IMMUNITY

The modern word "immunity" derives from the Latin immunis,

meaning exemption from military service, tax payments or
other public servicesThe concept of immunity has intrigued
mankind for thousands of years. The prehistoric view of disease
was that it was caused by supernatural forces,
IMMUNITY is the balanced state of having adequate biological
defenses to fight infection, disease, or other unwanted
biological invasion, while having adequate tolerance to avoid
allergy, and autoimmune diseases.

What is Immunity?
Immunity means being protected from something and being unaffected or not
bothered by it.

Amazingly, we already have a form of this superpower because of our immune

system. Our immune system protects us and helps fight off disease.
Microorganisms, small microscopic organisms, and viruses are everywhere.
Many microbes and viruses can cause disease and are termed pathogens.
With all these pathogens around, why aren't we sick every single moment? The
answer is our immune system gives us different types of immunity to protect us
from disease.

Types of immunity

Innate immunity

It is the capability of the body to resist harmful microorganisms or viruses from

entering it. Immunity involves both specific and nonspecific components. The
nonspecific components act either as barriers or as eliminators of wide range of
pathogens irrespective of antigenic specificity. Other components of the immune
system adapt themselves to each new disease encountered and are able to generate
pathogen-specific immunity.
The basic premise for the division of the immune system into innate and adaptive
components comes down to the innate system being composed of primitive bone
marrow cells that are programmed to recognise foreign substances and react, versus
the adaptive system being composed of more advanced lymphatic cells that are
programmed to recognise self substances and don't react. The reaction to foreign
substances is etymologically described as inflammation, meaning to set on fire,
while the non-reaction to self substances is etymologically described as immunity,
meaning to exempt. The interaction of these two components of the immune system
creates a dynamic biological environment where "Health" can be seen as an active
physical state where what is self is immunologically spared, and what is foreign is
inflammatorily and immunologically eliminated. Extending this concept, "Disease"
then can arise when what is foreign cannot be eliminated, or what is self is not
spared.

Innate immunity, also called natural or native immunity. This immunity is by virtue
of genetic constitutional make-up. It is there in the body without any external
stimulation or a previous infection. It is divided into two types:- (a) Non-Specific
innate immunity: A degree of natural resistance to all infections in general. (b)
Specific innate immunity: This is a natural resistance to a particular kind of germ
only. Some races or specific individual do not suffer from certain infectious
diseases.

Adaptive Immunity (acquired)

Adaptive immunity is often sub-divided into two major types depending on how the
immunity was introduced. 'Naturally acquired immunity' occurs through contact
with a disease causing agent, when the contact was not deliberate, whereas
'artificially acquired immunity' develops only through deliberate actions such as
vaccination. Both naturally and artificially acquired immunity can be further
subdivided depending on whether immunity is induced in the host or passively
transferred from an immune host. 'Passive immunity' is acquired through transfer of
antibodies or activated T-cells from an immune host, and is short lived—usually
lasting only a few months—whereas 'active immunity' is induced in the host itself
by antigen and lasts much longer, sometimes lifelong.
Passive immunity
Passive immunity is the transfer of active immunity, in the form of readymade
antibodies, from one individual to another. Passive immunity can occur naturally,
when maternal antibodies are transferred to the foetus through the placenta, and can
also be induced artificially, when high levels of human (or horse) antibodies
specific for a pathogen or toxin are transferred to non-immune individuals. Passive
immunization is used when there is a high risk of infection and insufficient time for
the body to develop its own immune response, or to reduce the symptoms of
ongoing or immunosuppressive diseases.[7] Passive immunity provides immediate
protection, but the body does not develop memory, therefore the patient is at risk of
being infected by the same pathogen later.[8]

