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E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
ADAPTIVE IMMUNITY
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Definitions
• Immune system = cells, tissues, and molecules that
mediate resistance to infections
• Immunology = study of structure and function of the
immune system
• Immunity = resistance of a host to pathogens and
their toxic effects
• Immune response = collective and coordinated
response to the introduction of foreign substances in
an individual mediated by the cells and molecules of
the immune system
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Role of the immune system
• Defense against microbes
• Defense against the growth of tumor cells
• kills the growth of tumor cells
• Homeostasis
• destruction of abnormal or dead cells
(e.g. dead red or white blood cells, antigen-antibody
complex)
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Immune System
1. Organs
2. Cells
3. Molecules
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Immune System:organs
(RES)
• Tonsils and adenoids
• Thymus
• Lymph nodes
• Spleen
• Payer’s patches
• Appendix
• Lymphatic vessels
• Bone marrow
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Immune system:
(2) cells
• Lymphocytes
• T-lymphocytes
• B-Lymphocytes, plasma cells
• natural killer lymphocytes
• Monocytes, Macrophage
• Granulocytes
• neutrophils
• eosinophils
• basophils
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Immune system:
(3) molecules
• Antibodies
• Complement
• Cytokines
• Interleukines
• Interferons
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Two types of immunity
1. Innate (non-adaptive)
• first line of immune response
• relies on mechanisms that exist before infection
2. Acquired (adaptive)
• Second line of response (if innate fails)
• relies on mechanisms that adapt after infection
• handled by T- and B- lymphocytes
• one cell determines one antigenic determinant
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Adaptive immunity:
• Based upon resistance acquired during life
• Relies on genetic events and cellular growth
• Responds more slowly, over few days
• Is specific
• each cell responds to a single epitope on an antigen
• Has anamnestic memory
• repeated exposure leads to faster, stronger response
• Leads to clonal expansion
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Adaptive Immunity:
active and passive
Active Immunity Passive Immunity
Natural clinical, sub-clinical
infection
via breast milk,
placenta
Artificial Vaccination:
Live, killed, purified
antigen vaccine
immune serum,
immune cells
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Adaptive immunity:
mechanisms
• Cell-mediated immune response (CMIR)
• T-lymphocytes
• eliminate intracellular microbes that survive within
phagocytes or other infected cells
• Humoral immune response (HIR)
• B-lymphocytes
• mediated by antibodies
• eliminate extra-cellular
microbes and their toxins Plasma cell
(Derived from B-lymphocyte,
produces antibodies)
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Cell-mediated immune response
1. T-cell
• recognizes peptide
antigen on macrophage
in association with major
histo-compatibility
complex (MHC) class
• identifies molecules on
cell surfaces
• helps body distinguish
self from non-self
2. T-cell goes into effectors
cells stage that is able to kill
infected cells
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
T lymphocytes
2 types
• helper T- lymphocytes (CD4+)
• CD4+ T cells activate phagocytes to kill microbes
• cytolytic T-lymphocyte (CD8+)
• CD8+ T cells destroy infected cells containing
microbes or microbial proteins
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Cell mediated immune response
Primary response
• production of specific clones of effector T cells and
memory clones
• develops in several days
• does not limit the infection
Secondary response
• more pronounced, faster
• more effective at limiting the infection
Example - cytotoxic reactions against intracellular parasites, delayed
hypersensitivity (e.g., Tuberculin test) and allograft rejection
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Humoral immune response
1. B lymphocytes recognize
specific antigens
• proliferate and
differentiate into
antibody-secreting
plasma cells
2. Antibodies bind to specific
antigens on microbes;
destroy microbes via
specific mechanisms
3. Some B lymphocytes
evolve into the resting state
- memory cells
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Antibodies (immunoglobulins)
•Belong to the gamma-globulin fraction of
serum proteins
•Y-shaped or T-shaped polypeptides
• 2 identical heavy chains
• 2 identical light chains
• All immunoglobulins are not antibodies
•Five kinds of antibodies
• IgG, IgM, IgA, IgD, IgE
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
IgG
• 70-75% of total immuniglobulin
• Secreted in high quantities in secondary exposures
• Cross the placenta
• Major functions / applications
• neutralize microbes and toxins
• opsonize antigens for phagocytosis
