Download infection and microbial pathogenecity (host microbe

IMMUNE RESPONSE
The specific reactivity induced in a host by an
antigenic stimulus.
Infectious
Antigen
Non-infectious
Out come of antigenic stimulus
• Beneficial response (Immunity)
• Injurious response (Hypersensitivity)
• No response (Tolerance)
AMI (Humoral)
Immune response
CMI (Cell mediated)
Humoral Imm Response
Scope:
Defense against external cell pathogens.
Pathogenesis of Type I, II & III Hypersensitivity and
some Auto immune diseases.
Primary and secondary Response
Primary: Facing antigenic stimulus for first time
Slow sluggish, short lived
A long lag phase
Low titre of antibody.
Do not persist for long.
Antibody, IgM in nature
Secondary response:
Subsequent stimuli with same Ag
Prompt, powerful prolonged.
No or short lag phase
High titer of antibody.
Persist for a long period
Antibody, IgG in nature
Primary response
Secondary Response
Factors influencing Ab Production
Genetic factor
Age, nutritional status
Route of administration
Size and No of doses.
Multiple antigens
Adjuvants
Immuno suppressive agents.
Effect of Ab
Factors Influencing……
Genetic factors:
Different individuals in a single species show
difference in immune response to same Ag.
Gene situated in the short arm of 6th
chromosome.
Embryo is immunologically immature. Capacity
to produce Ab starts after development of
lymphoid system.
When potential immuno competent cell comes in
contact with specific Ag, during embryonic life,
the response is elimination of cells or induction
of tolerance. This is believed to the basis of non
antigenicity to self Ag.
Imm competence is not complete at birth. Infant
has to depend on mother’s Ab till 3-6 months.
Full competence is achieved about the age of 4
years.
Nutritional Status:
Malnutrition affects Immune response adversely. Protein
caloric malnutrion affects both AMI and CMI.
Deficiency of amino acids and vitamins (A & B group)
cause ↓ in Ab production.
Route of administration:
Humoral response is better in parentral administration
Large particulate Ag (Bact.,Erythro)
more effective iv.
Sol Ag effective subcutaneously.
Route of administration may influence type of Ab
Oral, Nasal
Ig A.
Inhalation (Polen etc.)
Ig E, Parentral
Ig G
Application of chemicals to skin
CMI
Size and number of doses:
The antibody to Ag is dose dependent.
Effective only after a minimum dose.
The response is increased if the dose is increased up to a
critical level after which will inhibit immune response
(Immune Tolerance).
Immunological paralysis:
The antigenic stimulus appears to swap Ab producing
system and completely paralyse it.
Multiple Antigens
When 2 or more Ags are adminstered the effects vary.
Typhoid + Cholera vaccines
Toxoids + Bact. vaccines
Not influenced
Response to toxoid is
potentiated
For an optimal effect, the nature and relative
proportion of diff. Ags in a mixture should be carefully
adjusted.
Adjuvants

Confer immunogenicity to non-antigenic substances

Increase the concentration and persistence of Ab.

