Definition of immunology

Immunology is the study of our protection from foreign macromolecules or invading organisms and our responses to them. These invaders include viruses, bacteria, protozoa or even larger parasites

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 Or we can say . The branch of medical science which deals with the study of development and function of both cellular and humoral components of the immune system by which the body reacts to expel, destroy or neutralize foreign substances including pathogenic microorganisms.

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Application of Immunology
Diagnosis of disease: Antigen or antibody detection can help to diagnose various disease. Prevention and treatment of disease: Vaccination prevents many diseases by active and passive immunization.

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 Blood transfusion serology:

Blood grouping, typing and cross matching in blood transfusion . Tissue typing and histocompatibility testing: Necessary for organ and tissue transplantation. Forensic science; Paternity testing , stain identification.

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Branches of immunology
Immunochemistry: deals with the chemical nature of antigen, antibody and their chemical nature. Immunobiology: related to biological function of the cells and tissue components of immune system. Immunogenetics: deals with the study of immunoglobulin genes and the genetic basis of immune response.
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 Clinical immunology: deals with pathogenesis, diagnosis and treatment of immune mediated diseases. Immunotherapy: deals with prevention and treatment of diseases of immunological means. Eg: vaccination, immunoglobulin therapy, desensitization etc. Immunohematology: deals with immunological basis involved in different haemotological disorders.
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 Immunopharmacology: deals with the pharmacological action of different secreted molecules in immune responses. Serology: deals with the study of immune reactions mediated by antibodies or immunoglobulins present in the serum.

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Immunity
Immunity is a biological term that describes a state of having sufficient biological defences to avoid infection, disease, or other unwanted biological invasion. In other words, it is nothing but the capability of the body to resist harmful microbes from entering the body

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Types of immunity

Genetic Mechanical Humoral Cellular

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 Innate immunity, or nonspecific, immunity is the natural resistance with which a person is born. It provides resistance through several physical, chemical, and cellular approaches. Microbes first encounter the epithelial layers, physical barriers that line our skin and mucous membranes

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 Adaptive immunity(specific immunity): where a foreign body or antigen enters into the body and stimulates the immune system , that produces the antibody , The produced antibody destroys the antigen and restores the antigenic properties as a memory call .

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Table 1

Innate

Adaptive

Response is antigen-independent There is immediate maximal response

Response is antigen-dependent There is a lag time between exposure and maximal response

Not antigen-specific

Antigen-specific

Exposure results in no immunologic memory

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Exposure results in immunologic memory

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Beneficial and harmful effect of immunity

Benefits :
Prevention of many disease by vaccination. Eg : measels vaccine, polio vaccine . Production of immunoglobulins that gives protection to the host from clinical and subclinical infection.

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 Harmful effects:
Hypersensitive conditions like asthma, rheumatic fever etc. Auto immune disease like rheumatid arthritis , auto immune haemolytic anaemia, etc.

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Antigen and immunogen

Antigen : any agent/molecule/foreign body that binds to component of the immune response, such as lymphocytes and their receptors and antibodies.
Antigens may or may not induce the production of antibodies .

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 Immunogen: any agent capable of inducing immune response known as immunogen, Hapten: is antigenic but not immunogenic unless it is attached to a carrier molecule of some sort which supplies immunogenicity.

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All immunogens are antigens but all antigens are not immunogens .
An antigen is any molecule that is identified as non-self by components of the immune system. An immunogen is an antigen that is able to evoke an immune response, including production of antibody via the humoral response. All immunogens are antigens, but not all antigens are immunogens An antigen may not produce antibody because of its low molecular weight and absence of carrier molecule.
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An immunogen is always an antigen but it has all the carrier molecules and molecular weight to induce antibody production.

