This document provides an overview of basic immunology. It defines immunity and describes the innate and acquired immune systems. It discusses antigens, antibodies, and the different classes of antibodies. It also outlines the cells of the innate immune system like phagocytes, mast cells, basophils, etc. and how they help defend the body. It explains the mechanisms of innate immunity and describes both active and passive immunity in detail. Finally, it discusses antigen-antibody reactions and how antibodies help defend the body through opsonization, complement activation, neutralization and more.

1. BASIC IMMUNOLOGY
BY
MOHAMMAD AKHEEL
II YEAR PG
OMFS

2. BASIC IMMUNOLOGY
IMMUNITY
ANTIGENS
ANTIBODIES - IMMUNOGLOBULINS
ANTIGEN – ANTIBODY REACTIONS
COMPLEMENT SYSTEM
STRUCTURE AND FUNCTION OF IMMUNE SYSTEM
IMMUNE RESPONSE
HYPERSENSITIVITY
AUTOIMMUNITY
ORAL IMMUNOLOGY

3. IMMUNITY
The term Immunity is derived from the Latin word Immunitae, which
referred to the protection from the legal prosecution offered to Roman
Senators during their tenure in office.
Refers to the resistance exhibited by the host towards injury
caused by microorganisms and their products.
Protection against infectious diseases
Distinguishes self from non-self
Eliminate potentially destructive foreign substances from body

4. IMMUNITY
INNATE ACQUIRED
Non specific Specific Active Passive
Species Racial Artificial
Individual Natural

5. INNATE IMMUNITY ACQUIRED IMMUNITY
Resistance to infection which individual The resistance that an individual
possesses by virtue of his genetic and acquires during life
constitutional make up
Early defense response against Later defense response
microbes
Immune response Non specific Immune response is highly specific
Innate response do not alter on repeated Adaptive response improves with each
exposure successive encounter with same
pathogen
Memory effect absent Memory effect present
Not affected by immunisation or prior Is improved by immunisation
contact

6. INNATE IMMUNITY
It consists of cellular and biochemical defense mechanisms that are in place
even before infections and poised to respond rapidly to infections. These
mechanisms react only to microbes and not to non-infectious substances
Innate Immunity
Species Racial Individual

7. Species immunity
 Refers to the total or relative refractoriness to a pathogen, shown
by all members of species.
 Person obtains by virtue of being a part of the human species.
 Determines whether or not a pathogen can multiply in them.
For e.g.
 All human beings are totally unsusceptible to plant pathogens and to,
many animal pathogens, such as render pest or distemper.
Pasteur’s experiments on anthrax in frogs, which are naturally resistant
to the disease but become susceptible when their body temperature is
raised from 25° to 35°C.

8. Racial immunity
 Racial differences are known to be genetic in origin
For e.g.
 People of Negroid origin in USA are more susceptible than the
Caucasians to tuberculosis.
 Genetic resistance to Plasmodium falciparum Malaria seen in some
parts of Africa and Mediterranean coast. A hereditary abnormality of
red cells (sickling) prevalent in the area, confer immunity to infections
by malarial parasite.

9. Individual immunity
 The difference in innate immunity exhibited by different individuals
in a race
 The genetic basis of individual immunity is seen in twins.
For e.g.
Homozygous twins exhibit similar degrees of resistance or
susceptibility to Lepromatous leprosy and Tuberculosis.

10. Innate immunity does not recognize every possible antigen instead it
recognizes pathogen-associated molecular patterns. Receptors enable the
phagocyte to attach to these patterns so it can be engulfed and destroyed by
lysosomes.
Pathogen-Associated Molecular Patterns Binding to Endocytic Pattern-
Recognition Receptors on Phagocytes

11. Determinants of innate immunity
I. Species and strains
II. Age
III. Hormonal Influences
IV. Nutrition

12. MECHANISMS OF INNATE IMMUNITY
I. Epithelial surfaces
Skin
Mucosa of the respiratory tract
Human eye.
Flushing action of urine
II. Antibacterial substances in Blood and tissues
III. Inflammation
IV. Fever
V. Cellular factors

13. ACQUIRED IMMUNITY
A person is said to be immune when he possesses specific protective
antibodies or cellular immunity as a result of previous infection or
immunization or is so conditioned by such previous experience as to respond
adequately to prevent infection
Because this form of immunity develops as a response to infection and is
adaptive to the infection, it is called adaptive immunity.
The characteristics of adaptive immunity are
 Specificity for distinct molecules.
 An ability to remember and respond more vigorously to repeated exposure
to the same microbe.
Hence it is also called as specific immunity.

14. ACTIVE IMMUNITY PASSIVE IMMUNITY
1. Produced actively by host’s immune Received passively by the host
system
2. Induced by infection or by contact No participation by the host’s immune
with immunogens (vaccines, system
allergens etc).
3. Affords desirable and effective Conferred by introduction of
protection readymade antibodies
4. Immunity effective only after a lag Protection transient and less effective
period (time required for generation Immunity effective immediately
of antibodies).
5. Immunological memory present; No immunological memory
subsequent challenge more subsequent administration of
effective (booster effect) antibodies less effective due to
immune elimination
6. Negative phase may occur No negative phase
7. Not applicable in immunodeficient Applicable in immunodeficient hosts
hosts

15. Natural Active immunity
 This results from either a clinical or inapparent infection.
 Immunity following chicken pox and measles infection is usually life long
Artificial Active Immunity
This is the resistance induced by vaccines.
Vaccines are preparations of live or killed microorganisms or their products
used for immunization.

16. Types of Vaccine:
Immunizing agents that are used for immunoprophylaxis
 Bacterial vaccines:
Live (BCG vaccine for T.B.).
Killed (Cholera vaccine).
Subunit (Typhoid Vi antigen).
Bacterial products (Tetanus Toxoid).
 Viral Vaccine:
Live (Oral polio vaccine – Sabin).
Killed (Injectable polio vaccine – Salk).
Subunit (Hepatitis B-vaccine).
 Combinations
If more than one kind of immunizing agent is included in the vaccine, it is
called a mixed or combined vaccine.
DPT (Diphtheria – pertussis - tetanus)
MMR (Measles, mumps and rubella).
DPTP (DPT plus inactivated polio).

17. Natural Passive immunity
 This is the resistance passively transferred from the mother to the baby. In
human infants, maternal antibodies are transmitted predominantly through the
placenta.
 Human colustrum, which is also rich in IgA antibodies and resistant to intestinal
digestion.
Synthesis of antibodies (IgM) occurs at 20th week of IUL but its immunogenic
capacity is still inadequate at birth. It is only by about the age of three month that
the infants acquire a satisfactory level of immunological independence.

18. Artificial passive immunity
This is the resistance passively transferred to a recipient by administration
of antibodies.
Passive immunization is indicated for immediate and temporary protection
in a non-immune host
Employed for the suppression of active immunity, when the latter may be
injurious.
Used as treatment of some infections.
Hyper immune sera of animal or human origin, convalescent sera and
pooled human gamma globulins are used for prophylaxis and therapy.
Rh immune globulin is used during delivery to prevent immune response to
the Rhesus factor in Rh-negative women with Rh-positive babies.

19. Cells of the Innate Immune System:
Phagocytes
Macrophages play several roles in the immune responses:
 Phagocytosis.
 Required to process and present antigen to immunocompetent T cells for
induction of CMI.
 Production of cytokines, such as IL-1 and TNFα, which are proinflammatory
 Lyses tumor cells by secreting toxic metabolites and proteolytic enzymes
 Examples of tissue macrophages are
kuppfer cell of the liver,
microglial cells of brain,
mesangial phagocyte of the kidney,
alveolar macrophages of lungs and
osteoclasts of bone.

20. NEUTROPHILS:
Mediate the earliest phase of inflammatory response and aids in phagocytosis.
The cytoplasm contains enzymes such as lysozyme, collagenase, elastase
lactoferrin, acid hydrolase, and myeloperoxidase
and other microbicidal substances.
Enzymes
stimulates
Kallikrein
catalyzes
Bradykinin
promotes
Inflammation
They also possess receptors for IgG antibody. These receptors enable
neutrophils to participate in the inflammatory response and phagocytosis.

21. EOSINOPHILS
They are phagocytic cells.
contains receptors for immunoglobulins, growth factors and complement
components on the cell surface
Their primary function may be secretion and extracellular killing rather
than intracellular.
perform specialized function namely immediate hypersensitivity in
response to parasites and protozoa.
secrete destructive enzymes such as acid phosphatase, peroxidases and
proteinases and promotes inflammation

22. Mast cell
Has inflammatory mediators such as histamine, eosinophils chemotactic
factor, neutrophil chemotactic factor and heparin and zinc ions.
It also synthesizes SRS-A, TNFα and leukotriene C4. These cells possess
receptors for complement components (C3a and C5a) as well as receptors for
the Fc portions of the antibody molecules, IgE and IgG
The stimulation of these receptors can result in activation and secretion of
vasoactive substances that increase vascular permeability and dilation.

23. BASOPHILS
Basophils contain several enzymes, histidine carboxylase.
release histamine, leukotrienes, and prostaglandins, chemicals that
promotes inflammation
MONOCYTES
phagocytes.
Monocytes differentiate into macrophages serve as antigen-presenting cells in
the adaptive immune responses
LYMPHOCYTES
B-lymphocytes (B-cells) mediate humoral immunity
T-lymphocytes (T-cells) mediate cellular immunity

24. ANTIGENS
An antigen has been defined as any substance which when introduced
parenterally into the body stimulates the production of an antibody with which it
reacts specifically and in an observable manner
The two attributes of antigenicity are:
 Induction of an immune response (immunogenicity).
 Specific reaction with antibody or sensitized cells (immunological reactivity).
Based on the ability of antigens to carry out these two functions, they may be
classified into different types:
 Complete antigen is able to induce antibody formation and produce a
specific and observable reaction with the antibody so produced.
 Haptens are substances, which are incapable of inducing antibody formation
by themselves, but can react specifically with antibody.

