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IMMUNE RESPONSE
Immune response = collective and coordinated
response to the introduction of foreign substances
in an individual mediated by the cells, tissues,
organs and molecules of the immune system
Immune Response
 Review: Innate response - non-specific, limited
in its response (cannot handle too much
invasion)
 Adaptive Immune response
– Matures over person’s lifetime
– Takes time to start up
– More effective and very powerful
– Important Hallmark : MEMORY
– Complex, involves a network of cells: cytokines, B
cells, T cells, antibodies
Adaptive Immune Response
 2 types
- Humoral/ antibody mediated (AMI) immunity
- Cell mediated immunity (CMI)
Humoral Immunity - Applications
 Defense against
 most extracellular bacterial pathogens
 viruses that infect through the respiratory or intestinal
tracts
 Prevents recurrence of viral infections.
 We see antibody production
 Takes part in the pathogenesis of Immediate
(Types 1, 2 & 3) hypersensitivity & certain
autoimmune disorders.
Humoral Immunity
 Cells taking part in immune response
- Antigen presenting cells (APCs)
- B cells &
- T cells
 Production of antibodies consist of following
stages :
1. Ag capture & processing by APCs
2. Ag presentation
3. TH cell activation
4. B cell stimulation & differentiation
5. Ab production by plasma cells
1. Antigen Capture & Processing
 Captured by APCs (macrophages & dendritic
cells) – broken down in to small peptides.
 2 different pathways for Ag processing
depending on their origin
 Exogenous Ag – Endocytic (class II) pathway within
lysosomes
OR
 Endogenous Ag – Cytosolic (class I) pathway in the
Endoplasmic reticulum.
2. Antigen Presentation
 Peptides derived from
1. Exogenous Ags – presented with MHC class
II molecule, recognised by TH cells.
2. Endogeous Ags – presented with MHC class
I molecule, recognised by TC cells.
Capture, Processing and Presentation of Antigen
by an Antigen presenting cell (APC)
3. Helper T cell Activation
 Activation requires 2 signals:
1. Combination of TCR with the Ag peptide-MHC class II
complex.
2. Co-stimulatory signal : combination of B7 on APC &
CD28 on the T cell with release of IL-1 .
 Activated TH cells now produce IL-2 which
supports the growth of itself & other T cells.
 Also produce IL-4, IL-5 & IL-6 which stimulates
the growth & differentiation of B cells into
- Plasma cells & Memory B cells
Helper T cell Activation
4. B cell activation & differentiation
5. Ab production
 Ab production follows a characteristic
pattern consisting of :
1. Lag Phase – immediate stage following
antigenic stimulus during which Ab is not
detectable in the circulation.
2. Log Phase – steady rise in the titre of Abs.
3. Plateau or Steady Phase – equilibrium
between Ab synthesis & its catabolism.
4. Decline Phase – catabolism exceeds
production, fall in Ab titre.
Primary & Secondary Response
Primary Response
 Initial contact with
the Ag
 Slow, sluggish & short
lived.
 Long lag phase.
 Low titres of Ab, does
not persist for long.
 IgM – predominant.
Secondary Response
 Response to
subsequent exposure
to the same Ag.
 Prompt, powerful &
prolonged.
 Short or negligible lag
phase.
 Very high levels of Ab,
lasts for long periods.
 IgG - predominant
Phases
1. A single injection of an Ag helps in
sensitising / priming the immunocompetent
cells producing the particular Ab.
2. Subsequent injections of an Ag – Boosters –
induce effective levels of Ab.
 Hence multiple doses of non living vaccines
are administered to achieve effective levels
of immunity.
Phases
 With live vaccines, a single dose is sufficient
as multiplication of the organism will provide a
continuous stimulus.
 “Negative Phase” – when an Ag is injected
into an animal already carrying the specific Ab
in circulation, a temporary fall in the level of
Ab occurs due to the combination of Ag with
the Ab. It is then followed by a rise in Ab titre.
Cell Mediated Immunity
 Refers to the specific immune responses that
do not involve antibodies.
 CMI response 1st described by Jenner in
1798.
 1890 - Koch described the exaggerated
cutaneous reaction of tuberculous guinea
pigs to the I.D. injection of tubercle bacillus –
Delayed hypersensitivity (DH).
 DH- skin lesions appear 48-72 hrs after
administration of the Ag.
Applications of CMI
 CMI participates in following immunological
functions :
1. Delayed hypersensitivity.
2. Immunity in infectious diseases caused by
obligate & facultative intracellular parasites
Bacteria – Mycobacteria, Listeria
Fungi – Histoplasma, Blastomycetes
Protozoa – Leishmania,Trypanosoma
Viruses – Measles, Mumps
Applications of CMI
3. Transplantation immunity & graft-versus-
host reaction.
