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4
Types of Immunity
derived from
The word Immunity means the state of resistance from infection. It was
and more
the Latin term immunis, meaning exempt from charges. Immunity has less specific
immunity that offers
specific components. The less specific components constitute innate
the first line of defense in favour of any individual against any foreign invader, whereas, the
specific components constitute adaptive immunity that responds to the antigenic challenge of
the invader within five to six days after the initial exposure to that antigen,
Components of Innate Immunity: The components ofinnate immunity are already present
within an individual's body before the onset of infection, i.e. they are inherent. Hence, the innate
immunity is also called natural or nativeimmunity. The components include various cells and
biomolecules that recognize certain class of molecules (truly speaking certain patterns) that are
typical constituents of frequently encountered pathogens (invaders). Phagocytic cells, such as
macrophages and neutrophils, various forms of barriers of the body viz. physical, physiological
and others, and a variety of antimicrobial compounds viz. transferrin, C-reactive protein,
lectins, interferons, complement components etc. constitute the innate armour of the body. The
activities of the components are not seen against any particular pathogen (invader), hence the
activity is termed as non-specific. Moreover, the responses/activities of the components do not
increase on subsequent exposure of the invader. <Pnttern iog niz)
Components of Adaptive Immunity: The components of adaptive immunity are activated
only after exposure to the foreign (non-self) identity. Hence, this type of immunity is also
called acquired immunity. Here, the components respond to the antigenic challenge with a
high degree of specificity. The lymphocyte population mainly constitutes the cellular plank and
immunoglobulin molecules make the biomolecular part of adaptive immunity. The interaction
of antigenic mass and components of adaptive immunity (particularly receptors of lymphocytes
 36 Veterinary Immunology For The Beginners

and immunoglobulins) are highly specific; hence this type of immunity is also known as specific
immunity.
IMMUNE RESPONSES
biomolecules of blood
The innate immunity is executed by various cells (phagocytes) and
cells
and tissue fluid. Similarly,the body of an individual executes adaptive immunity through
(lymphocytes) and specific biomolecules (immunoglobulins) of blood and' secretions. The
In both innate
cells and biomolecules exert immunity through their activity and responses.
called cell mediated immuns
and adaptive immune responses when cells are involved, it is
termed as humoral immu.
responses (CMI) and the responses involving biomolecules are
body can be summariz.
responses. In short, the immune responses that are operating within the
in the following way:
Immune responses

Innate (nonspecific) Adaptive (specific)

Cellular Humoral Cellular Humoral

(by neutrophil, macrophage) (by transferrin, lectin etc.) (by Tlymphocytes) (by immunoglobulins

For effective resistance to infection the body can not rely on a single defense mechanism.
For effective and Teliable immune responses, body of vertebrates uses multiple strategies
Some are effectively used nonspecifically against wide varieties of foreign invaders. Some at
(specifically against any foreign invader viz. bacteria, virus, fungi, parasite etc. which encount
Ada the body system second time. Strategies may be adapted to eliminate invaders of body surfaces
and against those which are residing in mucosal surfaces or in blood circulation or even i
deeper tissues. Practically, innate and adaptive immune systems work in concert to provide a
high degree of protection for vertebrate animals including mammals and birds.
Interestingly, the adaptive (specific) immunity within an individual may be developed by
natural means or may be conferred artificially. After birth when an individual is exposed te
any infection or any non-self entity, the specific immunity is developed actively against tha
antigenic mass. Similarly, the specific natural immunity is generated passively by acquistiot
of antibodies through colostrums or through egg-yolk. On the other hand, artificially activë
immunity may be generated by immunizing the animals with vaccines or passive immunt)
by administering immune serum or sensitized lymphocytes. The different type of specit
immunity that are developed in an animal body are summarized in the following chart:
 Types of Immunity 37

Specific (adaptive) immunity

Natural Artificial

Active Passive Active Passive

(by exposure to infection) (by colostrum antibody) (by vaccine) (by immune serum/lymphocyte)
2

