3. • Introduction
• Terminology
• Types of immunity
• Factors affecting immunity
• Mechanisms affecting immunity
• Basic aspects of immunology
• Antigen
• Immunoglobulin or antibody
• Antigen- antibody reactions
• Complement system
4. • Structure and functions of immune system
• Cells of lympho reticular system
• Major histocompatibility complex
• Hypersensitivity reactions
• Monoclonal antibodies
• Autoimmunity
5.
6. • The definition of the immune system, which
comes from the latin word immunis,
meaning "exempt", is "a body’s system
(made up of many organs and cells) that
protects the body from infection, disease and
foreign substances by producing an immune
response."
7. • ~ 430 B.C: Peloponesian War, Thucydides describes plague –
the ones who had recovered from the disease could nurse the
sick without getting the disease a second time.
• 15th centurry: Chinese and Turks used dried crusts of
smallpox as ’’vaccine”
• 1798: Edward Jenner – smallpox vaccine.
• Noticed that milkmades that had contracted cowpox did NOT
get smallpox
8. • Test on an 8 year old boy, injected cowpox into him
(NOT very nice……)
• Follwed by exposure to smallpox.
• Vaccine was invented (latin vacca means ”cow”)
• Since 1901 there have been 19 Nobel Prizes for
immunological research.
• EXAMPLES: Discovery of human blood groups
(1930) and Transplantation immunology(1991)
9.
10. •The first person to identify microbes as causing disease
was Robert Koch.
•We still use Koch’s Postulates in disease identification.
(11 December 1843 – 27 May 1910)
13. -Natural immunity
-Present from birth
-1st
line of defence mechanism
a) NON-SPECIFIC – When there is resistance to infections in
general.
b) SPECIFIC – When resistance to a particular pathogen is
concerned.
14.
15. • 1.SPECIES.
Eg: Bacillus anthracis infects human beings but not chickens.
• 2.RACE.
Eg:Negroes in u.s.a are more susceptible than whites to
tuberculosis.
• 3.INDIVIDUAL.
17. 1.AGE :
•Two extremities of life—higher susceptibility to infectious diseases.
•Foetus protected from maternal infections due to placental barrier.
•But some pathogens cross and cause infections and death in foetus.
a)rubella b)cytomegalovirus c)toxoplasma gondii..lead to congenital
malformations in the newborn.
•New born animals more susceptible to experimental infections than older
ones.
•Old persons : high susceptibility to infections ….gradual waning of
resistance.
•Chicken pox and Poliomyelitis are more severe in adults than in young
children due to more active immune response which causes great tissue
damage.
18. 2.HORMONAL INFLUENCES
•Endocrine disorders enhance individual susceptibility to
infections
•1.diabetes mellitus.2.hypothyroidism.3.adrenal dysfunction.
•DIABETES .. high level of glucose provides medium for
growth of microorganisms.
•High incidence of staphylococcal infections in diabetes
mellitus patients due to increased levels of carbohydrates.
19. CORTICOSTEROIDS
•Suppress immune response.
•Depress host resistance by
•1.Anti inflammatory action.
•2.Antiphagocytic effect.
•3.Suppression of antibody formation.
•4.Hypersensitivity
•ONE BENEFICIAL EFFECT….
•they neutralize the harmful effect of bacterial products such as endotoxins.
20. • PREGNANCY :
• suppression of immune response
• lowered resistance.
• more prone to infections.
3.NUTRITION :
• Protein deficiency disorders…reduce immune response.
• KWASHIORKAR & MARASMUS protein deficiency
disorder.
• Both humoral and cell mediated immune responses are reduced
in malnutrition.
• Malnutrition predisposes to bacterial infections.
21. MECHANISMS OF INNATE IMMUNITY :
1.EPITHELIAL SURFACES
•Intact skin and mucous membranes give considerable
protection---act as mechanical barrier.
a ) Healthy skin provides bactericidal effect due to
1.Presence of high concentration of salt in drying sweat.
2.Sebaceous secretions.
3.Long chain fatty acids.
22. 2.MUCOSA OF THE RESPIRATORY TRACT:
•Has several innate mechanisms of defense.
