Immunity/certified fixed orthodontic courses by Indian dental academy

Learning objectives:
At the end of the seminar the learner should be
able to understand
• Immunity
• Types of immunity
• Various types of cells involved in immunity
• T - Lymphocytes
• B – Lymphocytes
• MHC complex
www.indiandentalacademy.com

Definition:
The human body has the ability to resist almost all
types of organisms or toxins that tend to damage the
tissues and organs. This capability is called immunity
or
The term ‘immunity’ has traditionally referred to the
resistance exhibited by the host toward the injury caused by
microorganism and their products.
The word 'immunity' is derived from the Latin word immunis
meaning 'free of burden’.

Types:

 The lymphocytes are major cells responsible for
acquired immunity;
Thus acquired immunity is further classified as:
1. Cellular immunity or cell mediated immunity
provided by T Lymphocyte.
2. Humoral immunity
provided by B Lymphocyte.

Innate immunity :
 Also known as Native immunity
 Innate immunity is one which an individual
possesses by virtue of his/her genetic and
constitutional makeup.
 It is not affected by prior contact with organism or
immunization
 Innate immunity may be non specific or specific
 It is considered at the level of species, race,
individuals.

Innate immunity :
 Types:
 Species immunity
 It is a total or relative refractoriness to a
pathogen shown by all member of a species.
Eg.: All humans are totally unsusceptible
to plant pathogen and to many
animal pathogens.

 Racial immunity
 With in a species, different races may shows
differences in susceptibility to infection.
Eg:
• A high resistance of Algerian sheep to
Anthrax
• Genetic resistance to Plasmodium
Falciparum malaria seen in some parts of
Africa, due to hereditary abnormality of red
cells (sickling).

 Individual immunity
 It is defined as the difference in innate immunity
exhibited by different individual in a race

 factors affecting the innate immunity of an
individual:
Age • Very young and very old individuals are more susceptible
to infectious disease
• Old person are more susceptible to infection due to
waning of immune response
• Pubertal conditions also play a role in immunity
• Some infection in the newborn are usually asymptomatic
as they require adequate immune response.
Hormonal
influences
•Endocrinal disorders increased susceptibility to infection
eg: diabetes mellitus , hypothyroidism ,adrenal dysfunction
•Increased level of steroid in body increase susceptibility to
infection; eg: in pregnancy
Nutrition •Both cellular and humoral immunity reduced when there is
malnutrition

Components of Innate immunity :
a. Epithelial surface . Resistance of the skin to invasion by organisms.
. Protective function of keratinized stratum corneum of
skin against bacteria and other organism
b. Secretions . Tears ( contains Antibodies, & lysozymes)
. Saliva ( contains IgA)
. Acidic gastro intestinal secretion ( destroys the
pathogens entering the digestive tract through food)
c. Enzymes . Lysozymes (contains glycoside hydrolases enzymes
that hydrolyse the peptidoglycan bond in cell wall of
bacteria)
d. Inflammation . Non specific defense mechanism
.eg: Acidic substance ( lactic acid ) found in muscle
tissue and in inflammatory zones causing degradation
of pathogens

e. Fever .Rise in temperature helps not only by accelerating the
physiological processes but actually destroying the
pathogens providing unfavorable condition.
f. Acute Phase protiens • CRP [C- reactive proteins]
it binds to Phosphocholine on dead or dying cells in
order to activate Complement system (sets of plasma
proteins)
• Mannose Binding Protein (MBP)
calcium dependent serum protein
Bind to carbohydrate on surface of pathogen and act as
opsonin or enhance Complement system

g. Cellular components • Natural defense against the pathogens is mediated by
certain phagocytic cells
Eg: Macrophages
(histiocytes, monocytes)
Microphages
(polymorphonuclear cell)
• Natural Killer cell is also important in nonspecific viral
infection and tumors.
h. Microbial Antagonism . The skin and mucosa contain many microbial flora which
prevent the colonization by pathogens or non indigenous
species

Acquired immunity :
The resistance that an individual acquires
during life is known acquired immunity.
Types:
 Active
• natural
• artificial
 Passive
• natural
• artificial

Active immunity:
• Is the resistance developed by an individual as a
result of an antigenic stimulus.
• And it is also known as Adaptive immunity
• It involves active functioning of the host immune
apparatus leading to synthesis of antibodies and
production of immunologically active cell
• Once it is developed, it last for long.

