Mediators/ Actors of Innate Immunity by ZainUlAbdin1

VIEWS: 14 PAGES: 43

									Mediators/ Actors of Innate Immunity

1) PRRs, TLRs, PAMPs, DAMPs
2) Complement System
PAMPs: Pathogen Associated Molecular Patterns
 PRRs: Pathogen Recognition Receptors
 TLRs: Toll Like Receptors (on innate immune cells)
   PAMPs




                       Intracellular Signalling Pathway




Activation of Nuclear Factor kappa B
Induction of gene transcription                           Cytokines
PAMPs/TLRs: Innate Immunity Signalling
TLR Signalling Pathway




                         Immunity 34, May 27, 2011
PAMPs/DAMPs and PPRs




           TRENDS in Immunology, 2007; Vol.28 No.10
DAMPs: Damage Associated Molecular Patterns




      Trends in Immunology April 2011, Vol. 32, No. 4
Complement Pathway
Complement Pathway: Outcome
ANTIGEN (Ag)
        ANTIGEN (Antibody generator)
Definition:

Any foreign material that provokes a specific
immune response upon entry of organism into the
body is termed as antigen.

                           Bacteria
        Virus   Allergen
 Immunogenicity is the ability to induce
 humoral or cell mediated immune response.


 Antigenicity is ability of Ag to combine
 specifically with the end products of humoral or
 cell mediated immune response.

 All molecules having immunogenicity also
 have antigenicity but the reverse is not
 possible.
Sites of entry of antigen (Ag)

The antigen can enter through:
• Skin
• Mucus membrane
• Wound
• Cuts/ abrasions
• Arthropods biting e.g Dengue virus
Characteristics of an Antigen

•Foreignness (Non-Self)
The antigen is not normally present in
the body and is foreign to the body

•Molecular Size
Large proteins act as potent
immunogens, molecules < 10,000 Da are
weakly immunogenic and very small one
are also non-immunogenic.
            FOREIGNNESS
 The degree of immunogenicity depends upon
  the degree of foreigness.
 A molecule must be recognized as non self by
  biological system.
 Ability to recognize as self/non self arise during
  lymphocytic development.
 The greater the difference between two species
  the greater will be the immunogenicity.
      MOLECULAR SIZE

 The best immunogen tend to have a
 size approaching 100000(lac) daltons.

 Substance having molecular size less
 than 5000-10000 daltons are poor
 immunogens.
  CHEMICAL COMPOSITION
 Synthetic homopolymers tend to lack
 immunogenicity regardless of their size.
 Copolymers having two or more different
 amino acids are immunogenic.
The addition of aromatic amino acid tend
 to enhance immunogenicity of the
 synthetic polymers.
Homopolymers:      Less immunogenic
Heteropolymers:     More immunogenic
    CONTRIBUTION OF
 BIOLOGICAL SYSTEM TO
    IMMUNOGENICITY


 Dose and route of immunogen
 Adjuvants
     DOSAGE AND ROUTE
 An insufficient dose will not stimulate a
 immune response either because it fails to
 activate enough lymphocytes or because it
 induces a non responsive state.
 An excessively high dose also can fail to
 induce a immune response because it
 causes lymphocytes to enter into a non
 responsive state.
            ADJUVANTS
 Adjuvants are the substances that when
 mixed with antigen and injected with them,
 enhance the immunogenicity of that
 antigen.
 Adjuvants are often used to boost the
 immune response when an antigen has
 low immunogenicity or small amounts of
 an antigens is available.
     Functions of Adjuvant

 Enhance immunogenicity and size of Ag.
 Prolong antigen persistence.
 Enhance co stimulatory signals.
 Induce granuloma formation.
 Stimulate lymphocytic proliferation non
 specifically.
EPITOPES (antigenic determinants)
The smallest unit of a complex antigen that is
 capable of inducing an immune response is
 called as epitope or Ag-determinant. An epitope
 is of roughly 5 amino acids or a sugar size.
          Virus
EPITOPES (antigenic determinants)
Epitopes are discrete sites on an antigen which
 are recognized by lymphocytes rather than the
 whole antigen.

These are immunologically active regions of
 antigen that bind to antigen specific membrane
 receptors on lymphocytes or secreted
 antibodies.
               HAPTENS
 Haptens are small organic molecules that
 are antigenic but not immunogenic.
 The conjugate formed by coupling a
 hapten to a large carrier protein is
 immunogenic and elicits production of
 antihapten antibodies when injected into
 an animal.
 Example is drug allergy (penicillin allergy)
Types of Antigen

1: Autoantigen

These are the molecules on self tissues for
which tolerance is inadequate. During
lymphocyte differentiation some body
molecules are not recognized and they act
as antigen later on in life e.g. cells in retina
of eye and in thyroid gland.
2: Alloantigen

Alloantigens are cell surface markers of one
individual that act as an antigen for other
individuals of the same species. These are
named after the Greek word “Allos” meaning
“other” e.g. different blood group mismatching
and organ transplant allergy.
3: Heterophilic Antigens
The molecules from unrelated species that bear
similar antigenic determinants leading to same
lymphocytic response e.g. carbohydrate residues
on surface of bacteria and RBCs, group A
streptococci and human heart tissue, cardiolipin a
phospholipid present in wide assortment of living
tissues.
4: Super Antigens

These are the bacterial toxins that are potent stimuli of
T-Cells. Their presence in an infection activates T-Cell
100 times more than an ordinary antigen. In this process
more cytokines are released leading to the cell death
e.g. TSS (Toxic Shock Syndrome), Staphylococcus
enterotoxins, Streptococcus pyrogenic exotoxins, these
toxins are active in very low concentration (10-9 mol/L).