•Nose/nasal orifices….inhaled bacteria arrested at the nasal orifices
by mucus at local site.
•Pass beyond—held by mucus lining epithelium---swept back to
pharynx---swallowed or coughed out.
•If swallowed—gastric juice destroys bacteria due to high acidity.
•Cough reflex is an important defensive mechanism of the host - as
microorganisms are coughed out sometimes.
23. 3.CILIA:
•Cilia present on the respiratory epithelial cells……….propels bacteria upwards
towards the exterior to be thrown out.
•Mucopolysacchrides….neutralize influenza and some other viruses.
•Particles that reach the pulmonary alveoli are ingested by the phagocytic cells.
4.MOUTH AND ORAL CAVITY :
Saliva contains non specific inhibitory substances which destroy or ward off
microorganisms.
In case they are swallowed….digestive juices destroy them.
High acidity of the stomach destroys most of the micro organisms
24. 5.CONJUNCTIVA :
•Lacrimal secretions flush…free…move the bacteria out…person who
sheds tears is more free from infections.
•Secondly, lacrimal secretions contain lysozyme a powerful
antibacterial enzyme…kills the bacteria.
•Action of lysozyme…splits the polysaccharide components of
susceptible bacteria.
•It occurs in phagocytic cells.
•High concentrations of lysozyme are lethal to many pathogens.
25. 6. URINE :
•Flushing action of urine eliminates bacteria from urethra.
•Spermine and zinc present in the semen have antibacterial activity.
7.VAGINA :
•Adult vagina is acidic due to fermentation of glycogen in the
epithelial cells by lactobacillus acidophilus.... normally present in
the vagina….destroys pathogens.
•In menopause…acid replaced will have alkaline ph.
•And this favours the growth of bacteria. Hence women who cross
45 yrs and enter menopause more prone for infections.
26. A )ANTI-BACTERIAL SUBSTANCES : PRESENT IN BLOOD AND
TISSUES.
•1.Properdin
•2.Complement
•3.Lysozyme
•4.Betalysin
•5.Basic polypeptides
•6.Interferons
B ) CELLULAR FACTORS :
1.Microphages –neutrophils
2.Macrophages
OTHER MECHANISMS
27. C) INFLAMMATION :
Leads to vasodilation, increased vascular permeability and
cellular infiltration. Due to increased vascular permeability, there is
an outpouring of plasma which helps to dilute toxic products.
D) FEVER : increased production of interferon helps in recovery
from viral infections.
E ) ACUTE PHASE PROTEINS :
following infections, sudden increase in plasma
concentrations of certain proteins
eg : C reactive protein, mannose binding proteins
28. The resistance that an individual acquires during life
Two types
A)ACTIVE :
resistance developed by an individual as a result of contact
with an antigen.
B) PASSIVE :
it is induced in an individual by preformed antibodies( in the
form of antiserum) against infective agent or toxin.
ACQUIRED IMMUNITY
29.
30. ACTIVE NATURALLY ACQUIRED IMMUNITY:
• Through clinical or subclinical infection
• Long lasting
Occurs when individuals suffer from natural infection & becomes
immune to that pathogen on recovery.
ACTIVE ARTIFICIALLY ACQUIRED IMMUNITY:
By means of vaccination.
Vaccines are prepared from live, attenuated or killed micro
organisms or their antigens or toxoids.
31. VACCINES:
• They produce active artificially acquired immunity.
• Most common method of immunization.
• Some are single dose vaccines while some require subsequent
doses.
• Vaccines are produced by a variety of mechanisms
1. LIVE ATTENUATION OF MICRO
ORGANISMS
Cowpox virus
Polio myelitis virus
32. 2. DEAD MICROBES
Anthrax
Rabies
3.VIRULENT COMPONENTS OF MICROBES
consists of substances isolated from virulent strains. Examples include
DPT.
4. VACCINATION BY EATING
genes that make an antigen effective against a microbe are cloned into
common food.
5. DNA VACCINES
Vaccines consisting of DNA fragments that can be transformed into host tissues.
once there the DNA is transcribed & translated & the protein produced is seen by
the body as foreign material.
