HISTORY
DEFINITIONS
TYPES OF IMMUNITY
INNATE IMMUNITY
ADAPTIVE IMMUNITY
ANTIGEN & ANTIBODY
CONCLUSION
BIBLIOGRAPHY
 Immunology- branch of biology concerned
with the body’s defence reactions.
 Derived from the latin word ‘immunis’ meaning ‘free of burden’.
 Maintain the integrity of the body – removing the myriad of
threatening micro organisms which could invade from the
environment.
 Internally, mutant cells with malignant potential, may also be
attacked by the immune system.
 800 B.C. - Sushruta – “Father of surgery” in India, used patient’s
own skin as ‘graft’ in case of severed nose. At this time, basis of
‘Immunity’ was not established.
 1798 – Edward Jenner, gave the first description of ‘cell mediated
immune’ response after injecting ‘vaccinia virus’ as vaccine for
‘small pox’. A local erythematous papule developed within 24-72
hrs. He called it as just as ‘Reaction of Immunity’.
 1890 - Koch, described an exaggerated cutaneous reaction to
intradermal injection of ‘tubercle bacillus’ which was a paradigm for
delayed hypersensitivity.
 1898 - Bordet, described ‘alexine’, Ehrlich, coined the term
‘complement’ for the factors which completes the immune response.
 1902 – Paul Ehrlich, described ‘horror autotoxicosis’ which was later
called as ‘autoimmune reaction’.
 1902 - Richet, coined the term ‘Anaphylaxis’.
 1903 – Wright, described ‘opsonisation’ & Arthus, described ‘arthus
reaction’.
 1905 – Von pirquet & Schick, described ‘serum sickness’.
 1906 – Von pirquet, coined the term ‘allergy’.
 1923 – Coca and Cooke, described ‘atopy’.
 1963 - Coombs & Gell, classified hypersensitivity reactions.
 1967 - Burnet, described ‘immuno surveillance’
 1975 – Kohler & Milstein, gave a large scale production of
monoclonal antibodies, for which they have received ‘noble prize for
medicine’ in 1984.
 1980 – Snell, Dausset & Benaceraff, described about Major Histo
Compatibility antigens & its genetic control in immune response.
 Immunity:
 Resistance exhibited by the host towards injury caused by
pathogenic microorganisms and their products.
•Recognition
•Antibody production
•Cell mediated reactions
•Memory
BODY DEFENSE
NORMAL
IMMUNNE
DEFICIENCY
DISORDERS
HYPERSENSITIVITY
REACTIONS
AUTOIMMUNE
DISEASES
ABNORMAL
IMMUNOPHYSIOLOGY
IMMUNOPATHOLOGY
• NON – SPECIFIC
• SPECIFICINNATE
IMMUNITY
• ACTIVE
• PASSIVEADAPTIVE
IMMUNITY
 Innate Immunity:
 the resistance to infections which an individual posses by virtue of
his genetic and constitutional makeup.
 Non-specific : degree of resistance to infection in general (to all
infections) eg. plant pathogens.
 Specific : degree of resistance to particular pathogens.
 divided into Species immunity, racial immunity and, individual
immunity.
 Species Immunity: total or relative refractoriness to a
pathogen shown by all members of a species.
eg: All human beings are not susceptible to plant pathogens.
 Racial Immunity: within species, different races may show
differences in susceptibility to infections.
eg: Negros are resistant to yellow fever and malaria.
 Individual Immunity: exhibited by different individuals in a race.
eg: Homozygous twins exhibit similar degree of resistance to
leprosy and tuberculosis. Such correlations are not seen in
heterozygous twins.
 1.Epithelial surfaces:
 The intact skin and mucous membrane covering the body
protect considerably against invasion of microorganisms.
 Healthy skin possess anti bacterial activity in form of high
concentration salt in the drying sweats, the sebaceous secretion
 Mucosa of respiratory tract has several innate mechanisms of
defense (cough reflex, secretion contain mucopolysaccharides
capable of neutralizing the bacterial products).
 The mouth is constantly bathed in saliva, which has an
inhibitory effect on many microorganisms.
 IgA, T-helper and suppressor cell, B-cell of the IgA, and IgM
isotopes and macrophages.
 High acidity of the stomach destroys most of the microbes.
 Conjunctiva by lacrymal secretion, tears contains the
antibacterial substance lysozyme.
 2. Antibacterial substance in blood and tissues:
eg. a. The complement system possesses bactericidal activity
and plays an important role in the destruction of
pathogenic bacteria that invade the blood and tissues.
b. Lenkins from leukocytes, plakins from platelets.
c. Lactic acid found in muscles, Lactoperoxidase in milk,
speruine in kidneys.
 3. Fever : physiological process that destroys the infecting
pathogens. Fever stimulates the production of interferon and aids
recovery from viral infections.
 5.Acute phase proteins (CRP): Infection or injury leads to production
of CRP, which activate the alternate pathway of complement.
 Acute phase proteins
 The acute phase response is a systemic reaction to
infection or tissue injury, where macrophages release
cytokines IL-1, IL-6 and TNF; these cytokines reach
the liver through the circulation. The liver responds
by increasing its production of certain plasma proteins.
eg.:
 • C-reactive protein
 • Serum amyloid A
 • Complement components
 • Fibrinogen
 Cells of the innate immune system:
 Phagocytes:
 Phagocytes belong to two major lineage
1. Monocyte / macrophage
2. PMN granulocyte
A. Neutrophil
B. Basophil
C. Eosinophil
 The mononuclear phagocyte system has two main functions, which
result from the activities of two different types of bone marrow
derived cells.
 A. ‘Professional’ phagocytic macrophages, whose main role is to
remove particulate antigens.
 B. Antigen presenting cells, whose role is to take up, process and
present antigenic peptide to T cells.
 The term macrophages is generally applied to the cells found free in
body cavities while histiocytes is applied to cells found fixed in
tissues.
 They possess:
 CR1, CR3, CR4, C5aR receptors and molecules important in
antigen presenting to an MHC class II receptor, CD1.
 Macrophages secrete molecules, engulf and remove excess
antigen and aid in the induction of immune response of presenting
determinants to T cells.
 An organism that successfully penetrates an epithelial surface
encounter phagocyte cells of the monocyte macrophage lineage.
 Phagocytic macrophages are found in many organs.
 Examples of these are :
 1. Epitheliod cells, found in granulomas.
 2. Myeloid progenitors in the bone marrow.
 3. Kupffer cells are long lived resident liver macrophages.
 4. Dendritic cells are characterized by numerous long, slender
processes and by irregularly shaped nuclei.
