Immunity to infectious diseases.

1. Immunity to infectious diseases. Prof. Mohamed Osman Gad El Rab. College of Medicine& KKUH.

2. Classification of immunity. Acquired immunity. active. passive. natural. artificial. natural. artificial. infections. immuniz. Maternal immuno - IgG. therapy.

3. Immunity to viral infections .

4. Innate (natural) immunity: many viruses induce : 1. production of type 1 interferons. ( INF- alpha & INF - beta.) 2. activation of NK - cells .

5. dsRNA produced during viralreplication induce the expression of interferons by the infected cells. * monocytes , macrophages & fibroblasts also synthesize interferons .

6. Viruses initiate infection by binding to specific host - cell membrane molecules . • e.g. 1. influenza virus bind to cell membrane glycoproteins . 2. rhinoviruses bind to intercellular adhesion molecules (ICAMs).

7. Mechanism of action : • Interferons bind to receptors that activate JAK-STAT pathways. These induce several genes . • One gene activate a ribonuclease that degrade viral RNA .

8. 2. Other genes activate protein kinases which inhibit proteinsynthesis . 3. binding of INFs to NK-cells induce lytic activity . * IL-12 produced by macrophages also enhance NK-cell activity .

9. Antibody- mediated immunity : • Anti-viral antibodies : 1. prevent spread during acute infection. 2. protect against reinfection .

10. Protective functions of antibodies : 1. secretory IgA blocks viral attachment . 2. complement - fixing antibodies may cause lysis of enveloped viruses 3.IgM antibody agglutinate viral particles .

11. Cell – mediated immunity is important for control & clearance of viral infections . CTL activity arises within 3 - 4 days, peak by 7-10 days & then decline when the infection is cleared .

12. Viruses can evade host defenses. 1. Hepatitis C virus : overcome anti - viral effect of INFs blocking the action of protein kinase. 2.Adenoviruses & CMV : reduce surface expression of MHC-1.

13. 3. Measles ,CMV & HIV : reduce MHC -11 levels . 4. A large no. of viruses cause generalized immunosuppression. . e.g. mumps , measles , EBV., CMV., & HIV.

14. Influenza virus .

15. Antigenic variation of influenzavirus . • In 1918-1919 an influenza pandemic killed over 20 million people . The structure of the virus contain : Hemagglutinins (HA ). Neuraminidase (NA ).

17. Shifting Nature of Influenza • Antigenic drift – small, ceaseless changes in the genetic structure. New strains continually replace old strains. • Antigenic shift – major change, usually occurs when species hosting virus trade viral genes. Novel strain appears without natural immunity in host population.

18. 1. Antigenic drift :gradual minor change in HA & NA. 2. Antigenic shift : sudden major change in HA & NA . ( new subtype emerge )

20. 1918 Hemagglutinin Causes Severe Lung Damage. M88/Hsp M88 Kobasa et al. Nature 2004;431:703

22. Immunity to bacterial infections.

23. If the inoculum (dose ) is small and the virulence of the bacteria is low . Tissue phagocytes may eliminate the bacteria .

24. The humoral response (antibody) is the main protective response against extracellular bacteria . • Antibodies act in several ways : 1. neutralize toxins . 2.activate complement . - generates anaphylatoxins. -release chemotactic agents .

25. Protective functions of antibodies.

26. Intracellular bacteria : • Initially activate NK – cells which provide early defense . Final control is by : cell - mediated immunity . ( this involve activated macrophages )

27. Cell-mediated immunity involve activated macrophages.

28. Bacteria can by-pass host defense: • 4 steps in bacterial infections : 1. attachment .(adherence). 2. proliferation . 3. invasion of host tissues . 4. toxin - induced damage.

29. Adherence

30. Penetration into the Host Cell Salmonella entering epithelial cells via invasins Figure 15.2

31. Secretory IgA block attachment , but some bacteria secrete proteases that break IgA . • Opsonization & phagocytosis prevent proliferation , but some bacterial surface structures inhibit phagocytosis, ( polyssacharide capsule ,Strp.pneum.)

32. Strep.pneumonae. Inhibit phagocytosis.

33. 3. Some bacteria resist complement lysis . 4. Mycobacteria survive intracellularly by resisting oxidative attack ,some prevent lysosomal fusion .

34. Complications of immune responses . In some cases disease is not caused by the bacteria but rather by the immune response.

35. Endotoxins of gram –ve bacteriaactivate macrophages which releasehigh levels of IL-1, & TNF - alpha, these may cause : Septic shock . • In staphylococcal food – poisoning , enterotoxins act as superantigens and cause direct massive T-cell activation . This may cause: Toxic shock syndrome .

36. Endotoxin Contrast the nature and effects of exotoxins and endotoxins. Figure 15.4b

37. Exotoxins Figure 15.4a

39. 3.Complications of streptococcus pyogenes throat infections • 1. Rheumatic fever :antibodies formed against antigen in the strep. cell wall cross –react with the sacrolemma of Human heart .Granuloma form in the heart (Aschoffs nodules). 2. Rheumatic heart disease :repeated attacks by strep. with different M types can result in damage to the heart valves.( certain children have a genetic predisposition to this immune-mediated disease ). ( high A.S.O. titer ).

40. 3. Acute glomerulonephritis : antibodies to strep . components combine to form immune- complexes which then deposit in the kidney glomeruli .

41. 4. In chronic intracellular infections e.g. T.B. excessive CMI responses lead to granuloma formation .

42. Granuloma formation ( T.B. )

43. The balance between TH1 & TH2 is important in immunity. It determine the clinical presentation of the disease .

44. 5. Immunological response in leprosy : The response decide the type of disease : 1.In tuberculoid leprosy the patient mount an effective cell-mediated response.Macrophages destroy the bacilli and contain the infection . 2. In lepromatous leprosy : the patient is unable to produce a cell-mediated response and organisms multiply and spread in the tissues >

45. Immunity to parasitic infections:

46. A. Protozoal diseases . These are unicellular organisms . e.g. malaria , trypansomiasis , toxoplasma, * They have complex life - cycles. some stages are free in the blood , other stages are intracellular.

47. The type of the immune response depend on the location of the parasite in the host . In the blood antibodies may be effective In the intracellular stage CMI may be effective.

48. Immunity to Malaria: • Caused by genus Plasmodium. • P.falciparum is the most virulent & prevalent. • Infect 10% of the population. • Causes 1 – 2 million deaths every year. • Have a complex life – cycle .

49. Life cycle of malaria : 3-stages.

50. During the life- cycle, many antigensappear : • Infection begin with mosquito bite. • Sporozoites enter the blood & disappear within 30 min. * Migrate to the liver & after 1 week release merozoites which infect RBCs.