4. Immunological surveillance & immunity
against cancer.
5. Pathogenesis of certain autoimmune
diseases
e.g. Thyroiditis
Cells involved in CMI
 CD8+T cells - recognise antigenic peptides in
association with MHC class I molecule on a
target cell.
 CD4+T cells - MHC class II restricted, secrete
cytokines which help in the growth &
differentiation of T lymphocytes.
Scheme of Immune
response
against T cell
dependent Ags
http://in.youtube.com/watch?v=
4kNsYa20EJU&eurl=http://rufusr
ajadurai.wetpaint.com/page/3D
+Medical+Animations?t=anon
Factors influencing Ab production
1. Genetic factors
2. Age
3. Nutritional status
4. Route of administration of Ag & site of injection
5. Size & number of doses
6. Multiple Ags
7. Adjuvants
8. Immunosuppressive agents
9. Effect of antibody
CYTOKINES
 Biologically active substances (intercellular
messengers) which are
– produced transiently
- exert their effects at very low (10–15) conc. &
- regulate immunological, inflammatory &
reparative host responses.
 Includes – Interleukin (product of leucocytes)
- Interferons
- Growth factors & others
Features of Cytokines
 Mediate their actions by binding to specific cell-
surface receptors.
 Produced by wide variety of cells like lymphocytes,
macrophages, platelets & fibroblasts.
 Cytokines can have
1. Paracrine effect – act locally near the producing
cells
2. Autocrine effect – act directly on the producing
cells
3. Pleiotropic effect – multiple effects on growth &
differentiation of various cell types.
Cytokines: Source & Function
Cytokines
IL-1
IL-2 T cells Proliferation and/or activation of T
& B cells
IL-4 T & B cells, mast cells, Activation of B cells, differentiation
of Th2 cells
IL-6 T cells, macrophages Differentiation of T & B cells
IL-10 T & B cells, macrophages Suppression of macrophages,
activation of B cells
IL-12 B cells, macrophages Differentiation of Th1 cells
IFN  Leucocytes Antiviral activity
IFN  Fibroblasts
IFN  T cells
Source : Immune cells Effects of Cytokines
Monocytes, macrophages Activation of T & B cells

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Adaptive Immune Response Overview

  • 1. IMMUNE RESPONSE Immune response = collective and coordinated response to the introduction of foreign substances in an individual mediated by the cells, tissues, organs and molecules of the immune system
  • 2. Immune Response  Review: Innate response - non-specific, limited in its response (cannot handle too much invasion)  Adaptive Immune response – Matures over person’s lifetime – Takes time to start up – More effective and very powerful – Important Hallmark : MEMORY – Complex, involves a network of cells: cytokines, B cells, T cells, antibodies
  • 3. Adaptive Immune Response  2 types - Humoral/ antibody mediated (AMI) immunity - Cell mediated immunity (CMI)
  • 4. Humoral Immunity - Applications  Defense against  most extracellular bacterial pathogens  viruses that infect through the respiratory or intestinal tracts  Prevents recurrence of viral infections.  We see antibody production  Takes part in the pathogenesis of Immediate (Types 1, 2 & 3) hypersensitivity & certain autoimmune disorders.
  • 5. Humoral Immunity  Cells taking part in immune response - Antigen presenting cells (APCs) - B cells & - T cells  Production of antibodies consist of following stages : 1. Ag capture & processing by APCs 2. Ag presentation 3. TH cell activation 4. B cell stimulation & differentiation 5. Ab production by plasma cells
  • 6. 1. Antigen Capture & Processing  Captured by APCs (macrophages & dendritic cells) – broken down in to small peptides.  2 different pathways for Ag processing depending on their origin  Exogenous Ag – Endocytic (class II) pathway within lysosomes OR  Endogenous Ag – Cytosolic (class I) pathway in the Endoplasmic reticulum.
  • 7. 2. Antigen Presentation  Peptides derived from 1. Exogenous Ags – presented with MHC class II molecule, recognised by TH cells. 2. Endogeous Ags – presented with MHC class I molecule, recognised by TC cells.
  • 8. Capture, Processing and Presentation of Antigen by an Antigen presenting cell (APC)
  • 9. 3. Helper T cell Activation  Activation requires 2 signals: 1. Combination of TCR with the Ag peptide-MHC class II complex. 2. Co-stimulatory signal : combination of B7 on APC & CD28 on the T cell with release of IL-1 .  Activated TH cells now produce IL-2 which supports the growth of itself & other T cells.  Also produce IL-4, IL-5 & IL-6 which stimulates the growth & differentiation of B cells into - Plasma cells & Memory B cells
  • 10. Helper T cell Activation
  • 11. 4. B cell activation & differentiation
  • 12.
