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IMMUNITY
Immunology and the Immune system
• Immunology
– The study of the molecular and cellular components
that comprise the immune system, including their
function and interaction, is the central science
of immunology.
• Immune System
– Molecules, cells, tissues and organs which provide non-
specific and specific protection against
• Microorganisms
• Microbial toxins
• Tumor cells
– Crucial to human survival
Immune response and Immunity
• Immune response
– Innate (non-specific)
– Adaptive (specific)
• Primary
• Secondary
• Immunity
– State of non-specific and specific protection
• Acquisition of Immunity
– Natural
– Artificial
The Immune System
• Human immune system begins to develop in the embryo.
• Starts with hematopoietic (from Greek, "blood-making")
stem cells.
• Stem cells differentiate into major cells in the immune
system
– granulocytes, monocytes, and lymphocytes
• Stems cells also differentiate into cells in the blood that
are not involved in immune function, such as erythrocytes
(red blood cells) and megakaryocytes (for blood clotting).
• Stem cells continue to be produced and differentiate
throughout ones lifetime.
Principal function of the Immune system
• To protect humans from pathogenic microorganisms
• Pathogenic microorganisms (Pathogens)
– Microorganisms capable of causing infection and/or disease
• Infection
– Ability of pathogen to enter host, multiply and stimulate an
immune response
• Disease
– Clinical manifestations associated with infection
Naturally Acquired immunity
• Active
– Antigens enter body naturally with response of
• Innate and adaptive immune systems
– Provides long term protection
• Passive
– Antibodies pass from mother to
• Fetus across placenta
• Infant in breast milk
– Provides immediate short term protection
Artificially Acquired Immunity
• Active
– Antigens enter body through vaccination with response of
• Innate and adaptive immune systems
– Provides long term protection
• Passive
– Antibodies from immune individuals injected into body
• Referred to as
– Immune serum globulins (ISG)
– Immune globulins (IG)
– Gamma globulins
– Provides immediate short term protection
Principle mechanisms of
innate and adaptive immunity
Innate Immune system
• Innate immunity refers  to  nonspecific 
defence  mechanisms  that  come  into 
play immediately or within hours of an 
antigen's appearance in the body. These 
mechanisms  include  physical  barriers 
such  as  skin,  chemicals  in  the  blood, 
and immune system  cells  that  attack 
foreign cells in the body.
Cells of innate immunity
NK cells
Dendritic cells
Mast cells
Neutrophils
Monocytes/Macrophages
Phagocytosis, inflammation
Phagocytosis, inflammation,
T-cell activation, tissue repair
Killing of infected or tumor cells
Eosinophils
Inflammation
Defense against parasites
Phagocytosis, activation of naive T-cells
Cell type Pricipal function(s)
AntigensAntigens
Some chemical that creates immune response
Most are proteinsproteins or large polysaccharidespolysaccharides
from a foreign organism.
– MicrobesMicrobes: Capsules, cell walls, toxins, viral
capsids, flagella, etc.
– NonmicrobesNonmicrobes: Pollen, egg white , red blood cell
surface molecules, serum proteins, and surface
molecules from transplanted tissue.
EpitopeEpitope: AntigensAntigens
Small part of an antigen that interacts
with an antibody. 10-12 amino acids
Any given antigen may have several
epitopes.
Each epitope is recognized by a
different antibody.
AntigensAntigens
Some chemical that creates immune response
Most are proteinsproteins or large polysaccharidespolysaccharides from a foreign 
organism.
– MicrobesMicrobes:    Capsules,  cell  walls,  toxins,  viral  capsids, 
flagella, etc.
– NonmicrobesNonmicrobes:  Pollen,  egg  white  ,  red  blood  cell 
surface  molecules,  serum  proteins,  and  surface 
molecules from transplanted tissue. 
– Lipids  and  nucleic  acids  are  only  antigenic  when 
combined with proteins or polysaccharides.
Cont….
• Epitope (Antigenic Determinant)
– Specific site on Ag that is recognized by the       
   immune system, where Ab binds
• Hapten: Small  foreign  foreign  molecule  that  is  not 
antigenic antigenic. Must be coupled to a carrier molecule 
to  be  antigenic.  Once  antibodies  antibodies  are  formed 
they will recognize hapten.
Karl Landsteiner Landsteiner discovered Hapten, who also
discovered blood group antigen and got noble prize.
Epitopes: Antigen Regions that
Interact with Antibodies
AntibodiesAntibodies
• Proteins Proteins  that  recognize  and  bind  to  a 
particular antigen with very high specificityspecificity.