• activate the complement
• protect the newborn
• 4-fold rise or fall
indicates active infection
• A single positive
sample indicates past
exposure
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
IgM
• Secreted initially during primary infection
• Cannot cross the placenta
• Major functions / applications
• secreted first during primary
exposure
• activates the complement
• used as a marker of recent
infection
•Presence in newborn
means infection
•Single positive sample in
serum or CSF indicates
recent or active infection
•Used to detect early
phase of infection
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
IgA
• Monomeric in serum
• Dimeric with secretory component in the lumen of the
gastro-intestinal tract and in the respiratory tract
• Major function / application
• neutralizes microbes and toxins
•Sero-diagnosis of
tuberculosis
•Synthicial respiratory
virus tests
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
IgD
• Monomeric
• Major functions / applications
• present on the surface of B lymphocytes
• functions as membrane receptor
• role unclear
• has a role in antigen stimulated lymphocyte
differentiation
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Serodiagnosis of infectious and
non infectious allergies
(e.g., allergic
bronchopulmonary
aspergillosis, parasitic
diseases)
IgE
• Mediates type I hypersensitivity
• Monomeric
• Major functions / applications
• associated with anaphylaxis
• plays a role in immunity to
helminthic parasites
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Sequential IgM-IgG humoral
response
•IgM
• produced as a first response to many antigens
• levels remain high transiently
•IgG
• produced after IgM
• higher levels persist in small amounts throughout life
• produced in large amounts during secondary
response
• persistence of antigen sensitive ‘memory cells’
after primary response
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
IgM – IgG sequential response
First stimulus
Time
Second stimulus
Antibody
titer
IgM
IgG
Anamnestic
response
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Failure of immune response
• Immune response helps individuals defend against
• microbes
• some cancers
• Immune response can fail
• hypersensitivity reactions undesirable response
produced by immune system.
• immunodeficiency
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Hypersensitivity reactions
• Cause cell damage through excessive immune
response to antigens
• Hypersensitivity
• overreaction to infectious agents
• Allergy
• overreaction to environmental substances
• Autoimmunity
• overreaction to self
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Immunodeficiency
• Loss or inadequate function of various components of
the immune system
• Can occur in any part or state of the immune system
• physical barrier, phagocytes, B lymphocytes, T
lymphocytes, complement, natural killer cells
• The immuno-compromised host
• has an impaired function of immune system
• is at high risk of infection
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Immunodeficiency
• Congenital (primary) immunodeficiency
• genetic abnormality
• defect in lymphocyte maturation
• Acquired (secondary) immunodeficiency
• results from infections, nutritional deficiencies or
treatments
• AIDS, chronic leukemia
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Altered immunity: immuno-compromised
Disorder Compromised function
Altered anatomic
barrier
Mucus membrane Reduction in IgA Microbe binding
Gastro-intestinal
tract
Elevated pH Bacteria killing
Change in flora Colonization resistance
Immune system Innate immunity Reduction of complement Activates phagocytosis
Opsonization of bacteria
Membrane attack complex
Neutropenia
Monocytopenia
Phagocytosis
Bacteria killing
Adaptive
immunity
Reduction of T cells Activation of macrophages
Activation of B lymphocytes
Hypo-gammaglobulinemia Neutralizes pathogens and
toxins, opsonization,
complement activation
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Summary (1)
• Innate immunity
• relies on mechanisms already existing before microbe
infects host
• is the first line of defense
• has no memory for subsequent exposure
• relies on non specific mechanisms
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Summary (2)
• Adaptive immunity
• develops following entry of microbe into the host
• comes into action after innate immunity fails to get rid
of microbe
• has memory to deal with subsequent exposure
• happens through specific cells
• T cells (cell mediated)
• B cells (antibody mediated)
E P I D E M I C A L E R T A N D R E S P O N S E
Laboratory Training for Field Epidemiologists
Summary (3)
• Primary immune response
• short lasting
• smaller in magnitude
• Secondary immune response
• longer in duration
• larger in magnitude
• develop ‘memory cells’ following primary response
• Failure of immune response can result in:
• hypersensitivity
• immunodeficiency

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ADAPTIVE IMMUNOLOGY FOR KMTC.ppt

  • 1. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists ADAPTIVE IMMUNITY
