Immunology and Serology.ppt

Immunology and serology is an important issue for medical science both veterinary and human medical science .The presentation shows general study about immunology and serology

1. Immunology and Serology
Immunology:Thestudyofallaspectsoftheimmune
systemincludingitsstructureandfunction,disordersofthe
immunesystem,bloodbanking,immunizationandorgan
transplantation.
Historyofimmunology:
Intheyear1798EdwardJennerdiscoveredthesmall
poxvaccinebyusingthecowpoxmaterialandinjected
intohealthyindividual.Thetermvaccinationwascoined
inhonoroftheworkEdwardJennerhenceinLatin
“Vacca”meanscow.
Inthe19
th
centuryFrenchscientistLouisPasteur
discoveredthevaccineofanthrax,rabies&fowl
cholera.(ARF)

2. ElieMetehnikoff(1883),hewasaRussianZoologist.
Hediscoveredtheprocessofphagocytosisby
experimentonstarfish.
VonBehrinsandKitasato(1890)theydevelopedthe
toxoidsofdiphtheriaandtetanus.
PaulEhrlich(1897)-hediscoveredside-chainreceptor
ofantibodysynthesis.
KarlLandgeiner(1900)-Bloodgroup,Agandtheir
crossespond

3. Immunity: “Free from burden”. Ability of
an organism to recognize and defend itself
against specificpathogens or antigens.
Immune Response: Third line of defense.
Involves production of antibodies and
generation of specialized lymphocytes
against specific antigens.
Antigen: Molecules from a pathogen or
foreign organism that provoke a specific
immune response.

4. The Immune System is the Third Line
of Defense Against Infection

5. Immunity: Immunity is the ability of an organism to recognize and defend itself
against agents that are “foreign” to it. In other word immunity means body
defense against the pathogens.
Types of immunity:
Broadly there are two types of immunity-
1. Non specific immunity
2. Specific immunity
NON SPECIFIC IMMUNITY :
The body possesses many mechanisms that impart nonspecific defenses that are
given bellow…
I.Mechanical and chemical barrier
II.Phagocytosis
III.Inflammation
IV.Moderate fever
V.Natural killer cell
VI.Complement

6. MECHANICAL AND CHEMICAL BARRIER
Mechanical and chemical barrier act as first line defense of non specific
immunity.
Mechanical barrier:
Skin:
The skin is the single largest organ of the body that cover the entire body
and prevent the entrance of microorganism into body.
The epidermis has several layers of dead epithelial cells that function as an
excellent barrier against injury and infection of deeper layers of the body.
The cells contain keratin, which prevents water-soluble substances from
entering the body.
Skin is some what dry due to dryness no growth and multiplication of
organism occur.

7. Mucous membrane:
Mucous membrane lined by epithelial cell and connective tissue.
That them prevent the entrance of organism into the body.
TheGobletcellsoftheepitheliallayerofthemucousmembranes
secretemucus,athickbutwaterysecretionthatformaprotective
layerovertheepidermalcells,preventingdryingandcrackingofthe
membrane.
Mucus also traps pathogens before they can establish an infection.
Cilia of the mucous membrane drivedthe trapping microorganism
into the mouth and nose.
Lacrimalapparatus:

8. Lacrimalapparatus secrete tear. Microorganism spell out through the
tear secreted by lacrimalapparatus.
Saliverygland:
Saliverygland secrete saliva that help to spell out of
organism through these saliva.
Chemical barrier:
Sebum:
Sebumsecretedbythesebaceousglandoftheskin.Sebumis
composedofprotein,fatandsalt.Thesesebumformafilmlayer
overtheskinasaresultmicroorganismcannotenterintothebody.
Sebum also contain unsaturated fatty acid as a result organism can
not grow and multiply.

9. Sebum (organic acids and lipids) is an oily secretion
maintains an acid pH in the skin that discourages bacterial
growth[[
Due to acidic condition of sebum microorganism can not
grow and multiply.

10. Perspiration:
Perspiration secreted by the sweat gland of the skin. Perspiration
contain lysosymeenzyme that disintegrate the cell wall of Gram +ve
and Gram –vebacteria.
However, perspiration keeps the skin salty and consequently an
inhospitable site for most microbial growth.
Gastric juice:
Gastric juice contain Hclthat maintain acidic pH of the stomach.
The high acidity of the stomach (pH 1.2 to 3.0) is especially
inhibiting of microorganism survival.
Hclitself also disintegrate microorganism.