• Active acquired immunity shows secondary response
more faster and quickly.
• And it is associated with immunological memory.
• Active acquired immunity is more effective than
passive acquired immunity.

 Active acquired immunity is of two types:
• It may be natural if an individual recovered from
an infection
Eg. After attack of measles, body develop natural
active immunity
• It is usually long lasting but longevity depends on the
type of pathogen

• And second is artificial if the resistance induced in an
individual by vaccine
Examples of vaccines (active artificial immunity) are as
follows:
1.Bacterial vaccines
a. live : BCG for Tuberculosis
b. Killed : Cholera vaccine
c. Subunit : Typhoid IV antigen
d. Bacterial Product : Tetanus toxoid
2.Viral vaccines
a. live oral polio vaccine- SABINE
b. killed injectable polio vaccine- SALK
c. Subunit : Hepatitis B vaccine

Passive immunity:
• Passive immunity is the resistance transmitted
passively to a recipient in a ready made form
• It do not require any antigenic stimulus.
• In passive immunity preformed antibodies are
administered in an individual.
• There is no secondary type of response seen in
passive immunity.
• In fact it diminishes in effect with repetition.
• And is less effectivewww.indiandentalacademy.com

Acquired Passive immunity is of two types:
• Natural passive immunity is the resistance passively
transferred from mother to baby through placenta and also
through Colostrum ( IgA & IgM resistant to intestinal
digestion.)
• Artificial passive immunity is the resistance passively
transferred to a recipient by administration of antibodies.
• Agents used for this purpose are
hyperimmune sera of animal or human
origin.
• Eg: anti-tetanus serum
Types:

Cells of Immune system
In a brief cells of immune system
are:
. W.B.C. or Leukocytes
. Natural Killer Cells
. Dendritic Cells
. Macrophages
. Mast Cells
. Plasma cell

W.B.C. or Leukocytes :
i. Granulocytes
 Neutrophils
 Eosinophils
 Basophils
ii. Agranulocytes
 Monocytes
 Lymphocytes

Neutrophils:
It comes under category of Granulocytes
10-14μ(micron)
They are also known as polymorphonuclear
leukocytes because of their multi lobed nuclei
The nuclei of neutrophils are larger than most of the
mononuclear blood cells.

 Neutrophils are short-lived (2–3 days).
 They migrate into tissues, particularly to sites of infection,
where they are involved in the acute response.
 It takes both acid and basic
stains.
 And no. of lobes depends
on the age of cells.

Basophils:
It also comes under
Granulocyte
It have bilobed nucleus
And a diameter of
8-10μ(micron)
It stain with basic dyes
It store histamine, and is secreted by the cells when
get stimulated.( which is also secreted by mast
cells )

 Like all circulating granulocytes, basophils can
be recruited out of the blood into a tissue when
needed.
Basophil

Mast cells:
 Also known as mastocyte and labrocyte
 Mast cells are very similar in both appearance and
function to the basophil.
 Mast cell contains many granules rich
in histamine and heparin.
 It play a major role in allergy and
anaphylaxis and also involved in wound
healing and defence against pathogens.
Mast cell

Eosinophils:
Comes under granulocytes
It have coarse larger granules
Eosinophil stain bright red and orange with eosin
It also have bilobed nucleus
And having a diameter of 10-14μ (micron)
Eosinophil

It contain many chemical mediators, such as
• histamines
And also contain many proteins such as
• Eosinophil peroxidase
• Ribonuclease (Rnase) ,
• Deoxyribonucleases ,
• lipase,
• plasminogen,
• major basic protein.
which are toxic to both parasite and host tissues.