  • 2. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Definitions • Immune system = cells, tissues, and molecules that mediate resistance to infections • Immunology = study of structure and function of the immune system • Immunity = resistance of a host to pathogens and their toxic effects • Immune response = collective and coordinated response to the introduction of foreign substances in an individual mediated by the cells and molecules of the immune system
  • 3. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Role of the immune system • Defense against microbes • Defense against the growth of tumor cells • kills the growth of tumor cells • Homeostasis • destruction of abnormal or dead cells (e.g. dead red or white blood cells, antigen-antibody complex)
  • 4. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Immune System 1. Organs 2. Cells 3. Molecules
  • 5. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Immune System:organs (RES) • Tonsils and adenoids • Thymus • Lymph nodes • Spleen • Payer’s patches • Appendix • Lymphatic vessels • Bone marrow
  • 6. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Immune system: (2) cells • Lymphocytes • T-lymphocytes • B-Lymphocytes, plasma cells • natural killer lymphocytes • Monocytes, Macrophage • Granulocytes • neutrophils • eosinophils • basophils
  • 7. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Immune system: (3) molecules • Antibodies • Complement • Cytokines • Interleukines • Interferons
  • 8. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Two types of immunity 1. Innate (non-adaptive) • first line of immune response • relies on mechanisms that exist before infection 2. Acquired (adaptive) • Second line of response (if innate fails) • relies on mechanisms that adapt after infection • handled by T- and B- lymphocytes • one cell determines one antigenic determinant
  • 9. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Adaptive immunity: • Based upon resistance acquired during life • Relies on genetic events and cellular growth • Responds more slowly, over few days • Is specific • each cell responds to a single epitope on an antigen • Has anamnestic memory • repeated exposure leads to faster, stronger response • Leads to clonal expansion
  • 10. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Adaptive Immunity: active and passive Active Immunity Passive Immunity Natural clinical, sub-clinical infection via breast milk, placenta Artificial Vaccination: Live, killed, purified antigen vaccine immune serum, immune cells
  • 11. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Adaptive immunity: mechanisms • Cell-mediated immune response (CMIR) • T-lymphocytes • eliminate intracellular microbes that survive within phagocytes or other infected cells • Humoral immune response (HIR) • B-lymphocytes • mediated by antibodies • eliminate extra-cellular microbes and their toxins Plasma cell (Derived from B-lymphocyte, produces antibodies)
  • 12. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Cell-mediated immune response 1. T-cell • recognizes peptide antigen on macrophage in association with major histo-compatibility complex (MHC) class • identifies molecules on cell surfaces • helps body distinguish self from non-self 2. T-cell goes into effectors cells stage that is able to kill infected cells
  • 13. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists T lymphocytes 2 types • helper T- lymphocytes (CD4+) • CD4+ T cells activate phagocytes to kill microbes • cytolytic T-lymphocyte (CD8+) • CD8+ T cells destroy infected cells containing microbes or microbial proteins
  • 14. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Cell mediated immune response Primary response • production of specific clones of effector T cells and memory clones • develops in several days • does not limit the infection Secondary response • more pronounced, faster • more effective at limiting the infection Example - cytotoxic reactions against intracellular parasites, delayed hypersensitivity (e.g., Tuberculin test) and allograft rejection
  • 15. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Humoral immune response 1. B lymphocytes recognize specific antigens • proliferate and differentiate into antibody-secreting plasma cells 2. Antibodies bind to specific antigens on microbes; destroy microbes via specific mechanisms 3. Some B lymphocytes evolve into the resting state - memory cells
  • 16. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Antibodies (immunoglobulins) •Belong to the gamma-globulin fraction of serum proteins •Y-shaped or T-shaped polypeptides • 2 identical heavy chains • 2 identical light chains • All immunoglobulins are not antibodies •Five kinds of antibodies • IgG, IgM, IgA, IgD, IgE
  • 17. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists IgG • 70-75% of total immuniglobulin • Secreted in high quantities in secondary exposures • Cross the placenta • Major functions / applications • neutralize microbes and toxins • opsonize antigens for phagocytosis • activate the complement • protect the newborn • 4-fold rise or fall indicates active infection • A single positive sample indicates past exposure