11. Lactoferrinand Transferrin:
Lactoferrinand Transferrinare iron binding protein present
in the blood. This iron binding protein bind with the iron of
the blood as a result the organism cannot grow and multiply
due to lack of iron.

12. Macrophage: is nothing but mono nucleated phagocyticcell.
Single, rounded or bean shaped or identednucleus
Posses cytoplasm that contain-
•Lysosome
•Endoplasmic reticulum
•Golgi apparatus
•Mitochondria
Development of Macrophage:
Monoblastis one originated from bone marrow stem cells
Convert into promonocytes
Monocytes
Go to the blood stream
Circulate into the blood for 3-4 days (before enter into tissue)
Then go to the tissue, where the microorganisms invade, enlarged and developed
in the duration of migration to tissue
Maturation take place and formation of active phagocyticmacrophage

13. Types of macrophage:
There are two types of macrophage
1.Permanent macrophage: are those , which remain in the organ or tisuues
Macrophages in the
connective tissueHistiocytes
Liver Von kupffercells
Lungs Alveolar macrophage/ dust cells
Brain Microglialcell
Bone Osteoclast
Kidney Mesangealcell
spleen Diplittoralcell
Skin Langerhan’scell
2.Wandering macrophage: are those type of macrophage are called wandering
macrophage, which roans in the tissues surrounding the infected area.
Macrophages in the reticuloendothelialsystem

14. Phagocytosis
Phagocytosis: Engulfment of microbes or foreign particle by the cell is called phagocytosis.
Phagocytosisinvolve several steps-
1.Chemotaxis:Chemo means chemical and taxis means attraction. So attraction of
the chemical substances by microorganisms is called chemotaxis.
Receptor located in the cell wall of the organism, pick up the stimuli from the
environmlent
Stimuli go to the movement organelles (flagella)
Attraction of the organisms to the favorable condition and away from the adverse
condition to stimuli
2.Adherence: Attachment of the microorganism to the plasma membrane of the host
tissue or the phagocyte. Some organism adhere quickly and some slowly.
Adherence depends on the opsonizationof the organisms.
Opsonization: When the microorganisms coated with the serum protein (opsonin), the
process is called oposonization. Opsonizedorganism easily adhere with the
plasmamenbraneof the phagocyticcells than the non opsonizedorganisms.

15. 3.Ingestion: The engulfment of the organisms by the macrophage during this
process. The plasma membrane of the microphage extend the projection called
pseudopod.
The pseudopodfused and form phagocyticvesicle called phagosome
The phagosomepinch off from the plasma membrane and enter into the cytoplasm
of the phagocytes
Then the phagosomecontact with the lysosomeand fused to form phagolysosome
4.Digestion:Lysosomesecrete some enzymes that disintegrate the different
structure of organism.
For example, Lysozymeenzyme break down the peptidoglycanof the bacterial
cell wall and lipase enzyme destroy the lipid of the microbes.
It will takes 10-30 minutes to phagocytizethe microorganism

17. Microbial Evasion of Phagocytosis
Some bacteria have structures that inhibit adherence. EgM protein
of Streptroccuspyogenesinhibits the attachment of phagorytesto
their surface.
Heavily encapsulated microorganism eg. Streptorocus
pneumoniaecan be phagocytizedonly if the phagocyte traps the
organism against rough surface, such as blood vessel, blood clot,
C.T. fiber.
Some microbes may be ingested but not killed.
eg. Staphylococcus
Produces
Leukocidins
Kills
Phagocytes release microbes
A number of intracellular pathogens
Secret
MAC

18. lyse
Phagolysosomemembrane
Release
Microbes into cytoplasm of phagocyte
Propagate
Secrete MAC
Lyseplasma membrane of phagocyte --relasethe microbes
Eg. Listeriamonocytogenes
Some microbes have the ability to survive inside the phagocyte
The microbes then multiply within the phagocyte

19. Completely filling it
Phagocytes dies
Microbes are released automatically and infect the other
hosts.
Eg. Mycobacterium tuberculosis
Some microbes remain dormant within phagocytes
for months or years at a time
Eg. Brucella

20. Some microbes survive within the phagocytes
Escape from a phagosomebefore it fuses with a
lysosome
Eg. Coxiellaburnetii, causative agent of Q feuer

21. Inflammation
Tissue damage
Release histamin(present in many cell of the body specially in mast cell in
connective tissue, circulating basophiland blood platelets) in react to response to
injury of the cells that contains it.
Kininpresent in blood plasma and play a role in chemotaxisby attracting
phagocyticgranulocyte, neutrophilto the injured area
Prostaglandins released by damaged cell and leukotrienesproduced by mast cell,
present in connective tissue of skin and respiratory system
Vasodilationand increase permeability of blood vessels
Help deliver clotting elements of blood into the injured area