Induce and enhances CMI
Examples: Al. hydroxide, Al-phosphate,
Freund’s incomplete adjuvant (Ag incorporated in water
phase, of a water in oil emulsion). Freunds Adjuvants
(Incomplete Freund + killed tubercle bacilli)
Immuno Suppressive Agents
They inhibit the immune responses.
Irradiation: Sub – lethal whole body irradiation
suppresses
Ab response.
Radiomimetic drugs: Cyclophosphamide, Nitrogen
mustard suppress Ab production.
Corticosteroids: cause depletion of lymphocytes from
blood and lymphoid organs. Therapeutic doses have little
effect.
Antimetabolites (Methotrexate 6-mercaptopurine inhibit
synthesis of DNA & RNA.
Effects of Antibody
The humoral response to an antigen can be
suppressed specifically by passive administration of
homologous antibody.
Eg:- Rh sensitization
AB mediated defense
Clumping followed by phagocytosis
Opsonization followed by phagocytosis
Neutralization
Complement mediated lyses
ADCC Mechanism
Activation of ‘B’ cells
Unlike ‘T’ cells, ‘B’ cells recognize the immunogen in its free
and unprocessed form.
Two signals are needed for ‘B’ cell activation
First signal is the specific binding of the antigenic receptor
with the membrane bound form of immunoglobin present in
the surface of the ‘B’ cells
Second signal provided by the activated helper ‘T’ cells (CD
40 L) binds to protein called CD 40 on ‘B’ cells.
MONOCLONAL ANTIBODIES
AND HYBRIDOMA TECHNIQUE
Introduction
Antibodies have many applications in diagnosis, therapy
and research.
Until recently antibodies were produced by inoculating Ag
into animal and taking serum some time latter.
The draw back with above conventional antisera is that they
are a heterogeneous mixture of antibodies of different
specificities, affinities and classes.
Sought after Ab might be present in low conc. In the serum.
Conventional antisera may produce unwelcome cross
reactions because of heterogenicity.
Definition
Ab produced by a single clone of cells directed against
a
single
antigenic
determinant.
The
antibodies
produced by single clone of cells are specific i.e
antibody of single class which have high affinity.
Hybridoma Technique
1975
Method devised by G. Kohler and C.
Milestein, Monoclonal antibodies of desired
specifically
1984
In recognition to this Hybridoma Tech. they
were awarded Nobel prize.
Principle: Fusion of an antibody producing ‘B’ cell with
myeloma cell to producing a hybrid myeloma
called Hybriodoma.
Hybriodoma possesses important properties of both of
its parent cells.
The ability to produce specific antibody of ‘B’ cells with
permanent growth and
High rate of secretion of myeloma cells for indefinite
times.
In short a ‘B’ cell can essentially be immortalized by
fusion with a myeloma cell
Applications
diagnostic, therapeutic and research applications.
Mabs are being employed in many areas where antisera
were formerly used like blood grouping, tissue typing,
hormone RIA.
Application Contd.
Pregnancy can be diagnosed 10 days after conception.
Mab to chorionic- gonadotrophin can be used to detect
chorionic- gonadotrophin in urine.
Rapid
diagnosis
of
Hepatitis,
influenza,
streptococcal and Chlamydia infection.
Mabs used to analyze complex biological system
(Molecules on the surface)
Herpes
Application Contd.
Cancer diagnosis and therapy
Diag: To isolate specific molecules.
Therapy: Carry cytotoxic drugs, immunotoxin directly to
tumor surface (magic bullets)
Cell mediated immune response
Specific immune response that does not involve antibody.
Scope of CMI:
Delayed hypersensitivity
Immunity against obligate and facultative intracellular
parasites.
Transplantation immunity.
Immunity against cancer
Pathogenesis of some autoimmune diseases (thyroiditis,
encephalitis etc.)
Bacteria:
M. tuberculosis, M. leprae
Brucella, Listeria etc.
Fungi:
Histoplasma capsulatum, Coccidioides immitis,
Blastomyces dermatitis.
Protozoa:
Leishmania spp. Trypanosoma spp.
Virus: smallpox, measles, mumps etc.
CELLS INVOLVED IN CMI
APC (Macrophage, B cells, dendrocytes etc)
T Helper cells (CD4, Th1 & Th2)
T suppressor cells (CD8 cells)
N.K. cells
Eosinophils.
CD4 Cell mediated CMI
Mostly for Exogenous Ag
T Lymphocytes that have the CD4 molecules on
their surface recognize antigen fragments in
association to MHC II mol of APC. These
activated ‘T’ cells secrete lymphokines.
Lymphokines serve 2 main functions
1) Recruit & activate other leucocytes and promote
and inflammatory response.
2) Act as growth and differentiating
and ‘B’ cells.
factors for ‘T’
CD8 cell mediated CMI
Mostly for Endogenous Ag (virus, Tumor cells
etc).
CD8 cells recognize fragments Ag in association
with MHC I molecule on a target cell and cause
cell lyses.
Lyses is brought about by liberation of some
substances from the granules of CD8 cells.
The granules contain
1) Perforin (act like C9)
2) Serene esterase
3) No of toxic molecules
•
TNF –α
•
TNF –β (Lymphotoxin)
•
Gama – interferon.
Cytokines
Peptide mediators or intracellular messengers.
Regulate immunological, inflammatory and reparative
host responses.
Produced by widely distributed cells (lymphocytes,
macrophages, platelets, fibroblasts etc)
Have paracrine and autocrine effect on the cells.
Cytokines (Classification)
A) Interleukins:
IL1 to IL13
IL1, IL10, IL8 - Macrophage
IL7 - stromal cells.
All others – T & B cells.
B) Colony stimulating factors,(CSF)
- Macrophage (M) CSF
- Granulocyte (G) CSF
- Gran . Macro (GM) CSF
C) Tumor Necrosis factor (TNF)
- TNF – Alpha – Macro
- TNF – Beta – ‘T’ cells.
D) Interferons
IFN – Alpha
IFN - Beta
IFN-Gamma-T cells
Lecocyte
Fibroblast
Antiviral
Antiviral
Macro Activation
NK cell activation
E) TGF – B (Trans
growth fact)
MHC I, MHC II exp.
LIF – Leuk inhib fact) – produced by T- cells
Act on stromal cells