5: Allergens
These are the antigens which provoke the allergic
reactions in the body e.g. pollen, penicillin drugs,
milk or fish proteins.
                  Viral Epitopes: Molecular Patterns




F-protein: Fusion protein in some viruses act as antigen
Fate of the Antigen in the Body

Antigen entry (Intravenous): becomes localized to liver,
spleen, bone marrow, kidney and lungs.

If by other routes: Ag localizes in lymphatic fluid and
concentrated by the lymph nodes.

Lymph nodes and the spleen are considered as very
important in filtering and concentrating the antigen and
circulate them to interact with the lymphocytes.
                     Fate of Ag in the Body




Th1 cytokines: IFN-γ, TNF-α
Th2 cytokines: IL-4, IL-5, IL-10, IL-13, IL-33


Abs Production                                   Chemoattraction &
                                                 engulfment of Ag
Structure of Antibody
Structure of Antibody
Structure of Antibody
               Classes of Antibody
IgG (Characteristics)
• 160 KDa MW,
• Gamma (γ) epitopes on its heavy chain
• Highest concentration in serum
• Plays a major role in antibody mediated defense
mechanisms
• Can opsonize and agglutinate the antigen
• Major isotype in secondary immune response
• Can activate complement system if sufficient molecules
are present
• Monomer in nature
• Class of Igs which can cross placenta
• Also present in clostrum
• Average life span in serum 23 days
IgM (Characteristics)
• 5-10% of the total serum
• As monomer on B-cells and pentamer when secreted
by plasma cells
• 180 KDa molecular weight
• Heavy chain have (μ) epitopes and have 10 antigen
binding sites
• J-chain join IgM molecule
• Major isotype in primary immune response
• Activates complement system, opsonization,
neutralization, agglutination of Ag
are major functions.
• First antibody synthesized in the neonate
• Monomeric IgM can be detected in chicken eggs and
day old chicks • It is thought to be derived from oviduct
secretions in hen • Average life span 5 days
IgA (Characteristics)

• 150 KDa molecular weight
• These are monomeric in blood as IgA
• These are also found as dimmer
• Synthesized by plasma cells
• These are major isotypes in secretions (13 %)
• In intestinal tract it is bind to a secretory component (S IgA which
protects it from
proteolytic enzymes).
• These are present in respiratory tract, UGT (uro-genital system),
mammary
glands, eyes and nasal secretions and prevent adherence of Ags
to mucosal
surfaces
• IgA cannot activate complement mediated Ag lysis
• It can agglutinate and neutralize the viruses (Ag)
• Production/ day of this Ig class is more than other Ig classes
• In Chicken (IgA)

• Chicken IgA in monomer form has 170 KDa and
in dimmer form it has the
weight of 340 KDa
• Chicken IgA has 4 heavy chain constant
domains where as mammalian IgA has 3.
• Average life span is 6 days
IgE (Characteristics)
• The molecular weight is 200 KDa
• These have a low concentration in serum up to 1%
• It mediates type-I hypersensitivity
• It is largely responsible for immunity to invading
parasites
• FC receptors are present on mast cells and basophiles
that lead to degranulation of
these cells resulting in increased release of histamine
causing allergic or
hypersensitivity reactions like asthma.
• It has a role in parasitic infections
• IgE is named because E is from E-Ag of ragweed
pollen that induces this class of
Ig
• Average life span of these Igs is 2.5 days
IgD (Characteristics)

• These are not found in serum
• It is primarily act as B-cell Ag receptor (BCR) found on
the surface of B-cells in
association with IgM
• These are monomers
• These don’t activate complement system
• These also play a role in immune suppression
• The average life span of these Igs is 3 days
• Its amount is 0.002% with respect to other Ig classes
which is less
Summary

• IgG can cross placenta
• IgG can activate and fix complement
• Fc receptor binds to phagocytes in (IgG, IgA), B-
lymphocytes (IgM, IgD)
• On mast cells and basophills (IgE) receptors present.
• IgM, IgG and IgD synthesized in spleen, lymph nodes
• IgA and IgE important in intestinal and respiratory tract
or mucosal surface infections
IgY (Vet. Immunology by C. Tizzard)

•It is the principal Ig in the chicken serum. It is somewhat similar to
IgG and IgE.
•It has 3 sub classes which are; IgY1, IgY2 and IgY3.
•It consists of two heavy and two light chains.
•Heavy chains are called as upsilon (υ), consists of one variable
and four constant domains.
•Its truncated isoform is also present that consists of two constant
domains having molecular weight of 120 KDa.
•These don’t have Fc region so cannot activate complement
system. These are produced from splicing of H-chains mRNA.
•Ducks and geese both have full sized and truncated IgY but the
chicken has only full sized IgY not truncated.
•This also lack hinge region, so these are somewhat inflexible and
•can cause precipitation or agglutination only.
IgY is related with anaphylaxis in chicken which has
following signs;

• Increased salivation
• Defecation
• Ruffled feathers
• Dyspnea
• Convulsions
• Cyanosis
• Collapse and finally death
The major organs involved are lungs that lead to death.
The chemical mediators involved are, histamine,
serotonin, kinins and leukotrines.

								
To top