22. Blood clots that form around the site of activity prevent the microbes or toxins
from spreading the other part of the body
As a result there may be localized collection of pus, mixture of dead cells and
body fluid in a cavity form by the break down of body tissues
Abscess formation
Flow of blood gradually decreases
Stick/attached the phagocyticcells with endothelial cells of blood vessels (this
condition is called marginaion)
Phagocyte squeeze within the endothelial cells of the blood vessel to reached the
damaged area
Migrate to the infected area (emmigration)
Phagocytosisof microorganism
Tissue repair

24. Moderate fever: Moderate fever is useful for host defense.
Due to activation of macrophage and/or microbial infection of the body
Endogenous pyrogen(IL-1) is produced in the body
Affect the hypothalamus
Stimulate the rising of body temperature
Increase cell metabolism
Increase phagocyticactivity of the
phagocyticcells
Killing of microbes
Rapid tissue repair
Constrict the blood vessel
Denying blood to the skin
Keppingheat within the body
Inhibit the growth and multiplication
of some bacteria
(Mesophilic& Psychrophilic)

25. Natural killer cell
Naturalkillercellrecognizeandkilltheabnormalcellofthebody(abnormalcellsare
cancercell,virusinfectedcell).Agroupofdefensivelymphocytespresentinthe
circulatingbloodarecallednaturalkillercells.
Thenaturalkillercellcontainseveralreceptorintheirsurface.Thesurfacereceptor
bindwiththetargetcellandformingacomplexbeforecelltocellinteractiontakes
place.
Thesurfacereceptorsitematchwithclass-IMHC(MajorHistocompatibility
complex)molecules,whicharefoundintheallbodycells.WhentheMHCmolecules
presentinnaturalkillercellsrecognizethetargetcellbymatchingtheMHC
moleculesandexpelledit.WhenMHCmoleculesareabsentorreducedinamountin
thecells,theNKcellsbindwiththetargetcell,damagethecellsurfaceandlysisof
cell.
Complement:
Complementaretheseriesofproteinmoleculesarrangesinacascadeproducedby
theliver,circulatinginthebloodandlymph.Complementmarksthepathogenfor
destruction.
Thecomplementproteinworkonthreepathway-
I.Classicalpathway
II.AlternativepathwayIII)LectinPathway

26. Antigen-antibody complex
Activate complement protein
Activate C
3
C
3
Pathogen
Bind with C
3
Hydrolizedto
C
3a C
3b
Vasodilationand increase permeability of blood
vessels
Inflamatoryresponse
C
5
Hydrolizedto
C
5a
C
5b
Opsonization
Phagocytosis
C
6
,C
7, C
8
,C
9
Membrane attack complexLysisof the pathogen by forming hole
in the surface of pathogen
Antigen-antibody complex activate C
1
C
2
, C
4
C
2a
, C
4a
Hydrolizedto
Classical path way
Lectinpath way Alternative path way

27. Innate or Genetic Immunity: Immunity an
organism is born with.
Genetically determined.
May be due to lack of receptors or other
molecules required for infection.
Innate human immunity to canine distemper.
Immunity of mice to poliovirus.
Acquired Immunity:Immunity that an
organism developsduring lifetime.
Not genetically determined.
May be acquired naturally or artificially.
Development of immunity to measles in response to
infection or vaccination.

28. Components of Human Immune System

29. Types of Acquired Immunity
I. Naturally Acquired Immunity: Obtained in
the course of daily life.
A. Naturally Acquired Active Immunity:
Antigensor pathogens enter body naturally.
Body generates an immune response to antigens.
Immunity may be lifelong (chickenpox or mumps)
or temporary (influenza or intestinal infections).
B. Naturally Acquired Passive Immunity:
Antibodiespass from mother to fetus via placenta
or breast feeding (colostrum).
No immune response to antigens.
Immunity is usually short-lived(weeks to months).
Protection until child’s immune system develops.

30. Types of Acquired Immunity (Continued)
II. Artificially Acquired Immunity: Obtained by
receiving a vaccine or immune serum.
1. Artificially Acquired Active Immunity:
Antigensare introduced in vaccines (immunization).
Body generates an immune response to antigens.
Immunity can be lifelong (oral polio vaccine) or temporary
(tetanus toxoid).
2. Artificially Acquired Passive Immunity:
Preformed antibodies(antiserum) are introduced into body
by injection.
Snake antivenom injection from horses or rabbits.
Immunity is short lived (half life three weeks).
Host immune system does not respond to antigens.