25. Determinants of Antigenicity:
Size: Large molecular size (6.75 million) : highly antigenic
Low molecular size (<5000) : less or non-antigenic
Chemical nature: Proteins and polysaccharides : highly antigenic.
Lipids and nucleic acids : 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 antigens that are foreign to the individual (non self) induce
an immune response.
Antigen Specificity:
It is the position of the antigenic determinant group in the antigenic
molecule at ortho, meta and para positions which determines antigen
specificity. It is not absolute. Cross reaction can occur between antigen
which bear stereo-chemical similarities

26. Antigen reacting only with particular Immunocytes
B-lymphocytes have sIg molecules on their surface that recognize epitopes
directly on antigens. Different B-lymphocytes are programmed to produce
different molecules of sIg, each specific for a unique epitope.

27. Iso specificity: Isoantigens are antigens found in some but not all member of a
species. A species may be grouped depending on the presence of different
antigens in its members e.g. human erythrocyte antigen based on which
individuals can be classified into different blood groups.
Autospecificity: Autologous or self-antigens are ordinarily non-antigenic but
there are exceptions.
Sequestered antigens that are not normally found free in circulation or
tissue fluids (such as lens protein normally, confined within its capsule) are not
recognized as self-antigens. Similarly antigens that are absent during embryonic
life and develop later (such as spleens) are also not recognize as self-antigens.

28. ANTIBODIES (IMMUNOGLOBULINS)
They are specific glycoprotein configurations produced by B-lymphocytes and
plasma cells in response to a specific antigen and capable of reacting with
that antigen.
Antibody Structure
A monomer has four glycoprotein chains:
 two identical heavy chains have a high molecular weight that varies with
the class of antibody.
 two identical light chains. The light chains come in two varieties: kappa or
lamda and have a lower molecular weight. The four glycoprotein chains are
connected to one another by disulfide (S-S) bonds and noncovalent bonds
Additional S-S bonds fold the individual glycoprotein chains into a number of
distinct globular domains. The area where the top of the "Y" joins the bottom is
called the hinge. This area is flexible to enable the antibody to bind to pairs of
epitopes at various distances apart on an antigen.
The two tips of the "Y" monomer are referred to as the Fab portions of the
antibody.

29. The Fab portion of the antibody has specificity for binding an epitope of an
antigen. The Fc portion directs the biological activity of the antibody.

30. Folding Domains of an Antibody
The Fab portion of the antibody has the complementarity-determining regions
(red) providing specificity for binding an epitope of an antigen. The Fc portion
(purple) directs the biological activity of the antibody. (S-S = disulfide bond; N =
amino terminal of glycoprotein; C = carboxy terminal of glycoprotein; CHO =
carbohydrate.)

31. Epitope of an Antigen Binding to Fab of an Antibody

32. Ways That Antibodies Help to Defend the Body
1. Opsonization: Using antibodies to attach microbes to phagocytes or
phagocytes to cells recognized as nonself.
2. MAC Cytolysis: Using antibodies to activate the classical complement
pathway resulting in the lysis of gram-negative bacteria and cells recognized
as nonself by way of the membrane attack complex (MAC).
3. Antibody-dependent Cellular Cytotoxicity (ADCC) by NK Cells: Using
antibodies to attach NK cells to infected cells and tumor cells.
4. Neutralization of Exotoxins: Using antibodies to prevent exotoxins from
binding to receptors on host cells.

33. 5. Neutralization of Viruses: Using antibodies to prevent viruses from
binding to receptors on host.
6. Preventing Bacterial Adherence to Host Cells: Using antibodies to
prevent bacteria from binding to receptors on host.
7. Agglutination of Microorganisms: Using antibodies to clump microbes
together for more effective phagocytosis.
8. Immobilization of Bacteria and Protozoans: Using antibodies to
against cilia and flagella to block motility.

34. The 5 Classes (Isotypes) of Human Antibodies
a. IgG (Immunoglobulin G; 4 subclasses)
IgG makes up approximately 80% of the serum antibodies.
The Fc portion of IgG can
activate the classical complement pathway.
bind to macrophage and neutrophils for enhanced phagocytosis.
bind to NK cells for antibody-dependent cytotoxicity (ADCC).
enables it to cross the placenta. (IgG is the only class of antibody that can
cross the placenta and enter the fetal circulation.)

35. IgG

36. A Bacterial Capsule Preventing C3b Receptors on Phagocytes from
Binding to C3b Attached to a Bacterial Cell Wall
In some bacteria, the capsule covers the opsonin C3b bound to the bacterial cell
wall so that it can't bind to C3b receptors (called CR1) on the surface of
phagocytes.

37. Opsonization of an Encapsulated Bacterium
The Fab portion of IgG binds to epitopes of a capsule. The Fc portion can now
attach the capsule to Fc receptors on phagocytes for enhanced attachment.
Once attached to the phagocyte by way of IgG, the encapsulated bacterium
can be engulfed more efficiently and placed in a phagosome.

38. b. IgM (Immunoglobulin M)
IgM makes up approximately 13% of the serum antibodies and is the first
antibody produced during an immune response.
The Fc portions of IgM are able to activate the classical complement
pathway. (IgM is the most efficient class of antibody for activating the classical
complement pathway.)
Monomeric forms of IgM are found on the surface of B-lymphocytes as B-
cell receptors or sIg.

39. IgM
IgM is a pentamer and, therefore, has 10 Fab sites.

40. c. IgA (Immunoglobulin A; 2 subclasses)
 IgA makes up approximately 6% of the serum antibodies
 IgA is found mainly in body secretions (saliva, mucous, tears, colostrum
and milk) as secretory IgA (sIgA) where it protects internal body surfaces
exposed to the environment by blocking the attachment of bacteria and
viruses to mucous membranes. While only 6% of the antibodies in the serum
are IgA
 The Fc portion of secretory IgA binds to components of mucous and
contributes to the ability of mucous to trap microbes.
 IgA can activate the alternative complement pathway.

41. Secretory IgA
Secretory IgA is a dimer and has 4 Fab sites. A secretory component helps
protect it from digestion in body secretions.

42. d. IgD: (Immunoglobulin D; 2 subclasses)
IgD makes up approximately 0.2% of the serum antibodies.
IgD is found on the surface of B-lymphocytes (along with monomeric
IgM) as a B-cell receptor or sIg where it may control of B-lymphocyte
activation and suppression.
IgD may play a role in eliminating B-lymphocytes generating self-
reactive autoantibodies.

43. e. IgE (Immunoglobulin E)
IgE makes up about 0.002% of the serum antibodies
Most IgE is tightly bound to basophils and mast cells via its Fc region.
The Fc portion of IgE made against parasitic worms and arthropods
can bind to eosinophils enabling opsonization.
The Fc portion of IgE can bind to mast cells and basophils where it
mediates many allergic reactions. Cross linking of cell-bound IgE by antigen
triggers the release of vasodilators for an inflammatory response.

44. ANTIGEN-ANTIBODY REACTIONS
Antigens and antibodies, by definition, combine with each other specifically and
in an observable manner.
In vivo, they form the basis of antibody mediated immunity in infectious
diseases, or of tissue injury in some types of hypersensitivity and autoimmune
diseases.
In vitro
In the laboratory, they help in the diagnosis of infections,in epidemiological
surveys, in the identification of infectious agents and of noninfectious antigens
such as enzymes.
In general, these reactions can be used for the detection and quantitation of
either antigens or antibodies. Antigen-antibody reactions in vitro are known as
serological reactions.

45. General features of antigen-antibody reactions
I. The reaction is specific, an antigen combining only with its homologous antibody
and vice versa.
2. Entire molecules react and not fragments. When an antigenic determinant
present in a large molecule or on a 'carrier' particle reacts with its antibody, whole
molecules or particles are agglutinated.
3. There is no denaturation of the antigen or the antibody during the reaction.
4. The combination occurs at the surface. Therefore, it is the surface antigens
that are immunologically relevant.

46. 5. The combination is firm but reversible. The firmness of the union is
influenced by the affinity and avidity of the reaction.
Affinity refers to the intensity of attraction between the antigen and
antibody molecules. It is a function of the closeness of fit between an
epitope and the antigen combining region of its antibody.
Avidity is the strength of the bond after the formation of the antigen-
antibody complexes.
6. Both antigens and antibodies participate in the formation of agglutinates
or precipitates.
7. Antigens and antibodies can combine in varyring proportions, unlike
chemicals with fixed valencies. Both antigens and antibodies are
multivalent.

47. SEROLOGICAL REACTIONS
Precipitation reaction
When a soluble antigen combines with its antibody in the presence of
electrolytes (NACI) at a suitable temperature and pH, the antigen-antibody
complex forms an insoluble precipitate.
When, instead of sedimenting, the precipitate remains suspended as
floccules, the reaction is known as flocculation.
Mechanism of precipitation
Marrack (1934) proposed the lattice hypothesis. Multivalent antigens combine
with bivalent antibodies in varying proportions. Precipitation results when a
large lattice is formed consisting of altemating antigen and antibody
molecules.
The lattice hypothesis holds good for agglutination also.

48. Antigens : Dark spheres
Antibodies : Spindles
Mechanism of Precipitation by lattice formation
A: Antigen excess C: Antibody excess (Lattice formation does not occur)
B: (Zone of equivalence) Lattice formation and precipitation occur optimally

49. Applications of precipitation reaction
It is very sensitive in the detection of antigens as little as 1 pg of protein can be
detected by precipitation tests.
Finds forensic application in the identification of blood and seminal stains, and
in testing for food adulterants.
The following types of precipitation and flocculation tests are in common use:
Ring test: Grouping of streptococci by the Lancefield technique.
Slide test: The VDRL test for syphilis is an example of slide flocculation.
Tube test: The Kahn test for syphilis is an example of a tube flocculation test.