 Eosinophil play a role in fighting viral infections.
 And also in fibrin removal during inflammation.
 Recently they have also been implicated in
antigen presentation to T cells.
Eosinophil

Monocytes:
It comes under category of
Agranulocytes.
 It have large kidney shaped or notched nucleus
 And it makes 3-8% percent of the leukocytes in the blood
 Monocytes are the largest corpuscles 14-18μ(micron)
in the blood
Monocytes

 Functions are
 Phagocytosis,
 Antigen presentation
 Cytokine production
 Those Monocytes which
migrate from the
bloodstream to
other tissues will then
differentiate into tissue
resident macrophages
or dendritic cells
 In the tissues monocytes
mature into different types
of macrophages at differe-
-nt anatomical locations
Monocytes

Macrophages :
 Macrophages are the cells
produced by the differentiation
of monocytes in tissues.
 Human macrophages
are about 21μ micrometres
or micron in size.
 Macrophages play its role by
• Phagocytosis or engulfing the pathogen
• And by digesting the cellular debris
 It remain as stationary or as Mobile cells.
macrophages

Name of cell Location
Dust cells /Alveolar macrophages pulmonary alveolus of lungs
Histiocytes connective tissue
Kupffer cells liver
Microglia neural tissue
Epithelioid cells granulomas
Osteoclasts bone
Sinusoidal lining cells spleen
Giant cells Connective Tissue
Peritoneal macrophages Peritoneal cavity
 Each type of macrophage, determined by its location,
has a specific name:

Dendritic cells (Langerhans cell):
 These are the antigen presenting cells
 And the function of dendritic cell is presenting
the antigen in front of T lymphocytes
Dendritic cells
Dendritic cells

 Dendritic cells present in tissues in contact with the
external environment, such as the
• Skin (Langerhans cells)
• The inner lining of the nose
• Lungs
• Stomach and intestines.
• They can also be found in an immature state in the
blood
 Two types of dendritic cell are found
 Myeloid dendritic cell (mDC)
Look similar to monocytes
 Plasmacytoid dendritic cell (pDC)
Look like plasma cells

Lymphocytes:
Lymphocytes also comes under the
category of Agranulocytes.
Lymphocytes can be divided into
• large lymphocytes
• small lymphocytes
 Small lymphocytes consist of
• T cells and B cells
Large granular lymphocytes include
• Natural killer cells (NK cells)
LYMPHOCYTES

B lymphocytes :
 It play a major role in Humoral immunity
 The B cells constitute 5–15% of human
blood lymphocytes.
 The main function of B cell is to secrete
soluble recognition molecules called
antibodies
 These antibodies also known as
immunoglobulins
 In fact, immunoglobulins are secreted form of a
B cell’s surface antigen receptors.

These antibodies is secreted after the activation of B
cells.
This activation process also usually requires
help from T cells.
.
 The activated B cell undergoes multiple divisions
and some of the resulting cells differentiate into
antibody-secreting cells
 These are known as plasma cells. and they
possess rough endoplasmic reticulum which
involved in antibody synthesis.

Plasma cells
 Plasma cells are large lymphocytes
 And have a considerable nucleus-to-cytoplasm ratio
 plasma cell shows characteristic appearance on light
microscopy.
cartwheel shape nucleus or clock face arrangement
Plasma
cell

. Plasma cell cytoplasm also contains a pale zone that
on electron microscopy contains
 Extensive Golgi apparatus
 Centrioles
 Abundant rough endoplasmic reticulum
makes plasma cells well-suited for secreting
immunoglobulins

T lymphocytes :
 It play a major role in Cellular immunity.
 The T cells constitute 70-80% of human blood
lymphocytes.
 The main function are to exert effects on other cells,
either by
• Regulating the activity of cells of the immune
system or
• By killing cells that are infected / malignant

 T cells cannot recognize antigens unless when they are
presented on the surface of antigen-presenting cells
[APCs] .(usually Macrophages and dendritic cells).
 There are four types of T cells:
• T Helper cell or CD4 cell
• Cytotoxic T cell or CD8 cell
• Suppressor T cell
• Memory T cell

T-LYMPHOCYTES

 T-cells or T-lymphocytes belong to a group of WBC
known as Lymphocytes.
 They play a central role in cell mediated immunity.
 They can be distinguished from other lymphocytes, such
as B cells & NK cells by the presence of T cell receptor
(TCR) on the cell surface.