31. Serum: Fluid that remains after blood has clotted
and cells have been removed.
Antiserum: Serum containing antibodies to a
specific antigen(s). Obtained from injecting an
animal (horse, rabbit, goat) with antigen (snake
venom, botulism or diphtheria toxin).
Serology: The study of reactions between
antibodies and antigens.
Gamma Globulins: Fraction of serum that
contains most of the antibodies.
Serum Sickness: Disease caused by multiple
injections of antiserum. Immune response to
foreign proteins. May cause fever, kidney
problems, and joint pain. Rare today.

32. Origin and Development of B-cell and T-cell
Haemopoieticstem cell
(Primitive cells of yolk sac, bone marrow and fetus liver)
Myeloid progenitor Lymphoid progenitor
(Responsible for the production of RBC (Responsible for the production of lymphocyte)
and most of the WBC)
Go the thymus
Maturation and addition of
surface protein
T lymphocyte
Circulation
Localized in lymphnode
and spleen
Remain in bone marrow
or bursa
Maturation and addition
of surface protein
B lymphocyte
Circulation
Localized in Different parts of the
body

33. Primary lymphoid organ: The organ where the lymphocyte produce and
differentiate. E.g. Bone marrow, Bursa, Thymus, Peyerspatches of the intestine.
Secondary Lymphoid organ: The organ developed at the late stage of foetus
life like lymphnode, spleen. This organs are richedof macrophage and dendritic
cell. This macrophage and dendriticcell trough the organism and processing the
antigen. This organ is also rich in T and B cell which are responsible for the
production of immune response.

34. Duality of Immune System
I. Humoral (Antibody-Mediated) Immunity
Involves production of antibodies against foreign
antigens.
Antibodies are produced by a subset of lymphocytes
called B cells.
B cells that are stimulated will actively secrete
antibodies and are called plasma cells.
Antibodies are found in extracellular fluids(blood
plasma, lymph, mucus, etc.) and the surface of B cells.
Defense against bacteria, bacterial toxins, and viruses
that circulate freely in body fluids, beforethey enter
cells.
Also cause certain reactions against transplanted
tissue.

35. Antibodies are Produced by B Lymphocytes

36. Antibodies are Proteins that Recognize Specific Antigens

37. Duality of Immune System (Continued)
II. Cell Mediated Immunity
Involves specialized set of lymphocytes called T cells
that recognize foreign antigens on the surface of cells,
organisms, or tissues:
Helper T cells
Cytotoxic T cells
T cells regulateproliferation and activity of other cells
of the immune system: B cells, macrophages,
neutrophils, etc.
Defense against:
Bacteria and viruses that are inside host cells and are
inaccessible to antibodies.
Fungi, protozoa, and helminths
Cancer cells
Transplanted tissue

38. Cell Mediated Immunity is Carried Out by T Lymphocytes

39. Antigens
Most are proteinsor large polysaccharidesfrom
a foreign organism.
Microbes: Capsules, cell walls, toxins, viral capsids,
flagella, etc.
Nonmicrobes: Pollen, egg white , red blood cell
surface molecules, serum proteins, and surface
molecules from transplanted tissue.
Lipids and nucleic acids are only antigenic when
combinedwith proteins or polysaccharides.
Molecular weight of 10,000 or higher.
Hapten: Small foreign molecule that is not antigenic. Must be
coupled to a carriermolecule to be antigenic. Once antibodies
are formed they will recognize hapten.

40. Antigens
Epitope:
Small part of an antigen that interacts
with an antibody.
Any given antigen may have several
epitopes.
Each epitope is recognized by a different
antibody.

41. Epitopes: Antigen Regions that Interact
with Antibodies

42. Antibodies
Proteins that recognize and bind to a particular
antigen with very high specificity.
Made in response to exposure to the antigen.
One virus or microbe may have several antigenic
determinant sites, to which different antibodies
may bind.
Each antibody has at least two identical sites
that bind antigen: Antigen binding sites.
Valence of an antibody: Number of antigen
binding sites. Most are bivalent.
Belong to a group of serum proteins called
immunoglobulins (Igs).

43. Antibody Structure
Monomer: A flexible Y-shaped molecule with
four protein chains:
2 identical lightchains
2 identical heavychains
Variable Regions: Two sections at the end of
Y’s arms. Contain the antigen binding sites
(Fab). Identical on the same antibody, but vary
from one antibody to another.
Constant Regions: Stem of monomer and lower
parts of Y arms.
Fc region: Stem of monomer only. Important
because they can bind to complement or cells.

