Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Humoral immunity

22,637 views

Published on

Humoral immunity

Published in: Health & Medicine, Technology

Humoral immunity

  1. 1. Humoral Immunity Antibody Mediated Dr.T.V.Rao MD Dr.T.V.Rao MD 1
  2. 2. Humoral Immunity• Results in production of proteins called “immunoglobulins” or “antibodies”.• Body exposed to “foreign” material termed “antigen” which may be harmful to body: virus, bacteria, etc.• Antigen has bypassed other protective mechanisms, ie, first and second line of defense. Dr.T.V.Rao MD 2
  3. 3. WHAT ARE ANTIBODIES?• Antigen specific proteins produced by plasma cells• Belong to immunoglobulin superfamily• Located in blood and extravascular tissues, secretions and excretions• Bind pathogenic microorganism and their toxins in extracellular compartments• Secreted form of immunoglobulins Dr.T.V.Rao MD 3
  4. 4. CLASSES (ISOTYPES) OF IMMUNOGLOBULINS• Classes based on constant region of heavy chains – Immunoglobulin A (IgA) – Immunoglobulin D (IgD) – Immunoglobulin E (IgE) – Immunoglobulin G (IgG) – Immunoglobulin M (IgM)• Differentiation of heavy chains – Length of C region, location of disulfide bonds, hinge region, distribution of carbohydrate• Classes have different effector functions Dr.T.V.Rao MD 4
  5. 5. Different classes of Antibodies Dr.T.V.Rao MD 5
  6. 6. Structural configuration of Antibody Dr.T.V.Rao MD 6
  7. 7. THREE DIMENSIONAL STRUCTURE OF ANTIBODIES• Antibodies function in setting of infectious process – Proteolytic enzymes, salt and pH differences• Antibodies remain stable based on – Sequence of domains• Single domain consists of – 100 – 110 amino acids folded into compact and stable conformation• Domains – Variable (V) • Single V domain in H and L chains – Constant (C) • Single C domain in L chains • Three to four (C) domains in H chains Dr.T.V.Rao MD 7
  8. 8. Antibodies are Produced by B Lymphocytes Dr.T.V.Rao MD 8
  9. 9. Immunoglobulin ClassesI. 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. Dr.T.V.Rao MD 9
  10. 10. Immunoglobulin ClassesII. 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. Dr.T.V.Rao MD 10
  11. 11. Immunoglobulin ClassesIII. 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. Dr.T.V.Rao MD 11
  12. 12. Immunoglobulin ClassesIV. 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. Dr.T.V.Rao MD 12
  13. 13. Immunoglobulin ClassesV. 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. Dr.T.V.Rao MD 13
  14. 14. CLASSES (ISOTYPES) OF IMMUNOGLOBULINS• Additional classification based on light chains – Kappa – Lambda• Each IG has either kappa or lambda, not both – IgG kappa – IgG lambda• No functional differences between light chains Dr.T.V.Rao MD 14
  15. 15. B Cell Receptors for Antigens• B cell receptors – Bind to specific, intact antigens – Are often called membrane antibodies or membrane immunoglobulins Antigen- Antigen- binding binding site site Disulfide bridge Light Variable chain regions Constant C C regions Transmembrane region Plasma membrane Heavy chains B cell Cytoplasm of B cell (a) A B cell receptor consists of two identical heavy chains and two identical Dr.T.V.Rao MD light chains linked by 15 several disulfide bridges.
  16. 16. Antibodies bond to antigenic determinants Antigenic determinants are portions of the antigen Dr.T.V.Rao MD 16
  17. 17. Antibodies are Proteins that Recognize Specific Antigens Dr.T.V.Rao MD 17
  18. 18. Epitopes: Antigen Regions that Interact with Antibodies Dr.T.V.Rao MD 18
  19. 19. Dynamics of Antibody Production• Primary immune response – Latent period – Gradual rise in antibody production taking days to weeks – Plateau reached – Antibody level declines Dr.T.V.Rao MD 19
  20. 20. Secondary Response• Second exposure to SAME antigen.• Memory cells are a beautiful thing.• Recognition of antigen is immediate.• Results in immediate production of protective antibody, mainly IgG but may see some IgM Dr.T.V.Rao MD 20
  21. 21. Dynamics of Antibody Production• Antibody production – Initial antibody produced in IgM – Lasts 10-12 days – Followed by production of IgG – Lasts 4-5 days – Without continued antigenic challenge antibody levels drop off, although IgG may continue to be produced. Dr.T.V.Rao MD 21
  22. 22. • In the secondary immune response – Memory cells facilitate a faster, more efficient response1 Day 1: First 3 Day 28: 4 Secondary response to anti- 2 Primary exposure to Second exposure gen A produces antibodies response to antigen A to antigen A; first to A; primary response to anti- antigen A produces anti- exposure to gen B produces antibodies to B bodies to A antigen B 104 Antibody concentration 103 (arbitrary units) 102 Antibodies Antibodies to A to B 101 100 0 7 14 21 28 35 42 49 56 Time (days) Dr.T.V.Rao MD 22
  23. 23. THE PRIMARY HUMORAL IMMUNE RESPONSE• Immune response initially produces IgM antibodies then switches to IgG antibodies• Question – Why switch from IgM to IgG?• Answer – Limited effector mechanisms for IgM – Range of effector mechanisms for IgG• Mechanism – Isotope or class switching Dr.T.V.Rao MD 23
  24. 24. Humoral (antibody-mediated) Immunity IL 1 Autocrine IL 2 stimulation Dr.T.V.Rao MD 24
