The antibody prepares the antigen for killing by the phagocytic cells. The term opsonin is used to describe substances that enhance phagocytosis. (Coating of the surface of pathogen by antibody is called opsonization).IgG is a good opsonin. Binding of IgG to Fc receptors on other types of cells results in the activation of other functions.

IgM

1. Structure
 IgM normally exists as a pentamer (19S immunoglobulin) but it can also exist as a monomer. In the pentameric form all heavy chains are identical and all light chains are identical. Thus, the valence is theoretically 10. IgM has an extra domain on the mu chain (CH4) and it has another protein covalently bound via a S-S bond called the J chain. This chain functions in polymerization of the molecule into a pentamer.

2. Properties

a) IgM is the third most common serum Ig.

b) IgM is the first Ig to be made by the fetus and the first Ig to be made by a virgin B cells when it is stimulated by antigen.

c) As a consequence of its pentameric structure, IgM is a good complement fixing Ig. Thus, IgM antibodies are very efficient in leading to the lysis of microorganisms.

d) As a consequence of its structure, IgM is also a good agglutinating Ig . Thus, IgM antibodies are very good in clumping microorganisms for eventual elimination from the body.

e) IgM binds to some cells via Fc receptors.

f) B cell surface Ig 

Surface IgM exists as a monomer and lacks J chain but it has an extra 20 amino acids at the C-terminus to anchor it into the membrane . Cell surface IgM functions as a receptor for antigen on B cells.

IgA

1. Structure

Serum IgA is a monomer but IgA found in secretions is a dimer as presented in Figure 10. When IgA exits as a dimer, a J chain is associated with it.

When IgA is found in secretions is also has another protein associated with it called the secretory piece or T piece; sIgA is sometimes referred to as 11S immunoglobulin. Unlike the remainder of the IgA which is made in the plasma cell, the secretory piece is made in epithelial cells and is added to the IgA as it passes into the secretions . The secretory piece helps IgA to be transported across mucosa and also protects it from degradation in the secretions.

2. Properties

a) IgA is the 2nd most common serum Ig.

b) IgA is the major class of Ig in secretions – tears, saliva, colostrum, mucus. Since it is found in secretions secretory IgA is important in local (mucosal) immunity.

c) Normally IgA does not fix complement, unless aggregated.

d) IgA can binding to some cells – PMN’s and some lymphocytes.

IgD

1. Structure

 IgD exists only as a monomer.

2. Properties

a) IgD is found in low levels in serum; its role in serum  is uncertain.

b) IgD is primarily found on B cell surfaces where it functions as a receptor for antigen.

c) IgD does not bind complement.

E. IgE

1. Structure

IgE exists as a monomer and has an extra domain in the constant region.

2. Properties

a) IgE is the least common serum Ig since it binds very tightly to Fc receptors on basophils and mast cells even before interacting with antigen.

b) Involved in allergic reactions – As a consequence of its binding to basophils and mast cells, IgE is involved in allergic reactions. Binding of the allergen to the IgE on the cells results in the release of various pharmacological mediators that result in allergic symptoms.

c) IgE also plays a role in parasitic helminth diseases. Since serum IgE levels rise in parasitic diseases, measuring IgE levels is helpful in diagnosing parasitic infections. Eosinophils have Fc receptors for IgE and binding of eosinophils to IgE-coated helminths results in killing of the parasite.

d) IgE does not fix complement.

THE PLASMIDS

The extrachromosomal genetic elements, called as plasmids are autonomously replicating , cyclic ,double stranded DNA molecules which are distinct from the cellular chromosome 

Classification

Plasmids can be broadly classified as conjugative and nonconjugative. 

Conjugative plasmids are large and self-transmissible i.e. they have an apparatus through which they can mediate their own transfer to another cell after coming in contact with the same. Example:  RF and certain bacteriocinogen plasmids.

Nonconjugative plasmids are small in size and can be mobilised for transfer into another cell only through the help of a conjugative plasmid. To this group belong some ‘r’ determinants and few bacteriocinogenic plasmids. Plasmids can also be transferred without cell contact by the process of transfection.

Properties of plasmids

Double stranded DNA , Autonomously replicate in host cell, Plasmd specific, Free DNA is transferred b transfection

Significance of Plasmids :The spread of resistance to antibiotics is one such well known example. These also play an important  role in the geochemical  cycle by spreading genes for the degradation of complex organic compounds.
 

ANTIGENS

Immunogen
A substance that induces a specific immune response.

Antigen (Ag)
A substance that reacts with the products of a specific immune response.

Hapten
A substance that is non-immunogenic but which can react with the products of a specific immune response. Haptens are small molecules which could never induce an immune response when administered by themselves but which can when coupled to a carrier molecule. Free haptens, however, can react with products of the immune response after such products have been elicited. Haptens have the property of antigenicity but not immunogenicity.

Epitope or Antigenic Determinant
That portion of an antigen that combines with the products of a specific immune response.

Antibody (Ab)
A specific protein which is produced in response to an immunogen and which reacts with an antigen.

FACTORS INFLUENCING IMMUNOGENICITY

- Larger the molecule the more immunogenic it is likely to be.

- More complex the substance is chemically the more immunogenic it will be.