44. Antibody Structure

45. Immunoglobulin Classes
I. IgG
Structure: Monomer
Percentage serum antibodies: 80%
Location:Blood, lymph, intestine
Half-life in serum: 23 days
Complement Fixation: Yes
Placental Transfer: Yes
Known Functions: Enhances phagocytosis,
neutralizes toxins and viruses, protects fetus and
newborn.

46. Immunoglobulin Classes
II. IgM
Structure: Pentamer
Percentage serum antibodies: 5-10%
Location:Blood, lymph, B cell surface (monomer)
Half-life in serum: 5 days
Complement Fixation: Yes
Placental Transfer: No
Known Functions: First antibodies produced
during an infection. Effective against microbes and
agglutinating antigens.

47. Immunoglobulin Classes
III. IgA
Structure: Dimer
Percentage serum antibodies: 10-15%
Location:Secretions (tears, saliva, intestine, milk),
blood and lymph.
Half-life in serum: 6 days
Complement Fixation: No
Placental Transfer: No
Known Functions: Localized protection of mucosal
surfaces. Provides immunity to infant digestive
tract.

48. Immunoglobulin Classes
IV. IgD
Structure: Monomer
Percentage serum antibodies: 0.2%
Location:B-cell surface, blood, and lymph
Half-life in serum: 3 days
Complement Fixation: No
Placental Transfer: No
Known Functions: In serum function is unknown.
On B cell surface, initiate immune response.

49. Immunoglobulin Classes
V. IgE
Structure: Monomer
Percentage serum antibodies: 0.002%
Location:Bound to mast cells and basophils
throughout body. Blood.
Half-life in serum: 2 days
Complement Fixation: No
Placental Transfer: No
Known Functions: Allergic reactions. Possibly
lysis of worms.

50. Characters IgG IgM IgA IgD IgE
Structure Monomer Pentamer Dimer Monomer Monomer
Molecular
weight
(Dalton)
1,80,0009,00,000 3,60,000 2,00,000 1,80,000
% of serum
antibody
80 5-10 10-15 0.2 0.002
Secretion inSpleen and
lymphnode
Spleen and
lymphnode
Respiratory
and intestinal
tract
Respiratory
and intestinal
tract
Spleen and
lymphnode
Location of
antibody
Blood,
lymph,
intestine
Blood, lymph,
Bursa cell
surface
Blood,lymph,
and secretion
like tear,
saliva
Blood, lymph,
Bursa cell
surface
Blood
Types of antibody

51. Characters IgG IgM IgA IgD IgE
Complement
fixation
Yes Yes No No No
Placental
transfer
Yes No No No No
Half life23 days 5 days 6 days 2 days 3 days
Specific
function
Phagocytosis
Neutralize bacterial
toxinand virus and
also
protect the fetus
•Act against
microorganism
also responsible
for agglutination
reaction.
•Initial Ab
production
through the
response of Ag
•Protection
of the local
mucosal cell
surface
•Immune
response
•Hyperse
nsitivity
reaction

52. How Do B Cells Produce Antibodies?
B cells develop from stem cellsin the bone
marrow of adults (liver of fetuses).
After maturation B cells migrate to lymphoid
organs (lymph node or spleen).
Clonal Selection: When a B cell encounters an
antigen it recognizes, it is stimulated and divides
into many clones called plasma cells, which
actively secrete antibodies.
Each B cell produces antibodies that will
recognize only one antigenic determinant.

53. Clonal Selection of B Cells is Caused
by Antigenic Stimulation

54. Humoral Immunity (Continued)
Apoptosis
Programmed cell death (“Falling away”).
Human body makes 100 million lymphocytes
every day. If an equivalent number doesn’t die,
will develop leukemia.
B cells that do not encounter stimulating antigen
will self-destruct and send signals to phagocytes
to dispose of their remains.
Many virus infected cells will undergo apoptosis,
to help prevent spread of the infection.

55. Humoral Immunity (Continued)
Clonal Selection
Clonal Selection: B cells (and T cells) that
encounter stimulating antigen will proliferate into
a large group of cells.
Why don’t we produce antibodies against our
own antigens? We have developed toleranceto
them.
Clonal Deletion: B and T cells that react against
selfantigens appear to be destroyed during fetal
development. Process is poorly understood.