 5. Multinucleated giant cells are formed by the fusion of
macrophages.
 Polymorphonuclear granulocytes:
 PMN granulocytes mainly consist of neutrophills and differentiate
completely with in bone marrow (14 days) are released from the
bone marrow at a rate of around 7 million per minute.

 They are short lived (2-3 days) relative to monocytes
/macrophages, which many live months or years.
 Granulocytes do not show any inherent specificity for antigens, but
they play an important role in acute inflammation, which provides a
primary nonspecific internal defense mechanisms.
 Chemotactic stimuli result in neutrophil margination and diapedesis.
 Neutrophils have a large arsenal of antibiotic proteins stored in two
main types of granules.
 The primary granules are lysosomes containing acid hydrolase,
myeloperoxidase and muranidase.
 The secondary granules contain lactoferrin and lysozyme.
In addition the granules also contain the antibiotic proteins
defensins, seprocidins, cathelicidins and bacterial permeability
inducing proteins.
 Eosinophils :
 2-5%of blood leukocytes in healthy, non-allergic individuals.
 Eosinophils limit inflammatory reactions of antagonizing the effects
of mediators.
 Release histaminase and arylsulphatase, which inactivates the
mast cell products histamine and some of the leukotriene.
 Eosinophils contain granules with eosinophilic basic protein which
are found to be toxic to certain parasites.
 Basophils:
 Very small numbers in the circulation, accounting for less than 0.2%
of leucocytes.
 Contain primarily histamine and leukotrienes which are potent
spasmogenic agents causing constriction of smooth muscle.
 Granules of basophils contain heparin, leukotrienes, histamine and
eosinophil chemotactic factor for anaphylaxis.
 The stimulus basophil degranulation is often an allergen. Mediators
such as histamine released by degranulation, cause the adverse
symptoms of allergy.
 On the positive side, they also play a role in immunity against
parasites by enhancing inflammation.
 Mast cells: The mast cell, which is not found in the circulation is
indistinguishable from the basophil.
 2 kinds a) mucosal mast cell
b) connective tissue mast cell
 Important in immediate inflammation -possess receptors for
complement components (C3a and C5a) as well as receptors for
the Fc portion of the antibody molecules IgE and IgG.
 Feature prominent cytoplasmic granules, termed lysosymes, which
store inflammatory mediators such as histamine, eosinophil
chemotactic factor, neutrophil chemotactic factor and heparin.
 Stimulation of these receptors > secretion of vasoactive substances
> increase vascular permeability and dilation (important signs of
anaphylaxis.)
 Analphylaxis can be life threatening if it is widespread (systemic)
but it is usually localized and is important in initiating inflammatory
response against local microbial invasion.
 Mast cells can synthesize denovo, other inflammatory mediators,
such as slow-reacting substance of anaphylaxis (SRS-A), tumor
necrosis factor (TNF-) and leukotriene .
 In addition mast cell interleukin has been shown to enhance
collagenase activity and heparin -may augment bone resorption.
 Platelets:
 Induce immune response and especially in inflammation.
 Derived from megakaryocytes in the bone marrow following injury to
endothelial cells, platelets aggregate at, the endothelial surface of
damaged vascular tissue.
 Release two types of granules which include serotonin and
fibrinogen > increased permeability, activation of complement
> attraction of leucocytes
From a anatomic stand point, the immune system has a
 a) Fixed compartment distributed through
Bone marrow
Thymus
Spleen
Lymph nodes
Tonsils
Peyer’s Patches
 b) Circulatory compartment represented by
diverse lymphocytes that move via the blood stream
into lymphoid organs and other part of the body where needed,
returning to the blood via the lymphatic channels.
 Cells, tissues and organs of the immune system:
 Lymphoid cells:
 Organized into tissues and organs in order to perform their
functions more effectively -lymphoid system.
 Comprises lymphocytes, accessory cells (macrophages) and in
some tissues, epithelial cells.
 The major lymphoid organs and tissues are classified into either
primary (central) or secondary (peripheral).
 Primary lymphoid organs:
 Major sites of lymphocyte development.
 The primary or central lymphoid organs include the
Thymus and Bone marrow.
 Secondary lymphoid organs:
 Generation of lymphocytes is followed by their migration into
peripheral secondary tissues.
 Comprise well organized encapsulated organs, the spleen and
lymphnodes and non-encapsulated accumulations of lymphoid
tissue (Mucosa Associated Lymphiod Tissue).
 Resistance that an individual acquires during his lifetime, which
may be weak or absent on first exposure but that increases
dramatically with subsequent exposures to same specific
pathogen.
ACTIVE
• NATURAL
• ARTIFICIAL
PASSIVE
• NATURAL
• ARTIFICIAL
ACQUIRED
IMMUNITY
 Active immunity -Resistance developed by an individual as a
result of an antigenic stimulus.
 Involves the active functioning of persons immune apparatus
leading to the synthesis of antibodies and production of
immunologically active cells.
 Natural active immunity - acquired due to infection
 Artificial active immunity - vaccination
eg. Bacterial vaccines: live (BCG) vaccine
killed (cholera) vaccine
Viral vaccines: live oral polio vaccine - sabine
killed injectable polio vaccine - salk
 Passive immunity -Resistance that is transmitted to a
recipient in a readymade form.
 No antigenic stimulus, instead preformed antibodies
are administered.
 Natural passive immunity
A mother’s antibodies pass across the placenta to
the foetus and remain for several months. EG:- IgG
antibody.
Artificial passive immunity
Used when a very rapid immune response is needed
e.g. after infection with tetanus
Antibodies come from blood donors who have
recently had the tetanus vaccination.
 Combined immunization: a combination of active and passive
method of immunization is employed.
 Adoptive immunity: Special type of immunization in which
immunologically competent lymphocytes are injected.
 Herd immunity: this refers to overall level of immunity in a
community and is relevant in the control of epidemic diseases.
 Cells of acquired immune system:
 Lymphocytes : lymphocytes includes three types of cells.
 T-lymphocytes or T cells, which are derived from the thymus and
play a role in cell-mediated immunity.
 B-lymphocytes or B-cells which are derived from liver, spleen and
bone marrow are precursors of plasma cells and play a role in
humoral immunity.
 Natural killer (NK) and killer (K) cells.
 T cells leave the bone marrow via the blood stream and move to
the thymus.
 T cell becomes able to differentiate between self and nonself
antigens.
 This process involves the immature T cells being presented with
cell surface molecules termed major histocompatibility complex
(MHC) molecules, of which there are two types termed class I
and class II.
 In the thymus, those T cells which react with very strongly or very
weakly with self MHC molecules are destroyed.