Characteristics of Adaptive Immunity

Adaptive im1munity is meant for recognizing and selectively eliminating specific foreign
entities (microorganisms, parasites or their products-biomolecules, termed as antigens) through
humoral and/or cellular immune responses. While performing various cellular and humoral
immune responses adaptive immunity displays the following characteristics
Antigenic specificity
Diversity
Immunologic memory
-Selfnon-self discrimination
The biomolecules (antibodies) and cells (lymphocytes) involved in adaptive immune
responses are entrusted for their specific reaction to the antigens in question. The antigenic
specificity of the body immune system permits it to distinguish any little difference among
the antigenic mass. The adaptive immune system can generate tremendous diversity in its
recognizing molecules (antibodies and receptors on lymphocytes) to recognize wide array of
unique structures on foreign antigens. Asecond encounter with the same antigen, after aprimary
immune response, leads to a heightened state of immune reactivity that is more rapid, often
qualitatively different from the first or primary response to antigen. Remembering the previous
exposure to the same antigen causes secondary response or anamnestic response (anamnesis
in Greek, means memory), due to immunologic memory, conferred by Tand Blymphocytes.
Cells (T lymphocytes) of an individual entrusted for adaptive immunity can discriminate self
and non-self (foreign) biomolecules that are exposed to the body immune system. Failure
of recognition to self components (biomolecules) of body by the immunological cells (T
Iymphocytes) may lead to autoimmunity which is considered as disease process.
Pattern Recognition Receptors-Recognition tool of Innate immunity
Invasion of any intruder into the body is recognized by certain cell associated bio-molecules
(surface receptor).These are expressed on somesentine cels(like night watchman or guard)
located in different entry points of the body, mainly mucosal surfaces of naturalorifices (that
of respiratory tract, gastrointestinal tract, uro-genital tract, mammary gland), eye and skin. The
(sentinel cells are macrophage, dendritic cells and mast cells) The receptors recognize certain
 i4ansPAMp fa
LE t As/s )
fetNop
38 [Link] yeterinary Immunology For The
specific molecular patterns of the invaders, viz. microorganisms, parasites,
alle rgensBegin
etc
ne
.
ns
biochemical structure of the molecules of the microbes makes certain
mol ecul ar The
called pathogen associated molecular patterns (PAMP), e.g. lipopolysaccharide patterns,
Gram negative bacteria, peptidoglycan layer of Gram positive bacteria,
(LAM) of mycobacteria, flagellin protein of flagellated bacteria, single and double
viral RNA. unmethylated CpG bacterial [Link] act as ligands for the
liporeceptarabinoomrsan an
strañdedon
surface of the sentinel cells and certain other cells (e.g. eosinophils and epithelial l
mucosal membrane), called pattern recognitión receptors (PRR). Based on the stre
coniposition and location, the receptors (PRR) are classified as toll like
receptors
(TLR).
Mannose-fucose recptors,NOD-like receptors, Peptidoglycan-recognition receptors, RJG
receptors, Scavenger receptor etc.
Toll like receptors (TLR): The term TOLL originally referred to a cell surface
governing dorsal/ventral orientation during early life of fruit fly, Drosophila [Link] or
it was found to play a crucial role in anti-fungal defense, besides stimulating production et
antimicrobial peptides. In 1990s, the first mammalian proteins structurally related to Drosönbil
TOLL were identified and named as Toll like receptor (TLR). So far 13 Toll Like Reentom
(TLR-1through TLR-13) have been identified in different animals and human. TOLL and TI P
family proteins are characterized by the presence of an extracellular domain with leucine-ich
repeats and an intra-cytoplasmic region containing a TOLL/interleukin-lreceptor homology
(TIR) domain, critical to both Drosophila TOLL and mammalian TLR signaling.

Leucine rich
repeat motifs

Cysteine rich
flanking motifs

TIR domain

Flg. 4.1. Structure of Toll like receptor

 Types of Immunity 39

Some TLRs are expressed on the cell surfaçes, viz. TLR-1, TLR-2, TLR-4TLR-7]and
some are expressed in the intra-cellular location (on the endosomal membrane), viz. TLR
fTLR-7TLR-9 (Fig. 4.2). The TLRs that are expressed on the surface of cells recognize
microbial componentslike peptidoglycan, LPS, lipoproteins, muramyl dipeptide, zymosan etc.
On the other hand, the intra-cellular TLRs recognize viral nucleic acid (double and single fns
stranded RNA, CpG sequence of bacterialDNA etc.) (Table 4.1).
TABLE 4.1. Various TLR and their ligands with their origin
3 ’Dt
TollLike Receptors Ligands of TLRs with their origin
(TLRS) identified so far
TLR-1 Modulin, Lipopeptides of Gram positive of bacteria