Naturally acquired passive immunity

Maternal passive immunity is a type of naturally acquired passive immunity, and
refers to antibody-mediated immunity conveyed to a foetus by its mother during
pregnancy. Maternal antibodies (MatAb) are passed through the placenta to the
foetus by an FcRn receptor on placental cells. This occurs around the third month of
gestation. IgG is the only antibody isotype that can pass through the placenta.
Passive immunity is also provided through the transfer of IgA antibodies found in
breast milk that are transferred to the gut of the infant, protecting against bacterial
infections, until the newborn can synthesize its own antibodies.[8]
Artificially acquired passive immunity
Artificially acquired passive immunity is a short-term immunization induced by the
transfer of antibodies, which can be administered in several forms; as human or
animal blood plasma, Passive transfer is used prophylactically in the case of
immunodeficiency diseases, such as hypogammaglobulinemia.[9] It is also used in
the treatment of several types of acute infection, and to treat poisoning.[7] Immunity
derived from passive immunization lasts for only a short period of time, and there is
also a potential risk for hypersensitivity reactions, and serum sickness, especially
from gamma globulin of non-human origin.[8]

The artificial induction of passive immunity has been used for over a century to
treat infectious disease, and prior to the advent of antibiotics, was often the only
specific treatment for certain infections.

Passive transfer of cell-mediated immunity

Passive or "adoptive transfer" of cell-mediated immunity, is conferred by the
transfer of "sensitized" or activated T-cells from one individual into another. It is
rarely used in humans because it requires histocompatible (matched) donors, which
are often difficult to find. It has, however, been used to treat certain diseases
including some types of cancer and immunodeficiency. This type of transfer differs
from a bone marrow transplant, in which (undifferentiated) hematopoietic stem
cells are transferred.
 Active immunity
Due to the formation of immunological memory, reinfection at later time points
leads to a rapid increase in antibody production and effector T cell activity. These
later infections can be mild or even unapparent.

When B cells and T cells are activated by a pathogen, memory B-cells and T- cells
develop, and the primary immune response results. Throughout the lifetime of an
animal these memory cells will "remember" each specific pathogen encountered,
and are able to mount a strong secondary response, if the pathogen is detected
again. The primary and secondary responses were first described in 1921 by English
immunologist Alexander Glenny[10] although the mechanism involved was not
discovered until later.This type of immunity is both active and adaptive because the
body's immune system prepares itself for future challenges. Active immunity often
involves both the cell-mediated and humoral aspects of immunity as well as input
from the innate immune system.

Naturally acquired active immunity

Naturally acquired active immunity occurs when a person is exposed to a live
pathogen, and develops a primary immune response, which leads to immunological
memory.[7] This type of immunity is "natural" because it is not induced by
deliberate exposure. Many disorders of immune system function can affect the
formation of active immunity such as immunodeficiency (both acquired and
congenital forms) .

Artificially acquired active immunity

Artificially acquired active immunity can be induced by a vaccine, a substance that
contains antigen. A vaccine stimulates a primary response against the antigen
without causing symptoms of the disease.[7] The term vaccination was coined by
Richard Dunning, a colleague of Edward Jenner, and adapted by Louis Pasteur for
his pioneering work in vaccination. The method Pasteur used entailed treating the
infectious agents for those diseases so they lost the ability to cause serious disease.
 Antibody

Each antibody binds to a specific antigen; an interaction similar to a lock and key.

An antibody (Ab), also known as an immunoglobulin (Ig),[1] is a large, Y-shaped

protein produced mainly by plasma cells that is used by the immune system to
identify and neutralize pathogens such as bacteria and viruses. The antibody
recognizes a unique molecule of the harmful agent, called an antigen. Each tip of
the "Y" of an antibody contains a paratope (analogous to a lock) that is specific for
one particular epitope (similarly analogous to a key) on an antigen, allowing these
two structures to bind together with precision. Using this binding mechanism, an
antibody can tag a microbe or an infected cell for attack by other parts of the
immune system, or can neutralize its target directly (for example, by blocking a part
of a microbe that is essential for its invasion and survival). Depending on the
antigen, the binding may impede the biological process causing the disease or may
activate macrophages to destroy the foreign substance. The production of antibodies
is the main function of the humoral immune system.

