1 / 51

MICR 201 Microbiology for Health Related Sciences

Lecture 10: Adaptive Immunity Edith Porter, M.D. MICR 201 Microbiology for Health Related Sciences. Lecture outline. Concept of immunity Innate immunity Adaptive immunity Humoral and cellular adaptive immunity Antigens and antibodies B cells and humoral immunity

eris
Download Presentation

MICR 201 Microbiology for Health Related Sciences

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Lecture 10: Adaptive Immunity Edith Porter, M.D. MICR 201 Microbiology for Health Related Sciences

  2. Lecture outline • Concept of immunity • Innate immunity • Adaptive immunity • Humoral and cellular adaptive immunity • Antigens and antibodies • B cells and humoral immunity • Effects of antigen-antibody binding • T cells and cellular immunity • Antigen presenting cells • Cytokines • Immunological memory

  3. Overview of host defenses First Line of Defense Second Line of Defense • NK cells

  4. Concept of immunity Innate immunity Adaptive immunity Acquired, available within days High specificity Memory In higher vertebrates • Functional at birth • Rapid responses: preformed or available within hours after infection • Limited specificity: pattern recognition via toll like receptors • Widely present in nature including in plants, invertebrates and vertebrates

  5. Humoral and cellular immunity The thymus is located in mediastinum • Humoral immunity • Transferable with serum • Highly specific • Mediated by antibodies and lymphocytes who produce these antibodies • These types of lymphocyte mature in the bone marrow and are called B lymphocytes (B cells) • Cellular immunity • Mediated by lymphocytes that mature in the thymus and are called T lymphocytes (T cells) • T cells orchestrate the immune response

  6. Lymphocytes http://www.aamdsglossary.co.uk/i/c/1_2_lymphocytes.jpg

  7. Differentiation of B and T cells B for Bone marrow T for Thymus

  8. The lymphatic system Primary Lymphatic tissue Secondary Lymphatic Tissue Antigen contact Spleen Lymph nodes Peyer’s patches Mucosa associated lymphatic tissue (MALT) • Lymphocyte formation and maturation • Bone marrow • Thymus

  9. Main tasks of lymphocytes • Recognize foreign agents (antigen) • Lymphocytes carry specific antigen receptors on their surface • B-cell receptor, T-cell receptor • Block and eliminate foreign agents • Through antibodies • By activating host defense cells via cytokines • By destroying infected host cells that have been taken over by infectious agents

  10. Antigen • Substances that causes the body to produce specific antibodies • Any molecule that can be recognized by and bound to an antibody (“antibody generating”) or a T cell • Typically proteins and carbohydrates • Epitop(or antigenic determinant) is part of the antigen and is the specific region with which an antibody interacts

  11. Antigenic Determinants

  12. Haptens • A molecule too small to stimulate antibody formation by itself • When combined with a larger carrier molecule it can initiate antibody production • Once antibodies are generated, hapten can be recognized by itself Example: Penicillin

  13. Antibodies • Globulin proteins (immunoglobulins or Ig) • Made in response to an antigen • A bacterium or virus has many antigenic determinants against which antibodies can be made • Bi-functional • One portion binds specifically to particular structures called antigen • The other part interacts with host cells

  14. Antibody structure • 2 heavy chains • 2 light chains • Connected with disulfide bridges • Variable regions in heavy and light chains: bivalent antigen binding sites, mediate specificity • Constant regions on heavy chain mediate effector function

  15. Antibody classes • Each class shares the constant region of the antibody molecule but has many different variable regions • Each class interacts with different types of host cells • Differ in their effector function • 5 classes: • IgG • IgM • IgA • IgD • IgE

  16. IgGantibodies • Monomer • 80% of serum antibodies • Fix and activate complement (classical pathway) • In blood, lymph, intestine • Cross placenta • Opsonin (enhance phagocytosis); neutralize toxins & viruses; protect fetus & newborn

  17. IgMantibodies • Pentamer • 5-10% of serum antibodies • FirstIg of an immune response • Fix and activate complement (classical pathway) • In blood, lymph, on B cells • Agglutinatesmicrobes

  18. IgAantibodies • Dimer • 10-15% of serum antibodies • In secretions(milk!!) • Protectionof mucosa • Mucosal pathogens like Haemophilus or Neisseria secrete IgA proteases

  19. IgDantibodies • Monomer • 0.2% of serum antibodies • Mainly on B cells • Maturation sign

  20. IgEantibodies • Monomer • ~0.002% of serum antibodies • Mainly on mast cells,basophils,and activatedeosinophils • Allergic reactions; defense against parasitic worms

  21. B cells • Bone marrow gives rise to B cells (B-lymphocytes) • Naïve but mature B cells migrate to secondary lymphatic tissue and become exposed to antigen • B cells recognizes epitopes with antigen specific B cell receptor • Each B-cell expresses a unique B cell receptor on its surface • B-cell receptor is actually the antibody produced by a particular B cell

  22. Consequences of antigen recognition by B cells • Clonal selection and expansion • Increased antibody production • Plasma cell or memory cell development

  23. Clonalselection and differentiation of B cells A clone originates from a single cell

  24. Effectorfunction of antibodies • Begin after antigen-antibody complex has been formed • Aggluntination • Opsonization • Enhanced phagocytosis • Complement activation • Opsonization and enhanced opsonophagocytosis via c3b • Microbial lysis through C5b-C9n • Inflammation through C5a, C3a, C4a • Neutralization • Toxins • Viruses • Antibody dependent cytotoxicity • Eosinophils: secrete toxic granules onto helminths • NK cells: induce apoptosis of virus infected cells