56. Consequences of Antigen-Antibody Binding
Antigen-Antibody Complex: Formed when an
antibody binds to an antigen it recognizes.
Affinity: A measure of binding strength.
1. Agglutination: Antibodies cause antigens
(microbes) to clump together.
IgM (decavalent) is more effective that IgG (bivalent).
Hemagglutination: Agglutination of red blood cells.
Used to determine ABO blood types and to detect
influenza and measles viruses.
2. Opsonization: Antigen (microbe) is covered with
antibodies that enhances its ingestion and lysis by
phagocytic cells.

57. Consequences of Antibody Binding

58. Humoral Immunity (Continued)
3. Neutralization: IgG inactivates viruses by
binding to their surface and neutralize toxins by
blocking their active sites.
4. Antibody-dependent cell-mediated cytotoxicity:
Used to destroy large organisms (e.g.: worms).
Target organism is coated with antibodies and
bombarded with chemicals from nonspecific
immune cells.
5. Complement Activation:Both IgG and IgM
trigger the complement system which results in
cell lysis and inflammation.

59. Consequences of Antibody Binding

60. Immunological Memory
Antibody Titer: The amount of antibody in the
serum.
Pattern of Antibody Levels During Infection
Primary Response:
After initialexposure to antigen, no antibodies are
found in serum for several days.
A gradual increase in titer, first of IgM and then
of IgG is observed.
Most B cells become plasma cells, but some B cells
become long living memory cells.
Gradual decline of antibodies follows.

61. Immunological Memory (Continued)
Secondary Response:
Subsequent exposure to the same antigen displays
a faster and more intense antibody response.
Increased antibody response is due to the
existence of memory cells, which rapidly produce
plasma cells upon antigen stimulation.

62. Antibody Response After Exposure to Antigen

63. T Cells and Cell Mediated Immunity
Antigens that stimulate this response are mainly
intracellular.
Requires constant presence of antigen to remain
effective.
Unlike humoral immunity, cell mediated immunity
is not transferred to the fetus.
Cytokines: Chemical messengers of immune cells.
Over 100 have been identified.
Stimulate and/or regulate immune responses.
Interleukins: Communication between WBCs.
Interferons: Protect against viral infections.
Chemokines: Attract WBCs to infected areas.

64. T Cells and Cell Mediated Immunity
Cellular Components of Immunity:
T cells are key cellular component of immunity.
T cells have an antigen receptor that recognizes
and reacts to a specific antigen (T cell receptor).
T cell receptor only recognize antigens combined
with majorhistocompatability(MHC) proteins on
the surfaceof cells.
MHC Class I: Found on all cells.
MHC Class II: Found on phagocytes.
Clonal selection increases number of T cells.

65. T Cells Only Recognize Antigen Associated
with MHC Molecules on Cell Surfaces

66. T Cells and Cell Mediated Immunity
Types of T cells
1. T Helper (T
H) Cells: Central role in immune
response.
Most are CD4
+
Recognize antigen on the surface of antigen presenting
cells (e.g.: macrophage).
Activate macrophages
Induce formation of cytotoxic T cells
Stimulate B cells to produce antibodies.

67. Central Role of Helper T Cells

68. Types of T cells (Continued)
2. Cytotoxic T (Tc) Cells: Destroy target cells.
Most are CD4 negative (CD4
-
).
Recognize antigens on the surface of all cells:
•Kill host cells that are infected with viruses or bacteria.
•Recognize and kill cancer cells.
•Recognize and destroy transplanted tissue.
Release protein called perforinwhich forms a pore in
target cell, causing lysis of infected cells.
Undergo apoptosiswhen stimulating antigen is gone.

69. Cytotoxic T Cells Lyse Infected Cells

70. Types of T cells (Continued)
3. Delayed Hypersensitivity T (T
D) Cells: Mostly T
helper and a few cytotoxic T cells that are
involved in some allergic reactions (poison ivy)
and rejection of transplanted tissue.
4. T Suppressor (Ts) Cells: May shut down
immune response.

71. Nonspecific Cellular Components
1. Activated Macrophages: Stimulated phagocytes.
Stimulated by ingestion of antigen
Larger and more effective phagocytes.
Enhanced ability to eliminate intracellular bacteria,
virus-infected and cancerous cells.
2. Natural Killer (NK) Cells:
Lymphocytes that destroy virus infected and tumor
cells.
Not specific. Don’t require antigen stimulation.
Not phagocytic, but must contact cell in order to lyse it.