 The remaining T cells then mature and are able to recognize foreign
antigens in conjunction with MHC molecules.
 The T cells recognize antigen through surface molecules termed the
T cell receptor (TCR).
 Each T cell possesses a different TCR to allow it to recognize a
different antigen. After leaving the thymus T cells locate in lymph
nodes and spleen.
 The T lymphocytes are associated with two types of immunological
functions, effector and regulatory.
 The effector functions include activities such as killing of virally
infected cells and tumors.
 The regulatory functions are represented by their ability to amplify
or suppress through cytokines or other effector lymphocytes
including B and T cells.
 T cells are divided into several subsets with different functions.
1. T helper cell/T-inducer cells (Th)
2. T-suppressor cells (Ts)
3. T-cytotoxic cells (Tc)
 1.T helper cells/T-inducer cells:
 T cells have CD4 surface marker, MHC class II restriction,
stimulates the growth of T cells and macrophages.
 TH1 cells with CD4 molecule produce cytokines IL-2 which activate
macrophages, IFN-y -involved in hypersensitivity reactions.
 TH2 express CD4 molecule on their surface and function by
secreting cytokines (IL-4, IL-5, IL-6, IL-10) that promote B cells to
produce antibodies.
 T-suppressor cells:
 Suppressor effector T cells bind antigen and release factor that
inactivate T-helper cells.
 T-suppressor cells can
 (1) suppress delayed –type hypersensitivity reactions
 (2) prevent proliferation and antibody secretion by antigen-
binding B cells, and
 (3) suppress antibody secretion by having CD8 surface marker
and MHC class I restriction.
 T-Cytotoxic cells:
 These cells recognize certain histocompatibility antigens and are
capable of killing foreign cells (i.e., virus) and altered self-cells (i.e.
tumor antigens).
 Important in the cytotoxicity of graft reactions and graft-versus-host
reactions.
 B lymphocytes are primarily defined by surface immunoglobulins
S(Ig).
 Common in areas of antibody production, such as the germinal
centers of the lymph nodes and diffuse lymphoid tissue of mucosal
systems.
 B lymphocyte development and maturation results in the formation
of plasma cells, the antibody producing cells of the body.
 Bone marrow -major repository of stem cells for B lymphocytes.
 Mature B lymphocytes are the products of lymphoid stem cells that
undergo a sequence of differentiation.
 In mammals the differentiation occurs first in the fetal liver and
subsequently in the bone marrow.
 The B cell development can be divided into two stages, antigen
dependent and antigen independent.
 On encountering an antigen, the mature B cells are driven to
undergo cell activation, proliferation and differentiation, giving rise to
plasma cells that synthesize and secrete Ig, (Ig M, IgD, IgG, IgA
,IgE ) which requires T cell. However they seldom divide and have a
life span of 2 to 3 days.
 Separate lineage of B lymphocytes -predominant in fetal and early
neonatal life, express the T cell marker CD5 on their surface -
named as B1 cells.
 They secrete low affinity poly reactive IgM antibodies.
 Responsible for the T independent natural IgM antibacterial
antibodies which appear in neonates without antigenic stimulus.
 CD5+ B cells may be relevant in the casuation of autoimmune
conditions.
 Circulating lymphocytes are classified by their surface markers into
T and B lymphocytes, about 5 – 10 %of the cells are found to lack
features of either type -called NULL cells.
 Large Granular Lymphocytes having heterogenous group of cells
with differences in their functional and surface marker features. The
most important of this group is called NATURAL KILLER CELLS.
 NK cells -destroy antibody-coated target cells irrespective of the
presence of MHC molecules, a process known as antibody-
dependent cell mediated cytotoxicity. This occurs because killing is
initiated by cross-linking of receptors for the Fc portion of IgG1 and
IgG3.
 NK cells are not clonally restricted, have no memory and are not
very specific in their action.
 An antigen has been defined as any substance which, when
introduced partially into the body, stimulates the production of an
antibody with which it react specifically.
 An antigen introduced into the body reacts only with those
particular immunocytes which carry the specific marker for that
antigen and which produce antibody complimentary to that antigen
only.
 The discrete portions of the antigen that bind to the antibodies
antigen combining site are called epitopes.
 An antigen may possess several epitopes. The containing area on
the antibody molecule corresponding to the epitope is called
paratope.
 Epitope consists of four or five amino acids possessing a specific
chemical structure, electric charge and spatial configuration capable
of sensitizing an immunocyte and of reacting with its
complementary site on the specific antibody or T-cell receptor.
 Complete antigen: Is able to induce antibodies formation and
produce a specific and observable reaction with the antibody
produced.
 Haptens: Low molecular weight molecules which by itself do not
elicit immune response until and unless complexed with an
immunogenic carrier, such as protein.
 Size : Antigenicity bears a relation to molecular size. Very large
molecules are highly antigenic.
 Chemical matrix : Most naturally occurring antigens are proteins
and polysaccharides. Lipids and nucleotides are less antigenic.
 Susceptibility to tissue enzymes : Only substances which are
metabolized and are susceptible to the action of tissue enzymes
behave as antigens.
 Foreignness : Only antigen which are ‘foreign’ to the individual (non
self) induce an immune response. Breakdown of this homeostatic
mechanism result in autoimmunization and auto immune disease.
 Depending on their ability to induce antibody formation, antigens
are classified.
Antigens
T cell dependent
(TD) antigens
T cell
independent (TI)
antigens
Biological classes of antigens
T cell dependent (TD)
antigens
T cell independent (TI)
antigens
STRUCTURALLY SIMPLE STRUCTURALLY COMPLEX
NO. OF EPITOPES LIMITED NO. OF EPITOPES UNLIMITED
IMMUNOLOGICAL MEMORY-DO NOT
SHOW
IMMUNOLOGICAL MEMORY- SHOW
METABOLISEDVERY SLOWLY METOBILISED RAPIDLY
REMAIN IN BODY FOR LONG PERIODS REMAIN IN BODY FOR SHORT
PERIODS
IMMUNE RESPONSE DOSE
DEPENDENT
IMMUNE RESPONSE NOT DOSE
DEPENDENT
ANTIBODY RESPONSE IgM & IgG3 ANTIBODY RESPONSE IgM, IgG, IgA &
IgE
 Processing involves the internalization and partial degradation of
antigens by antigen-presenting cells (APCs).
 The resultant fragments of antigen are transported back to the APC
surface, where they are bound by class II histocompatibility
antigens.
 The antigen fragment class II complex is subsequently recognized
by T cells bearing complementary T cell receptors.
