Adaptive Immunity

• Innate Immune System

  • PRRs recognize broadly-conserved PAMPs
  • PAMPs are molecules that are essential for pathogen survival
  • limited specificity
  • broad cross-reactivity across many pathogens
  • perfect self: non-self discrimination
  • common to many lifeforms
  • immediate response
  • no memory
• Adaptive Immune System

  • B cells and T cells have receptors that can recognize specific antigens
  • antigens can be any kind of molecule
  • protein/lipid/carb
  • receptors are generated by recombining a few genes
  • almost unlimited repertoire of specificities
  • extremely narrow cross-reactivity
  • very specific
  • mistakes are uncommon
  • REALLY good, but imperfect self: non-self discrimination
  • mistakes can happen
  • restricted to jawed vertebrates
  • initial responses are slow
  • 3-5 days to initiate
  • memory
• why is innate immunity important?

  without an immune system, you cant get on top of the infection, and thats why you need the connection between the innate and adaptive systems
• the adaptive system finds and eliminates with precision, almost any pathogen or abnormal cell
• 3 key features of the adaptive immune system

  1. it is specific
  2. directly against particular pathogens or foreign substances that initiated an innate, non-specific response
  3. it is systemic
  4. not restricted to the initial infection site
  5. it has memory
  6. after an initial exposure (where the system is "primed") subsequent responses are faster and stronger

  • ANTIGEN RECOGNITION is required for these features to occur
• Cells of the adaptive immune system

  • B cells
  • T cells (lymphocytes)
• B cells and T cells (lymphocytes)

  • both derived from the common lymphoid progenitor in the red bone marrow
  • B cells stay and develop in the Bone marrow
  • T cells go and develop in the Thymus
  • develop immunocompetence and learn self-tolerance
  • naïve B and T cells (never seen antigen before) travel to lymph nodes to away antigen exposure
• why are B and T cells special?

  • some have a very long life-span (plasma cells/memory T cells)
  • can divide/regenerate rapidly
  • each cell has a unique receptor to recognize antigen
• B cell receptor

  • 2 antigen recognition sites
  • can be membrane bound (i.e. be the BCR) or released as antibody (Ab)
  • variable regions make up the binding sites
• T cell receptor

  • 1 antigen recognition site
  • membrane bound
  • variable regions make up the binding sites
• antibodies can be secreted by B cells

  • can also be found on the surface of a B cell
  • if they bind to the surface of the antigen, then they are a receptor
• How are the B and T cell receptors so specific?

  • by rearranging and recombine a few genes
  • almost unlimited number of combination
• CD4 and CD8 T cells are named after the type of molecule that pairs with the T cell receptor (TCR)
• CD4

  • helper T cell
  • the TCR recognizes antigens presented on MHCII
  • help activate B cells
• CD8

  • cytotoxic T cell
  • TCR recognizes antigens presented on MHCI
  • kill infected altered cells
• Antigen (Ag)

  • any molecule that can bind specifically to an antibody
  • "antibody generating"
  • may be a pathogen or a toxin, also can be non-toxic foreign molecules (ex. food antigens) or self molecules presented at the wrong time/place
  • ex. bacterial structures, bacterial toxins, pollens, dust, egg albumin, incompatible blood or tissue cells
  • may be proteins, polysaccharides or (sometimes) lipids
• Epitope

  • part on antigen that does the binding
  • can induce an immune response by binding an antibody or receptor on a B or T cell
  • most antigens will have several epitopes
  • also called antigenic determinants
• Professional Antigen Presenting Cells (APCs)

  • process and display antigenic peptides on cell-surface molecules
  • activate T cells
  • can do this because of the presence of MHC class II on the surface
  • dendritic cells (DCs) are best at being APCs
  • macrophages can be APCs too, but they're better phagocytes
• Major Histocompatibilty Complex (MHC)

  • glycoproteins found in the plasma membrane
  • your "self-antigens"
  • mark your cells as yours – strongly antigenic to other individuals
  • every person has unique MHC on nucleated cells
  • function: to help T cells recognize self from non-self
  • 2 types: MHC class 1 and 2
• In an organ transplant, you look for compatibility of donors and recipients by looking for the MHCs
• Antigen processing and presentation