• Made  in  response  to  exposure  to  the 
antigen.
• One  virus  or  microbe  may  have  several 
antigenic determinant sitesantigenic determinant sites,  to  which 
different antibodies may bind.
• Each  antibody  has  at  least  two  identical 
sites  that  bind  antigen:    Antigen bindingAntigen binding
sitessites.
• Belong to a group of serum proteins called 
immunoglobulins (Igs).immunoglobulins (Igs).
Antibody Structure
How Do B Cells Produce Antibodies?How Do B Cells Produce Antibodies?
– B cells develop from stem cellsstem cells in the bone marrow of
adults (liver of fetuses).
– After maturation B cells migrate to lymphoid organs (lymph
node or spleen).
– Clonal SelectionClonal Selection: When a B cell encounters an antigen it
recognizes, it is stimulated and divides into many clones
called plasma cellsplasma cells, which actively secrete antibodies.
– Each B cell produces antibodies that will recognize only one
antigenic determinant.
Immunoglobulin
• Heavy Chain – 110 amino acids longHeavy Chain – 110 amino acids long
– 100 distinct V segments100 distinct V segments
– 30 D segments30 D segments
– 6 J segments6 J segments
– Enzymes choose one V segment, one D segment and one JEnzymes choose one V segment, one D segment and one J
segment and fuse them togethersegment and fuse them together
– 18,000 combinations in encoding antibody molecule18,000 combinations in encoding antibody molecule
– Splice this variable region to the constant regionSplice this variable region to the constant region
• Light Chain – 211 amino acids longLight Chain – 211 amino acids long
– 10,000 combinations10,000 combinations
– Total of 180,000,000 distinct B cellsTotal of 180,000,000 distinct B cells
• Fusion is sloppy, can create other variantsFusion is sloppy, can create other variants
Classes of Antibodies (Immunoglobulins)
Immunity and Immune Response
Made up of two cellular systems:
• Humoral or circulating antibody system
– B cells
• Cell mediated immunity
– T cells
Overview of the Immune Response
Humoral or B-Cell Mediated Immune
Response
Produces secreted antibodies (proteins)
• Bind to antigens and identify the antigen
complex for destruction.
• Antibodies act on antigens in the serum and
lymph
• B-cell produced antibodies may be
– attached to B-cell membranes or
– Free in the serum and lymph.
• Each B lymphocyte makes a unique antibody
molecule (immunoglobulin or Ig)
• Over a million different B lymphocytes are
produced in each individual
– So, each individual can recognize more
than a million different antigens
Cell Mediated Immune System:
T lymphocytes
• T-cells mature in the thymus (thus the name T-cell)
• Act on antigens appearing on the surface of individual cells.
• Over a million different kinds of T-cells
– Each produces a different receptor in the cell membrane
– Each receptor is composed of 1 molecule each of two
different proteins
– Each receptor binds a specific antigen but has only one
binding site
– Receptor only recognizes antigens which are
"presented" to it within another membrane protein of
the MHC type (major histocompatibility complex)
• Recognizes specific antigens bound to the antigen-
presenting structures on the surface of the
presenting cell.
• Recognizes antigens presented by B-cells,
macrophages, or any other cell type
T Cells and their Functions
• Have a specific receptor for a fragment of antigen
• Cytotoxic T-cells:
– Contain a surface protein called CD8
– Destroy pathogen infected cells, cancer cells, and foreign cells
(transplanted organs)
• Helper T-cells:
– Contain a surface protein called CD4
– Regulate both cellular and humoral immune systems
– This regulation reduces autoimmunity.