 Antigen presenting cells are
 1. Macrophages
 2. Dendrites cells
 3. B cells during secondary immune response
 4. Langerhans cells
 The genetic basis of immune response, which had been suggested
by many early observations ,was proved by BENACERRAF and
COLLEAGUES, who established that the ability to respond
immunologically to an antigen was conditioned by specific genes
called the immune response genes.
 For this work on MHC and genetic control of immune response,
SNELL ,DUSSET and BENACERRAF were awarded the nobel
prize for Medicine in 1980.
 The major antigens determining histocompatibility in human beings
are alloantigens, characteristically found on the surface of
leucocytes.
 Human MHC antigens are therefore synonymous with human
leukocyte antigen(HLA).
 The HLA complex of genes is located on the short arm of
chromosome 6.
 It consists of 3 separate clusters of genes.
 1. Class I consisting of A, B and C loci.
 Determine histocompatibility -acceptance or rejection of allografts.
 2. Class II or the D region consisting of D or DQ and DP loci.
 Regulate immune response.
 3. Class III or the complement region containing genes for
complement components C2 and C4 of the classical pathway
as well as properdin factor B of alternative pathway.
 HLA Class I molecules consists of a heavy peptide chain (α
chain) non convalently linked to a much smaller peptide called
β2 microglobulin (β chain). The β chain has a constant
aminoacid sequence and is coded for by a gene on
chromosome 15.
 The α chain consists of three globoid domains ( α1, α 2, α3)
which protrude from the cell membrane and a small length of
transmembrane C terminus reaching into the cytoplasm.
 The distal domains α1 & α 2 have highly variable amino acid
sequences and are folded to form a cavity or groove between
them.
Structure of MHC class I molecules
 Protein antigens processed by macrophages or dendritic cells to
form small peptides are bound to groove for presentation to CD8 T
cells.
 T cell will recognize the antigen only when presented as a complex
with the MHC class I molecule and not otherwise (MHC restriction).
 When so presented, the CD8 cytotoxic killer cell destroys the target
cell ( for example, a virus infected cell).
 Class II antigens are heterodimers, consisting of an α and β chain.
 HLA class II antigens are heterodimers, consisting of an alpha and
beta chain .Each chain has 2 domains, the proximal domain being
the constant region and the distal the variable.
 The two distal domains constitute the antigen binding site, for
recognition by CD4 lymphocytes, in a fashion similar to the
recognition of the class I antigen peptide complex by CD8 T cells.
 HLA class II molecules are primarly responsible for the graft versus
host response and the mixed leucocyte reaction .
 HLA class III molecules are heterogenous. They include
complement components linked to the formation of C3 convertases,
heat shock protiens and tumour necrosis factors. They also show
polymorphysim.
Structure of MHC class II molecules
 The host responds to oral bacteria and their products by plasma cell
production of immunoglobulins or antibodies.
 In 1964 endorsed by WHO, the generic term, “Immunoglobulin” was
internationally accepted for proteins of animal origin endowed with
known antibody activity and for certain other protein related to them
by chemical structure.
 Immunoglobulin provides a structural and chemical concept, while
the term ‘antibody’ is a biological and functional concept.
 ALL THE ANTIBODIES ARE IMMUNOGLOBULINS BUT ALL
IMMUNOGLOBULINS MAY NOT BE ANTIBODIES.
 Antibodies which are glycoproteins, are found in blood, tissue fluids
and secretions and are the effectors of humoral immunity. They are
highly specific and sensitive.
 All classes and subsets of immunoglobulins have similar structural
organizations, but they differ according to their biologic properties,
carbohydrate content, weight and amino acid sequences.
 Every antibody molecule has a variable region which, because of its
unique amino acid sequence and tertiary structure of its antibody
combining site, allows it to react highly specifically with a particular
antigen.
 Studies involving the cleavage of the Ig molecule, pioneered by
Porter, Edelman and their colleageus, have led to a detailed
picture of its structure.
Each molecule of Ig is split into one Fc portion (crystallisable),
and two Fab fragments (antigen binding).
Ig constitutes 20-25% of the total serum proteins.
Based on physiochemical and antigenic differences, five classes
of Ig have been recognized - IgG, IgA, IgM, IgD and IgE. (Both Ig
and g are accepted abbreviations for immunoglobulins).
 All the immunoglobulin constant region domains (C) maintain a
similar basic structure. The variable region domains (V) have a
slightly different structure. The polypeptide strand connecting the V
and C domains is called the hinge and is important to and body
structure because of the flexibility it allows between the V and C
domains. Heavy chains can be divided into three functional regions;
Fd, hing and Fc.
 The Fd in combination with a light chain forms the Fab region,
which has all the antigen-binding properties of an intact
immunoglobulin.
 The Fc fragment bears the effector functions of the immunoglobulin
molecule
 Immunoglobulins (antibodies):
 IgM is the first antibody to arrive in our body. It initiates the
complement cascade and is the main antibody in response to T
independent antigens.
 IgG is the next antibody to arrive; it remains longest.
 Having several subclasses, IgG1, IgG2, IgG3 and IgG4 is also the
most predominant antibody. It coats antigens (opsonization) for
destruction by phagocytes, prepares other antigens for destruction
by killer cells.
 IgA is found in the saliva (secretory IgA) and other areas
where there is mucous membrane. It is the first line of
defense against microorganisms that would invade via the
mucosa, IgA antibodies deter microorganisms from
penetrating epithelial cells. it is composes of two subclasses
IgA1 and IgA2.
 IgD is a trace antibody and differentiates B cells. it
disappears after differentiation.
 IgE is the reaginc antibody it is in low concentration and
responsible for acute allergic reactions, binds to mast cells
and basophils stimulating the release of vasoactive
substances such as histamine, prostaglandins and
leukotrienes.
Type Number of
ag binding
sites
Site of action Functions
IgG 2 •Blood
•Tissue fluid
•CAN CROSS
PLACENTA
•Increase
macrophage
activity
•Antitoxins
•Agglutination
IgM 10 •Blood
•Tissue fluid
Agglutination
IgA 2 or 4 •Secretions (saliva,
tears, small
intestine, vaginal,
prostate, nasal,
breast milk)
•Stop bacteria
adhering to host
cells
•Prevents bacteria
forming colonies
on mucous
membranes
IgE 2 Tissues •Activate mast
cells
 HISTAMINE
•Warm response
 Recent investigations have revealed that not all
strains of a specific microbial species are equal in
their capacity to cause disease and not all hosts are
equal in their susceptibility to disease.
 The challenge for the future is to be able to better
identify the more virulent bacterial strains and more
susceptible host.