50. AGGLUTINATION REACTION
When a particulate antigen is mixed with its antibody in the presence of
electrolytes at a suitable temperature and pH, the particles are clumped or
agglutinated.
Agglutination is more sensitive than precipitation for the detection of
antibodies. The same principles govern agglutination and precipitation.
Agglutination occurs optimally when antigens and antibodies react in
equivalent proportions.

51. Applications of agglutination reaction
Slide agglutination: When a drop of the appropriate antiserum is added to
a smooth, uniform suspension of a particulate antigen in a drop of saline
on a slide or tile, agglutination takes place. A positive result is indicated by
the clumping together of the particles an the clearing of the drop. It is the
method used for
blood grouping and
cross matching.
Tube agglutination: This is a standard quantitative method for the
measurement of antibodies. When a fixed volume of a particulate antigen
suspension is added to an equal volume of serial dilutions of an antiserum
in test tubes, the agglutination titre of the serum can be estimated.
Tube agglutination is routinely employed for the serological diagnosis of
typhoid,
brucellosis and
typhus fever.

52. COMPLEMENT SYSTEM:
The term complement refers to a system of factors, which occur in normal
serum and are activated characteristically by Antigen antibody interaction and
subsequently mediate a number of biologically significant consequences.
It is a non-specific serologic reagent in that complement from one species can
react with antibody from other species.
Complement ordinarily does not bind to free antigen or antibody but only to
antibody, which has combined with its antigen.
All classes of Immunoglobulins do not fix to complement, only IgM. IgG3, 1 and 2
in that order fix complement on the Fc portion of the Immunoglobulin molecule.
But not IgG4, A, D & E
Complement is a complex of different fractions called C1 to C9. The fraction of C1
occurs in serum as a calcium ion dependent complex, which on chelation with
EDTA yields three proteins subunits called C1q, r, and s. This complex is made up
of a total of 11 different proteins.

53. Assembly of C1 during the Classical Complement Pathway
The Fab of IgG or IgM bind to epitopes on an antigen. C1q, C1r, and C1s then
assembles on the Fc portion of the antibodies to form C1, the first enzyme of
the classical complement pathway. The enzyme C1 is able to cleave C4 into
C4a and C4b, as well as C2 into C2a and C2b.

54. Formation of C3 Convertase during the Classical Complement Pathway
The enzyme C1 is able to cleave C4 into C4a and C4b. The C4b binds to
adjacent proteins and carbohydrates on the surface of the antigen. C2 then binds
to the C4b and C1 cleaves C2 into C2a and C2b. The C4b2a functions as a C3
convertase that can subsequently cleave hundreds of molecules of C3 into C3a
and C3b.

55. Formation of C5 Convertase during the Classical Complement Pathway
The C4a2b functions as a C3 convertase that can subsequently cleave
hundreds of molecules of C3 into C3a and C3b. Much of the C3b binds to
adjacent proteins and carbohydrates on the antigen to participate in
opsonization while C3a can stimulate inflammatory responses. Some of the C3b
binds to C4b2a to form C4b2a3b, a C5 convertase that can cleave C5 into C5a
and C5b.

56. The Membrane Attack Complex (MAC) Causing Cell Lysis
This C5b6789n, or membrane attack complex (MAC), puts pores into lipid
bilayer membranes of human cells to which antibodies have bound. This
results in cell lysis. MAC can also damage the envelope of enveloped viruses
and put pores in the outer membrane and cytoplasmic membrane of gram-
negative bacteria causing their lysis.

57. Benefits of C5a and C3b
Most C3b binds to antigens on the microbial surface. Some C3b combines
with C2a and C4b to form the third enzyme of the complement pathway that is
able to split C5 into C5a and C5b. C5a stimulates mast cells to release
histamine for inflammation and diapedesis. It also functions as a
chemoattractant for phagocytes. The phagocytes are then able to bind to the
C3b attached to the surface of the microorganism allowing for opsonization
(enhanced attachment).

58. COMPLEMENT FIXATION TEST (CFT)
Ability of antigen antibody complexes to 'fix' complement is made use of in
the complement fixation test (CFT).
This is a very versatile and sensitive test, applicable with various types of
antigens and antibodies and capable of detecting as little as 0.04 mg of
antibody nitrogen and 0.1 mg of antigen.
CFT is a complex procedure consisting of two steps and five reagents-
Antigen,
Antibody,
Complement,
Sheep erythrocytes and
Amboceptor (rabbit antibody to sheep red cells).

59. Inactivated serum incubated at Wassermann Guinea
pig
of patient 37deg.C for 1hr. with Antigen
Complement
( 2 units )
If complement is
Fixed (utilised) not fixed (not utilised)
Patient serum has Patient serum has no
Syphilitic antibody Syphilitic antibody
(Complement is left intact)
Sheep RBC coated with Haemolysin
Incubated at 37deg.C for 30 min.
If no lysis of RBC If lysis of RBC
Complement was utilised in I step Complement was not utilised
SERUM HAS ANTIBODIES SERUM – NO ANTIBODIES

60. LECTIN PATHWAY
Mediated by mannan-binding lectin (also known as mannan-binding
protein or MBP).
MBP is a protein that binds to the mannose groups found in many microbial
carbohydrates but not usually found in the carbohydrates of humans. The MBP
is equivalent to C1q in the classical complement pathway.
Activation of the lectin pathway begins when mannan-binding protein (MBP)
binds to the mannose groups of microbial carbohydrates.

61. Activation of the Lectin Pathway
Activation of the lectin pathway begins when mannan-binding protein (MBP)
binds to the mannose groups of the microbial carbohydrates. Two more lectin
pathway proteins called MASP1 and MASP2 (equivalent to C1r and C1s of
the classical pathway) now bind to the MBP. This forms an enzyme similar to
C1 of the classical complement pathway that is able to cleave C4 and C2 to
form C4bC2a, the C3 convertase capable of enzymatically splitting hundreds
of molecules of C3 into C3a and C3b.

62. ALTERNATIVE COMPLEMENT PATHWAY
The alternative complement pathway is mediated by C3b, produced
either by the classical or lectin pathways or from C3 hydrolysis by water.
(Water can hydrolize C3 and form C3i, a molecule that functions in a
manner similar to C3b.)

63. Activation of the Alternative Complement Pathway
and Formation of C3 Convertase
Activation of the alternative complement pathway begins when C3b (or
C3i) binds to the cell wall and other surface components of microbes.
Alternative pathway protein Factor B then combines with the cell-bound
C3b to form C3bB. Factor D then splits the bound Factor B into Bb and Ba,
forming C3bBb. A serum protein called properdin then binds to the Bb to
form C3bBbP that functions as a C3 convertase capable of enzymatically
splitting hundreds of molecules of C3 into C3a and C3b.

64. Formation of C5 Convertase during
the Alternative Complement Pathway
Some of the C3b subsequently binds to some of the C3bBb to form C3bBb3b,
a C5 convertase capable of enzymatically splitting hundreds of molecules of
C5 into C5a and C5b.

65. Functions of Complement system include:
 Control of inflammatory reactions and chemotaxis.
 Clearance of immune complexes.
 Cellular activation and antimicrobial defense.
 Development of antibody responses
 Contributes to pathogenesis of
Hereditary angioneurotic edema
Nephrotoxic nephritis
Paroxysmal nocturnal hemoglobinuria
Infectious mononucleosis
Autoimmune hemolytic anaemia
 Complement mediates immunological membrane damage (cytolysis
bacteriolysis).
 Participates in pathogenesis of Type II & Type III hypersensitivity reaction.
 Antiviral activity.
 Promotes phagocytosis and immune adherence.
 It also interacts with the coagulation, fibrinolytic and kininogenic systems of
blood.

66. Cytokines
Cytokines are mediators that function as up and down regulation of
immunogenic, inflammatory and reparative host responses to injury. Soluble
mediators called cytokines control many critical interactions among cells of
the immune system.
They generally act over very short distances, being
“autocrine” (acting on the cells that produce them) or
“paracrine” (acting on cells close by)
Cytokines can be of two types:
Lymphokines : produced by lymphocyte.
Monokines :produced by monocytes or macrophages.
Interleukins, Interferons, Tumour necrosis factor and Growth factors are
grouped under Cytokines

67. Interleukin 1 (IL-1):
mediates host inflammatory response to infections
promote neutrophil margination and migration into an inflamed site.
In low conc., as a mediator of local inflammation.
in larger conc., exerts endocrine effects.
are endogenous pyrogens (i.e. they induce fever)
early hematopoietic progenitor in the bone marrow.

68. Interleukin 2 (IL-2):
 This is a growth factor for antigen stimulated T lymphocytes and is responsible
for T cell clonal expansion after antigen recognition and stimulus for antibody
synthesis.
 Potentiates apoptotic death of antigen activated T cells.
Interleukin 3 (IL-3):
 Induces growth of all types of hematopoetic cells known as multi colony
stimulating factor

69. Interleukin 4 (IL-4):
It is secreted by activated CD4+ T cells of the TH2 subset and by mast
cells.
IL-4 suppresses the induction and function of TH1 cells
Enhances IL-3 mediated mast cell growth
Increase macrophage expression of class II MHC proteins
Interleukin 5 (IL-5):
stimulate the production of eosinophils
enhances the activities of basophil

70. Interleukin 6 (IL-6):
Promotes
B-cell differentiation and
IgG production
Interleukin 7 (I- 7):
A growth factor for both B and T cell progenitor and mature T cells as well as
macrophages and monocytes
Increases macrophage cytotoxic activity and induces cytokine secretion by
monocytes.
Interleukin 8 (IL-8):
Acts as a neutrophil chemotactic factor

71. Interferons:
In 1957, it was discovered that cells exposed to inactivated viruses
produces soluble factor that can “interfere” with viral replication when
applied to newly infected cells. The factor was named interferon (IFN).
Interferons do not exert their antiviral effects by acting on viral particle but
rather by inducing an antiviral state within the host cell that makes it
inhospitable to viral replication. This as well as the antiproliferative and
immunomodulatory effects of interferon reflects their ability to regulate
specific gene expression in their target cells.
They can be classified into three distinct types:
 INF-α (leukocyte interferon) – type I
 INF-β (fibroblast interferon) – type I
 IFN-γ (immune interferon) – Type II.