Central Role of Helper T Cells
Cytotoxic T Cells Lyse Infected Cells
Antigen-Antibody Interactions
• Quality and quantity are important in resolution of
disease
• May contribute to pathology
• Useful in immunological assays
Immune Precipitation
AntigenAntigen
AntibodyAntibody
Agglutination
RBC
RBC
RBC
RBC
IgM AntibodyIgM Antibody
IgG AntibodyIgG Antibody
RBC
RBCRBC
RBC RBC
RBCRBC
Enzyme (ELISA) Immunoassay
AntigenAntigen
anti-antigen
antibody
Enzyme conjugated to
anti-Ig antibody
(“second antibody”)
Add
substrate
for enzyme
IMMUNITY by Juhi Mishra (Medical Advisor)

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IMMUNITY by Juhi Mishra (Medical Advisor)

  • 2. Immunology and the Immune system • Immunology – The study of the molecular and cellular components that comprise the immune system, including their function and interaction, is the central science of immunology. • Immune System – Molecules, cells, tissues and organs which provide non- specific and specific protection against • Microorganisms • Microbial toxins • Tumor cells – Crucial to human survival
  • 3. Immune response and Immunity • Immune response – Innate (non-specific) – Adaptive (specific) • Primary • Secondary • Immunity – State of non-specific and specific protection • Acquisition of Immunity – Natural – Artificial
  • 4. The Immune System • Human immune system begins to develop in the embryo. • Starts with hematopoietic (from Greek, "blood-making") stem cells. • Stem cells differentiate into major cells in the immune system – granulocytes, monocytes, and lymphocytes • Stems cells also differentiate into cells in the blood that are not involved in immune function, such as erythrocytes (red blood cells) and megakaryocytes (for blood clotting). • Stem cells continue to be produced and differentiate throughout ones lifetime.
  • 5. Principal function of the Immune system • To protect humans from pathogenic microorganisms • Pathogenic microorganisms (Pathogens) – Microorganisms capable of causing infection and/or disease • Infection – Ability of pathogen to enter host, multiply and stimulate an immune response • Disease – Clinical manifestations associated with infection
  • 6. Naturally Acquired immunity • Active – Antigens enter body naturally with response of • Innate and adaptive immune systems – Provides long term protection • Passive – Antibodies pass from mother to • Fetus across placenta • Infant in breast milk – Provides immediate short term protection
  • 7. Artificially Acquired Immunity • Active – Antigens enter body through vaccination with response of • Innate and adaptive immune systems – Provides long term protection • Passive – Antibodies from immune individuals injected into body • Referred to as – Immune serum globulins (ISG) – Immune globulins (IG) – Gamma globulins – Provides immediate short term protection
  • 8. Principle mechanisms of innate and adaptive immunity
  • 9.
  • 10. Innate Immune system • Innate immunity refers  to  nonspecific  defence  mechanisms  that  come  into  play immediately or within hours of an  antigen's appearance in the body. These  mechanisms  include  physical  barriers  such  as  skin,  chemicals  in  the  blood,  and immune system  cells  that  attack  foreign cells in the body.
  • 11. Cells of innate immunity NK cells Dendritic cells Mast cells Neutrophils Monocytes/Macrophages Phagocytosis, inflammation Phagocytosis, inflammation, T-cell activation, tissue repair Killing of infected or tumor cells Eosinophils Inflammation Defense against parasites Phagocytosis, activation of naive T-cells Cell type Pricipal function(s)
  • 12. AntigensAntigens Some chemical that creates immune response Most are proteinsproteins or large polysaccharidespolysaccharides from a foreign organism. – MicrobesMicrobes: Capsules, cell walls, toxins, viral capsids, flagella, etc. – NonmicrobesNonmicrobes: Pollen, egg white , red blood cell surface molecules, serum proteins, and surface molecules from transplanted tissue.
  • 13. EpitopeEpitope: AntigensAntigens Small part of an antigen that interacts with an antibody. 10-12 amino acids Any given antigen may have several epitopes. Each epitope is recognized by a different antibody.
  • 14. AntigensAntigens Some chemical that creates immune response Most are proteinsproteins or large polysaccharidespolysaccharides from a foreign  organism. – MicrobesMicrobes:    Capsules,  cell  walls,  toxins,  viral  capsids,  flagella, etc. – NonmicrobesNonmicrobes:  Pollen,  egg  white  ,  red  blood  cell  surface  molecules,  serum  proteins,  and  surface  molecules from transplanted tissue.  – Lipids  and  nucleic  acids  are  only  antigenic  when  combined with proteins or polysaccharides.
  • 15. Cont…. • Epitope (Antigenic Determinant) – Specific site on Ag that is recognized by the           immune system, where Ab binds • Hapten: Small  foreign  foreign  molecule  that  is  not  antigenic antigenic. Must be coupled to a carrier molecule  to  be  antigenic.  Once  antibodies  antibodies  are  formed  they will recognize hapten. Karl Landsteiner Landsteiner discovered Hapten, who also discovered blood group antigen and got noble prize.
