INFECTION Pathogen circumvents: specific defence innate defence

INFECTION 1990 worldwide (WHO figures) 600 million infected individuals 20 million deaths

INFECTION 7 million respiratory infection deaths 4 million gastric infection deaths 3 million tuberculosis deaths 2 million malaria deaths 2 million hepatitis deaths 200,000 schistosome deaths

INFECTION Specific and non-specific mechanisms Immune response patterns vary: viruses bacteria protozoa helminths

VIRAL INFECTIONS Need rapid cell entry Free virus in blood stream easily neutralised Infected cells destroyed

VIRAL INFECTIONS Humoral response Antibody (IgA) Blocks binding GAM ab Blocks virus host cell fusion GM ab Opsonisation IgM Agglutinates particles Complement Opsonisation, lysis

VIRAL INFECTIONS Cell mediated response IFN (Th or Tc) Antiviral action CTL Kill infected cells NK, Macrophage ADCC killing

VIRAL INFECTIONS 3-4 days post infection CTL activity increases Peaks at 7-10 days then declines 7-10 days virions eliminated Parallels development of CTL CTL eliminates virus infected cells

VIRAL EVASION Interfere with specific or non-specific defence Adenovirus, EBV block action of DAI Vaccinia protein binds C4b (inhibits classical) HSV glycoprotein binds C3b (inhibits both)

VIRAL EVASION Influenza changes coat antigen Rhinovirus, HIV, show antigenic variation Mumps, measles, EBV, HIV, CMV cause immune suppression

VIRAL EVASION Viral infection of lymphocyte HIV Cytokine imbalance EBV produces BCRF1 (which is homologous to IL10 and suppresses IL2, TNF, INF production) Inhibition of class 1 MHC expression CMV

BACTERIAL INFECTION Enter host via respiratory tract gastrointestinal tract genitourinary tract skin break

BACTERIAL INFECTION Number of organisms and virulence determine defence mechanism employed Low number or virulence – phagocytes active High number or virulence – immune response

BACTERIAL INFECTION IgA(s) Block attachment to host cell Ab C3b Opsonisation, Prevent proliferation Complement Cell lysis, Prevent proliferation Ab Neutralise toxins

BACTERIAL INFECTION Intracellular infection Tdth cells Influx inflammatory cells – macrophage 1890 Robert Koch TB infection – localised inflammation on injection of filtrate from mycobacterial culture – tuberculin reaction Tuberculin reaction now called delayed type hypersensitivity

BACTERIAL INFECTION Sensitisation (1-2 weeks) Th cell activation (Tdth) Second contact – effector phase Tdth secrete IFN, TNF, IL2 Macrophage recruitment

BACTERIAL INFECTION Activated macrophages kill infected cells by lytic enzyme release Prolonged DTH – continuous macrophage activation – granuloma formation (macrophages adhere together) – lytic enzyme release – tissue damage

BACTERIAL EVASION Neisseria, HI Secrete protease lyses IgA(s) N.gonorrhoea Pilli Antigenic variation B.pertussis Secrete adhesion molecules S.pneumoniae Polysaccharide capsule (84 serotypes) prevents phagocytosis

BACTERIAL EVASION Strep pyogenes M protein inhibits phagocytosis Staphylococci Coagulase, forms fibrin coat round organism Pseudomonas Elastase secretion inhibits C3a and C5a

BACTERIAL EVASION Mycobacterium Escape from phagolysosome Live in cytoplasm M.avium Block phagosome/lysosome fusion

PROTOZOAN INFECTION Amoebiasis Chagas disease Sleeping sickness Malaria Toxoplasmosis Leishmaniasis Immune response depends on location of parasite in host

PROTOZOAN INFECTION Blood stage Humoral immunity Tissue stage Cell mediated immunity Plasmodium fulciparium (malaria) Transmitted by Anopheles mosquito bite Mosquito – sporozoites – human blood – liver – merozoites – RBC – gametocytes - mosquito

PROTOZOAN INFECTION Excessive production of cytokines (TNF) may cause some of symptoms associated with malaria Antibody produced to sporozoites but only poor response as sporozoites only present in blood for short time

PROTOZOAN EVASION Surface antigen variation Intracellular phase Outer coat sloughing

WORM INFECTION Helminths – multicellular organisms Do not multiply in humans Not intracellular Few parasites carried Poor immune response

WORM INFECTION Ascaris Schistosoma Schistosomiasis Snail – larvae – human – liver – intestinal mesentery (bladder veins) – male + female (adult worms) – eggs – faeces/urine - snails

WORM INFECTION Immune response not sufficient to kill IgG + IgE produced IL5 (eosinophil production) IL3 (mast cell growth) Antibody dependent cell mediated cytotoxicity Eosinophil basic protein toxic to worms

WORM EVASION Decreased antigen expression by adult Glycolipid/glycoprotein coat (host derived) (ie. utilises host self antigens)

IMMUNISATION Passive – preformed antibody transferred Transplacental transfer Colostrum Inject preformed antibody Tetanus toxoid Snake venom

IMMUNISATION Active immunisation Elicits – protective immunity immunological memory Achieved by – natural infection vaccine administration

VACCINES Inactivated (killed) Attenuated (avirulent) Bacteria or viruses Toxoid vaccines (inactivated toxins)

VACCINES Attenuated Inactivated Booster single multiple Stability less more Immunity humoral humoral cell mediated Reversion may cannot

VACCINES Recombinant antigen Recombinant vector DNA vaccines Synthetic peptide Multivalent subunit Anti idiotype vaccine

TISSUE DAMAGE Acute inflammation trauma (surgical) necrosis (MI) neoplasia Damage mainly due to response rather than by injurious agent