Development
 Mammalian stem cells differentiate into several kinds of
blood cell within the bone marrow- haematopoiesis.
 All lymphocytes originate, during this process, from a
common lymphoid progenitor before differentiating into
their distinct lymphocyte types.

 The formation of lymphocytes is known as
lymphopoiesis.
 B cells mature into B lymphocytes in the bone
marrow, while T cells migrate to and mature in a
distinct organ, called the thymus.

 Following maturation, the lymphocytes enter the
circulation and peripheral lymphoid organs (e.g. the
spleen and lymph nodes) where they survey for invading
pathogens and / or tumor cells.
 The lymphocytes involved in adaptive immunity (i.e. B
and T cells) differentiate further after exposure to an
antigen; they form effector and memory lymphocytes.

 Effector lymphocytes function to eliminate the antigen,
either by releasing antibodies (in the case of B cells),
cytotoxic granules (cytotoxic T cells) or by signaling to
other cells of the immune system (helper T cells).
 Memory cells remain in the peripheral tissues and
circulation for an extended time ready to respond to the
same antigen upon future exposure.
 They live weeks to several years to a whole lifetime,
which is very long compared to other leukocytes

 There are several subsets of T cells, each with a distinct
function.
TYPES:
 Helper cells
 Cytotoxic cells
 Memory cells
 Regulatory cells
 Natural killer cells

 T helper cell (TH cells) assist other white blood cells in
immunologic processes, including maturation of B cells
into plasma cells and memory B cells, and activation of
cytotoxic T cells and macrophages.
 These cells are also known as CD4+ T cells because
they express the CD4 protein on their surface.
 Helper T cells become activated when they are
presented with peptide antigens by MHC class II
molecules, which are expressed on the surface of
antigen presenting cells (APCs).

 Once activated, they divide rapidly and secrete small
proteins called cytokines that regulate or assist in the
active immune response.
 These cells can differentiate into one of several subtypes,
including TH1, TH2, TH3, TH17, or TFH, which secrete
different cytokines to facilitate a different type of immune
response.
 Signalling from the APC directs T cells into particular
subtypes.[

 Cytotoxic T cells (TC cells, or CTLs) destroy virally
infected cells and tumor cells.
 These cells are also known as CD8+ T cells since they
express the CD8 glycoprotein at their surface.
 These cells recognize their targets by binding to antigen
associated with MHC class I, which is present on the
surface of nearly every cell of the body.

 Memory T cells are a subset of antigen-specific T cells
that persist long-term after an infection has resolved.
They quickly expand to large numbers of effector T cells
upon re-exposure to their cognate antigen, thus providing
the immune system with "memory" against past
infections.
 Memory T cells comprise two subtypes: central memory
T cells (TCM cells) and effector memory T cells (TEM cells).
Memory cells may be either CD4+ or CD8+.

 Regulatory T cells (Treg cells), formerly known as
suppressor T cells, are crucial for the maintenance of
immunological tolerance.
 Their major role is to shut down T cell-mediated
immunity toward the end of an immune reaction and to
suppress auto-reactive T cells that escaped the process
of negative selection in the thymus.
 Two major classes of CD4+ Treg cells have been
described — naturally occurring Treg cells and adaptive
Treg cells.

 Naturally occurring Treg cells (also known as
CD4+CD25+FoxP3+ Treg cells) arise in the thymus and can
be distinguished from other T cells by the presence of an
intracellular molecule called FoxP3.
 Adaptive Treg cells (also known as Tr1 cells or Th3 cells)
may originate during a normal immune response.