Antibodies are secreted by B cells of the adaptive immune system, mostly by

differentiated B cells called plasma cells. Antibodies can occur in two physical
forms, a soluble form that is secreted from the cell to be free in the blood plasma,
and a membrane-bound form that is attached to the surface of a B cell and is
referred to as the B-cell receptor (BCR). The BCR is found only on the surface of B
cells and facilitates the activation of these cells and their subsequent differentiation
into either antibody factories called plasma cells or memory B cells that will survive
in the body and remember that same antigen so the B cells can respond faster upon
future exposure.[6] In most cases, interaction of the B cell with a T helper cell is
necessary to produce full activation of the B cell and, therefore, antibody generation
following antigen binding.[7] Soluble antibodies are released into the blood and
tissue fluids, as well as many secretions to continue to survey for invading
microorganisms.

Antibodies are glycoproteins belonging to the immunoglobulin superfamily.[4] They

constitute most of the gamma globulin fraction of the blood proteins. They are
typically made of basic structural units—each with two large heavy chains and two
small light chains. There are several different types of antibody heavy chains that
define the five different types of crystallisable fragments (Fc) that may be attached
to the antigen-binding fragments. The five different types of Fc regions allow
antibodies to be grouped into five isotypes. Each Fc region of a particular antibody
isotype is able to bind to its specific Fc Receptor (except for IgD, which is
essentially the BCR), thus allowing the antigen-antibody complex to mediate
different roles depending on which FcR it binds. The ability of an antibody to bind
to its corresponding FcR is further modulated by the structure of the glycan(s)
present at conserved sites within its Fc region. The ability of antibodies to bind to
FcRs helps to direct the appropriate immune response for each different type of
foreign object they encounter. For example, IgE is responsible for an allergic
response consisting of mast cell degranulation and histamine release. IgE's Fab
paratope binds to allergic antigen, for example house dust mite particles, while its
Fc region binds to Fc receptor ε. The allergen-IgE-FcRε interaction mediates
allergic signal transduction to induce conditions such as asthma.
A typical human B cell will have 50,000 to 100,000 antibodies bound to its
surface.Upon antigen binding, they cluster in large patches, which can exceed 1
micrometer in diameter, on lipid rafts that isolate the BCRs from most other cell
signaling receptors. These patches may improve the efficiency of the cellular
immune response. In humans, the cell surface is bare around the B cell receptors for
several hundred nanometers, which further isolates the BCRs from competing
influences.

Antibody–antigen interactions
The antibody's paratope interacts with the antigen's epitope. An antigen usually
contains different epitopes along its surface arranged discontinuously, and dominant
epitopes on a given antigen are called determinants.

Antibody and antigen interact by spatial complementarity (lock and key). The
molecular forces involved in the Fab-epitope interaction are weak and non-specific
– for example electrostatic forces, hydrogen bonds, hydrophobic interactions, and
van der Waals forces. This means binding between antibody and antigen is
reversible, and the antibody's affinity towards an antigen is relative rather than
absolute.

Often, once an antibody and antigen bind, they become an immune complex, which
functions as a unitary object and can act as an antigen in its own right, being
countered by other antibodies.

Isotypes
Antibodies can come in different varieties known as isotypes or classes. In placental
mammals there are five antibody isotypes known as IgA, IgD, IgE, IgG, and IgM.
They are each named with an "Ig" prefix that stands for immunoglobulin, a name
sometimes used interchangeably with antibody, and differ in their biological
properties, functional locations and ability to deal with different antigens, as
depicted in the table. The different suffixes of the antibody isotypes denote the
different types of heavy chains the antibody contains, with each heavy chain class
named alphabetically: α (alpha), γ (gamma), δ (delta), ε (epsilon), and μ (mu). This
gives rise to IgA, IgG, IgD, IgE, and IgM, respectively.

Antibody isotypes of mammals

Name Types Description Antibody complexes
Found in mucosal areas, such as the gut, respiratory
tract and urogenital tract, and prevents colonization by
IgA 2
pathogens.[14] Also found in saliva, tears, and breast
milk.
Functions mainly as an antigen receptor on B cells that
have not been exposed to antigens.[15] It has been
IgD 1
shown to activate basophils and mast cells to produce
antimicrobial factors.[16]

Binds to allergens and triggers histamine release from

IgE 1 mast cells and basophils, and is involved in allergy. Also
protects against parasitic worms.[5]