72. STRUCTURES AND FUNCTIONS OF IMMUNE SYSTEM
THE LYMPHOID SYSTEM
The body uses the lymphoid system to enable lymphocytes to encounter
antigens and it is here that adaptive immune responses are initiated.
a. Primary lymphoid organs
The bone marrow and the thymus constitute the primary lymphoid organs.
B-lymphocytes mature in the bone marrow while T-lymphocytes
migrate to the thymus and mature there.
b. Lymphatic vessels
Lymphatic vessels are responsible for flow of lymph within the lymphoid
system and are a part of the body's fluid recirculation system.
c. Secondary lymphoid organs
Adaptive immune responses require antigen-presenting cells, such as
macrophages and dendritic cells,
lymph nodes and the spleen

73. Number of surface antigens or markers have been identified on Lymphocytes.
These markers reflect the stage of differentiation and functional properties of cells.
When a cluster of monoclonal antibodies was found to react with a particular antigen,
it was defined as a separate marker and given a CD (cluster of differentiation)
number.
CD Cell type association
number
CD 1 Thymocytes, Langerhans cells
CD 2 T cell SRBC receptors
CD 3 T cell antigen receptor complex
CD 4 Helper T cell (receptor for HIV)
CD 8 Suppressor/cytotoxic T cells
CD 19 B cells

74. Antigen-Presenting Cells (APCs)
APCs include dendritic cells, macrophages, and B-lymphocytes.
1. Dendritic Cells
Captures and present protein antigens to naive T-lymphocytes . (Naive
lymphocytes are those that have not yet encountered an antigen.)
2. Macrophages
Captures and present protein antigens to effector T-lymphocytes. (Effector
lymphocytes are lymphocytes that have encountered an antigen, proliferated,
and matured into a form capable of actively carrying out immune defenses.)
3. B-lymphocytes
Captures and present protein antigens to effector T4-lymphocytes.
triggers the T4-cell to produce and secrete various cytokines that enable that
B-lymphocyte to proliferate and differentiate into antibody-secreting plasma
cells.

75. T4-Lymphocytes (T4-Helper Cells, CD4+ Cells)
T-lymphocytes displaying CD4 molecules on their surface that regulate the
immune responses through their production of cytokines. T4-lymphocytes
recognize epitopes bound to MHC-II molecules by way of the T-cell receptors
(TCR) and CD4 molecules on their surface.
Have a shape, capable of recognizing peptides from exogenous antigens
bound to MHC-II molecules on the surface of APCs and B-lymphocytes. The
TCR recognizes the peptide while the CD4 molecule recognizes the MHC-II
molecule.
overall role of these effector T4-lymphocytes is to:
1. activate macrophages and NK cells.
2. produce cytokines that enable activated B-lymphocytes to produce antibodies
and T-lymphocytes into effector cells.

76. Different types of effector T4-lymphocytes based on the cytokines they
produce are Th1 cells and Th2 cells.
a. Th1 lymphocytes
Th1-lymphocytes recognize antigens presented by macrophages and function
primarily to activate and heighten cell-mediated immunity by producing
cytokines such as interleukin-2 (Il-2), interferon-gamma (IFN-gamma),
lymphotoxin, and tumor necrosis factor-beta (TNF-beta).
b. Th2 lymphocytes
Th2-lymphocytes recognize antigens presented by B-lymphocytes. They
produce cytokines such as interleukins 2, 4, 5, 10, and 13 that promote
antibody production.

77. Activation of a Macrophage by a Th1 Lymphocyte
1. Bacteria are engulfed by a macrophage and placed in a phagosome. A lysosome fuses with the
phagosome forming a phagolysosome.
2.An activated Th1 lymphocyte binds to a peptide/MHC-II complex on a macrophage by way of its TCR
and CD4 molecule.
3.Co-stimulatory molecules such as CD40L on the Th1 cell then bind to CD40 on a macrophage.
4. The Th1 lymphocyte secretes the cytokine interferon-gamma (IFN-gamma) that binds to IFN-gamma
receptors on the macrophage.
5. The IFN-gamma activates the macrophage enabling it to produce more hydrolytic lysosomal enzymes,
nitric oxide, and toxic oxygen radicals that destroy the microorganisms within the phagosomes and
phagolysosomes.

78. T8 -LYMPHOCYTES
T-lymphocytes displaying CD8 molecules on their surface and carrying out cell-
mediated immunity. T8-lymphocytes recognize epitopes bound to MHC-I
molecules by way of the T-cell receptors (TCR) and CD8 molecules on their
surface.
During its development, each T8-lymphocyte becomes genetically
programmed, by gene-splicing reactions, to produce a TCR with a unique
shape capable of binding epitope/MHC-I complex with a corresponding shape
One of the body's major defenses against viruses, intracellular bacteria, and
cancers is the destruction of infected cells and tumor cells by cytotoxic T-
lymphocytes or CTLs.

79. B-lymphocytes (B-cells)
B-lymphocytes refer to lymphocytes that are produced in the bone marrow and
require bone marrow stromal cells and their cytokines for maturation. During its
development, each B-lymphocyte becomes genetically programmed through a
series of gene-splicing reactions to produce an antibody molecule with a unique
specificity - a specific 3-dimensional shape capable of binding a specific epitope
of an antigen
Antibodies on the surface of B-lymphocytes that function as B-cell receptors are
also known as surface immunoglobulin (sIg)

80. a. Activation of naive B-lymphocytes by T-dependent antigens
Most proteins are T-dependent antigens. In order for naive B-lymphocytes to
proliferate, differentiate and mount an antibody response against T-dependent
antigens, these B-lymphocytes must interact with effector T4-lymphocytes.
b. Activation of B-lymphocytes by T-independent antigens
T-independent (TI) antigens are usually large carbohydrate and lipid molecules
with multiple, repeating subunits. B-lymphocytes mount an antibody response
to T-independent antigens without the requirement of interaction with T4-
lymphocytes.

81. CLONAL SELECTION:
The selection and activation of specific B-lymphocytes and T-lymphocytes by
the binding of epitopes to B-cell receptors or T-cell receptors with a
corresponding fit.
CLONAL EXPANSION:
The proliferation of B-lymphocytes and T-lymphocytes activated by clonal
selection in order to produce a clone of identical cells. This enables the body
to have sufficient numbers of antigen-specific lymphocytes to mount an
effective immune response.

82. Clonal Selection, Step-1
During its development, each B-lymphocyte becomes genetically programmed,
through a process called gene translocation, to make a unique B-cell receptor.
Molecules of that B-cell receptor are placed on its surface where it can react
with epitopes of an antigen.

83. Clonal Selection, Step-2
B-lymphocyte with an appropriately fitting B-cell receptor can now react with
epitopes of an antigen having a corresponding shape. This activates the B-
lymphocyte.

84. An Effector T4-Lymphocyte Recognizing Epitope/MHC-II on an Activated B-
Lymphocyte
An effector T4-lymphocyte uses its TCR and CD4 molecule to bind to a
complementary shaped MHC-II molecule with attached peptide epitope on an
activated B-lymphocyte. This interaction, along with the binding of co-stimulatory
molecules such as CD40 and B7 on the B-lymphocyte with their complementary
ligands on the effector T4-lymphocyte triggers the T4-lymphocyte to produce
cytokines that enable the activated B-lymphocyte to proliferate, differentiate into
antibody-secreting B-lymphocytes and plasma cells, and switch classes of the
antibodies being made.

85. Proliferation and Differentiation of a B-Lymphocyte after Interaction with
an Effector T4-Helper Lymphocyte
An effector T4-helper lymphocyte, by way of its TCR and CD4, binds to the MHC-II/epitope
on the activated B-lymphocyte. This, along with co-stimulatory signals that result from the
binding of costimulatory molecules such as CD40 and B7 on the B-lymphocyte with their
corresponding ligands on the activated T4-lymphocyte enable the T4-helper cell to release
cytokines such as IL-4, IL-5, IL-6, and IL-10. These cytokines then bind to cytokine receptors
on the activated B-lymphocyte triggering its proliferation into a large clone of identical B-
lymphocytes. The clone of B-lymphocytes eventually differentiates into antibody-secreting B-
lymphocytes and plasma cells. Some of the B-lymphocytes also differentiate into B-memory
cells for heightened secondary response against that T-dependent antigen.

86. Differentiation of B-lymphocytes into Plasma Cells and B-Memory Cells
The B-lymphocytes now differentiate into plasma cells that secrete
large quantities of antibodies that "fit" the original epitope. Some B-
lymphocytes differentiate into B-memory cells capable of anamnestic
response.

87. Natural Killer Cells (NK Cells)
Participate in both innate immunity and adaptive immunity.
NK cells are lymphocytes that lack B-cell receptors and T-cell receptors. They
are designed to kill certain mutant cells and virus-infected cells in one of
two ways:
1. They kill cells to which antibody molecules have attached through a process
called antibody-dependent cellular cytotoxicity (ADCC); and
2. They also are able to kill cells lacking MHC-I molecules on their surface.

