1. INFECTION
Pathogen circumvents:
specific defence
innate defence

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

3. 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

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

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

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

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

8. 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

9. 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)

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

11. 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

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

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

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

15. 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

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

17. 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

18. 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

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

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

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

22. 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

23. 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

24. PROTOZOAN EVASION Surface antigen variation Intracellular phase
Outer coat sloughing

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

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

27. 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

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

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

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

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

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

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

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