  • 18. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists IgM • Secreted initially during primary infection • Cannot cross the placenta • Major functions / applications • secreted first during primary exposure • activates the complement • used as a marker of recent infection •Presence in newborn means infection •Single positive sample in serum or CSF indicates recent or active infection •Used to detect early phase of infection
  • 19. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists IgA • Monomeric in serum • Dimeric with secretory component in the lumen of the gastro-intestinal tract and in the respiratory tract • Major function / application • neutralizes microbes and toxins •Sero-diagnosis of tuberculosis •Synthicial respiratory virus tests
  • 20. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists IgD • Monomeric • Major functions / applications • present on the surface of B lymphocytes • functions as membrane receptor • role unclear • has a role in antigen stimulated lymphocyte differentiation
  • 21. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Serodiagnosis of infectious and non infectious allergies (e.g., allergic bronchopulmonary aspergillosis, parasitic diseases) IgE • Mediates type I hypersensitivity • Monomeric • Major functions / applications • associated with anaphylaxis • plays a role in immunity to helminthic parasites
  • 22. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Sequential IgM-IgG humoral response •IgM • produced as a first response to many antigens • levels remain high transiently •IgG • produced after IgM • higher levels persist in small amounts throughout life • produced in large amounts during secondary response • persistence of antigen sensitive ‘memory cells’ after primary response
  • 23. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists IgM – IgG sequential response First stimulus Time Second stimulus Antibody titer IgM IgG Anamnestic response
  • 24. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Failure of immune response • Immune response helps individuals defend against • microbes • some cancers • Immune response can fail • hypersensitivity reactions undesirable response produced by immune system. • immunodeficiency
  • 25. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Hypersensitivity reactions • Cause cell damage through excessive immune response to antigens • Hypersensitivity • overreaction to infectious agents • Allergy • overreaction to environmental substances • Autoimmunity • overreaction to self
  • 26. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Immunodeficiency • Loss or inadequate function of various components of the immune system • Can occur in any part or state of the immune system • physical barrier, phagocytes, B lymphocytes, T lymphocytes, complement, natural killer cells • The immuno-compromised host • has an impaired function of immune system • is at high risk of infection
  • 27. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Immunodeficiency • Congenital (primary) immunodeficiency • genetic abnormality • defect in lymphocyte maturation • Acquired (secondary) immunodeficiency • results from infections, nutritional deficiencies or treatments • AIDS, chronic leukemia
  • 28. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Altered immunity: immuno-compromised Disorder Compromised function Altered anatomic barrier Mucus membrane Reduction in IgA Microbe binding Gastro-intestinal tract Elevated pH Bacteria killing Change in flora Colonization resistance Immune system Innate immunity Reduction of complement Activates phagocytosis Opsonization of bacteria Membrane attack complex Neutropenia Monocytopenia Phagocytosis Bacteria killing Adaptive immunity Reduction of T cells Activation of macrophages Activation of B lymphocytes Hypo-gammaglobulinemia Neutralizes pathogens and toxins, opsonization, complement activation
  • 29. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Summary (1) • Innate immunity • relies on mechanisms already existing before microbe infects host • is the first line of defense • has no memory for subsequent exposure • relies on non specific mechanisms
  • 30. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Summary (2) • Adaptive immunity • develops following entry of microbe into the host • comes into action after innate immunity fails to get rid of microbe • has memory to deal with subsequent exposure • happens through specific cells • T cells (cell mediated) • B cells (antibody mediated)
  • 31. E P I D E M I C A L E R T A N D R E S P O N S E Laboratory Training for Field Epidemiologists Summary (3) • Primary immune response • short lasting • smaller in magnitude • Secondary immune response • longer in duration • larger in magnitude • develop ‘memory cells’ following primary response • Failure of immune response can result in: • hypersensitivity • immunodeficiency