33. PASSIVE IMMUNITY :
It is induced in an individual by preformed antibodies( in the form of antiserum)
against infective agent or toxin.
PASSIVE NATURALLY ACQUIRED:
Occurs when individuals receive antibodies from their mother.
Breast milk
Placental transfer
PASSIVE ARTIFICIALLY ACQUIRED:
When individuals are injected with pooled serum from immune individuals.
The serum contains immunoglobulins.
34. COMPARISON OF ACTIVE AND PASSIVE
IMMUNITY
ACTIVE IMMUNITY
•Produced actively by host
•Induced by infection
•Durable and effective
•Effective after a lag period
•Immunological memory
•Negative phase may occur
•Not applicable in
immunodeficient host
•Used for prophylaxis to
increase body resistance
•Eg :BCG Vaccine
PASSIVE IMMUNITY
•Received passively by host
•Introduction of antibodies
•Transient and less
•Effective immediately
•No memory
•No negative phase
•Applicable in
immunodeficient host
•Used for treatment of acute
infections
39. FACTORS OF ANTIGENICITY
•Foreginess
•Size
•Chemical nature
•Susceptible to tissue enzymes
•Species specificity
-Isospecificity
-Autospecificity
-Organ specificity
-Heterophile specificity
•FORSSMAN ANTIGEN
•PAUL BUNNEL TEST
40. • Where they are present?
• Chemical nature?
• How they are Synthesised?
• Consistute.
• Types of Antibodies.
ANTIBODY STRUCTURE
Aminoterminus
(NH2)
(COOH)
Carboxyterminus
(Specificity)
41. •H- chains are structurally & antigenically distinct for
each class.
1. IgG– gamma
2. IgA– alpha
3. IgM– mu
4. IgD– delta
5. IgE– epsilon
Major immunoglobulin, appears late.
Precipitation, c-fixation, neutralisation.
2nd
major, milk, saliva, tears, swats.....
Millionarie molecule, appears early
5-immunoglobulin sub-units & 1 j chain.
Produced in linings of respiratory & gastro
intestinal tract. Mediates type I hypersensitivity
reaction.
Present on surface of unstimulated B- lymphocytes
along with IgM. Mostly intravascular.
44. Ag & Ab Reactions
• Precipitation reaction
• Agglutination reaction
• Compliment fixation test
• Neutralization test
• Immunofluorescence
• Radioimmunoassay
• Elisa
45. 1. PRECIPITATION REACTION
• When a soluble antigen combines with it’s antibody in the
presence of electrolytes like Nacl, suitable temp, appropriate
Ph forms an insoluble Precipitate –precipitation.
• May occur in liquid media or in gels such as agar, agarose or
polyacrylamide.
• Floculation is a type of precipitation.
Eg :VDRL test, Lancefields grouping
of Streptococcus, in forensic application.
48. Antigen solution
Precipitate ring appears
RING TEST
Antiserum
Ex:
C-reactive protein (CRP) test,
streptococcal grouping by the
lancefield technique.
49. FLOCCULATION TEST:
When instead of sedimenting, the precipitate is suspended
as floccules, the reaction is called flocculation.
This is a modified form of precipitation.
Ex: A serological test (VDRL)
ab
A drop of inactive pt’s
Serum is added and mixed
by shaking, floccules appear.
SLIDE
TEST
IMMUNODIFFUSION TESTS:
These tests are done in gel (!% agar gel)
50. • When a particulate antigen combines with it’s antibody in the
presence of electrolytes like Nacl ,suitable temp. and PH., results
in visible clumping of particles.
• More sensitive in detection of antibodies.
• Takes better with IgM than with IgG antibody.
• Lattice hypothesis and zone phenomenon
2. AGGLUTINATION
51. 1.Slide agglutination test
2.Tube agglutination test
3.The Antiglobulin (coombs test )
4.Heterophil agglutination test
5.Passive agglutination test
i) Latex agglutination test
ii) Haemagglutination test
iii) Coagglutination test
TYPES OF AGGLUTINATION
52. 1) Slide agglutination test :
•Uniform suspension of antigen is made in a drop of saline on a slide
and a drop of appropriate antiserum added.