- Particulate antigens are more immunogenic than soluble ones and denatured antigens more immunogenic than the native form.

- Antigens that are easily phagocytosed are generally more immunogenic. This is because for most antigens (T-dependant antigens, see below) the development of an immune response requires that the antigen be phagocytosed, processed and presented to helper T cells by an antigen presenting cell (APC).

- Some substances are immunogenic in one species but not in another. Similarly, some substances are immunogenic in one individual but not in others (i.e. responders and non-responders). The species or individuals may lack or have altered genes that code for the receptors for antigen on B cells and T cells or they may not have the appropriate genes needed for the APC to present antigen to the helper T cells.

Method of Administration

1. Dose
The dose of administration of an immunogen can influence its immunogenicity. There is a dose of antigen above or below which the immune response will not be optimal.

2. Route
Generally the subcutaneous route is better than the intravenous or intragastric routes. The route of antigen administration can also alter the nature of the response

3. Adjuvants
Substances that can enhance the immune response to an immunogen are called adjuvants. The use of adjuvants, however, is often hampered by undesirable side effects such as fever and inflammation.

TYPES OF ANTIGENS

T-independent Antigens
T-independent antigens are antigens which can directly stimulate the B cells to produce antibody without the requirement for T cell help In general, polysaccharides are T-independent antigens. The responses to these antigens differ from the responses to other antigens.
Properties of T-independent antigens

1. Polymeric structure
These antigens are characterized by the same antigenic determinant .

2. Polyclonal activation of B cells
Many of these antigens can activate B cell clones specific for other antigens (polyclonal activation). T-independent antigens can be subdivided into Type 1 and Type 2 based on their ability to polyclonally activate B cells. Type 1 T-independent antigens are polyclonal activators while Type 2 are not.

3. Resistance to degradation
T-independent antigens are generally more resistant to degradation and thus they persist for longer periods of time and continue to stimulate the immune system.

T-dependent Antigens
T-dependent antigens are those that do not directly stimulate the production of antibody without the help of T cells. Proteins are T-dependent antigens. Structurally these antigens are characterized by a few copies of many different antigenic determinants as illustrated in the Figure 2.

HAPTEN-CARRIER CONJUGATES

Hapten-carrier conjugates are immunogenic molecules to which haptens have been covalently attached. The immunogenic molecule is called the carrier.

Structure
Structurally these conjugates are characterized by having native antigenic determinants of the carrier as well as new determinants created by the hapten (haptenic determinants). The actual determinant created by the hapten consists of the hapten and a few of the adjacent residues, although the antibody produced to the determinant will also react with free hapten. In such conjugates the type of carrier determines whether the response will be T-independent or T-dependent.

SUPERANTIGENS

When the immune system encounters a conventional T-dependent antigen, only a small fraction (1 in 104 -105) of the T cell population is able to recognize the antigen and become activated (monoclonal/oligoclonal response). However, there are some antigens which polyclonally activate a large fraction of the T cells (up to 25%). These antigens are called superantigens .

Examples of superantigens include: Staphylococcal enterotoxins (food poisoning), Staphylococcal toxic shock toxin (toxic shock syndrome), Staphylococcal exfoliating toxins (scalded skin syndrome) and Streptococcal pyrogenic exotoxins (shock).

The cell cycle

1) Labile cells (GI tract, blood cells)
- Described as parenchymal cells that are normally found in the G0 phase that can be stimulated to enter the G1
- Undergo continuous replication, and the interval between two consecutive mitoses is designated as the cell cycle
- After division, the cells enter a gap phase (G1), in which they pursue their own specialized activities
•    If they continue in the cycle, after passing the restriction point (R), they are committed to a new round of division
•    The G1 phase is followed by a period of nuclear DNA synthesis (S) in which all chromosomes are replicated
•    The S phase is followed by a short gap phase (G2) and then by mitosis
•    After each cycle, one daughter cell will become committed to differentiation, and the other will continue cycling

2) Stable cells (Hepatocytes, Kidney)

- After mitosis, the cells take up their specialized functions (G0). 
- They do not re-enter the cycle unless stimulated by the loss of other cells

3) Permanent cells (neurons)

- Become terminally differentiated after mitosis and cannot re-enter the cell cycle
- Which cells do not have the ability to differentiate ->  Cardiac myocytes

CROSS INFECTION AND STERLIZATION IN DENTISTRY

Cross infection is defined as the transmission of infectious agents amongst patients and staff with in hospital environment.

Routes of Infection 
Two routes are important : transdermal  and respiratory. 

 In transdermal route microorganisms enter the tissues of the recipient by means of injection through intact skin or mucosa (usually due to an accident involving a sharp instrument) or via defects in the skin e.g. recent cuts and abrasions.
 
Microorganisms causing cross infection in dentistry

Transmitted through skin 

Bacteria : Treponema pallidum, Staphylococcus aureus

Viruses :Hepatitis virus, HIV ,Herpes simplex virus, Mumps, Measles , Epstein-Barr virus

Fungi: Dermatomycoses, Candidiasis, 

Transmitted through aerosols

Bordetella pertussis, Myco.tuberculosis, Streptococcus pyogenes, Influenza virus
Rhinovirus,  Rubella