 In this manner it may be possible to predict
accurately the individuals at risk for future disease
and to develope more effective strategies to prevent
the onset and progression of disease.
Immunity

Immunity

  • 2.
    HISTORY DEFINITIONS TYPES OF IMMUNITY INNATEIMMUNITY ADAPTIVE IMMUNITY ANTIGEN & ANTIBODY CONCLUSION BIBLIOGRAPHY
  • 3.
     Immunology- branchof biology concerned with the body’s defence reactions.  Derived from the latin word ‘immunis’ meaning ‘free of burden’.  Maintain the integrity of the body – removing the myriad of threatening micro organisms which could invade from the environment.  Internally, mutant cells with malignant potential, may also be attacked by the immune system.
  • 4.
     800 B.C.- Sushruta – “Father of surgery” in India, used patient’s own skin as ‘graft’ in case of severed nose. At this time, basis of ‘Immunity’ was not established.  1798 – Edward Jenner, gave the first description of ‘cell mediated immune’ response after injecting ‘vaccinia virus’ as vaccine for ‘small pox’. A local erythematous papule developed within 24-72 hrs. He called it as just as ‘Reaction of Immunity’.
  • 5.
     1890 -Koch, described an exaggerated cutaneous reaction to intradermal injection of ‘tubercle bacillus’ which was a paradigm for delayed hypersensitivity.  1898 - Bordet, described ‘alexine’, Ehrlich, coined the term ‘complement’ for the factors which completes the immune response.  1902 – Paul Ehrlich, described ‘horror autotoxicosis’ which was later called as ‘autoimmune reaction’.
  • 6.
     1902 -Richet, coined the term ‘Anaphylaxis’.  1903 – Wright, described ‘opsonisation’ & Arthus, described ‘arthus reaction’.  1905 – Von pirquet & Schick, described ‘serum sickness’.  1906 – Von pirquet, coined the term ‘allergy’.
  • 7.
     1923 –Coca and Cooke, described ‘atopy’.  1963 - Coombs & Gell, classified hypersensitivity reactions.  1967 - Burnet, described ‘immuno surveillance’  1975 – Kohler & Milstein, gave a large scale production of monoclonal antibodies, for which they have received ‘noble prize for medicine’ in 1984.  1980 – Snell, Dausset & Benaceraff, described about Major Histo Compatibility antigens & its genetic control in immune response.
  • 8.
     Immunity:  Resistanceexhibited by the host towards injury caused by pathogenic microorganisms and their products.
  • 9.
    •Recognition •Antibody production •Cell mediatedreactions •Memory BODY DEFENSE NORMAL IMMUNNE DEFICIENCY DISORDERS HYPERSENSITIVITY REACTIONS AUTOIMMUNE DISEASES ABNORMAL IMMUNOPHYSIOLOGY IMMUNOPATHOLOGY
  • 10.
    • NON –SPECIFIC • SPECIFICINNATE IMMUNITY • ACTIVE • PASSIVEADAPTIVE IMMUNITY
  • 11.
     Innate Immunity: the resistance to infections which an individual posses by virtue of his genetic and constitutional makeup.  Non-specific : degree of resistance to infection in general (to all infections) eg. plant pathogens.  Specific : degree of resistance to particular pathogens.  divided into Species immunity, racial immunity and, individual immunity.
  • 12.
     Species Immunity:total or relative refractoriness to a pathogen shown by all members of a species. eg: All human beings are not susceptible to plant pathogens.  Racial Immunity: within species, different races may show differences in susceptibility to infections. eg: Negros are resistant to yellow fever and malaria.  Individual Immunity: exhibited by different individuals in a race. eg: Homozygous twins exhibit similar degree of resistance to leprosy and tuberculosis. Such correlations are not seen in heterozygous twins.
  • 13.
     1.Epithelial surfaces: The intact skin and mucous membrane covering the body protect considerably against invasion of microorganisms.  Healthy skin possess anti bacterial activity in form of high concentration salt in the drying sweats, the sebaceous secretion  Mucosa of respiratory tract has several innate mechanisms of defense (cough reflex, secretion contain mucopolysaccharides capable of neutralizing the bacterial products).
  • 14.
     The mouthis constantly bathed in saliva, which has an inhibitory effect on many microorganisms.  IgA, T-helper and suppressor cell, B-cell of the IgA, and IgM isotopes and macrophages.  High acidity of the stomach destroys most of the microbes.  Conjunctiva by lacrymal secretion, tears contains the antibacterial substance lysozyme.
  • 15.
     2. Antibacterialsubstance in blood and tissues: eg. a. The complement system possesses bactericidal activity and plays an important role in the destruction of pathogenic bacteria that invade the blood and tissues. b. Lenkins from leukocytes, plakins from platelets. c. Lactic acid found in muscles, Lactoperoxidase in milk, speruine in kidneys.
  • 16.
     3. Fever: physiological process that destroys the infecting pathogens. Fever stimulates the production of interferon and aids recovery from viral infections.  5.Acute phase proteins (CRP): Infection or injury leads to production of CRP, which activate the alternate pathway of complement.
  • 17.
     Acute phaseproteins  The acute phase response is a systemic reaction to infection or tissue injury, where macrophages release cytokines IL-1, IL-6 and TNF; these cytokines reach the liver through the circulation. The liver responds by increasing its production of certain plasma proteins. eg.:  • C-reactive protein  • Serum amyloid A  • Complement components  • Fibrinogen
  • 18.
     Cells ofthe innate immune system:  Phagocytes:  Phagocytes belong to two major lineage 1. Monocyte / macrophage 2. PMN granulocyte A. Neutrophil B. Basophil C. Eosinophil
  • 19.
     The mononuclearphagocyte system has two main functions, which result from the activities of two different types of bone marrow derived cells.  A. ‘Professional’ phagocytic macrophages, whose main role is to remove particulate antigens.  B. Antigen presenting cells, whose role is to take up, process and present antigenic peptide to T cells.
  • 20.
     The termmacrophages is generally applied to the cells found free in body cavities while histiocytes is applied to cells found fixed in tissues.  They possess:  CR1, CR3, CR4, C5aR receptors and molecules important in antigen presenting to an MHC class II receptor, CD1.
  • 21.
     Macrophages secretemolecules, engulf and remove excess antigen and aid in the induction of immune response of presenting determinants to T cells.  An organism that successfully penetrates an epithelial surface encounter phagocyte cells of the monocyte macrophage lineage.
  • 22.
     Phagocytic macrophagesare found in many organs.  Examples of these are :  1. Epitheliod cells, found in granulomas.  2. Myeloid progenitors in the bone marrow.  3. Kupffer cells are long lived resident liver macrophages.  4. Dendritic cells are characterized by numerous long, slender processes and by irregularly shaped nuclei.  5. Multinucleated giant cells are formed by the fusion of macrophages.