JILR-2 () Lipoprotein, peptidoglycan, lipoteichoic acid of

Gram positive bacteria:
(i) Modulin of Staphylococcus;
(i) Lipoarabinomannan, lipopeptide of mycobacteria
(v) Zymosan of yeast
(v) LPS of spirochetes
TLR-3 (dsDNAof virus
TLR (0 PSof Gram negative bacteria
() Lipoteichoic acid, mannuronic acid poymer of
Gram positive bacteria h
(in) Heat shock protein
(iv) Heparan sulphate

LRS Flageliny of Gram negative and Gram positive bacteria

TLR-6 Modulin, lipoprotein of Gram positive bacteria
TLR-7 Single and double viral RNA
TLR-8 Single stranded viral RNA
TLR-9 Unmethylated CpG-DNA of bacteria
TLR-10 Not known

Upon infection, antigen presenting cells (APC) such as macrophages and dendritic cells
express TLR on their surface and bind pathogen associated molecular patterns (PAMP) of
microbes. This results in the initiation of signaling pathway that stimulates the host defenses
through induction of reactive oxygen intermediates (ROI) and nitrogen intermediates
(RNI), Moreover, signal transduction through cytosol results in generation ot an increase in
fanseription factor, mainly, nuclear factor kappa B(NE-«B).This intern activates transcription
 Veterinary Immunology For
40
The
of genes related to cytokines (e.g. IL-I, IL-6, TNF-. chemokines (e.g. CC and
adhesion molecules (LEA-1, ICAM-1) (Fig. 4.2).
Begjn a
TLR 2 TLR4
00000DO01
TLR2 -000000004 TLR 5 TLR 2TLR6

TLR 1

Plasma
membrane

Recruitment of
adapter protein

Recruitment and activation

ODO0A-TLR3
of protein kinase HO00000AH-TLR 7
Activation of HOO000HO-LR8
transcription factors
OCOA-TLR9
Gene
transcription

Expression of
cytokines, chemokines
and adhesion molecules Endosomal
membrane

Fig. 4.2. Consequence of activaion of the Toll like receptors

Nucleotide-binding oligomerization domain (NOD) -like Receptors (NLRS): Thex

are intra-cellular pattern recognition receptors that can recognize bacterial components (eg
muramyl dipeptide, peptidoglycan etc.). It results into initiation of signal transduction like
TLRs toactivate nuclear factors for cytokine gene transcription.
Peptidoglycan recognition receptors: They are widely present in cattle and pig besides
human tissues. Peptidoglycans, present in Gram positive and Gram negative bacteria, art
recognized by these receptors resulting bactericidal activities. In pigs, these receptors are
present in kidney, spleen, skin bone marrow and skin. In cattle anti-microbial peptides v
defensins are liberated by the neutrophils by the activity of these receptors,
 Types of Immunityh
41
Retinoic acid inducible gene (RIG) ike receptors (RLRO: The RIG-like
are also
receptors
patterm recognition receptors. They are located in the cytoplasm of cells. They bind
viral RNA present in the cytosol and initiate cellular anti-viral
immune by response liberating
interferon likecytokines.
Link between Innate and Adaptive Immunity
Activation of adaptive immunity is done through [Link] occurs in several steps.
Antigen
presenting cells, especially dendritic cells, having TLR)on their surface act as(linking cells
for innate andadaptive immunity. Initially, immature dendritic cells in the peripheral tissues
recognize pathogens by TLR, leading to the up-regulation of cell-surface expression of certain
co-stimulatory/adhesion molecules,e.g. CD80 and CD86, and MHC-II (Fig.4.3). Moreover, the
pathogens may be captured by endocytosis and subsequently bound to TLR-9. Concomitantiy.
captured pathogens are processed and presented to T cells as antigen-MHC complexes. TLRs
also induce expression of cytokines, viz. IL-12, chemokines and their
receptors. Induction of
CD80/86 on APC by TLRs leads to the activation ofT cells specific for pathogens that
trigger
TLR signaling. It is observed that IL-12 induced by TLR contributes to the differentiation of
najve andor activated T cells into Thl. Interestingly, it is noted that
activation of TLR play a
role in the induction of Th2 response also. However, it is not clear that whether this is
partially
mediated by soluble factors secreted by DC. Observing the above facts it may be inferred that
establishment of adaptive immunity is greatly influenced by TLR-stimulated DC.
PAMP
2TLR lL-12
pathogen
IFNg

Endocytic
PRR

CD80/86 CD28
Naive T-cell

DC MHC-|| TCR

IL-4,
IL-5,
IL-10 S
lo

IL-4, IL-10
Fig. 4.3. Linking of innate and adaptive immunity by Toll like
raceptors