 Natural killer T cells (NKT cells – not to be
confused with natural killer cells of the innate
immune system) bridge the adaptive immune
system with the innate immune system. Unlike
conventional T cells that recognize peptide antigens
presented by major histocompatibility complex
(MHC) molecules, NKT cells recognize glycolipid
antigen presented by a molecule called CD1d.

 Once activated, these cells can perform functions
ascribed to both Th and Tc cells (i.e., cytokine production
and release of cytolytic /cell killing molecules).
They are also able to recognize and eliminate some
tumor cells and cells infected with herpes viruses.

Disorders
 Deficiency
 Causes of T cell deficiency include lymphocytopenia of
T cells and/or defects on function of individual T cells.
 Complete insufficiency of T cell function can result from
hereditary conditions such as severe combined
immunodeficiency (SCID) and Cartilage-hair hypoplasia.
 Causes of partial insufficiencies of T cell function include
acquired immune deficiency syndrome (AIDS), and
hereditary conditions and B-cell and T-cell combined
disorders such as ataxia telangiectasia (AT) and Wiskott-
Aldrich syndrome (WAS).

 The main pathogens of concern in T cell deficiencies
are intracellular pathogens, including Herpes simplex
virus, Mycobacterium and Listeria.
 Also, fungal infections are also more common and
severe in T cell deficiencies.
 Cancer of T-cells termed T-cell lymphoma.

 Lymphocytes are small, round cells found in
peripheral blood, lymph, lymphoid organs
 Total count is 1012
 As per size- small (5-8µm), medium (8-12µm), large
(12-15µm)
 As per life span- short lived and long lived

 Recognition of antigen
 Storage of immunological memory
 Immune response to specific antigen
 Stimulated T-cells produce lymphokines and cell
mediated immunity
 B-cells divide and transform to plasma cells and
synthesize immunoglobulins.

Pro B-cell
Pre B- cell
Immature B-cell
Migrate to periphery and Ig isotype switching

Expression of IgD( IgM, IgG, IgA or IgE) on the surface
Ressortment of Ig gene
B-cells capable of producing Ig molecule react with all
possible epitopes
Allelic exclusion
B- cells become programmed to form only 1 chain of Ig
& become specific for a single epitope

On contact with appropriate antigen these mature B-
cells undergo clonal proliferation
long memory cells plasma
cells
Antibody secreting

 Special separate lineage of B –cells in neonatal and
early life which have CD5 (T-cell) marker expression
 Secrete low affinity polyreactive IgM antibody
 T- independent natural IgM antibacterial antibody
which appear without any antigenic stimulus
 May be relevant in autoimmune condition.

Distinguishing features of B & T Lymphocytes
properties T cells B cells
CD3 + -
Surface Ig - +
EAC rosette - +
SRBC rosette + -
Thymus specific antigen + -
Microvilli - +

Major histocompatibility complex (MHC) is a cell
surface molecule encoded by a large gene family in all
vertebrates.
. MHC is a peptide displaying system of adaptive
immunity.
MHC molecule are product of genes that evokes
rejection of transplanted organs.
 Their name derived from the recognition that they
are responsible for tissue compatibility between
individuals. www.indiandentalacademy.com

SCHEMATIC DIAGRAM OF PEPTIDE DISPLAYING SYSTEM

In humans the gene encoding the MHC
molecule are clustered on a small segment of
chromosome 6.
MHC or human leukocyte antigen (HLA)
complex so named because, in humans MHC
encoded proteins were initially detected on
leukocyte by binding of antibodies.

Functions:
The physiological function of MHC molecule
is to display peptide fragments of proteins
for recognition by antigen- specific T-cell.
MHC determines compatibility of donors for
organ transplant as well as one's
susceptibility to an autoimmune disease.

•On the basis of their structure ,cellular function
MHC gene product are classified into 3
groups:
1. Class I MHC molecule
2. Class II MHC molecule
3. MHC locus

They are expressed on all nucleated cells and
platelets .
They are encoded by 3 closely linked loci HLA-A,
HLA-B,HLA-C.
Each class I molecule is a heterodimer consisting
of a polymorphic α heavy chain linked non-
covalently to a smaller peptide called β2-
microglobulin .