  • 23.
     Polymorphonuclear granulocytes: PMN granulocytes mainly consist of neutrophills and differentiate completely with in bone marrow (14 days) are released from the bone marrow at a rate of around 7 million per minute.   They are short lived (2-3 days) relative to monocytes /macrophages, which many live months or years.  Granulocytes do not show any inherent specificity for antigens, but they play an important role in acute inflammation, which provides a primary nonspecific internal defense mechanisms.
  • 24.
     Chemotactic stimuliresult in neutrophil margination and diapedesis.  Neutrophils have a large arsenal of antibiotic proteins stored in two main types of granules.  The primary granules are lysosomes containing acid hydrolase, myeloperoxidase and muranidase.  The secondary granules contain lactoferrin and lysozyme. In addition the granules also contain the antibiotic proteins defensins, seprocidins, cathelicidins and bacterial permeability inducing proteins.
  • 25.
     Eosinophils : 2-5%of blood leukocytes in healthy, non-allergic individuals.  Eosinophils limit inflammatory reactions of antagonizing the effects of mediators.  Release histaminase and arylsulphatase, which inactivates the mast cell products histamine and some of the leukotriene.  Eosinophils contain granules with eosinophilic basic protein which are found to be toxic to certain parasites.
  • 26.
     Basophils:  Verysmall numbers in the circulation, accounting for less than 0.2% of leucocytes.  Contain primarily histamine and leukotrienes which are potent spasmogenic agents causing constriction of smooth muscle.  Granules of basophils contain heparin, leukotrienes, histamine and eosinophil chemotactic factor for anaphylaxis.  The stimulus basophil degranulation is often an allergen. Mediators such as histamine released by degranulation, cause the adverse symptoms of allergy.  On the positive side, they also play a role in immunity against parasites by enhancing inflammation.
  • 27.
     Mast cells:The mast cell, which is not found in the circulation is indistinguishable from the basophil.  2 kinds a) mucosal mast cell b) connective tissue mast cell  Important in immediate inflammation -possess receptors for complement components (C3a and C5a) as well as receptors for the Fc portion of the antibody molecules IgE and IgG.  Feature prominent cytoplasmic granules, termed lysosymes, which store inflammatory mediators such as histamine, eosinophil chemotactic factor, neutrophil chemotactic factor and heparin.
  • 28.
     Stimulation ofthese receptors > secretion of vasoactive substances > increase vascular permeability and dilation (important signs of anaphylaxis.)  Analphylaxis can be life threatening if it is widespread (systemic) but it is usually localized and is important in initiating inflammatory response against local microbial invasion.  Mast cells can synthesize denovo, other inflammatory mediators, such as slow-reacting substance of anaphylaxis (SRS-A), tumor necrosis factor (TNF-) and leukotriene .  In addition mast cell interleukin has been shown to enhance collagenase activity and heparin -may augment bone resorption.
  • 29.
     Platelets:  Induceimmune response and especially in inflammation.  Derived from megakaryocytes in the bone marrow following injury to endothelial cells, platelets aggregate at, the endothelial surface of damaged vascular tissue.  Release two types of granules which include serotonin and fibrinogen > increased permeability, activation of complement > attraction of leucocytes
  • 30.
    From a anatomicstand point, the immune system has a  a) Fixed compartment distributed through Bone marrow Thymus Spleen Lymph nodes Tonsils Peyer’s Patches  b) Circulatory compartment represented by diverse lymphocytes that move via the blood stream into lymphoid organs and other part of the body where needed, returning to the blood via the lymphatic channels.
  • 31.
     Cells, tissuesand organs of the immune system:  Lymphoid cells:  Organized into tissues and organs in order to perform their functions more effectively -lymphoid system.  Comprises lymphocytes, accessory cells (macrophages) and in some tissues, epithelial cells.  The major lymphoid organs and tissues are classified into either primary (central) or secondary (peripheral).
  • 32.
     Primary lymphoidorgans:  Major sites of lymphocyte development.  The primary or central lymphoid organs include the Thymus and Bone marrow.  Secondary lymphoid organs:  Generation of lymphocytes is followed by their migration into peripheral secondary tissues.  Comprise well organized encapsulated organs, the spleen and lymphnodes and non-encapsulated accumulations of lymphoid tissue (Mucosa Associated Lymphiod Tissue).
  • 33.
     Resistance thatan individual acquires during his lifetime, which may be weak or absent on first exposure but that increases dramatically with subsequent exposures to same specific pathogen.
  • 34.
    ACTIVE • NATURAL • ARTIFICIAL PASSIVE •NATURAL • ARTIFICIAL ACQUIRED IMMUNITY
  • 35.
     Active immunity-Resistance developed by an individual as a result of an antigenic stimulus.  Involves the active functioning of persons immune apparatus leading to the synthesis of antibodies and production of immunologically active cells.  Natural active immunity - acquired due to infection  Artificial active immunity - vaccination eg. Bacterial vaccines: live (BCG) vaccine killed (cholera) vaccine Viral vaccines: live oral polio vaccine - sabine killed injectable polio vaccine - salk
  • 36.
     Passive immunity-Resistance that is transmitted to a recipient in a readymade form.  No antigenic stimulus, instead preformed antibodies are administered.  Natural passive immunity A mother’s antibodies pass across the placenta to the foetus and remain for several months. EG:- IgG antibody. Artificial passive immunity Used when a very rapid immune response is needed e.g. after infection with tetanus Antibodies come from blood donors who have recently had the tetanus vaccination.
  • 37.
     Combined immunization:a combination of active and passive method of immunization is employed.  Adoptive immunity: Special type of immunization in which immunologically competent lymphocytes are injected.  Herd immunity: this refers to overall level of immunity in a community and is relevant in the control of epidemic diseases.
  • 38.
     Cells ofacquired immune system:  Lymphocytes : lymphocytes includes three types of cells.  T-lymphocytes or T cells, which are derived from the thymus and play a role in cell-mediated immunity.  B-lymphocytes or B-cells which are derived from liver, spleen and bone marrow are precursors of plasma cells and play a role in humoral immunity.  Natural killer (NK) and killer (K) cells.
  • 39.
     T cellsleave the bone marrow via the blood stream and move to the thymus.  T cell becomes able to differentiate between self and nonself antigens.  This process involves the immature T cells being presented with cell surface molecules termed major histocompatibility complex (MHC) molecules, of which there are two types termed class I and class II.
  • 40.
