Immunity to infections.

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

2. Classification of immunity. classification of acquired immunity. active. passive. natural. artificial. natural. artificial. infections. immuniz. Maternal immuno - IgG. therapy. Subclinical. Clinical. Vaccines. IgG from mother to fetus. Ready made antibodies .

3. General features : First encounter with any microbe ( at any age ) : * Primary immune response. * 4 phases : 1. lag .( no antibodies ) 2. log. (antibodies appear ) 3. plateau.( no more synthesis ) 4. decline.( antibody disappear ).

4. Primary immune response : 1. takes a longer time ( recognition of antigen, differentiation & proliferation of cells ) . 2. antibody class mainly IgM . 3. memory cells generated .

5. General features : Second encounter with same microbe : Secondary immune response : 1.require small amount of antigen. 2. fast reaction ( memory cells ). 3. high levels of antibody ( IgG ).

6. Nature of infecting microbe determine type of response . extracellular microbes . ( bacteria) Th 2 helper cells. antibody- mediated immunity.

7. intracellular microbes . ( viruses , intracellular bacteria , fungi ) Th-1 helper cells . cell- mediated immunity .

8. Th1 , Th2 cells down-regulate each other. 1. each cell type secrete different cytokines. 2. balance between Th1 & Th2 determine the clinical presentation of the disease .

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

10. Many factors influence immune response to infections : 1. structure of the microbe antigen. 2. dose of infection (optimum dose, good response). 3. route of entry into the tissues .( determine site of reaction ). 4. host factors : - genetic constitution. - age .

11. Immunity to bacterial infections : extracellular. intracellular. protection by : antibody- mediated cell-mediated immunity. immunity.

12. Adherence

13. protective functions of antibodies : 1. neutralizing action : - prevent pathogens from binding to tissues. - prevent the action of toxins . 2. activate complement . 3. stimulate phagocytosis . 4. stimulate NK-cell-mediated killing .

14. Penetration into the host Cell Salmonella entering epithelial cells via invasins Figure 15.2

15. Protective functions of antibodies.

16. microbial strategies to avoid the immune system : e.g. Pneumococcus. has large polysaccharide coat . * can evade phagocytosis . Mycobacteria . have waxy coat & secrete catalase. * can block respiratory burst.

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

18. Granuloma formation ( T.B. )

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

20. Endotoxins of gram –ve bacteriaactivate macrophages which releasehigh levels of IL-1, & TNF - alpha, these may cause : Septic shock .

21. In staphylococcal food – poisoning , enterotoxins act as superantigens and cause direct massive T-cell activation . This may cause: Toxic shock syndrome .

22. immunity to viral infections : initially : 1. interferon, secreted by : - infected cells. - inflammatory cells. 2. NK- cells.

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

24. adaptive immune mechanisms : cell-mediated immunity . * activation of CD8 T-cells. - inhibit viral replication. - kill infected cells .

25. 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.

26. Influenza virus .

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

30. Immunity to parasitic infections:

31. 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.

32. 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 . ( many antigens appear during infection )

33. Life cycle of malaria : 3-stages.

34. 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.

35. Sporozoites stay for only 30 min. in the blood, therefore induce a poor immune response. • The intracellular stage in the liver cells and RBC ,reduce the degree of immune activation generated by the pathogen.

36. Immunity to parasitic worms (helminthes): • Helminthes are large multicellular organisms e.g. Schistosoma (Bilharzia ). Have complex life- cycle .

38. Cercaria enter the blood stream and become schistosomules which enter capilleries.then pass to the lungs & liver. then become adult worms.

39. Humoral immune responses to parasitesare characterized by : 1. elevated IgE. 2. blood eosinophilia . Eosinophils mediate ADCC to damage the parasite.