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Characteristics of good antigen/immunogen

There are three characteristics that a substance must have to be immunogenic: foreignness, high molecular weight and chemical complexity

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 Foreignness is required so that the immunized animal does not recognize and ignore the substance as "self." Generally, compounds from an organism are not immunogenic to that same individual and are only poorly immunogenic to others of the same or related species

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 high molecular weight. Small compounds (MW less than 1000), such as penicillin, progesterone and aspirin, as well as many moderately sized molecules (MW from 1000 to 6000), are not immunogenic. Most compounds with a molecular weight greater than 6000 are immunogenic. Compounds smaller than this can often be bound by mIgM on the surface of the B-lymphocyte, but they are not large enough to facilitate crosslinking of the mIgM molecules.
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 some degree of chemical complexity is required for a compound to be immunogenic. For example, even high molecular weight homopolymers of amino acids and simple polysaccharides seldom make good immunogens because they lack the chemical complexity necessary to generate an immune response.
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 Haptens Peptides and other small molecules that are used as antigens are referred to as haptens. Or , haptens are low molecular weight chemical substances which themselves are not immunogenic but when conjugated with some carrier protein they can induce immune response . They are able to act as recognition sites for production of specific antibodies but cannot by themselves stimulate the necessary immune response.
hapten Carrier
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Antigen

Antibody

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Epitopes
An epitope is the specific site on an antigen to which an antibody binds.
For very small antigens, practically the entire chemical structure may act as a single epitope. Depending on its complexity and size, an antigen may effect production of antibodies directed at numerous epitopes. Polyclonal antibodies are mixtures of serum immunoglobulins and collectively are likely to bind to multiple epitopes on the antigen. Monoclonal antibodies by definition contain only a single antibody clone and have binding specificity for one particular epitope.
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Paratope
The part of the antibody or T cell receptor, which is complementary to the epitope and interacts with the epitope, is known as paratope.

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Adjuvants To enhance the immune response to an immunogen, various additives called adjuvants can be used. When mixed and injected with an immunogen, an adjuvant will enhance the immune response. An adjuvant is not a substitute for a carrier protein because it enhances the immune response to immunogens but cannot itself render haptens immunogenic. Adjuvants are nonspecific stimulators of the immune response, helping to deposit or sequester the injected material and causing a dramatic increase in the antibody response.
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Classification of antigens
A : according to chemical nature:
Proteins: mostly all proteins are antigens in appropriate route in susceptible individual. Polysaccharides: these are potentially but not always antigenic, eg, ABO blood group antigen. Lipids: these usually are not antigenic but may act as heptens.

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 B: on the basic of source:

Auto antigen: derived from individuals own tissue. Iso-antigen: derived from genetically identical individual , eg. Twin babies. Allo-antigen: derived from genetically non identical member of same species. Xeno-antigen: derived from different species.

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 C: on the basis of mode of action:

Thymus dependent antigens: which do not activate the B cell directly, rather they take the help of helper T cell to activate B cell. Majority of the antigens are of this type, all proteins are T cell dependent antigens thymus independent antigens: which activates the B cell directly without the help of T cell. They are very few in number. Eg: pneumococcal polysaccharide.
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 D: on the basis of epitope or antigenic determinant:

Unideterminant univalent: single epitope of a given specificity, eg: hapten. Unideterminant multivalent: two or more epitope of the same kind. Eg: manny polysaccharides. Multideterminant multivalent: multiple determinants and different kinds. Eg: proteins.
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Super antigen
Super antigens are those antigens that are able to bind and stimulate T-cells directly without processing by the antigen presenting cells. Thus they can produce exaggerated immune response in short time.
Example: enterotoxin of staphylococcus, toxic shock syndrome toxin.

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Heterophil antigen
The antigens that cross reacts with the antibody which was not produced by themselves, are called heterophil antigens.
Heterophil antigens are used in many diagnostic purposes.