72. Relationship Between Cell-Mediated
and Humoral Immunity
1. Antibody Production
T-Dependent Antigens:
Antibody production requires assistance from T helper cells.
A macrophage cells ingest antigen and presents it to T
Hcell.
T
Hcell stimulates B cells specific for antigen to become plasma
cells.
Antigens are mainly proteins on viruses, bacteria, foreign red
blood cells, and hapten-carrier molecules.
T-Independent Antigens:
Antibody production does not require assistance from T cells.
Antigens are mainly polysaccharides or lipopolysaccharides with
repeating subunits (bacterial capsules).
Weaker immune response than for T-dependent antigens.

73. Humoral Response to T Dependent Antigens

74. Humoral Response to T Dependent Antigens

75. Relationship Between Cell-Mediated
and Humoral Immunity
2. Antibody Dependent Cell Mediated
Cytotoxicity
Target cell is covered with antibodies, leaving Fc
portion sticking outwards.
Natural killer and other nonspecific cells that have
receptors for Fc region are stimulated to kill targeted
cells.
Target organism is lysed by substances secreted by
attacking cells.
Used to destroy large organisms that cannot be
phagocytosed.

76. Destruction of Large Parasites by ADCC

77. T-Cell
T-Cells: The cells containing receptor in their surface which is protein substances
linked by dipeptidebond cells . T cells are the key cellular component of immunity.
T cells develop from stem cells in the bone marrow.
Classification of T cell:
According to the function T-cells are 4 types
1)Helper T-cells (T
H)
2)CytotoxicT-cells (T
C)
3)Suppressor T-cell (T
S )
4)Delayed hypersensitivity T-cell (T
D)
Functions of different T cells:
Helper T cell: Two types of helper T cells
i.T
H1 cells: Activate the cells associated with immune response.
Eg. Macrophage, NK-cells, CD8+T cell
ii.T
H2Cells: Stimulate the production of eosinophils, Ig-M, Ig-E, Ig-A
CytotoxicT cell (T
C): Destroy the infected cells by cell to cell contact
Suppressor T-cell (T
S ) : Regulate the immune system/response and help to
maintain tolerance of the body.
Delayed hypersensitivity T-cell (T
D): Protect the body from infection by the
production of allergic reaction.

78. Cytokines
Cytokines: The cells of immune system secreted a variety of proteinaceoussubstances which
regulate the immune responses by signaling between cells.
Interleukin: The cytokines act as a chemical mediators which regulate the interaction between the
lymphocytes and other leukocytes population, so they are called interleukin. The number of interleukin
is based on amino acid sequence. When the much information is known including amino acid sequence
of the cytokines that are numbered by the international committee. The number of cytokines are 26.
Functions of some important cytokines:
1)Interleukin-1 (IL-1):
It activate the helper T cell and binding the antigen processing cells in presence of antigen
peptide.
Chemo-attraction of macrophage to the inflammatory response
2)Interleukin-2 (IL-2):
Proliferate the antigen binding helper T cells
Proliferate and differentiate B cell
Activate the cytotoxicT cells (Tccell) and natural killer cell
3)Interleukin-8 (IL-8):
chemo-attraction of immune cells and phagocytosisto the site of inflammation
4)Interleukin-12 (IL-12):
Differentiate CD 4
5)Gamma-interferon (γ-IFN):
Inhibit the replication of the infecting agent like virus
Activate the phagocyticcell

79. 6)Tumor necrosis factor β(TNF-β):
Cytotoxicof tumor cells
Increase the activity of the macrophage
7)Granulocytes-Macroophagecolony stimulating factor (GM-CSF):
Stimulate the production of red and white blood cells from stem cell
Cluster of Differentiation (CD)
Cluster of Differentiation (CD):
CD are the glycoproteinslocated on the surface of the all nucleated cells of the body and also
in the surface of macrophage.
It acts co-receptor involve in the T-cell.
On the basis of co-receptor T cells are two types-
1.CD4:
Found in the surface of helper T cell (T
H)
Responsible for the production of antibody mediated immunity
Recognize the antigen peptide associated with class-II MHC molecule
2.CD8:
found in the surface of cytotoxicT cell
Responsible for the production of cell mediated immunity
Recognize the antigen peptide associated with MHC class-I molecules in infected
cells

80. Specific Antigeanis injected into mouse
The antibody is produced against specific antigen
Spleen of mouse is removed from the body and make a suspension of spleen
Spleen containing B cell having the capability of to produce antibody
Suspension of spleen mixed with myolomacell culture
The mixed cell having the power to proliferate but not capability to produce antibody
Some spleenicB cell and myolomacells fused with B cells to form another type of cells is called
hybrid cells
This hybrid cell having the capability to produce antibody
When this hybrid cells grow in selective media is to form hybridomacells
This hybridomacells are responsible for the production of monoclonal antibody