  25. Effector functions of antibodies

  26. Anti-helminthiccytotoxicity of eosinophils

  27. Natural killer cells • Large granular lymphocyte-like cells • Part of first line of defense (innate immunity) • Activated by interferons (produced by virus infected cells) and other cytokines • Target altered host cells • Virus infected • Infected with intracellular organism • Tumor cells • Induce cell suicide (apoptosis) • Cells covered with antibodies (antibody dependent cytotoxicity) • Direct sensing of altered cells

  28. The kiss of death Tumor Cell • After NK cell have recognized their target they release their large granules containing • Pore-forming toxins • Enzymes that induce suicide of target cell NK-Cell t0 t60’

  29. T-cell mediated immunity • After differentiating in the thymus, T cells migrate to lymphoid tissue • T cells become activated effector T cells when stimulated by an antigen • T cells respond to digestedantigens via T-cell receptor • T cells recognize antigen only when presented by other cells on special molecules • Major histocompatibility complex (MHC) • Some effector T cells become memory cells

  30. T-Ly T-cell antigens • Short contiguous amino acid (aa) sequence • Processed antigens • Antigen must have been unfolded and degraded • Primary aa structure • Only when bound to a specialized antigen presenting molecule (MHC) MHC APC

  31. MHCmolecules • Major HistocompatibilityComplex • Same as HLA (human leukocyte antigen) • Determine compatibility of donor and recipient in transplantation • Every individual as a unique set of MHC molecules • Within an individual all cells are equipped with the same set • Have a peptide binding groove onto which antigen can be loaded • MHCI: peptides newly synthesized and degraded in cytoplasma (endogenous) • MHC II: peptide fragments generated in phagolysosome (exogenous)

  32. Classification of T cells • Depends on surface molecules on T cells that determine the interaction with MHC molecules and their type of response • Cytokine release • Sending trigger to target cell to commit cell suicide • T helper cells • Cytotoxic T cells (“T killer cells”) • Regulatory T cells

  33. T-helper cells • Express the surface molecule CD4 • Recognizes exogenous digested antigen presented on MHC type II molecule • Interact with antigen presenting cells • Macrophages • Dendritic cells • B-cells • Respond with secretion of cytokines and activate immune cells

  34. Antigen presenting cells • Express MHC II • Highly specialized in uptake of foreign antigen, degradation and presentation to T helper cells via MHC II • Macrophages and dendritic cells • Take up antigen via phagocytosis • B cells • Bind antigen with surface antibody and internalize the complex

  35. The CD4 : MHC II Interaction TH Cell Cytokines TCR CD4 Digested Ag MHC II Microbe Ag Presenting Cell

  36. T helper cells in action

  37. T helper cell subclasses • TH1 • Secrete the cytokine IFNg • Activates macrophages • Promotes IgG antibody production in B cells • TH2 • Secrete the cytokine IL4 • Promotes IgE production in B cells • Pro-allergic

  38. Cytotoxic T cells • Express the surface molecule CD8 • Recognizes endogenous antigen presented on MHC type I molecule • Can interact with any nucleated cell • Respond with secretion of perforin and granzyme • Kill target cells via apoptosis in a highly specific manner

  39. The CD8 : MHC I Interaction CTL TCR CD8 Endogenous Ag MHC I Endogenous Ag Any Nucleated Cell

  40. CTL mediated cytotoxicity

  41. Regulatory T cells • Treg and TH3 • Differentiate from T helper cells • Turn off immune response when Ag no longer present • Use inhibitory cytokines (IL10)

  42. Summary for cell mediated immunity

  43. Principals cells in the adaptive immune response

  44. Summary for cytokines

  45. Superantigens • Activate simultaneously up to 20% of all TH cells • Cause an intense immune response due to release of cytokines from host cells (“cytokine storm”) • Fever, nausea, vomiting, diarrhea, sunburn-like rash, shock, death • Examples : Toxic Shock Syndrome Toxin

  46. Immunological memory • Once lymphocytes have encountered their specific antigen they undergo clonal expansion • Some of these cells develop further into memory cells • Can circulate for many years • Upon re-contact with the same antigen they quickly proliferate and resume effector function • B cells: antibody production • T cells: cytokine production (TH, Treg) and cytotoxicity (CTL)

  47. Example: Primary and secondary immune responses to an antigen • IgM is always the first antibody • IgG follows IgM • IgG level does not go back to baseline • Re-exposure to the same antigen will lead to an augmented and accelerated immune response with higher residual antibody levels

  48. Types of adaptive immunity

  49. Important to remember • Key players in adaptive immunity • Antibodies • B-cells • T-cells • Lock- key principle: Ag-Ab • B cells make antibodies • 5 Types of antibodies : IgM (first), IgG (placenta), IgD (maturation), IgA (mucosa), IgE (allergies) • Antibodies can agglutinate, activate complement, promote phagocytosis, neutralize and initiate cell lysis by NKcells • T cells recognize digested antigen when presented to them on MHC molecules • Main effector T-cells • Helper T-cells: strengthen defense cells • Cytotoxic T-cells: kill infected cells • Regulatory T cells: down regulate immune response • Cytokines serve cell-to-cell communication

More Related