Structure of MHC class I molecule

The extracellular region of α chain is divided into
3 domains:
α1,
α2,
α3.
Class I MHC molecule display peptide that are
derived from proteins such as viral antigens. That
are located in cytoplasm and usually produced in
the cell and class I associated peptides are
recognized by CD8 + T lymphocytes.

Peptides are produced by the cytosol and
transported to endoplasmic reticulum, where
they bind to class I MHC molecules.
The peptide MHC complexes are transported
to the cell surface and displayed for
recognition by CD8 + T cells.

MHC class II molecule are encoded by
locus HLA-D, which has 3 sub regions:
HLA-DP, HLA-DQ, HLA-DR.
It consist of heterodimer consisting of a
non covalently associated α and β chain,
both of which are polymorphic.

Structure of class II MHC molecule

The extracellular portion of α and β chains have
2 domains each :α1α2 and β1β2.
Class II MHC molecule presents antigens that
are internalized into vesicles , and derived from
extracellular microbes and soluble proteins.

In this, proteins are ingested into
vesicles and degraded into peptides
,which bind to class II MHC molecule
being transported in the same vesicles
.
The class II MHC peptide complexes
are expressed on cell surface &
recognized by CD4 + T cells.

 Class II MHC pathway

It also contains genes that encode
complement components and the TNF , as
well as some proteins that have no
apparent role in immune system.

Characteristic MHC-I pathway MHC-II pathway
Composition of the stable
peptide-MHC complex
Polymorphic chain α and β2
micro globulin, peptide bound
to α chain
Polymorphic chains α and β,
peptide binds to both
Types of antigen presenting
cells (APC)
All nucleated cells
Dendritic cells, mononuclear
phagocytes, B lymphocytes,
some endothelial cells,
epithelium of thymus
T lymphocytes able to respond
Cytotoxic T lymphocytes
(CD8+)
Helper T lymphocytes (CD4+)
Origin of antigenic proteins
Cytosolic proteins (mostly
synthetized by the cell; may
also enter from the
extracellular medium via
phagosomes )
Proteins present in endosomes
or lysosomes (mostly
internalized from extracellular
medium)
Location of loading the peptide
on the MHC molecule
Endoplasmic reticulum
Specialized vesicular
compartment
Characteristics of the antigen processing pathways

MHC molecule plays key role in regulating T-
cell mediated immune responses.
Firstly, different antigenic peptides binds to
different MHC molecule , it follows that an
individual mounts an immune response against
a protein antigen only if he or she inherits the
gene for those MHC molecule.

Secondly, MHC molecule ensures that correct
immune response is mounted against
different microbes – CTLs against cytoplasmic
microbes and antibody and macrophage
against extracellular microbes.

HLA and Disease Association
A variety of diseases are associated with the
inheritance of certain HLA alleles .
The most striking of these is the association
between ankylosing spondylitis and HLA-
B27; individuals who inherit this class I HLA
allele have a 90-fold greater chance (relative
risk) of developing the disease as compared
with those who do not carry HLA-B27.

The diseases that show association with the HLA
locus can be broadly grouped into the following
categories:
•Inflammatory diseases, including ankylosing
spondylitis and several post infectious
arthropathies
•Autoimmune diseases, including autoimmune
endocrinopathies
•Inherited errors of metabolism like
hemochromatosis

Disease HLA Allele Relative Risk (%)
Ankylosing spondylitis B27 90–100
Postgonococcal
arthritis
B27 14
Acute anterior uveitis B27 14
Rheumatoid arthritis DR4 4
Chronic active
hepatitis
DR3 13
Primary Sjögren
syndrome
DR3 9
Type 1 diabetes DR3 5
DR4 6
DR3/DR4 20
Association of HLA Alleles and Inflammatory Diseases

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