•Mixing done with a wire loop or rocking the slide.
uses :
Eg : Salmonella species, blood grouping and cross matching.
Ag Ab
53. 2) Tube agglutination test :
• Standard quantitative method for determination of antibodies.
•Serum diluted serially by doubling dilution in test tubes.
•Equal vol of particulate antigen is added to all tubes.
•Highest dilution of serum at which agglutination occurs is antibody titre
54. Uses :
• A)serological diagnosis of
• a) enteric fever (widal test )
• b) Typhus fever ( weil- Felix reaction )
• c) Infectious mononucleosis (paul –Bunnel test )
• d) brucellosis
B) for diagnosis of primary atypical pneumonia
Complications :
a) prozone phenomenon
b) blocking antibody
55. C ) THE ANTI GLOBULIN TEST (COOMBS TEST ) :
Devised originally by Coombs , Mourant
and Race for the detection of incomplete
anti –Rh antibodies.
Principle :
sera containing incomplete anti-Rh antibodies
are mixed with corresponding Rh-positive
erythrocytes, incomplete antibody globulin coats the erythrocytes but no
agglutination occurs. Such coated erythrocytes are treated with antiglobulin or
coombs serum - cells are agglutinated.
56. Uses of coomb’s test :
1. For the detection of anti Rh antibodies
2. For demonstration of any type of incomplete antibody
eg: brucellosis
57. 4. HETEROPHILE AGGLUTINATION TEST :
• Heterophile antibodies have a property to react with micro-
organisms or cells of unrelated species due to common antigenic
sharing.
i) Paul – Bunnel test
ii) Streptococcus MG agglutination test
5.PASSIVE AGGLUTINATION TEST :
a precipitation reaction can be converted to
agglutination test by attaching soluble antigens to the surface of
carrier particles such as latex ,betnonite, and RBC.
58. • Procedure :
• Serum ( to be tested ) should be inactivated by
heating at 56C for 30 mins.
• Antigen may be soluble or particulate.
• Fresh guinea pig serum – source of complement.
C. COMPLEMENT FIXATION TEST
59.
60. D) NEUTRALISATION TEST:
•Bacterial toxins are capable of producing neutralising antibodies(antitoxins) which
play a role in protection Against disease such as diptheria and tetanus.
•The toxicity of bacterial endotoxins is not neutralised by antisera.
•Viruses may also be neutralised by theirantibodies and these are named as
virus neutralisation tests
SHICK TEST
62. F) RADIOIMMUNOASSAY
RIA is based on competition for a fixed amounts of specific antibody
between a known unlabelled antigen. This competition is determined by
by the level of the test antigen present in the reacting system
67. AUTOIMMUNITY
Is a condition in which the structure /functional damage is caused by the action of
Immunologically competent cells or antibodies against the normal components of
the body.
Actually implies Autoimmunity – “Protection against Self”
Later Autoallergy – “Injury to Self”
FEATURES:
a) An elevated levels of immunoglobulin.
b) Demonstrable autoantibodies.
c) Deposition of Igs or their derivatives at sites of election, such as renal glomeruli
d) Accumulation of lymphocytes & plasma cells at the sites of lesion.
e) Incidence higher among females.
f) Chronic and usually non reversible.
68. MECHANISM OF
AUTOIMMUNIZATION:
Cells /tissues may undergo antigenic alteration as a result of
physical, chemical or biological influences. Such altered or
‘Neoantigens’ may elicit an immune response.
• CLASSIFICATION;
*Localised (organ specific) autoimmune disease.
*Systemic (non organ specific) autoimmune
disease.
71. MONOCLONA
L ANTIBODIES• When a clone of lymphocytes or plasma cells undergo
selective proliferation, Ab’s with a single antigenicity
accumulate. Such Ab’s produced by single clone & directed
against a single antigenic determinant are called Monoclonal
Antibodies.
• Hybridomas (Kohler & Milstein, 1975): somatic cells
produced by fusing Ab forming spleen cells with Myeloma
cells. The resultant hybrid retains the Ab producing capacity
of the spleen cell and ability of myeloma cells to multiply
indefinitely.