Lecture 19

• adaptive immunity branches

  humoral

  cell-mediated
• humoral

  involves antibodies made by B cells

  depends against extracellular pathogens
• cell-mediated

  involves T cells

  largely defends against intracellular pathogens
• antibodies (immunoglobin)

  proteins made by B cells

  found in blood, mucosal surfaces and tissues

  bind antigens - neutralize or opsonize
• affinity

  strength that antibody binds antigen
• epitopes

  parts of an antigen that antibodies bind

  one antigen can have several epitopes, each can bind a different antibody
• 5 antibody classes/ isotypes

  IgM, IgG, IgA, IgE, IgD
• IgM

  first Ig after antigen exposure, IgM secreting plasma cells can switch and produce another Ig class
• IgG

  Major If in blood, can cross placenta, can activate complement
• IgA

  major Ig in secretions (saliva, breast milk, tears)
• IgE

  allergic reactions
• IgD

  found on B cell surfaces, role in signaling
• Half life of Ig

  days

  most stable at about 20 days
• antibody classes

  have unique superstructures

  all antibodies have the same basic structure

  4 polypeptide chains

  • 2 identical heavy and 2 light
• monomer

  IgD, IgE, IgG

  
• dimer

  IgA

  
• pentamer


  IgM

  
• basic structure of an antibody

  antibody classes (isotopes) differ in Fc region

  bottom region can bind Fc receptor on other cells

  A) heavy

  B) light

  C) fab fragment

  D) antigen binding site

  E) variable region

  F) constant region

  G) Fc fragment

  
• from birth, our naive immune system is able to recognize millions of possible foreign antigens
• VDJ recombination

  major mechanism of naive immune system that involves the rearrangement of antibody gene segments

  process occurs during clonal selection
• clonal selection p1

  random rearrangement of antibody gene segments occurs as B cells develop in the bone marrow, early in embryonic life, before infection

  generates vast array of B cells, each preprogrammed to bind a specific antigen

  tolerance
• tolerance


  removal of self-reactive B cells
• clonal selection

  remaining B cells travel to lymphoid organs and tissues

  upon infection, antigen "selects" B cell with antibody that matches it

  B cell proliferates, forming clone of identical cells, each with antibody for the antigen
• clonal selection diagram step 1

  single progenitor cell gives rise to a large number of lymphocytes, each with a different specificity

  A) B cell

  B) antibodies

  
• clonal selection diagram p2

  removal of potentially self-reactive immature lymphocytes by clonal deletion (tolerance)

  removal of B cells recognizing self antigens

  largely occurs in bone marrow

  breakdown is one basis of autoimmunity

  A) self antigens

  
• clonal selection diagram p3

  pool of mature naive lymphocytes

  infection

  A) foreign antigen

  
• clonal selection diagram p4

  proliferation and differentiation of activated specific lymphocytes to form a clone of effector cells

  A) effector cells

  
• adaptive immunity has specificity and memory

  primary and secondary response

  lag phase: 4-10 days

  antigens A + B: faster, greater, memory B cells activated, basis of immunization

  A) Days

  
• T cells

  originate in bone marrow, mature in thymus

  activated when their receptors bind antigens presented by other cells

  helper T cells and cytotoxic T cells
• helper T cells

  make cytokines, activate B cells, macrophages, or other T cells
• cytotoxic T cells

  kill cells expressing foreign antigens used

  preforins: form spores

  granzymes: induce apoptosis
• Cluster of differentiation (cd) molecules

  in addition to specific receptors, immune cells have other membrane proteins called CDs that can function as co-receptors

  CD molecules can also be used to determine a cell's identity
• T cell receptors

  bind antigens (usually peptides) presented to them by other cells, but only when presented by MHC molecule

  expressed from gene segments rearranged in thymus
• MHC

  collection of genes encoding cell surface proteins for self/nonself recognition

  in humans: HLA complex, 2 sets of MHC genes (one from each parent)

  closer 2 people related, more similar their HLA's, important in donor selection for tissue, bone marrow and organ transplant (HLA typing)
• HLA

  human leukocyte antigen
• class 1 mhc

  on all nucleated cells

  present peptides that originate in cytoplasm from intracellular pathogens

  present peptides to CD8 Cytotoxic cells
• Class 2 MHC

  only on antigen presenting cells (dendritic cells, macrophages, B cells)

  present peptides from extracellular pathogens, taken up by phagocytosis
• MHC 1 and 2 inform the immune system of the presence of nonself (pathogen) by binding and presenting foreign peptides
• antigen processing

  dendritic cells take up pathogen for degradation

  pathogen is taken apart inside dendritic cell

  pathogen proteins are unfolded and cut into small pieces

  peptides bind MHC molecules and complexes go to cell surface

  TCRs bind to peptide, MHC complexes on dendritic cell surface (antigen presentation)

  peptides are 8-25 amino acids
• nucleated target cell

  MHC class 1

  T cell releases granzymes, preforins

  target cell with intracellular pathogen killer

  A) CD8

  B) peptide

  C) TCr