1. The Immune System: How does it work and were does it fail?
Einar K. Kristoffersen
Department of Immunology and Transfusion Medicine
The Gade Institute
Haukeland University Hospital
University of Bergen

2. Know Thy Enemy
Downloaded from: StudentConsult (on 7 June :08 PM)
© 2005 Elsevier

3. The Immune System The seventh sense Natural vs. adaptive Desentralized
Immun cells
Lymphocytes, phagocytes, dendritic, etc
Immune tissues
Bonemarrow
Thymus
Lymphatic system
Immunoproteins
Antibody, complement, CRP, etc
Natural vs. adaptive

4. Organsystemer

5. Bone marrow
Where immune cells are made

6. What are our weapons? Phagocytes Lymphocytes Bacteria and fungi
B cells
Antibody: bacteria, toxins, virus
T cytotoxic og Natural killers(NK)
Virus
T helper cells
Bacteria, virus, antibody, etc.

7. Downloaded from: StudentConsult (on 7 June 2005 08:08 PM)
© 2005 Elsevier

8. What are our weapons?
Phagocytes
Bacteria and fungi

9. Natural cellular immunity
The Phagocytes
In blood: granulocytes
~ 1011/d
Short-lived
Eat and kill

10. Natural cellular immunity
The Phagocytes
In blood: granulocytes
~ 1011/d
Short-lived
Eat and kill
In tissues: macrophages

11. Macrophages

12. Natural cellular immunity
Phagocytes
Granulocytes
Eat and kill
In tissues: macrophages
In all tissues
”Housecleaning”, eat, kill, activation and regulation

13. Phagocytosis Binding til receptor Lysosomal nedbrytning
Cytokinfrigjøring
Inflammasjon
Aktivering
Lysosomal nedbrytning
Fagocytose

14. Phagocyte hunting:

15. Immunological proteins
Complement
Network of serumproteins
Induced by immune stimuli
Binds and perforates
Extracellular bacteria

16. Phagocytosis Binding til receptor Lysosomal nedbrytning
Cytokinfrigjøring
Inflammasjon
Aktivering
Lysosomal nedbrytning
Fagocytose

17. Immunological proteins
Complement
Cytokines
The ”hormones” of immune cells

18. Immunological proteins
Complement
Cytokines
The ”hormones” of immune cells
Acute phase proteines
CRP etc

20. Natural cellular immunity
Phagocytes
Granulocytes
Eat and kill
In tissues: macrophages
In all tissues
”Housecleaning”, eat, kill, activation and regulation
Natural killer cells: NK
Kill virusinfected cells

21. Killing virus infected cells Stimulerer makrofager
NK cells
Killing virus infected cells
Stimulerer makrofager

22. Natural cellular immunity
Phagocytes
Granulocytes
Eat and kill
In tissues: macrophages
In all tissues
”Housecleaning”, eat, kill, activation and regulation
Natural killer
Kills virusinfected cells
Dendritic cells
Activation and regulation

24. Adaptive cellular immunity
T cells from bone marrow: naïve
Matures in thymus
Most die there
Enormous potential specificities: ~1018

25. Lymphatic system

26. Lymphoid circulation

28. Adaptive cellular immunity
T helper CD4 activated
Activates B cells, macrophages, NK, T-cytotoxic
T cytotoxic: virus infected cells

29. T cytotoxic cells

30. Adaptive humoral immunity
B cells made and matured in bone marrow
B cells activated divides in lymph nodes
Plasma cells: specific antibody: ~5 x 1013
Memory B cells

32. Antibody
Fab-del
Fc-del

33. Antibody isotypes

34. IgA and IgM

36. Antibody: Immune-glue

38. Adaptive cellular immunity
T lymphocytes in marrow matures
Potentially endless specificities: ~1018
T lymphocytes activates:
B cells, macrophages, NK, T-cytotoxic
Memory T cells
Regulatory T cells

