Lecture 9 - Adaptive Immunity and Antibodies

Unit II introduction

  • dendritic cells are phagocytic cells that engulf pathogen to display parts to B and T cells

    • follicle dendritic cells are in lymph nodes and bits are exposed within the lymph for B and T cells to recognize

    • B cells develop in bone marrow → travel to lymph nodes and stay; do not always depend on dendritic cells; secondary lymphoid organs are where they see bugs

    • T cells develop in thymus → these cells depend on dendritic cells to see pathogen and become activated and stimulate division to become effector T cells; migrate to infection site to kill pathogen

Basic functions of B cells and T cells

  • B cells

    • humoral immunity

    • generate antibodies

    • memory B cells store memory

  • T cells

    • cell-mediated immunity

    • Tc cells directly kill infected or tumor cells

    • TH cells activate other immune cells

      • secrete cytokines to direct cytotoxic T cells like NK cells to kill infectious agent/ infected cells

    • T cells can also store memory

Immunoglobins

  • Ig: BCR or Ab

  • B cell receptor (BCR): membrane-bound immunoglobin

    • what mediates an Ab being secreted vs staying a BCR?

      • hydrophobic region embeds in the membrane of B cell and gets cleaved; facilitates survival in water

  • Antibody: secreted immunoglobins

  • same genetic loci

    • during transcription and translation, one is made as a membrane bound receptor and the other as a secreted protein complex

  • antigen: any molecule that can be bound by an antibody, B cell receptor or T cell receptor

    • B cell receptors/Ab can bind any type of macromolecular antigen

    • T cell receptors can only bind protein-based antigens

  • epitope: the specific piece of the antigen that is directly bound

  • affinity: describes the strength of the antigen-antibody interaction

    • strong bind = higher affinity

    • Ab and antigens interact through NCI’s such as electrostatic forces, hydrogen bonds, van der waals force, and hydrophobic interactions

Ig basic structure

  • variable region binds the antigen; both regions are identical

    • complementarity-determining regions (CDRs) are critical for conferring antigen binding specificity

  • constant region is recognized by other immune cells or other immune molecules or intracellular signals

  • many immune receptors include Ig domains

  • Ig protein structure

    • 4 polypeptide chains (2 heavy and 2 light)

    • can be produced in a membrane-bound or secreted form

    • Fc receptor complement binding site is present on constant region

Major functions of antibodies against pathogens

  • neutralization

    • since a potential entry method of bacteria and viruses is to bind to cell surface receptors and induce endocytosis, neutralizing antibodies bind to pathogens and prevent entry

      • these Ab can also neutralize pathogen-derived toxins

  • agglutination

    • Ab bind to multiple antigens and cross-link them

    • any pathogens that are agglutinated can efficiently be removed through ciliary movements or peristalsis

  • opsonization

    • covering a microbe in antibodies or recognizable components to signal phagocytosis

  • complement activation

    • antibody binding initiates the classical complement pathway and deposits complement components on pathogens

      • this enhances opsonization and phagocytosis for degradation

  • antibody-dependent cell-mediated cytotoxicity

    • infected or tumor cells express antigens signaling distress

      • antibodies bind these ligands; NK cells or cytotoxic T cells recognize the Fc region via Fc receptors (e.g., FcγRIII/CD16) and kill the bound target cell

      • depends on both antibodies and effector cells.

    • antibodies recognize and bind to tumor antigens or virus proteins on an infected cell

    • cytotoxic immune cells recognize the Fc region of the antibodies, bind and kill the target cell

  • degranulation

    • granulocytes such as neutrophils, mast cells, basophils, and eosinophils recognize coated pathogens through Fc receptors

Immune cells bind antibodies through Fc receptors

  • Fc = fragment crystallized

  • Fab = fragment antigen binding

  • Fc receptors use antibodies to move across cells (transcytosis)

    • from blood to extracellular space and into the lumen of the gut