  • 13. 5. Ab production  Ab production follows a characteristic pattern consisting of : 1. Lag Phase – immediate stage following antigenic stimulus during which Ab is not detectable in the circulation. 2. Log Phase – steady rise in the titre of Abs. 3. Plateau or Steady Phase – equilibrium between Ab synthesis & its catabolism. 4. Decline Phase – catabolism exceeds production, fall in Ab titre.
  • 14.
  • 15. Primary & Secondary Response Primary Response  Initial contact with the Ag  Slow, sluggish & short lived.  Long lag phase.  Low titres of Ab, does not persist for long.  IgM – predominant. Secondary Response  Response to subsequent exposure to the same Ag.  Prompt, powerful & prolonged.  Short or negligible lag phase.  Very high levels of Ab, lasts for long periods.  IgG - predominant
  • 16. Phases 1. A single injection of an Ag helps in sensitising / priming the immunocompetent cells producing the particular Ab. 2. Subsequent injections of an Ag – Boosters – induce effective levels of Ab.  Hence multiple doses of non living vaccines are administered to achieve effective levels of immunity.
  • 17. Phases  With live vaccines, a single dose is sufficient as multiplication of the organism will provide a continuous stimulus.  “Negative Phase” – when an Ag is injected into an animal already carrying the specific Ab in circulation, a temporary fall in the level of Ab occurs due to the combination of Ag with the Ab. It is then followed by a rise in Ab titre.
  • 18. Cell Mediated Immunity  Refers to the specific immune responses that do not involve antibodies.  CMI response 1st described by Jenner in 1798.  1890 - Koch described the exaggerated cutaneous reaction of tuberculous guinea pigs to the I.D. injection of tubercle bacillus – Delayed hypersensitivity (DH).  DH- skin lesions appear 48-72 hrs after administration of the Ag.
  • 19. Applications of CMI  CMI participates in following immunological functions : 1. Delayed hypersensitivity. 2. Immunity in infectious diseases caused by obligate & facultative intracellular parasites Bacteria – Mycobacteria, Listeria Fungi – Histoplasma, Blastomycetes Protozoa – Leishmania,Trypanosoma Viruses – Measles, Mumps
  • 20. Applications of CMI 3. Transplantation immunity & graft-versus- host reaction. 4. Immunological surveillance & immunity against cancer. 5. Pathogenesis of certain autoimmune diseases e.g. Thyroiditis
  • 21. Cells involved in CMI  CD8+T cells - recognise antigenic peptides in association with MHC class I molecule on a target cell.  CD4+T cells - MHC class II restricted, secrete cytokines which help in the growth & differentiation of T lymphocytes.
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  • 25. Scheme of Immune response against T cell dependent Ags http://in.youtube.com/watch?v= 4kNsYa20EJU&eurl=http://rufusr ajadurai.wetpaint.com/page/3D +Medical+Animations?t=anon
  • 26. Factors influencing Ab production 1. Genetic factors 2. Age 3. Nutritional status 4. Route of administration of Ag & site of injection 5. Size & number of doses 6. Multiple Ags 7. Adjuvants 8. Immunosuppressive agents 9. Effect of antibody
  • 27. CYTOKINES  Biologically active substances (intercellular messengers) which are – produced transiently - exert their effects at very low (10–15) conc. & - regulate immunological, inflammatory & reparative host responses.  Includes – Interleukin (product of leucocytes) - Interferons - Growth factors & others
  • 28. Features of Cytokines  Mediate their actions by binding to specific cell- surface receptors.  Produced by wide variety of cells like lymphocytes, macrophages, platelets & fibroblasts.  Cytokines can have 1. Paracrine effect – act locally near the producing cells 2. Autocrine effect – act directly on the producing cells 3. Pleiotropic effect – multiple effects on growth & differentiation of various cell types.
  • 29. Cytokines: Source & Function Cytokines IL-1 IL-2 T cells Proliferation and/or activation of T & B cells IL-4 T & B cells, mast cells, Activation of B cells, differentiation of Th2 cells IL-6 T cells, macrophages Differentiation of T & B cells IL-10 T & B cells, macrophages Suppression of macrophages, activation of B cells IL-12 B cells, macrophages Differentiation of Th1 cells IFN  Leucocytes Antiviral activity IFN  Fibroblasts IFN  T cells Source : Immune cells Effects of Cytokines Monocytes, macrophages Activation of T & B cells