In its four forms, provides the majority of antibody-

based immunity against invading pathogens.[5] The only
IgG 4
antibody capable of crossing the placenta to give
passive immunity to the fetus.
Expressed on the surface of B cells (monomer) and in a
secreted form (pentamer) with very high avidity.
IgM 1 Eliminates pathogens in the early stages of B cell-
mediated (humoral) immunity before there is sufficient
IgG.[5][15]

The antibody isotype of a B cell changes during cell development and activation.
Immature B cells, which have never been exposed to an antigen, express only the
IgM isotype in a cell surface bound form. The B lymphocyte, in this ready-to-
respond form, is known as a "naive B lymphocyte." The naive B lymphocyte
expresses both surface IgM and IgD. The co-expression of both of these
immunoglobulin isotypes renders the B cell ready to respond to antigen. [17] B cell
activation follows engagement of the cell-bound antibody molecule with an antigen,
causing the cell to divide and differentiate into an antibody-producing cell called a
plasma cell. In this activated form, the B cell starts to produce antibody in a
secreted form rather than a membrane-bound form. Some daughter cells of the
activated B cells undergo isotype switching, a mechanism that causes the
production of antibodies to change from IgM or IgD to the other antibody isotypes,
IgE, IgA, or IgG, that have defined roles in the immune system.

Antibody isotypes not found in mammals

Name Description
IgY Found in birds and reptiles; related to mammalian IgG.
IgW Found in sharks and skates; related to mammalian IgD.

Structure
Antibodies are heavy globular plasma proteins. They have sugar chains (glycans)
added to conserved amino acid residues. In other words, antibodies are
glycoproteins. The attached glycans are critically important to the structure and
function of the antibody.[4] Among other things the expressed glycans can modulate
an antibody's affinity for its corresponding FcR(s).

The basic functional unit of each antibody is an immunoglobulin (Ig) monomer

(containing only one Ig unit); secreted antibodies can also be dimeric with two Ig
units as with IgA, tetrameric with four Ig units like teleost fish IgM, or pentameric
with five Ig units, like mammalian IgM.[21]

The variable parts of an antibody are its V regions, and the constant part is its C
region.

Heavy chain

There are five types of mammalian Ig heavy chain denoted by the Greek letters: α,
δ, ε, γ, and μ.[2] The type of heavy chain present defines the class of antibody; these
chains are found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively. Distinct
heavy chains differ in size and composition; α and γ contain approximately 450
amino acids, whereas μ and ε have approximately 550 amino acids.

Each heavy chain has two regions, the constant region and the variable region. The
constant region is identical in all antibodies of the same isotype, but differs in
antibodies of different isotypes. Ig domains, and a hinge region for added
flexibility; heavy chains μ and ε have a constant region composed of four
immunoglobulin domains.[2] The variable region of each heavy chain is
approximately 110 amino acids long and is composed of a single Ig domain.

Light chain

In mammals there are two types of immunoglobulin light chain, which are called
lambda (λ) and kappa (κ). A light chain has two successive domains: one constant
domain and one variable domain. The approximate length of a light chain is 211 to
217 amino acids. Each antibody contains two light chains that are always identical;
only one type of light chain, κ or λ, is present per antibody in mammals.

Function
The main categories of antibody action include the following:

 Neutralisation, in which neutralizing antibodies block parts of the surface of a

bacterial cell to render its attack ineffective.
 Agglutination, in which antibodies "glue together" foreign cells into clumps
that are attractive targets for phagocytosis.
 Complement activation (fixation), in which antibodies that are latched onto a
foreign cell encourage complement to attack it with a membrane attack
complex, which leads to the following:
o Lysis of the foreign cell.
o Encouragement of inflammation by chemotactically attracting
inflammatory cells.

Activated B cells differentiate into either antibody-producing cells called plasma

cells that secrete soluble antibody or memory cells that survive in the body for
years afterward in order to allow the immune system to remember an antigen and
respond faster upon future exposures.
 Autoimmunity
Autoimmunity is the system of immune responses of an organism against its own
healthy cells and tissues. Any disease that results from such an aberrant immune
response is termed an autoimmune disease. Prominent examples include diabetes
mellitus type 1, Graves' disease, rheumatoid arthritis (RA), and Autoimmune
diseases are very often treated with steroids.