39. Lymphocytes Antibody B cells Activates phagocytes T cells
Memory
T cell
Regulatory T
T helper cells
T cytotoxic
Direct
killing
NK cells

40. Specific immune response
Activated specific T cells
Cytotoxic specific T cells
Hyperactivated macrophages
Activated specific B cells
Specific antibody

42. Inflammasjon

44. The Lymphnode

46. Immune response Stamceller Komplement m.m. NK T B Fagocytter celler
Tymus
Fagocytter NK
celler T
celler B
celler
Cellular
responses
Humoral
responses

47. Antobody production B cells become plasma cells
”Short-cut”: IgM producing in lymphnode
Longlived: IgG producing in bonemarrow

48. Immune response Stamceller Komplement m.m. NK T B Fagocytter celler
Tymus
Fagocytter NK
celler T
celler B
celler
Cellular
responses
Humoral
responses

49. Immune response

51. Immune System Stemcells Komplement Cytokiner NK T B Spiseceller celler
Tymus
Spiseceller NK
celler T
celler B
celler
Cellular
responses
Humoral
responses
Protein

52. Immune responses Stamceller T helper cells B cells Komplement
T cytotoxic
B cells
Phagocytes
Komplement
m.m.
Tymus
Fagocytter NK
celler T
celler B
celler
Cellular
responses
Antibody
responses

53. Immunodefects vs. microbes

54. Severe combined immunodeficiency SCID
Stem cells
Komplement
m.m.
Tymus
Phagocytes
X-linked SCID common gammachain many IL receptors
Tyrosine kinase T-B+NK-
IL7R T- B+NK+
RAG1 T-B-NK+ NK
cells T
cells B
cells
Cellular
responses
Antibody
responses

55. DiGeorge T cell def Stem cells Komplement m.m. NK T B Phagocytes cells
Tymus
Phagocytes
22q11 deletion Cardiac malformations, immundeficiency, hypocalcemia(parathyroid)
HIES: STAT3 mutation no Th17
IPEX: immundysfunction polyendocrinopathy enteropathy x-linked: lack of regulatory T cells NK
cells T
cells B
cells
Cellular
responses
Antibody
responses

56. Common variable immunodeficiency
Stem cells
Complement
Cytokines
Agamma-globulinemia
Common variable immunodeficiency
Tymus
Fagocytter
Multigenetic, NK
celler T
cells B
cells
Cellemediert
responser
Antibody
responses

57. Chronic granulomatous disease leukocyte adhesion deficiency
Stamceller
Komplement
m.m.
Tymus
Phagocytes
CGD: feil i intracellulær bakteriedrap pga sviktende O2- danning
NK: perforin defekt lav NK celle aktivitet NK
cells T
cells B
cells
Celular
responses
Antibody
responses

58. Phagocyte hunting:

59. Interferon gamma receptor
C2 deficiency
Interferon gamma receptor
Stamceller
Complement
Cytokines
Tymus
Fagocytter
INFgR def mycobact inf NK
celler T
celler B
celler
Cellular
responses
Antibody
responses

60. Immune System Stem cells Complement Cytokines NK T B Phagocytes cells
Tymus
Phagocytes NK
cells T
cells B
cells
Cellular
responses
Antibody
responses

61. Primary immunodeficiencies
Combined T&B
Well-defined syndromes
Predominantly antibody deficiencies
Immune dysregulation
Phagocytes
Innate disorders
Auto-inflammatory disorders
Complement deficiencies
Combined T&B: ADA def
Well-defined syndromes: Wiscot-Aldrich Di George
Predominantly antibody deficiencies: CVID, Brutons
Immune dysregulation: Chediak Higashi (lysosomes) FHL
Phagocytes: CGD, LAD
Innate disorders: CMC (IL17)
Auto-inflammatory disorders: HIDS,
Complement deficiencies: terminal (Neisseria)

63. CD4 T helper cells
Th1
T memory
Th2
T memory
Treg
T memory?
Th17
TFH