  25. 25. ISOTYPE OR CLASS SWITCHING• Process by which B cell changes class of IG produced while preserving antigenic specificity• Involves somatic recombination which attaches different heavy chain constant region to variable region• Occurs only during active immune response• Mechanisms involves recombination between – Switch sequences (regions) Dr.T.V.Rao MD 25
  26. 26. • Clonal selection of B cells – Generates a clone of short-lived activated effector cells and a clone of long-lived memory cells Antigen molecules Antigen molecules bind to the antigen B cells that receptors of only one differ in of the three B cells antigen shown. specificity Antigen receptor The selected B cell proliferates, forming a clone of identical cells bearing receptors for the selecting antigen. Some proliferatingSome proliferating cells cells develop into develop into long-lived Antibody short-lived plasma memory cells that can molecules cells that secrete respond rapidly upon antibodies specific subsequent exposure for the antigen. to the same antigen. Clone of memory cells Dr.T.V.Rao MD Clone of plasma cells 26
  27. 27. Humoral (antibody-mediated) Immunity Memory Cells Dr.T.V.Rao MD 27
  28. 28. Benefits of Immunological Memory Dr.T.V.Rao MD 28
  29. 29. Clonal Selection Only one type of antibody—and one type of B cell— responds to the antigenic determinant That cell type then produces a large number of clonesDr.T.V.Rao MD 29
  30. 30. FUNCTIONS AND PROPERTIES OF ANTIBODY• Neutralization – Direct inactivation of pathogen or toxin thereby preventing its interaction with human cells• Opsonization – Coating of pathogens for more efficient phagocytosis• Activation of complement – More efficient phagocytosis – Direct killing Dr.T.V.Rao MD 30
  31. 31. DIVERSIFICATION OF ANTIBODIES AFTER B-CELLS ENCOUNTER ANTIGEN• Mature, naïve B cell has membrane bound IgM and IgD antigen receptors• Binding of antigen initiates proliferation and differentiation of B-cells into plasma cells• During differentiation, B cells switch from making immunoglobulin to antibody M and D isotypes• IgM – Produced in large amounts – Provides protective immunity• IgD – Produced in small amounts – No known function Dr.T.V.Rao MD 31
  32. 32. DIVERSIFICATION OF ANTIBODIES AFTER B-CELLS ENCOUNTER ANTIGEN• Following antigen activation of B- cells, additional diversification occurs in V domain by – Somatic hyper mutation• Somatic hyper mutation – Introduction of random single nucleotide substitutions (point mutations) throughout V regions of H and L chains – Mechanism poorly understood – More common in hyper variable regions (CDRs) Dr.T.V.Rao MD 32
  33. 33. OUTCOME OF SOMATIC HYPERMUTATION• Gives rise to some antibodies with higher – Affinity for antigen• Affinity – Strength of binding of one molecule to another by a single binding site• Higher affinity antibodies are produced as immune response proceeds – Affinity maturation Dr.T.V.Rao MD 33
  34. 34. IgM ANTIBODY OF THE IMMUNE RESPONSE• First isotype produced in primary response – May or may not be produced in secondary response – Produced before B cells undergo somatic hypermutation• Occurs as pentamer with J chain – Found primarily in blood and lymph• Multiple binding sites confers high avidity and compensates for low affinity of monomers• Highly effective in complement activation• Functions as rheumatoid factor Dr.T.V.Rao MD 34
  35. 35. IgG ANTIBODY OF THE IMMUNE RESPONSE• Second isotype produced in primary response• Primary isotype of – Secondary immune response – Memory immune response• Represents approximately 75% of total serum IG• Four subclasses (1-4) – Different effector functions• Transported across placenta• Functions as rheumatoid factor Dr.T.V.Rao MD 35
  36. 36. IgA ANTIBODY OF THE IMMUNE RESPONSE• Two subclasses (IgA1 and IgA2) and two forms (monomeric and dimeric)• Monomeric – Located in blood and extracellular spaces – Predominately IgA1 • Ratio of IgA1 to IgA2 is 10:1 – Functions as rheumatoid factor• Dimeric – Located in mucous membranes and secretions – Predominately IgA2 – Ratio of IgA2 to IgA1 is 3:2 – J chain like IgM Dr.T.V.Rao MD 36
  37. 37. IgE AND IgD ANTIBODIES OF THE IMMUNE RESPONSE• IgE – Binds with high affinity to receptors on mast cells, basophils and activated Eosinophils – Longer half-life when cell bound – Initiates a strong inflammatory reaction to parasites – Involved in allergic reactions• IgD – Antigen receptor on mature B-cells – No other known function Dr.T.V.Rao MD 37
  38. 38. Immunological MemoryAntibody Titer: The amount of antibody in the serum.Pattern of Antibody Levels During InfectionPrimary Response:– After initial exposure 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. Dr.T.V.Rao MD 38
  39. 39. 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. Dr.T.V.Rao MD 39
  40. 40. ANTIBODIES AS DIAGNOSTIC AND THERAPEUTICS AGENTS• Based on specificity and affinity of antibodies• Both applications require large quantities of identical antibodies – Monoclonal antibodies• Monoclonal antibodies are produced using hybridoma cell line• Hybridoma cell line – Derived from single antibody producing cell fused with myeloma cell (neoplastic plasma cell) Dr.T.V.Rao MD 40
  41. 41. • Programme Created By Dr.T.V.Rao MD for basic learning for Medical and Paramedical Students in the Developing World • Email • doctortvrao@gmail.com Dr.T.V.Rao MD 41

×