     In thethymus, those T cells which react with very strongly or very weakly with self MHC molecules are destroyed.  The remaining T cells then mature and are able to recognize foreign antigens in conjunction with MHC molecules.  The T cells recognize antigen through surface molecules termed the T cell receptor (TCR).  Each T cell possesses a different TCR to allow it to recognize a different antigen. After leaving the thymus T cells locate in lymph nodes and spleen.
  • 41.
     The Tlymphocytes are associated with two types of immunological functions, effector and regulatory.  The effector functions include activities such as killing of virally infected cells and tumors.  The regulatory functions are represented by their ability to amplify or suppress through cytokines or other effector lymphocytes including B and T cells.
  • 42.
     T cellsare divided into several subsets with different functions. 1. T helper cell/T-inducer cells (Th) 2. T-suppressor cells (Ts) 3. T-cytotoxic cells (Tc)
  • 43.
     1.T helpercells/T-inducer cells:  T cells have CD4 surface marker, MHC class II restriction, stimulates the growth of T cells and macrophages.  TH1 cells with CD4 molecule produce cytokines IL-2 which activate macrophages, IFN-y -involved in hypersensitivity reactions.  TH2 express CD4 molecule on their surface and function by secreting cytokines (IL-4, IL-5, IL-6, IL-10) that promote B cells to produce antibodies.
  • 44.
     T-suppressor cells: Suppressor effector T cells bind antigen and release factor that inactivate T-helper cells.  T-suppressor cells can  (1) suppress delayed –type hypersensitivity reactions  (2) prevent proliferation and antibody secretion by antigen- binding B cells, and  (3) suppress antibody secretion by having CD8 surface marker and MHC class I restriction.
  • 45.
     T-Cytotoxic cells: These cells recognize certain histocompatibility antigens and are capable of killing foreign cells (i.e., virus) and altered self-cells (i.e. tumor antigens).  Important in the cytotoxicity of graft reactions and graft-versus-host reactions.
  • 46.
     B lymphocytesare primarily defined by surface immunoglobulins S(Ig).  Common in areas of antibody production, such as the germinal centers of the lymph nodes and diffuse lymphoid tissue of mucosal systems.  B lymphocyte development and maturation results in the formation of plasma cells, the antibody producing cells of the body.  Bone marrow -major repository of stem cells for B lymphocytes.
  • 47.
     Mature Blymphocytes are the products of lymphoid stem cells that undergo a sequence of differentiation.  In mammals the differentiation occurs first in the fetal liver and subsequently in the bone marrow.  The B cell development can be divided into two stages, antigen dependent and antigen independent.  On encountering an antigen, the mature B cells are driven to undergo cell activation, proliferation and differentiation, giving rise to plasma cells that synthesize and secrete Ig, (Ig M, IgD, IgG, IgA ,IgE ) which requires T cell. However they seldom divide and have a life span of 2 to 3 days.
  • 48.
     Separate lineageof B lymphocytes -predominant in fetal and early neonatal life, express the T cell marker CD5 on their surface - named as B1 cells.  They secrete low affinity poly reactive IgM antibodies.  Responsible for the T independent natural IgM antibacterial antibodies which appear in neonates without antigenic stimulus.  CD5+ B cells may be relevant in the casuation of autoimmune conditions.
  • 49.
     Circulating lymphocytesare classified by their surface markers into T and B lymphocytes, about 5 – 10 %of the cells are found to lack features of either type -called NULL cells.  Large Granular Lymphocytes having heterogenous group of cells with differences in their functional and surface marker features. The most important of this group is called NATURAL KILLER CELLS.  NK cells -destroy antibody-coated target cells irrespective of the presence of MHC molecules, a process known as antibody- dependent cell mediated cytotoxicity. This occurs because killing is initiated by cross-linking of receptors for the Fc portion of IgG1 and IgG3.  NK cells are not clonally restricted, have no memory and are not very specific in their action.
  • 50.
     An antigenhas been defined as any substance which, when introduced partially into the body, stimulates the production of an antibody with which it react specifically.  An antigen introduced into the body reacts only with those particular immunocytes which carry the specific marker for that antigen and which produce antibody complimentary to that antigen only.  The discrete portions of the antigen that bind to the antibodies antigen combining site are called epitopes.
  • 51.
     An antigenmay possess several epitopes. The containing area on the antibody molecule corresponding to the epitope is called paratope.  Epitope consists of four or five amino acids possessing a specific chemical structure, electric charge and spatial configuration capable of sensitizing an immunocyte and of reacting with its complementary site on the specific antibody or T-cell receptor.
  • 52.
     Complete antigen:Is able to induce antibodies formation and produce a specific and observable reaction with the antibody produced.  Haptens: Low molecular weight molecules which by itself do not elicit immune response until and unless complexed with an immunogenic carrier, such as protein.
  • 53.
     Size :Antigenicity bears a relation to molecular size. Very large molecules are highly antigenic.  Chemical matrix : Most naturally occurring antigens are proteins and polysaccharides. Lipids and nucleotides are less antigenic.  Susceptibility to tissue enzymes : Only substances which are metabolized and are susceptible to the action of tissue enzymes behave as antigens.  Foreignness : Only antigen which are ‘foreign’ to the individual (non self) induce an immune response. Breakdown of this homeostatic mechanism result in autoimmunization and auto immune disease.
  • 54.
     Depending ontheir ability to induce antibody formation, antigens are classified. Antigens T cell dependent (TD) antigens T cell independent (TI) antigens Biological classes of antigens
  • 55.
    T cell dependent(TD) antigens T cell independent (TI) antigens STRUCTURALLY SIMPLE STRUCTURALLY COMPLEX NO. OF EPITOPES LIMITED NO. OF EPITOPES UNLIMITED IMMUNOLOGICAL MEMORY-DO NOT SHOW IMMUNOLOGICAL MEMORY- SHOW METABOLISEDVERY SLOWLY METOBILISED RAPIDLY REMAIN IN BODY FOR LONG PERIODS REMAIN IN BODY FOR SHORT PERIODS IMMUNE RESPONSE DOSE DEPENDENT IMMUNE RESPONSE NOT DOSE DEPENDENT ANTIBODY RESPONSE IgM & IgG3 ANTIBODY RESPONSE IgM, IgG, IgA & IgE
  • 56.
     Processing involvesthe internalization and partial degradation of antigens by antigen-presenting cells (APCs).  The resultant fragments of antigen are transported back to the APC surface, where they are bound by class II histocompatibility antigens.  The antigen fragment class II complex is subsequently recognized by T cells bearing complementary T cell receptors.
  • 57.