88. Anamnestic (Memory) Response
A subsequent exposure to that same antigen results in a more rapid
production of antibodies, in greater amounts, and for a longer period of
time.
The primary response to a new antigen generally peaks at 5 - 10 days,
however, because of the numerous circulating B-memory cells, the secondary
anamnestic response peaks in only 1 - 3 days
Because of clonal expansion and affinity maturation, there is now a
pool of B-memory cells and pool of T4-memory cells enable an accelerated
helper function.

89. MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)
The primary function of the immune system is the recognition and
elimination of foreign cells and antigens that enter the body. Tissues and
organs grafted from one individual to another of same species are
recognized as foreign and rejected.
MHC Molecules are originally characterized as the antigens responsible
for the rejection of organs hence the name (histo or tissue compatibility).
also known as human leukocyte antigens or HLA, are the products of a
cluster of genes in the human DNA known as the major histocompatibility
complex (MHC). These antigens are present on various human cells and
enable T-lymphocytes to recognize epitopes and discriminate self from
nonself.

90. A. MHC-I Molecules (Class I HLA Molecules)
These molecules are made by all nucleated cells in the body. They bind
peptide epitopes from endogenous antigens to enable immune recognition
by T8-lymphocytes.
Endogenous antigens are proteins found within the cytosol of human
cells
a. The TCRs and CD8 molecules on the surface of naive T8-lymphocytes
are designed to recognize peptide epitopes bound to MHC-I molecules on
antigen-presenting cells (APCs).
b. The TCRs and CD8 molecules on the surface of cytotoxic T-lymphocytes
(CTLs) are designed to recognize peptide epitopes bound to MHC-I
molecules on infected cells and tumor cells.

91. Binding of Epitopes from Endogenous Antigens to MHC- I Molecules
by an Antigen Presenting Cell (APC)
1. Exogenous antigens, such as viruses, are engulfed and placed in a phagosome.
2. Lysosomes fuse with the phagosome forming an phagolysosome.
3. During phagocytosis, some proteins escape from the phagosome or the
phagolysosome and enter the cytosol of the APC and become endogenous
antigens.
4. These endogenous antigens pass through proteasomes where they are
degraded into a series of peptides.

92. 5. The peptides are transported into the rough endoplasmic reticulum (ER)
by a transporter protein called TAP.
6. The peptides then bind to the grooves of newly synthesized MHC-I
molecules.
7. The endoplasmic reticulum transports the MHC-I molecules with bound
peptides to the Golgi complex.
8. The Golgi complex, in turn, transports the MHC-I/peptide complexes by
way of an exocytic vesicle to the cytoplasmic membrane where they
become anchored. Here, the peptide and MHC-I/peptide complexes can be
recognized by naive T8-lymphocytes by way of TCRs and CD8 molecules
having a complementary shape.

93. B. MHC-II Molecules (Class II HLA Molecules)
Class II HLA molecules are made primarily by antigen-presenting cells (APCs,
eg, macrophages and dendritic cells) and B-lymphocytes. They bind peptide
epitopes from exogenous antigens to enable immune recognition by T4-
lymphocytes.
MHC-II molecules have a deep groove that can bind peptide epitopes, from
10-30 but optimally from 12-16 amino acids long, from exogenous antigens.
Exogenous antigens are antigens that enter from outside the body such as
bacteria, fungi, protozoa, and free viruses.
Binding of Epitopes from Exogenous Antigens to MHC-II Molecules in a
Macrophage takes place in same manner as binding in MHC-I molecules but
Here, the peptide and MHC-II complexes can be recognized by T4-
lymphocytes by way of TCRs and CD4 molecules having a complementary
shape.

94. An MHC- II Molecule on an Antigen-Presenting Cell Presenting a Bound
Viral Epitope to a Naive T4-Lymphocyte with a Matching TCR/CD4 on its
Surface
Naive T4-lymphocytes via the unique T-cell receptors and CD4 molecules on
their surface recognize peptide epitopes from exogenous antigens bound to
MHC-II molecules on antigen presenting cells (APCs). Different T-cell receptors
recognize different epitopes.

95. HLA and Disease association:
Inflammatory disease including ankylosing spondylitis and several post
infectious arthropathies are all associated with HLA B27
(Rheumatoid arthritis and HLA DR4).
Inherited errors of metabolism such as 21 hydroxylase deficiency (HLA
Bw47).
Autoimmune disease including autoimmune endocrinopathy associated with
certain DR alleles, HLA DRS.

96. IMMUNE RESPONSE
The specific reactivity induced in a host by an antigenic stimulus is
known as the immune response. In infectious disease it is generally
equated with protection against invading microorganisms.
Immune response includes reactions against any antigen, living or non-
living. It may lead to consequences that are beneficial, indifferent or
injurious to the host. It also includes the state of specific non reactivity
(tolerance) induced by certain types of antigenic stimuli.
The immune response can be of two types:
1. Humoral (Antibody mediated) response.
2. Cellular (cell mediated) response.

97. Two major branches of the adaptive immune responses are
1. Humoral immunity :
Involves the production of antibody molecules in response to an antigen
and is mediated by B-lymphocytes.
2. Cell-mediated immunity
Involves the production of cytotoxic T-lymphocytes, activated macrophages,
activated NK cells, and cytokines in response to an antigen and is mediated by
T-lymphocytes.

98. Humoral immune response:
The production of antibodies consists of three steps:
 The entry of the antigen, its distribution and fate in the tissues and its
contact with appropriate immunocompetent cells (afferent limb).
 The processing of antigens by cells and the control of the antibody
forming process (central functions).
 The secretion of antibody, its distribution in tissues and body fluids and
the manifestations of its effects (efferent limb).

99. Antibody production follows a characteristic pattern consisting of:
3
2 4
1
Primary Immune response. An antigen stimulus
1. Latent period or lag phase
2. Rise in titre of serum antibody
3. Steady state of antibody titre
4. Decline of antibody titre

100. The primary response is slow, sluggish and short lived with a long lag phase and
low titre of antibodies that does not persist for long. The antibody formed - IgM
In contrast the secondary response is prompt, and a much higher level of
antibodies that lasts for long periods. The antibody formed - IgG.
4
2
3
1
A B C
Effect of repeated antigenic stimulus. A, B, C antigenic stimulus
1. Primary immune response 2. Secondary immune response
3. Negative phase 4. High level of Ab following Booster Inj.

101. Cellular immune response:
CMI refers to the specific immune response that does not involve
antibodies. They include delayed hypersensitivity (DH), which results in
injury rather than protection.
CMI participates in the following immunological functions:
 Delayed hypersensitivity.
 Immunity in infectious diseases caused by obligate and facultative
intracellular parasites.
bacteria (for example, tuberculosis, leprosy, listeriosis, brucellosis)
fungi (for ex. Histoplasmoses, coccidioidomycosis, bastomycosis),
protozoa (ex. Leishmaniasis, trypanosomiasis) and
viruses (for ex: measles, mumps).
 Transplantation immunity and graft versus host reactions.
 Immunological surveillance and immunity against cancer.
 Pathogenesis of certain autoimmune diseases (thyroiditis
encephalomyelitis).

102. THEORIES OF IMMUNE RESPONSE:
Theories of immunity fall into two categories, instructive and selective.
Instructive theories postulate that an immunocompetent cell is capable of
synthesizing antibodies of any specificity. The antigen encounters an
immunocompetent cell and instructs it to produce the complementary
antibody.
Selective theories, on the contrary, shift the emphasis from the antigen to
the immunocompetent cell. They postulate that immunocompetent cells have
only a restricted immunological range. The antigen exerts only a selective
influence by stimulating the appropriate immunocompetent cell to synthesize
an antibody.

103. Side chain theory:
by Ehrlich (1900).
Cells were considered to have surface 'receptors' capable of reacting with
substances having complementary ‘side chains'.
When foreign antigens are introduced into the body, they combine with those
cell receptors, which have at complementary fit.
This inactivates the receptors and interferes with the absorption of nutrients.
As a compensatory mechanism, there is an overproduction of the same type of
receptors, which spill over into the blood and circulate as antibodies.
This theory explained elegantly the specificity of the antibody response.
However, when Landsteiner demonstrated that antibodies could be formed not
only against natural antigens but also against various synthetic chemicals, this
theory was abandoned because a large number of receptors would be needed to
for antibody specificity.

104. Direct template theories:
 by Breinl and Haurowitz (1930), Alexander (1931) and Mudd (1932).
 Antigen (or the antigenic determinant) enters antibody-forming cells and
serves as a template against which antibody molecules are synthesized so that
they have combining sites complementary to the antigenic determinant.
 These are therefore known as ‘direct template’ theories.
Indirect template theory:
 by Burnet and Fenner (1949) proposed this instructive theory to explain the
synthesis of antibody as an adaptive protein.
 entry of the antigenic determinant into the antibody-producing cell induces in
it a heritable change.
 A 'genocopy' of the antigenic determinant was thus incorporated in its
genome and transmitted to the progeny cells (indirect template).
This theory explained specificity and the secondary response but became
untenable with advances in the molecular biology of protein synthesis.

