Immune response to pathogens

• Immune response to bacteria (overview) 


  • complement activation (destruction, phagocytosis).
  • Macrophage phagocytosis and activation TLR’s (toll like receptors) SR
  • Ig production (neutralising, blocking Complement activation, opsonisation.
  • T helper cell activation
• extracellular immune response 


  • on cell surfaces or in blood.
  • viruses, fungi, worms, bacteria
  • protective immunity- antibodies, complement, phagocytosis and neutralisation
• intracellular immune response 


  • antibody cannot cross the cell membrane so protective immunity is- cytotoxic T cells and NK cells.
  • Cellular mediated immune response - cytoplasmic or vesicular.
  • Organisms that attack this way- viruses, Protozoa
• Immune response to virus (overview) 


  • type 1 interferon release - alert immune system its been infected
  • NK lysis
  • Macrophage phagocytosis and activation (TLR’s SR)
  • IG production (neutralising, blocking complement activation, opsonisation )
  • Cytotoxic T cell activation
• Immune response against parasites (overview) 


  • antibody, neutralising -IgE
  • Neutrophils
  • Macrophages
  • Cytotoxic CD8 T cells
  • Th2 T cells- IL-4, IL-5, IL-6
  • All above help remove parasites
  • ADCC- antibody dependent cell-mediated cytotoxicity - reactions
• immune response to viruses

  • enveloped viruses can be damaged by complement attack, some directly bind C1q.
  • phagocytes can take up and destroy antibody and complement coated viruses.
  • the key players in antiviral immunity are interferon, NK cells, antibody CTL and TH1 cells
• contribution to defend against viruses

  innate immune response - TNFa, IL-12, IFNa + NK cell killing.

  Adaptive immune response- T cells killing and antibody production

  
• What happens when a cell gets infected by a virus innate immunity response


  • cell produces interferons - IFN-a and IFN-b
  • Interferons Induce resistance to viral replication in all cells.
  • Increase MHC class I expression and antigen presentation in all cells.
  • Alerts NK cells that the infected cell is infected.
  • When cell infected its appearance alters - NK cells recognise this and become activated and kill it.
• Adaptive immunity to viruses 


  • B cell recognised antigen in its natural State
  • T cells recognise processed antigen degraded by B cells.
  • CD4 And T cells provide help and signals to B cells
  • Antigen recognition induces expression of CD40 ligand and cytokines - these activate the B cell
  • Th2 response produces IL-4, IL-5, IL-6
  • B cells proliferate and differentiate into plasma cells.
• Neutralising function of IgG


  • Neutralising antibodies suffocate viruses by binding to toxin blocking them from binding to the cell surface receptors.
• Cytotoxic T cells 


  • have cytotoxic function Also known as CD8 T cells
  • Effector T cells kill cells infected with viruses or other intracellular pathogens.
  • CD8 T cells recognise its corresponding peptide presented by an MHC class I molecule.
  • Determine strict specificity
• what’s in the lytic granules


  • produced by Cytotoxic T cells
  • lytic granules contain
  • perforin - which punch holes into the targets cell membrane.
  • granzymes - proteases which trigger a cascade of enzymes leading to programmed cell death of the target cell -apoptosis
  • CTL - kill their targets by binding of Fas ligand to Fas on the target cell, Fas instructs the target cell to kill itself (apoptosis)
• what is the antigenic drift 


  • body makes antibody for hemagglutinin - (structure on antibody surface). Antibody binds to it and stops it from entering the cell.
  • Viruses mutate - mutations occur to the hemagglutinin and the previously made antibody no longer works.
  • This is why the body gets the flu more than once.
• What cell type can directly kill virally infected cells


  • CD8 T cells
• main benefit of producing an IgG response in comparison to IgM response against a virus is


  • IgG has neutralising activity
  • high affinity antibody
• Immune response against bacteria 


  • innate immunity - complement, phagocytosis
  • Antibody (toxin)
  • IgA plays an important role in organism that infect mucosal surfaces- respiratory tract, GIT, genitourinary tract.
  • Th1 activated macrophages
• Antigen presentation by macrophages


  • macrophage takes up microbe via its pattern recognition receptors - eg Toll like receptors
  • break down microbe, destroy some of it and present some of it to T cells Eg Th1 T cell
  • This also gives T cells and B cells their 2 signals
  • After TH1 receives the second signal it will produce cytokines (IFN-y) that will make macrophages and Dendritic cells - to then Destroy microbes.
• bacterial infections can lead to production of TH2 response. how?


