SPECIFIC (ADAPTIVE) IMMUNITY T and B lymphocytes

1. SPECIFIC (ADAPTIVE) IMMUNITYT and B lymphocytes Immunology, 3rd year

2. Contents Specific immunity: Basics Immunoglobulins and T cell receptor B and T development T cell function Innate-like lymphocytes Examples: B and T cell function

3. Tgd+ Specific, adaptive Non-specific, innate Main cell types

4. Contents Specific immunity: Basics Immunoglobulins and T cell receptor B and T development T cell function Innate-like lymphocytes Examples: B and T cell function

5. Antibody (immunoglobulin) structure   variable part (Ag binding) ,,,, constant part (function)

6. Isotypes

7. Antibody functions • neutralizing • opsonization • complement activation • sensitizing for NK cell killing (ADCC), or for granulocyte activation • mast cell, Eo etc. sensitizing IgG, IgA IgG IgM, IgG3 >G1>G2,IgA IgG IgE

8. Igisotypes, facts Serum conc Iso type Mol mass Localization T (1/2)biol Function (kDa) (g/l) (days) serum, intersticial opsonization; neutralization; IgG 155 8-18 21 fluid crosses placenta; secondary response 160- serum, mucosae, mucosal defense, opsonization IgA 0.9-3.5 6 350 tears, saliva serum, B-cell surface complement activation; primary IgM 900 0.9-2.5 6 response; Ag receptor Ag receptor serum, B-cell surface IgD 180 0.1 3 serum, intersticial anti-parasite defense IgE 190 3x10-4 2 fluid

9. Ig after birth, physiological infants % of adult values maternal IgG (trans-placental) birth age (yrs) gestation age (wks)

10. Neonatal Fc Receptor (FcRn) Beta-2-microglobulin FcRn transport across placenta extends T1/2

11. Antibody response

12. B cell receptor

13. T cell receptor

14. NK cells: no specific antigen receptor

15. CD nomenclature CD3 = T lineage CD4 = T helpers* CD8 = cytotoxic T* CD19 = B lineage CD10 = immature lymphoid cells* CD34 = progenitors* *also other cells CD40/CD40L

16. Contents Specific immunity: Basics Immunoglobulins and T cell receptor B and T development T cell function Innate-like lymphocytes Examples: B and T cell function

18. Antigen specificity - clonal theory

19. Immunoreceptor gene rearrangement V D J

20. Genes for various chains.. Allelic exclusion

21. B lymphocytes - development

22. Germinal center close-up nemůžu najít obrázek

24. Somatic hypermutation mutation in variable loci Ig genes in germinal centers together with isotype switch AID (activation induced deaminase)

25. Disrupted CD40, CD40L, or AID HyperIgM syndrome high IgM very low IgG,A,E antibodies with low affinity CD40 CD40L

26. Thymus-independent antigens often polysaccharides, lipids mostly IgM children under 2 yrs: weak response

27. T lymphocyte development

28. Contents Specific immunity: Basics Immunoglobulins and T cell receptor B and T development T cell function Innate-like lymphocytes Examples: B and T cell function

29. T lymphocyte subpopulations CD 8 - Tc, cytotoxic lymphocytes CD4 - Th - helpers, Treg- regulatory [attacked by HIV] Normal frequency in blood: CD4/CD8 cca 2

30. Cytotoxic T lymphocyte

31. NK and Tc cells: granules perforin granzymes granulysin

32. Perforin deficiency

33. Cytotoxic T lymphocyte: other mechanisms Fas ligand cytokines interferon  TNF α TNF β

35. MIGRATION

36. If macrophages cannot eat it..

37. Main functional types of CD4 T cells (n)Treg

38. Allergy: possible role of T[reg] cells

39. Contents Specific immunity: Basics Immunoglobulins and T cell receptor B and T development T cell function Innate-like lymphocytes Examples: B and T cell function

40. Innate-like lymphocytes limited repertoir specific function and localization mostly autonomous T B1 NKT

41. Contents Specific immunity: Basics Immunoglobulins and T cell receptor B and T development T cell function Innate-like lymphocytes Examples: B and T cell function

42. B and T lymphocyte disorders - lymphopenia: • decreased production • inborn errors (T, B, T and B) • malnutrition • tuberculosis and other infections • increased destruction • steroids, radiation, chemotherapy • AIDS (T) • losses (gut, chylothorax,..) (T and B)

43. B and T lymphocyte disorders - lymphocytosis: normal absolute counts vary throughout age virus infections other infections (mycoplasma, syphilis, ..) dif. dg.: clonal proliferations (incl. leukemias)

44. B and T lymphocyte disorders - functional defects: antibody deficiency IgA hereditary mutation CD40/CD40L polymorphism of V(D)J in some ethnic groups

45. EBV, Epstein-Barr virus Function and disorders of B and T ly: EBV • 95% world population • Primoinfection: • infants, preschool kids: mostly asymptomatic or indistinguishable from other infections • adolescence (rarely at different age): inf. mononucleosis

46. Life cycle, EBV Function and disorders of B and T ly: EBV

47. Infectious mononucleosis: clinics Function and disorders of B and T ly: EBV +fever splenomegaly up to 50% patients hepatomegaly (10%) elevated transaminases, LDH petechiae in mouth eye-lid oedemas exanthemas (up to 15%) (typically no stomachache)

48. Severe EBV complications Function and disorders of B and T ly: EBV Severe lymphoproliferations virus-associated hemophagocytic syndrome familiar hemofagocytic lymfohistiocytosis X-linked lymphoproliferation malignities: nasofaryngeal carcinoma endemic Burkitt lymphoma other malignancies (Hodgkin, non-Hodgkin lymphoma,...)

49. Burkitt lymphoma Function and disorders of B and T ly: EBV