105. Natural selection theory:
 By Jerne (1955)
 This postulated that about a million globulin (antibody) molecules were
formed in embryonic life, which covered the full range of antigenic specificities
called by ‘natural antibodies’.
 When an antigen was introduced, it combined selectively with the globulin
that had the nearest complementary ‘fit’ and stimulates to synthesize the same
kind of antibody.
Selection was postulated at the level of the antibody molecule.
It did not explain the fact that immunological memory resides in the cells, and
not in serum

106. Clonal selection theory:
 By Burnet (1957)
 He shifted immunological specificity to the cellular level.
 During immunological development, cells capable of reacting with different
antigens were formed by a process of somatic mutation.
 Elimination of ‘forbidden clones’ during embryonic life.
 Their persistence or development in later life by somatic mutation could lead
to autoimmune processes. Each immunocompetent cell was capable of
reacting with one antigen introduced into the body.
 Result of the contact - is cellular proliferation to form clones synthesizing the
antibody.
The clonal selection theory is more widely accepted than the other theories,
though it is unable to account for all the features of the immune response.

108. CLASSIFICATION
Immediate hypersensitivity (B cell or antibody mediated)
 Anaphylaxis Type I
 Atopy
 Antibody mediated cell damage Type II
 Arthus phenomenon
 Serum sickness Type III
Delayed hypersensitivity (T cell mediated)
 Infection (tuberculin) type Type IV
 Contact dermatitis type

109. Type I Hypersensitivity
(Anaphylactic, IgE or reagin dependent)
 Antibodies (‘cytotropic’ lgE antibodies) are fixed on the surface of
tissue cells (mast cells and basophils) in sensitized individuals.
 These cells carry large numbers of receptors called Fc ER
receptors, IgE molecules attach to these receptors by their Fc end.
 The antigen combines with the cell fixed antibody, this increases the
permeability of the cells to calcium ions and leads to degranulation,
with release of vasoactive amines which produce the clinical
reaction.
 Anaphylaxis: the acute, potentially fatal, systemic form
 Atopy: the chronic or recurrent, nonfatal, typically localized form

110. Type- I Hypersensitivity: Production of IgE in Response to an Allergen
The allergen enters the body and is recognized by sIg on a B-
lymphocyte. The B-lymphocyte proliferates and differentiates into
plasma cells that produce and secrete IgE against epitopes of the
allergen.

111. Type- I Hypersensitivity: Allergen Interaction with IgE on the Surface of
Mast Cells Triggers the Release of Inflammatory Mediators
The next time the allergen enters the body, it cross-links the Fab
portions of the IgE bound to the mast cell. This triggers the mast cell to
degranulate, that is, release its histamine and other inflammatory
mediators.

112. Anaphylaxis
(ana = without, phylaxis = protection)
classical immediate hypersensitivity reaction
The inflammatory agents released, causes:
 dilatation of blood vessels.
 increased capillary permeability.
 constriction of bronchial airways.
 stimulation of mucous secretion.
 stimulation of nerve endings.

113. PRIMARY MEDIATORS OF ANAPHYLAXIS
Histamine:
 formed by the decarboxylation of histidine
 found in the granules of mast cells, basophils and in platelets.
 stimulates sensory nerves, producing burning and itching.
 Flare effect : vasodilatation and hyperemia by an axon reflex
and
Wheal effect : edema by increasing capillary permeability.
 Histamine induces smooth muscle contraction in intestines, uterus
and bronchioles.
 secretogogue effect.

114. Serotonin (5-hydroxy tryptamine)
 Derived by decarboxylation of tryptophan.
 Found in the intestinal mucosa, brain tissue and platelets.
 Smooth muscle contraction, increases capillary permeability and
vasoconstriction.
Eosinophil Chemotactic factors: (ECF-A)
 Acidic tetrapeptides released from mast cell granules.
 Contributes to the eosinophilia accompanying many hypersensitivity.
Heparin
Acidic mucopolysaccharide.
Contributes to anaphylaxis in dogs, but apparently not in human

115. SECONDARY MEDIATORS OF ANAPHYLAXIS
Prostaglandins and leukotrienes
Derived by pathways from arachidonic acid, which is formed from
disrupted cell membranes of mast cells and other leucocytes.
The Lipoxygenase pathway leukotrienes,
cyclo-oxygenase pathway prostaglandins and thromboxane.
Slow Reacting Substance Of Anaphylaxis (SRS-A) produces low,
sustained contraction of smooth muscles, identified as a family of
leukotrienes (LTB4, C4, D4, E4).
Prostaglandin F2a and thromboxane A2 are powerful, but transient,
bronchoconstrictors.
Prostaglandins also affect secretion by mucous glands, platelet
adhesion, permeability and dilatation of capillaries and the pain
threshold.

116. Treatment of Type I hypersensitivity
epinephrine. 0.3 – 0.5ml of 1:1000 Epinephrine s.c. or i.m. with
repeated doses, if required at 20 mts. intervals
If not corrected, Hypoxia due to airway obstruction or related to
cardiac arrhythmias is considered then O2 is given
Epinephrine relaxes smooth muscle, constricts blood vessels, and
stimulates the heart. It is used for severe systemic reactions.
antihistamines diphenhydramine 50-100mg i.m. / i.v.
Block the binding of histamine to histamine receptors on target
cells.
Nasally administered steroids. Corticosteroids are potent anti-
inflammatory agents.
sodium cromolyn. Sodium cromolyn prevents mast cells from
releasing histamines.
Aminophylline 0.25-0.5 gm i.v. for bronchospasm

117. Blocking Type-1 Hypersensitivity Using Monoclonal Antibodies
Against IgE
A new experimental approach to treating and preventing Type-I
hypersensitivity involves, giving the person with allergies, the
injections of monoclonal antibodies that have been made against
the Fc portion of human IgE. This, in turn, blocks the attachment of
the IgE to the Fc receptors on mast cells and basophils and the
subsequent release of histamine by those cells upon exposure to
allergen.

118. ATOPY: (out of place or strangeness)
Refer to naturally occurring familial hypersensitivities of human beings,
typified by hay fever and asthma.
Inhalants (for example, pollen, house dust)
Ingestants (for example, eggs, milk).
Generally not good antigens when injected parenterally but induce IgE
antibodies.
It is difficult to induce atopy artificially.
Often associated with a deficiency of IgA. This association has led to
the suggestion that IgA deficiency may predispose to atopy.
Clinical features includes
conjunctivitis,
rhinitis,
gastrointestinal symptoms and dermatitis following exposure through the
eyes, respiratory tract, intestine or skin, respectively.

120. Type II (cytotoxic and cytolytic)
 These reactions involve a combination of IgG (or rarely IgM)
antibodies with the antigenic determinants on the surface of cells
leading to cytotoxic or cytolytic effects.
Cell or tissue damage occurs in the presence of complement or
mononuclear cells.
Mechanism:
Either IgG or IgM is made against normal self antigens as a result
of a failure in immune tolerance or
a foreign antigen resembling some molecule on the surface of host
cells enters the body and IgG or IgM made against that antigen then
cross reacts with the host cell surface.

121. Opsonization During Type-II Hypersensitivity
IgG reacts with epitopes on the host cell membrane. Phagocytes then bind to
the Fc portion of the IgG and discharge their lysosomes.

122. MAC Lysis During Type-II Hypersensitivity
IgG or IgM reacts with epitopes on the host cell membrane and activates the
classical complement pathway. Membrane attack complex (MAC) then causes
lysis of the cell.

123. Examples include:
 AB and Rh blood group reactions;
 Autoimmune diseases such as:
Rheumatic fever where antibodies result in joint and heart valve
damage;
Idiopathic thrombocytopenia purpura where antibodies result in the
destruction of platelets;
Myasthenia gravis where antibodies bind to the acetylcholine
receptors on muscle cells causing faulty enervation of muscles;
Goodpasture's syndrome where antibodies lead to destruction of
cells in the kidney;
Graves' disease where antibodies are made against thyroid-
stimulating hormone receptors of thyroid cells leading to faulty
thyroid function;
Multiple sclerosis where antibodies are made against the
oligodendroglial cells
Some drug reactions
Type II hypersensitivity also participates in early transplant rejections.

124. TYPE III (IMMUNE COMPLEX - MEDIATED)
A hypersensitivity resulting from large quantities of soluble antigen-
antibody complexes passing between endothelial cells of the blood
vessels and becoming trapped on the surrounding basement membrane.
The antigen/antibody complexes then activate the classical complement
pathway.
This may cause:
a. massive inflammation
b. influx of neutrophils
c. MAC lysis of surrounding tissue cells
d. aggregation of platelets

125. Type-III Hypersensitivity: Immune Complex
Large quantities of soluble antigen-antibody complexes form in the blood and
are not completely removed by macrophages. These antigen-antibody
complexes lodge in the capillaries between the endothelial cells and the
basement membrane. The antigen-antibody complexes activate the classical
complement pathway and complement proteins and antigen-antibody
complexes attract leukocytes to the area. The leukocytes then discharge their
killing agents and promote massive inflammation. This leads to tissue death
and hemorrhage

126. Examples include:
 Serum sickness, a combination type I and type III
 Hypersensitivity;
 Autoimmune acute glomerulonephritis;
 Rheumatoid arthritis;
 Systemic lupus erythematosus;
 Some cases of chronic viral hepatitis; and
 Skin lesions of syphilis and leprosy.

127. ARTHUS REACTION
Arthus (1903) observed that when; rabbits were repeatedly
injected subcutaneously with normal horse serum, the initial injections
had no local effect but with later injections, there occurred intense
local reaction consisting of edema, induration and hemorrhagic
necrosis. This is known as the Arthus reaction
The tissue damage is due to formation of antigen-antibody precipitates
causing complement activation and release of inflammatory
molecules. This leads to increased vascular permeability and
infiltration of the site with neutrophils.
Leucocyte-platelet thrombi are formed that reduces the blood supply
and lead to tissue necrosis.
For example, intrapulmonary Arthus-like reaction to inhaled antigens,
such as thermophilic actinomycetes from mouldy hay or grain
causes Farmer's lung and other types of hypersensitivity pneumonitis.