     Antigen presentingcells are  1. Macrophages  2. Dendrites cells  3. B cells during secondary immune response  4. Langerhans cells
  • 58.
     The geneticbasis of immune response, which had been suggested by many early observations ,was proved by BENACERRAF and COLLEAGUES, who established that the ability to respond immunologically to an antigen was conditioned by specific genes called the immune response genes.  For this work on MHC and genetic control of immune response, SNELL ,DUSSET and BENACERRAF were awarded the nobel prize for Medicine in 1980.
  • 59.
     The majorantigens determining histocompatibility in human beings are alloantigens, characteristically found on the surface of leucocytes.  Human MHC antigens are therefore synonymous with human leukocyte antigen(HLA).
  • 60.
     The HLAcomplex of genes is located on the short arm of chromosome 6.  It consists of 3 separate clusters of genes.  1. Class I consisting of A, B and C loci.  Determine histocompatibility -acceptance or rejection of allografts.  2. Class II or the D region consisting of D or DQ and DP loci.  Regulate immune response.  3. Class III or the complement region containing genes for complement components C2 and C4 of the classical pathway as well as properdin factor B of alternative pathway.
  • 61.
     HLA ClassI molecules consists of a heavy peptide chain (α chain) non convalently linked to a much smaller peptide called β2 microglobulin (β chain). The β chain has a constant aminoacid sequence and is coded for by a gene on chromosome 15.  The α chain consists of three globoid domains ( α1, α 2, α3) which protrude from the cell membrane and a small length of transmembrane C terminus reaching into the cytoplasm.  The distal domains α1 & α 2 have highly variable amino acid sequences and are folded to form a cavity or groove between them.
  • 62.
    Structure of MHCclass I molecules
  • 63.
     Protein antigensprocessed by macrophages or dendritic cells to form small peptides are bound to groove for presentation to CD8 T cells.  T cell will recognize the antigen only when presented as a complex with the MHC class I molecule and not otherwise (MHC restriction).  When so presented, the CD8 cytotoxic killer cell destroys the target cell ( for example, a virus infected cell).  Class II antigens are heterodimers, consisting of an α and β chain.
  • 64.
     HLA classII antigens are heterodimers, consisting of an alpha and beta chain .Each chain has 2 domains, the proximal domain being the constant region and the distal the variable.  The two distal domains constitute the antigen binding site, for recognition by CD4 lymphocytes, in a fashion similar to the recognition of the class I antigen peptide complex by CD8 T cells.  HLA class II molecules are primarly responsible for the graft versus host response and the mixed leucocyte reaction .  HLA class III molecules are heterogenous. They include complement components linked to the formation of C3 convertases, heat shock protiens and tumour necrosis factors. They also show polymorphysim.
  • 65.
    Structure of MHCclass II molecules
  • 66.
     The hostresponds to oral bacteria and their products by plasma cell production of immunoglobulins or antibodies.  In 1964 endorsed by WHO, the generic term, “Immunoglobulin” was internationally accepted for proteins of animal origin endowed with known antibody activity and for certain other protein related to them by chemical structure.  Immunoglobulin provides a structural and chemical concept, while the term ‘antibody’ is a biological and functional concept.  ALL THE ANTIBODIES ARE IMMUNOGLOBULINS BUT ALL IMMUNOGLOBULINS MAY NOT BE ANTIBODIES.
  • 67.
     Antibodies whichare glycoproteins, are found in blood, tissue fluids and secretions and are the effectors of humoral immunity. They are highly specific and sensitive.  All classes and subsets of immunoglobulins have similar structural organizations, but they differ according to their biologic properties, carbohydrate content, weight and amino acid sequences.  Every antibody molecule has a variable region which, because of its unique amino acid sequence and tertiary structure of its antibody combining site, allows it to react highly specifically with a particular antigen.
  • 68.
     Studies involvingthe cleavage of the Ig molecule, pioneered by Porter, Edelman and their colleageus, have led to a detailed picture of its structure. Each molecule of Ig is split into one Fc portion (crystallisable), and two Fab fragments (antigen binding). Ig constitutes 20-25% of the total serum proteins. Based on physiochemical and antigenic differences, five classes of Ig have been recognized - IgG, IgA, IgM, IgD and IgE. (Both Ig and g are accepted abbreviations for immunoglobulins).
  • 70.
     All theimmunoglobulin constant region domains (C) maintain a similar basic structure. The variable region domains (V) have a slightly different structure. The polypeptide strand connecting the V and C domains is called the hinge and is important to and body structure because of the flexibility it allows between the V and C domains. Heavy chains can be divided into three functional regions; Fd, hing and Fc.  The Fd in combination with a light chain forms the Fab region, which has all the antigen-binding properties of an intact immunoglobulin.  The Fc fragment bears the effector functions of the immunoglobulin molecule
  • 71.
     Immunoglobulins (antibodies): IgM is the first antibody to arrive in our body. It initiates the complement cascade and is the main antibody in response to T independent antigens.  IgG is the next antibody to arrive; it remains longest.  Having several subclasses, IgG1, IgG2, IgG3 and IgG4 is also the most predominant antibody. It coats antigens (opsonization) for destruction by phagocytes, prepares other antigens for destruction by killer cells.
  • 72.
     IgA isfound in the saliva (secretory IgA) and other areas where there is mucous membrane. It is the first line of defense against microorganisms that would invade via the mucosa, IgA antibodies deter microorganisms from penetrating epithelial cells. it is composes of two subclasses IgA1 and IgA2.  IgD is a trace antibody and differentiates B cells. it disappears after differentiation.  IgE is the reaginc antibody it is in low concentration and responsible for acute allergic reactions, binds to mast cells and basophils stimulating the release of vasoactive substances such as histamine, prostaglandins and leukotrienes.
  • 73.
    Type Number of agbinding sites Site of action Functions IgG 2 •Blood •Tissue fluid •CAN CROSS PLACENTA •Increase macrophage activity •Antitoxins •Agglutination IgM 10 •Blood •Tissue fluid Agglutination IgA 2 or 4 •Secretions (saliva, tears, small intestine, vaginal, prostate, nasal, breast milk) •Stop bacteria adhering to host cells •Prevents bacteria forming colonies on mucous membranes IgE 2 Tissues •Activate mast cells  HISTAMINE •Warm response
  • 74.
     Recent investigationshave revealed that not all strains of a specific microbial species are equal in their capacity to cause disease and not all hosts are equal in their susceptibility to disease.  The challenge for the future is to be able to better identify the more virulent bacterial strains and more susceptible host.  In this manner it may be possible to predict accurately the individuals at risk for future disease and to develope more effective strategies to prevent the onset and progression of disease.