  • 16. Epitopes: Antigen Regions that Interact with Antibodies
  • 17. AntibodiesAntibodies • Proteins Proteins  that  recognize  and  bind  to  a  particular antigen with very high specificityspecificity. • Made  in  response  to  exposure  to  the  antigen. • One  virus  or  microbe  may  have  several  antigenic determinant sitesantigenic determinant sites,  to  which  different antibodies may bind. • Each  antibody  has  at  least  two  identical  sites  that  bind  antigen:    Antigen bindingAntigen binding sitessites. • Belong to a group of serum proteins called  immunoglobulins (Igs).immunoglobulins (Igs).
  • 19. How Do B Cells Produce Antibodies?How Do B Cells Produce Antibodies? – B cells develop from stem cellsstem cells in the bone marrow of adults (liver of fetuses). – After maturation B cells migrate to lymphoid organs (lymph node or spleen). – Clonal SelectionClonal Selection: When a B cell encounters an antigen it recognizes, it is stimulated and divides into many clones called plasma cellsplasma cells, which actively secrete antibodies. – Each B cell produces antibodies that will recognize only one antigenic determinant.
  • 20.
  • 21. Immunoglobulin • Heavy Chain – 110 amino acids longHeavy Chain – 110 amino acids long – 100 distinct V segments100 distinct V segments – 30 D segments30 D segments – 6 J segments6 J segments – Enzymes choose one V segment, one D segment and one JEnzymes choose one V segment, one D segment and one J segment and fuse them togethersegment and fuse them together – 18,000 combinations in encoding antibody molecule18,000 combinations in encoding antibody molecule – Splice this variable region to the constant regionSplice this variable region to the constant region • Light Chain – 211 amino acids longLight Chain – 211 amino acids long – 10,000 combinations10,000 combinations – Total of 180,000,000 distinct B cellsTotal of 180,000,000 distinct B cells • Fusion is sloppy, can create other variantsFusion is sloppy, can create other variants
  • 22.
  • 23. Classes of Antibodies (Immunoglobulins)
  • 24. Immunity and Immune Response Made up of two cellular systems: • Humoral or circulating antibody system – B cells • Cell mediated immunity – T cells
  • 25. Overview of the Immune Response
  • 26. Humoral or B-Cell Mediated Immune Response Produces secreted antibodies (proteins) • Bind to antigens and identify the antigen complex for destruction. • Antibodies act on antigens in the serum and lymph • B-cell produced antibodies may be – attached to B-cell membranes or – Free in the serum and lymph. • Each B lymphocyte makes a unique antibody molecule (immunoglobulin or Ig) • Over a million different B lymphocytes are produced in each individual – So, each individual can recognize more than a million different antigens
  • 27. Cell Mediated Immune System: T lymphocytes • T-cells mature in the thymus (thus the name T-cell) • Act on antigens appearing on the surface of individual cells. • Over a million different kinds of T-cells – Each produces a different receptor in the cell membrane – Each receptor is composed of 1 molecule each of two different proteins – Each receptor binds a specific antigen but has only one binding site – Receptor only recognizes antigens which are "presented" to it within another membrane protein of the MHC type (major histocompatibility complex) • Recognizes specific antigens bound to the antigen- presenting structures on the surface of the presenting cell. • Recognizes antigens presented by B-cells, macrophages, or any other cell type
  • 28. T Cells and their Functions • Have a specific receptor for a fragment of antigen • Cytotoxic T-cells: – Contain a surface protein called CD8 – Destroy pathogen infected cells, cancer cells, and foreign cells (transplanted organs) • Helper T-cells: – Contain a surface protein called CD4 – Regulate both cellular and humoral immune systems – This regulation reduces autoimmunity.
  • 29. Central Role of Helper T Cells
  • 30. Cytotoxic T Cells Lyse Infected Cells
  • 31. Antigen-Antibody Interactions • Quality and quantity are important in resolution of disease • May contribute to pathology • Useful in immunological assays
  • 33. Agglutination RBC RBC RBC RBC IgM AntibodyIgM Antibody IgG AntibodyIgG Antibody RBC RBCRBC RBC RBC RBCRBC
  • 34. Enzyme (ELISA) Immunoassay AntigenAntigen anti-antigen antibody Enzyme conjugated to anti-Ig antibody (“second antibody”) Add substrate for enzyme

Editor's Notes

  1. Study Guide Why do soluble antigens and antibodies precipitate?
  2. Study Guide What is the difference between precipitation and agglutination?
  3. Study Guide Radioimmunoassays (RIA) and Immunfluorescence Assays (IFA) depend on the detection of a radionuclide or a fluorescent probe attached to the second antibody, instead of the enzyme. In those cases, no substrate is needed. How would you use this assay to measure the concentration or detect the presence of an antigen?