The misconception that an individual's immune system is totally incapable of

recognizing self antigens is not new. wherein a "normal" body does not mount an
immune response against its own tissues. Thus, any autoimmune response was
perceived to be abnormal and postulated to be connected with human disease. Now,
it is accepted that autoimmune responses are an integral part of vertebrate immune
systems (sometimes termed "natural autoimmunity"), normally prevented from
causing disease by the phenomenon of immunological tolerance to self-antigens.

Treatments
Treatments for autoimmune disease have traditionally been immunosuppressive,
anti-inflammatory.

Helminthic therapy is an experimental approach that involves inoculation of the

patient with specific parasitic intestinal nematodes (helminths). There are currently
two closely related treatments available, inoculation with either Necator
americanus, commonly known as hookworms, or Trichuris Suis Ova, commonly
known as Pig Whipworm Eggs.

T cell vaccination is also being explored as a possible future therapy for

autoimmune disorders.

Nutrition
Vitamin D/Sunlight
  Because most human cells and tissues have receptors for vitamin D,
including T and B cells, adequate levels of vitamin D can aid in the
regulation of the immune system.

Rheumatoid arthritis

Rheumatoid arthritis (RA) is a long-lasting autoimmune disorder that primarily

affects joints. It typically results in warm, swollen, and painful joints. Most
commonly, the wrist and hands are involved, with the same joints typically
involved on both sides of the body. The disease may also affect other parts of the
body. This may result in a low red blood cell count, inflammation around the lungs,
and inflammation around the heart. Fever and low energy may also be present.
Often, symptoms come on gradually over weeks to months.

Causes
RA is a chronic autoimmune disorder the causes of which are not completely
understood. It is a systemic (whole body) disorder principally affecting synovial
tissues. There is no evidence that physical and emotional effects or stress could be a
trigger for the disease. Half of the risk for RA is believed to be genetic.

Smoking is the most significant non-genetic risk with RA being up to three times
more common in smokers than non-smokers, particularly in men, heavy smokers,
and those who are rheumatoid factor positive. Modest alcohol consumption may be
protective.

Prevention
There is no known prevention for the condition other than the reduction of risk
factors.

Management
There is no cure for RA, but treatments can improve symptoms and slow the
progress of the disease. Disease-modifying treatment has the best results when it is
started early and aggressively.

The goals of treatment are to minimize symptoms such as pain and swelling, to
prevent bone deformity , and to maintain day-to-day functioning.
 Immunology
It is a branch of biology that covers the study of immune systems in all organisms.
It was the Russian biologist Ilya Ilyich Mechnikov who boosted studies on
immunology, and received the Nobel Prize in 1908 for his work. It was Mechnikov
who first observed the phenomenon of phagocytosis, in which the body defends
itself against a foreign body, and coined the term. the physical, chemical and
physiological characteristics of the components of the immune system in vitro, in
situ, and in vivo. Immunology has applications in numerous disciplines of medicine,
particularly in the fields of organ transplantation, oncology, virology, bacteriology,
psychiatry, and dermatology.

Immunotherapy
Immunotherapy is the "treatment of disease by inducing, enhancing, or
suppressing an immune response". Immunotherapies designed to elicit or amplify
an immune response are classified as activation immunotherapies, while
immunotherapies that reduce or suppress are classified as suppression
immunotherapies.

Immunomodulatory regimens often have fewer side effects than existing drugs,
including less potential for creating resistance when treating microbial disease.[2]
Vaccination
Antimicrobial immunotherapy, which includes vaccination, involves activating the
immune system to respond to an infectious agent.

Allergies

Immunotherapy is used to treat allergies. While allergy treatments (such as

antihistamines or corticosteroids) treat allergic symptoms, immunotherapy can
reduce sensitivity to allergens, lessening its severity.

Immunotherapy may produce long-term benefits. Immunotherapy is partly effective

in some people and ineffective in others, but it offers allergy sufferers a chance to
reduce or stop their symptoms.

The therapy is indicated for people who are extremely allergic or who cannot avoid
specific allergens. Immunotherapy is generally not indicated for food or medicinal
allergies. This therapy is particularly useful for people with asthma.