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Hypersensitivity
Hypersensitivity (also called hypersensitivity reaction) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a pre-sensitized (immune) state of the host.
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Coombs and Gell classification

The four-group classification was expounded by P. H. G. Gelland Robin Coombs in 1963.
Type V is an additional type that is sometimes (often in the UK) used as a distinction from Type 2

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Comparison of hypersensitivity types Type I (seconds to minute) Alternative names Allergy (immediate) Often mentioned disorders Atopy Anaphylaxis Asthma Autoimmune hemolytic anemia Thrombocytopenia Erythroblastosis fetalis Goodpasture's syndrome Mediators IgE and IgG4

II (hours to day)

Cytotoxic, antibodydependent

IgM or IgG (Complement)

III (hours to day)

Immune complex disease

Serum sickness Arthus reaction Rheumatoid arthritis Systemic lupus erythematosus (SLE) Extrinsic allergic alveolitis (Hypersensitivity pneumonitis)

IgG (Complement)

IV (2 to 3 days)

V(hours to day)

Delayed-type Contact dermatitis hypersensitivity[(DTH), cellMantoux test mediated immune memory Chronic transplant rejection response, antibodyMultiple sclerosis independent Autoimmune disease, Graves' disease surja das receptor mediated. Myasthenia Gravis

T-cells

IgM or IgG (Complement)

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On the basis of onset of action

Immediate : requires minutes to hours
Eg: type I,II,III and V.

Delayed : requires hours to days

Eg: type IV.

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On the basis of mechanism of action

Cell mediated: eg: type IV hypersensitivity

Antibody mediated: eg: type I,II,III and V.

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 Allergy : it means altered reactivity of tissue or body to subsequent exposer of some antigen, it is also known as type I hypersensitivity . Allergen: they are immunogens that can produce type I hypersensitivity. Atopy: atopy is a genetically determined state of type I hypersensitivity to common environmental and mediated by IgE.

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Type I hypersensitivity /Anaphylaxis

Anaphylaxis may be defined as an immediate hypersensitivity response triggered by IgE mediated mast cell degranulation, leading to anaphylactic shock due to vasodilation and smooth muscle contraction.

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 First exposure:
Antigen enters into the body Taken up by macrophages Macrophage process and present it to helper T cell. Helper T cell stimulate B cell Plasma cells formation and IgE production IgE fix with mast cells and basophil Cells get sensitized

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 Second exposure :
Same antigen enters to the body Pre sensitized IgE cross link with antigen Degranulation of mast cells and basophils Release of histamine and mediators . Increase vascular permeability Increase glandular secretion as in asthma, allergic rhinitis Contraction of smooth muscle. Anaphylactic shock Anaphylaxis
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Type I

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Type II / cytotoxic hypersensitivity

Either IgG or IgM is made against normal self antigens as a result of a failure in immune tolerance , or a foreign antigen resembling some molecule on the surface of host cells enters the body and IgG or IgM made against that antigen then cross reacts with the host cell surface. The binding of these antibodies to the surface of host cells then leads to: Death of the host cells
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 Antigen(on the cell surface)+ antibody (IgG or IgM) Activation of compliment system Formation of membrane attack complex Formation of drilling holes through lipid bilayer of cell membrane Disruption of cell membrane integrity Disruption involves: RBC, WBC, platelet .

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Type III / immune-complex hypersensitivity

This is caused when soluble antigen-antibody (IgG or IgM) complexes, which are normally removed by macrophages in the spleen and liver, form in large amounts and overwhelm the body . These small complexes lodge in the capillaries, pass between the endothelial cells of blood vessels - especially those in the skin, joints, and kidneys - and become trapped on the surrounding basement membrane beneath these cells. The antigen/antibody complexes then activate the classical complement pathway . This may cause: a. Massive inflammation b. Influx of neutrophils c. Activation of macrophages

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Type IV / delayed hypersensitivity

Delayed hypersensitivity is cell-mediated rather than antibody-mediated. Mechanism: Delayed hypersensitivity is the same mechanism as cell-mediated immunity. T8-lymphocytes become sensitized to an antigen and differentiate into cytotoxic Tlymphocytes while effector T4-lymphocytes become sensitized to an antigen and produce cytokines . CTLs, cytokines, eosinophils, and/or macrophages then cause harm rather than benefit.
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Type V / stimulatory hypersensitivity

Antibodies are made against a particular hormone receptor on a hormone-producing cell. This leads to the overstimulation of those hormone-producing cells. An example is Graves' disease where antibodies are made against thyroid-stimulating hormone receptors of thyroid cells. The binding of the antibodies to the TSH receptors results in constant stimulation of the thyroid leading to hyperthyroidism.
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