  • how a pathogen enters a cells determines whether it is presented on MHCI or MHCII
  • T cell can only "see" antigens if they're presented on an MHC molecules
• MHC Class I

  • in the plasma membrane of all nucleated cells
  • binds to and presented cytosolic peptides
  • endogenous antigens – present inside the cell
  • ex. viruses or intracellular bacteria
  • presents antigen to CD* T cells
• viruses can only live inside the cell, so the cell makes the proteins for the virus then express those proteins on the MHC class I
• MHC Class II

  • on the professional antigen-presenting cells
  • binds peptides from intracellular vesicles
  • theses are exogenous antigens that have been brought into the cell from outside
  • ex. through phagocytosis or specific binding
  • ex. bacteria or viruses that have been phagocytosed
  • presents antigen to CD4 T cells
• Adaptive immune system divisions

  1. humoral immunity
  2. cell-mediated immunity
• Humoral Immunity

  • antibody mediated
  • antibodies are produced by B cells and circulate freely in blood and lymph
  • bind to bacteria, toxins, free virus
  • functions of antibodies:
  • opsonization, neutralization, activation of complement
  • "marked for destruction"
• Cell-Mediated Immunity

  • mediated by living cells and has cellular targets
  • "cell on cell violence"
  • largely mediated by T cells
  • infected cells, cancer cells forming cells are killed
  • can be either direct or indirect
  • T cells killing other cells
• T helper cells aid both types of immunity

  • humoral
  • cell-mediated
• the 2 types of immunity (humoral and cell mediated) are inter-related and can work together
• Generation of effector T cells

  • a naïve T cell gets activated by a specific antigen
  • once the T cell is activated it proliferates and differentiates
  • now capable of "doing its job" & is called an effector T cell
  • attack or help mount a response
• there are different types of mature, effector T cells:

  • cytotoxic T cells (CD8)
  • helper T cells (CD4)
  • TH1, TH2
  • memory T cells
  • regulatory T cells
• T cells cannot "see" antigens directly

  • must have antigen "present" to them on MHC
• Naïve T cells need 2 signals to become activated

  • "2-step" hypothesis of T cell activation
  • prevents immune responses from happening accidentally
  • in the absence of co-stimulation the T cell becomes inactivated
• activated APCs present antigen to T cells in the lymph nodes

  • this event elicits the primary cell-mediated response
  • T cells differentiate and proliferate to become effectors
  • some of those will become memory T cells
  • protect against subsequent challenges
• T cell Activation

  • signals 1 & 2 are required to activate a naïve T cell
  • signal 3 tells that T cell what its supposed to do
  • often a chemical signal from the environment
  • in the form of cytokines
  • ex. what kind of T helper cell am I supposed to be?
• cytokines tell the cells what to do
• CD8

  • "killer" T cells
  • activation of naïve T cells:
  • T cell receptor binds to antigen presented on MHCI
  • co-stimulatory signal required
  • activated T cells now proliferate and differentiate = clonal selection
  • Activated cytotoxic T cells
  • kill via perforin and granzyme
  • do not require costimulatory signal to act
  • Memory T cells
  • do not require co-stimulation for activation
  • they don't need that second signal because they already know what to do
• Cytotoxic T cells

  • activated CTL leave the lymph nodes and travel to the site of infection; follow chemotactic trail to infection
  • recognize pathogenic epitopes in the context of MHCI on infected cells
  • kill them via perforin/granzyme
  • also produce IFN-γ which can activate tissue macrophages
• CD4

  • activation of naive T cells:
  • T cell receptor binds to antigen presented on MHCII
  • costimulatory signal also required
  • 3rd, cytokine signal to "give the cell instructions"
  • activated T cells now proliferate and differentiate
  • activated helper T cells secrete cytokines
  • help stimulate immune responses, enhance proliferation of T cells, B cells and NK cells
  • memory T cells
  • do not require co-stimulation for activation
• Memory T cells

  • T cells that remain after a cell-mediated response
  • if there is a subsequent exposure to the same antigen:
  • memory cells are available for a faster, more vigorous response
  • have their own activation characteristics, do not require co-stimulation
  • "get to work faster" because there are more of them our there and they already know what to do
  • they are effectors and divide into more cells
  • thought to persist for the life of the individual
  • subsequent responses to the same Ag are primarily mediated by memory cells and naïve responses are suppressed