128. SERUM SICKNESS
by von Pirquet and Schick (1905), this appeared 7-12 days following
single injection of a high concentration of foreign serum such as the
diphtheria antitoxin.
The clinical syndrome consists of fever, lymphadenopathy,
spleenomegaly, arthritis, glomerulonephritis, endocarditis, vasculitis,
urticarial rashes, abdominal pain, nausea and vomiting.
The plasma concentration of complement falls due to massive
complement activation and fixation by the antibody complexes. The
disease is self-limited.
The latent period of 7-12 days is required only for serum sickness
following a single injection. With subsequent injections, the disease
manifests earlier. Serum sickness differs from other types of
hypersensitivity reaction in that a single injection can serve both as
the sensitizing dose and the shocking dose.

129. TYPE IV (DELAYED HYPERSENSITIVITY)
It is cell-mediated rather than antibody-mediated.
Mechanism:
T8-lymphocytes become sensitized to an antigen and differentiate
into cytotoxic T-lymphocytes, while Th1 type T4-lymphocytes
become sensitized to an antigen and produce cytokines.
CTLs, cytokines, and/or macrophages then cause harm rather
than benefit.

130. Examples include:
tuberculosis, leprosy, smallpox, measles, herpes infections,
candidiasis, and histoplasmosis;
the skin test reactions seen for tuberculosis and other infections;
contact dermatitis like poison ivy;
type-1 insulin-dependent diabetes
multiple sclerosis, where T-lymphocytes and macrophages secrete
cytokines that destroy the myelin sheath that insulates the nerve fibers
of neurons;
chronic transplant rejection as seen in host versus graft rejection or
graft versus host rejection.

131. Tuberculin (infection) type
When a small dose of tuberculin is injected intradermally in an
individual sensitized to tuberculoprotein by prior infection or
immunisation, an indurated inflammatory reaction develops at the
site within 48-72 hours. In unsensitized individuals, the tuberculin
injection provokes no response.
The tuberculin test therefore provides useful indication of the state
of
delayed hypersensitivity (cell mediated immunity) to the bacilli.
Tuberculin type hypersensitivity develops in many infections with
bacteria, fungi, viruses and parasites, especially when the infection
is
subacute or chronic and the pathogen intracellular.

132. Contact dermatitis type
Delayed hypersensitivity usually occurs due to skin contact with a variety
of substances–
 Sensitization is particularly liable when contact is with an
inflamed area of skin and when the chemical is applied in an oily
base.
 The substances involved are in themselves not antigenic but may
acquire antigenicity on combination with skin proteins. Sensitization
requires percutaneous absorption.
 Langerhans cells of the skin capture locally applied hapten and
migrate to the draining lymph nodes, present hapten along with MHC
molecules, to T cells. The sensitized T cells travel to the skin site,
where on contacting the antigen they release various lymphokines

133.  Contact with the allergen in a sensitized individual leads to
‘contact dermatitis’, characterized by maculopapular lesions to
vesicles that break down, leaving behind raw weeping areas
typical of acute eczematous dermatitis.
 Hypersensitivity is detected by the ‘patch test’. The allergen is
applied to the skin under an adherent dressing. Sensitivity is
indicated by itching appearing in 4-5 hours, and local reaction,
which may vary from erythema to vesicle or blister formation, after
24-28 hours.
Metals : nickel and chromium,
Chemicals : dyes, picryl chloride, dinitrochlorobenzene,
Drugs : penicillin

134. Shwartzman reaction
Shwartzman (1928) observed that if a culture filtrate of S. typhi is
injected intradermally in a rabbit, followed 24 hours later by the same
filtrate intravenously, a hemorrhagic necrotic lesion develops at the
site of the intradermal injection.
The intradermal and intravenous injections need not be of the same
or even related endotoxins. This absence of specificity and the short
interval between the two doses preclude any immunological basis for
the reaction.
The four types of immunopathogenic mechanisms described are not
mutually exclusive. Any given hypersensitive reaction may comprise
the components of more than one, or all of these mechanisms.

135. AUTOIMMUNITY
 The immune reaction to self-antigens
 Autoimmunity is a condition in which structural or functional
damage is produced by the action of immunologically competent
cells or antibodies against the normal components of the body.
 Autoimmunity literally means ‘protection against self’ but it
actually implies injury to self. It is also known as ‘Autoallergy’.
 Autoimmunity also implies loss of self-tolerance.

136. Features of diseases of autoimmune origin
1. An elevated level of immunoglobulins
2. Demonstrable autoantibodies
3. Deposition of immunoglobulins at sites of election
4. Accumulation of lymphocytes and plasma cells at site of lesion
5. Benefit from immunosuppressive therapy like corticosteroid
6. Occurrence of more than one type of autoimmune lesion
7. A genetic predisposition towards autoimmunity
8. Incidence higher among females
9. Chronicity. Usually nonreversible

137. Immunologic tolerance: is a state in which an individual is incapable of
developing an immune response against a specific antigen. Self-
tolerance specifically refers to a lack of immune responsiveness to one’s
own tissue antigens.
Central tolerance: This refers to the deletion of self-reactive T and B-
lymphocytes during their maturation in central lymphoid organs. Any
developing T cell or B cell that expresses a receptor for such self-
antigen is deleted by apoptosis.
Peripheral tolerance: Self-reactive T cells that escape negative
selection in the thymus can potentially dangerous outside in peripheral
lymphoid organs.
Anergy: This refers to prolonged or irreversible inactivation (rather than
apoptosis) of lymphocytes induced by encounter with antigens under
certain conditions.

138. Mechanisms of Autoimmune Disease
Breakdown of one or more of the mechanisms of self-tolerance can
unleash an immunologic attack on tissues that leads to the development
of autoimmune diseases.
Failure of tolerance
Failure of Activation induced Cell Death: Defects in this pathway
may allow persistence and proliferation of autoreactive T cells in
peripheral tissues, which may lead to autoimmune disease.
Breakdown of T-Cell Anergy: Autoreactive T cells that escape central
deletion are rendered anergic when they encounter self-antigens in the
absence of costimulation.

139. Molecular Mimicry: Some infectious agents share epitopes with self-
antigens, and an immune response against such microbes will elicit
similar responses to the cross-reacting self-antigen.
Polyclonal B cell activation: While an antigen generally activates only
its corresponding B cell, certain stimuli nonspecifically turn on multiple
B cell clones. These polyclonal antibodies are IgM in nature.
Release of Sequestered antigens: Any self-antigen that is completely
sequestered during development is likely to be viewed as foreign if
subsequently introduced to the immune system. Spermatozoa and
ocular antigens fall into this category.

140. AUTOIMMUNE DISEASES
Localized
Hemolytic (organ specific)
Systemic Transitory
(non organ specific)

141. HEMOLYTIC AUTOIMMUNE DISEASES
1. Autoimmune hemolytic anemias: Autoantibodies against RBC are
demonstrable. Two group of anemias are:
Cold autoantibodies: Complete agglutinating antibodies belonging
to IgM class
Warm autoantibodies: Incomplete nonagglutinating antibodies
belonging to IgG class
2. Autoimmune thrombocytopenia: Autoantibodies directed against
platelets eg. In Idiopathic thrombocytopenia purpura
3. Autoimmune leucopenia: nonagglutinating antileucocyte antibodies
in serum of SLE and RA patients

142. LOCALIZED (ORGAN SPECIFIC) AUTOIMMUNE DISEASES
1. Autoimmune diseases of thyroid gland: Hashimoto’s disease and
Thyrotoxicosis (Graves’ disease)
2. Addison’s disease: Antibodies directed against cells of Zona
glomerulosa
3. Autoimmune Orchitis: Antibodies against sperms and germinal cells
4. Myasthenia Gravis: Antibody against acetyl choline receptors on
myoneural junctions of striated muscles

143. 5. Autoimmune diseases of Eye: In cataract surgery autoimmune
response to lens protein leads to intraocular inflammation
(phacoanaphylaxis)
6. Pernicious anemia: Antibodies directed against parietal cell of gastric
mucosa and intrinsic factor
7. Autoimmune disease of Skin: Pemphigus vulgaris, Bullous
pemphigoid and dermatitis herpetiformis

144. SYSTEMIC (NONORGAN SPECFIC) AUTOIMMUNE DISORDERS
1. Systemic lupus erythematosus: Autoantibodies directed against:
Cell nuclei, intracytoplasmic cell constituents, immunoglobulins and
thyroid gland
2. Rheumatoid arthritis: Presence autoantibody called as Rheumatoid
factor against the Fc fragment of immunoglobulin
3. Polyarteritis nodosa
4. Sjogren’s syndrome
TRANSITORY AUTOIMMUNE PROCESSES
Includes conditions like Anemias, thrombocytopenias or nephritis that
follow infection or drug therapy. They induces antigenic alteration in
self antigens. Disease is transient.

145. ORAL IMMUNOLOGY
The health of the mouth is dependent on the integrity of mucosa,
saliva, gingival crevicular fluid and their immune components, which
does not normally allow microorganisms to penetrate.
The oral tissues are drained by an anatomically well defined collection
of extraoral lymph nodes and intraoral lymphoid tissue aggregations.
I The tonsils (palatine and lingual)
2 Salivary gland, plasma cells and lymphocytes
3 Gingival aggregation of plasma cells, lymphocytes, macro-phages
4 The scattered submucosal lymphoid cells

146. The functional significance of the intraoral lymphoid tissue has not
been clearly defined. It appears that
 The tonsils guards the entry into the digestive and respiratory
tracts
 The gingival lymphoid aggregation responding to the dental
bacterial plaque accumulation.
 The salivary lymphoid tissue for secretary IgA synthesis and
protection against infection within the salivary gland.
The secretary IgA in saliva may combine with microorganisms and
prevent their adherence to the mucosal surface.