  • B cells binds to bacterial component
  • bacteria internalised and degraded -
  • presented to TH2 T cells which activate the B cell
  • activated B cell produce antibodies either against the bacterial surface or its toxins.
• cytokine IL-4 info sheet


  • produced by Th2 cells
  • act on - activated B cells, macrophages and T cells
  • activity- proliferation and differentiation IgG1 and IgE synthesis, MHC class II, proliferation
  • drives Th2 response
• cytokine IL-5 info sheet


  • produced by Th2 cells, monocytes and macrophages
  • act on- activated B cells and plasma cells
  • activity - proliferation and differentiation, IgA synthesis, differentiation into plasma cells, antibody secretion
• cytokine IL-6 info sheet


  • produced by Th2 cells and stomal cells
  • Act on - stem cells
  • activity - differentiation, acute phase response
• cytokine IL-10 info sheet


  • produced by Th2 celLPs
  • Act on - macrophages and B cells
  • Activity - cytokine production and activation
• antibodies facilitate phagocytosis - how?


  • variable region binds to antigen
  • Tail region can be recognised by different WBCs and they’re known as Fc receptors
  • Antibody coated bacterium then binds to Fc receptors
  • Undergo phagocytosis
  • This can also be done by complement
• compliment facilitate phagocytosis - how?


  • some of the by products of complement can coat bacteria - allowing that complex to be recognised ( in particular by neutrophils).
  • neutrophils have a receptor called the complement receptor
  • neutrophils able to phagocytosis bacteria coated with complement
• what white blood cell can phagocytose bacteria coated in complement


  • neutrophils - have complement receptors
• antibodies prevent bacteria and viruses attaching to cell surface how?

  • bind to virus receptor preventing antigen from binding to cell surface receptor.
  • Antibodies bind to bacterial adhesins block colonisation and uptake of bacteria - these replicate inside the cell
• Immune response to parasites 


  • range of mechanisms protect against Protozoa similar to anti-bacterial mechanisms.
  • Neutralising antibody - block cell receptor for entry
  • Antibody + complement - eg lysis of blood dwelling parasites (trypanosomes)
  • Antibody / complement plus neutrophils or macrophages
  • Activated macrophages can be effective against Many intracellular protozoa.
  • CD8 + cytotoxic T cells fight against parasite infected host cells.
• Immune response against parasites 


  • helminths( type of parasite) are too big to phagocytose.
  • So induce T helper type 2 responses characterised by cytokine pattern with IL-4, IL-5, IL-6, IL-9, IL-13 plus eosinophils and antibody responses including - IgE, characteristic ADCC (antibody- dependent cell-mediated cytotoxicity) reactions
• Eosinophils attacking schistosome larva

  • large parasite type - like Worms cannot be ingested by phagocytes
  • Once worms are coated with IgE
  • Eosinophils can attack using IgE Fc receptors
• IgE cross linking mast-cell surface 


  • mast cells have high affinity IgE Fc receptors on their surface - occupied by IgE molecules
  • antigen cross linking of bound IgE cross links the Fc receptors.
  • this triggers degranulation of mast cell and the release of inflammatory mediators (histamine)
  • this is followed by hay fever symptoms
  • this is called type 1 hypersensitivity
• Antibody dependent cellular cytotoxicity 


  • neutrophils, eosinophils, phagocytes an NK cells all mediate ADCC.
  • Ligation of the low affinity Fc gamma RIII (CD16) molecule activates the lytic machinery.
  • ADCC is only triggered by complexes of antigen and antibody.
  • In this way Fc regions form an array to inc the avidity of the interaction thus avoiding ADCC from being triggered by free immunoglobulin.
  • Need various WBCs to trigger ADCC
• A bacterial response involving the activation of macrophages is facilitated by

  CD4 Th1 T cells
• which antibody associated with mast cell degranulation

  IgE