81. Process of cell mediated cytotoxicity
Antigen presenting cells (macrophage) engulf the antigen
Encounter, enter and digest the antigen
Antigen become fragmented and antigen peptide bind with MHC Class-II molecules
Present on the surface of APC
CD 4 of the helper T-cells recognizes the antigen peptide and MHC Class-II molecules
T
H Cells bind with the complex of antigen peptide and MHC class-II molecule
The T
H cell stimulate the APC to secrete IL-1
IL-1 stimulate the T
H cells to secrete the IL-2
The T
Hcells become proliferate
Produce clone of T
Hcells
Some clone of T
Hcells go to the tissue for long period as a memory cells
Other clone of T
Hcells secrete the IL-2 this activate the T
C cells
Continued

82. Proliferate the T
C cells and clone of T
C cells
Migrate to lymph and gland and ultimately go to the infected area
Bind with the infected cells at antigen peptide associated with Class-I MHC molecules
Then the T
C cells release the perforinand granzymeenzyme. They form a pore in the
membrane of target cell causing lysis

83. Overview of the Immune Response

84. Vaccine
Vaccine: is a suspension of microorganism or portion of microbes, which is induced to
produce immunity.
Types of vaccine:
1.1
st
Generation vaccine:When the whole microorganisms either live or inactivated or
killed used for production of vaccine, is called 1
st
generation vaccine. Live vaccine and
killed vaccine are used in Bangladesh.
Livevaccine:actasanintracellularantigenandstimulateimmuneresponsebycell
mediatedcytotoxicity.Sometimeslivevaccinesarehazardous,duetoresidualvirulence.
i.e.thevaccinevirusproducethedisease(instressconditionofthebody)
Killed vaccine: acts as an extracellular and stimulate the immune response dominated by
CD4+Helper T-cells. Sometimes killed vaccine can not produce appropriate immune
response, but they are safer. Both vaccines are ideal and highly antigenic. They have no
adverse side effect.
2.2
nd
Generation vaccine/sub-unit vaccine:
When the part of the microbes/sub-unit of the microorganisms used for the production of
vaccine called 2
nd
generation/sub-unit vaccine.
E.g. piliof the organism, extracted and purified for vaccine. The piliproduce the antipili
antibody and bind with piliand resulting the bacteria loss their adhering capability.
Conjugate vaccine: is 2
nd
generation vaccine composed of different polysaccharide of
capsule of different strain of same microrganism.

85. 3.3
rd
Generation vaccine/synthetic vaccine:
ThisoneissophisticatedpromisingvaccineproducedbyrecombinantDNAtechnology.
Immunestimulatingantigenmustbeidentified.Livingcellsmustbere-engineeredto
producethedesiredantigen.Theantigenmustbeincreasedtopromotephagocytosisand
immuneresponse.
CharacteristicsofIdealvaccine:
I.Anidealvaccinemustproduceprolongedstrongimmunity
II.Theidealvaccinemustbefreefromadversesideeffect
III.Theidealvaccinemustbecheaper,stableandadaptabletomassvaccination
IV.Anidealvaccinemustproduceanimmuneresponsedistinguishablefromthatdueto
naturalinfectionsothatimmunizationanderadicationmayproceedsimultaneously
V.Effectivenessofvaccinehavefourcriticalproperties-
Stimulateantigenpresentingcellsandtheyprocesstheantigenandproducethe
remarkableinterleukin(cytikine)
StimulateB-lymphocyteandT-lymphocyteasaresultgenerationoflargenumber
ofmemorycells
StimulatehelperT-cellandTc
Havingthecapabilitytopersisttheantigeninthesuitableareainthelymphoid
systemandasaresultgenerationoftheimmunecellsandproducelongrunning
immunity.

86. Causes of vaccine failure:
Wrong strain of organism and insufficient antigen in vaccine leads to
vaccine failure
Lack of proper storage leads to death of live vaccine resulting vaccination
failure
Non-conventional route of vaccination leads to vaccination failure
Wrong manufacturing process
Presence of other microorganism (mixed infection)
If not maintain proper cool chain
If persistent infection present in the host
Over dose of vaccine
Inadequate dose of vaccine
The use of antibiotic with live bacterial vaccine
Vaccination given too late, incubating the disease already
Vaccination failure due to high infectious disease against which herd
immunity is poor
In case of immunosuppressedanimal