147. Sources of Immunoglobulin in whole saliva

148. Synthesis, assembly and secretion of IgA

149. Local and systemic immunity affecting the tooth
Tooth surface is influenced by both local salivary and systemic immune
mechanisms. The division between the two immune mechanisms
occurs near the gingival margin, the only site of the body where an
interphase can be found between the local secretory and systemic
immune mechanisms. The salivary domain depends on the function of
secretary IgA and the gingival domain is controlled by immune
components found in blood.

150. Blood Crevicular Gingival
fluid
crevicular
IgG, IgM, IgA domain
Protein Complement
Enzymes Electrolytes
Polymorphs Oral fluid
B, T Lymphocytes
Macrophages sIgA
IgG, IgA Salivary
Proteins domain
Enzymes
sIgA Electrolytes
Proteins Polymorphs
Enzymes
Electrolytes
Salivary Salivary Salivary
gland fluid domain
Humoral and Cellular components in crevicular, salivary and oral fluids

151. IMMUNOLOGY OF DENTAL BACTERIAL PLAQUE
DENTAL PLAQUE COMPONENTS
CARIOGENIC IMMUNOPOTENTIATING AND PERIODONTOPATHIC
MICRO-ORGANISMS IMMUNOSUPPRESIVE AGENTS MICRO-ORGANISMS
Streptococcus mutans Lipopolysaccharides, Dextrans, Actinomyces,
Actinomyces viscosus Levan, Lipoteichoic acid Actinobacillus,
Lactobacilli Veillonella, Eikenalla,
Spirochaetes
IMMUNE RESPONSE
ANTIBODY COMPLEMENT CHEMOTAXIS: PHAGOCYT- T- AND B -
ACTIVATION PMNL, OSIS: PMNL LYMPHOCYTES
IgA, IgM, Classical and MACROPHAGES Killing, Suppression,
IgA, sIgA, Alternative Lysosomal Proliferation,
IgE pathway enzymes Memory, Help
CARIES GINGIVITIS, PERIODONTITIS

152. IMMUNOLOGY OF PERIODONTAL DISEASE
Local immunopathological and systemic immune responses during four
stages of development of periodontal disease

153. TYPE I TYPE II TYPE III TYPE IV
IgE Antibodies Immune complex Lymphocytes
Mast cell Opsonic Cell lysis: ADCC Complement Platelet Lymphokines:
adherence C5 – 9 activation aggregation Mitogenic factor
MIF
Lymphotoxin
OAF
Vasoactive Phagocytes Histamine, Micro thrombi
Amines Chemotaxis Vocative
of polymorphs amines
Killing
The complex nature of immune responses in immunopathogenesis of periodontal
disease

154. IMMUNOLOGY OF DENTAL CARIES
Serum IgG, salivary IgA and IgM antibodies and cell mediated immunity
to Streptococcus mutants can be correlated with the DMF index of caries.
Principal immunological mechanisms of protection against caries
includes
Direct immunization of the minor salivary glands or of the gut associated
lymphoid tissue, so that salivary IgA antibodies thus secreted prevent S.
mutans from adhering to the tooth surface and thereby prevent caries.
Humoral and cellular components elicited by systemic immunization.
Antibodies, complement, PMN, lymphocytes and macrophages pass from
the gingival blood vessels to the gingival domain of the tooth and
mediates IgG-induced opsonization, binding and phagocytosis.
Local gingivo-salivary immunization with synthetic peptides induces a
dual gingival IgG and salivary IgA antibodies to S. mutans.

155. Time
TOOTH
CARIES
Bacteria Sugar
NO
CARIES
Antibodies
Five principles factors in the development of caries

156. Local passive immunization with monoclonal antibodies against S. mutans
prevents colonization of this organism and is a local non-invasive method of
prevention of caries.

158. 4 – phase hypothesis of mechanism of prevention of colonization of S. mutans by
Specific Monoclonal Antibodies

159. Four preventive immuno – microbiological measures from gestation to childhood

160. IMMUNOLOGY OF ORAL INFECTIONS
Immunopathology of Herpes virus infection
Herpes simplex virus is a DNA virus
2 types: Type 1 and Type 2
3 genes: Alpha, beta and gamma
Beta gene codes for viral glycoproteins gB, gC, gD and gE.
 gB is involved in viral penetration of the cell membrane,
 gC constitutes the C3b receptor (binding the activated C3b),
 gF is the Fc receptor for IgG and
 Antibodies against gD neutralize HSV and block penetration of HSV.

161. Primary herpetic infection
The incubation period is between 2 and 7 days.
Within the first week of onset of clinical manifestations sensitized
lymphocytes to HSV can be detected in the peripheral blood but no
significant antibodies or macrophage migration inhibition factor (MIF).
After 2 weeks significant antibody titres and MIF appear. Recovery
from infection coincides therefore with the appearance of antibody and
of MIF.
Recurrent HSV infection
A deficiency of MIF production and decreased cytotoxicity by sensitized
CD8 cells may play a part in re-current infection.
CD4-T cells produce interferon and decreased interferon production
has been correlated with an increased fre-quency of recurrent HSV
infections.
Due to selective deficiency in cell-mediated immunity

162. IMMUNOLOGICAL FEATURES OF CANDIDIASIS
Candidiasis is seen in patient with defective generation or differentiation of
lymphoid stem cells
T-cell immune responses prevents muco-cutaneous candidiasis and serum
IgG and IgM antibodies prevents systemic candidiasis.
Immunodeficiencies of cellular, humoral or phagocytic components play an
important part in candidiasis.
Oral candidiasis is found in patients with AIDS who have a deficiency of CD4
cells.
Patients with B-lympho-cyte defects alone are not susceptible to candidiasis,
unless they also have a concurrent T-cell deficiency, as in the severe
combined immunodeficiency syndrome.

163. IMMUNLOGICAL AND AUTOIMMUNE DISORDERS OF ORAL MUCOSA
Recurrent aphthous ulcers
Patients with RAU show an association with HLA-B12 and it offers
immunogenic basis for development of the disease
Cell mediated immunity is involved in RAU
This induces type III and type IV hypersensitivity reactions
Immunohistological investigation reveals increase in no. of CD4 and CD8
cells, Langerhans cells and macrophages.

164. Pemphigus vulgaris
Association with DR4 or DRw6
Autoantibodies to intercellular substance of epithelial cells (IgG type)
circulating and bound to keratinocytes at site of disease
Epithelial cells with autoantibodies release plasminogen activators
which activate plasmin and leads to acantholysis
Benign mucous membrane pemphigoid (BMMP)
Presence of circulating anti-basement membrane antibodies (IgG, IgA
and IgM) with or without complement
Autoantibodies react with the lamina lucida of basement membrane

165. Lichen planus
Histology shows a increase in Langerhans cells and well defined T-cell
(CD4 and CD8) infiltration of lamina propria
Lichen planus usually develops in mouth and/or skin of patients in
which Graft versus host reaction takes place
Variety of drugs can induce lichenoid reactions in the mouth
Sjogren’s syndrome
Presence of
Antinuclear factor
Organ specific antibodies
Salivary duct antibodies

166. IMMUNE RESPONSES IN DENTAL PULP AND PERIAPICAL TISSUES
Pulp of normal tooth contains T-cells with the CD4 and CD8 cells in a
ratio of 1:2 reverse to that found in circulation (2:1)
B-cell are not found in normal pulp, so they have to home to pulp during
inflammatory reaction
Pulp and periapical tissues possess the cellular components to mount
hypersensitivity reactions namely Type III, II and I
Immune responses to dental caries leads to development of Chronic
pulpitis and periapical granulomas
Cysts shows plasma cell infiltration in cyst conc. Of IgG, IgM and IgA in
cyst fluid

167. IMMUNE FUNCTION TESTS
A careful history and physical examination will usually indicate whether
the major problem involves the Antibody – Complement phagocyte
system or Cell mediated immunity

168. HUMORAL IMMUNITY
TEST COMMENT
Immunoglobulin survey (serum protein General assessment of B cell function
electrophoresis, Ig quantification) To assess levels of IgG, A, M, D and E
Isohemagglutinin titer (anti-A, anti-B) General indication of IgM production
Titers before and after immunization Demonstrates the in vivo ability to
with a specific vaccine (TT, respond to known antigen
pneumovax, Typhoid – paratyphoid)
B cell enumeration by surface sIg or Measures the no. of circulating B cells
flow cytometry
Biopsy of bone marrow, lymph node, Assessment of presence and/or
or gut location of lymphocytes (germinal
centers, plasma cells)

169. CELL MEDIATED IMMUNITY
TEST COMMENT
Peripheral WBC count and General assessment of T cell
morphology presence
T cell enumeration by nonimmune Measures the total no. T cells in
rosetting or flow cytometry (CD3) peripheral blood
Enumeration T cell subsets (CD4, The TH / TS ratio is usually 2:1
CD8)
Measurement of lymphokine Assessment of T cell ability to secrete
production (MIF, IL-2) lymphokine
Response to phytohemagglutinin or Evaluation of T cell ability to undergo
mixed lymphocyte culture blastogenesis

170. Response to phytohemagglutinin or Evaluation of T cell ability to undergo
mixed lymphocyte culture blastogenesis
Delayed hypersensitivity skin testing to Assessment of in vivo function of T cell
recall antigens (PPD, histoplasmin, to a previously encountered antigen
Candida, mumps, streptokinase)
Dinitrochlorobenzene skin (DNCB) Assessment of in vivo function of T cell
sensitization to respond to a newly encountered
antigen
Biopsy of lymph node Assessment of the presence of T cell in
thymus – dependent areas
Complement CH50 assays (classic and alternative
pathway)
Phagocyte function Reduction of Nitroblue tetrazolium
Chemotaxis assays, Bactericidal activity

171. THANK YOU