Structure and Functions of the Immune System.ppt

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2. Organisationoflymphoidsystemlymphoid
cells
Centralandperipherallymphoidorgans
CharacteristicsofTcellsandBcells
Phagocyticcells,nullcells
Majorhistocompatibilitycomplex

3. Immune response
Humoral Cellular
or or
Antibody Mediated Cell Mediated
Plasma Cells Sensitised lymphocyte

4. Development of T and B cell systems

5. Lymphoid Cells Lymphoid Organs
Lymphocytes Primary Secondary
Plasma cells (Central) (Peripheral)
Lymphoepithelial Spleen, LN
Thymus Bursa of (BM) fabricius
Cellular Humoral

6. Firstorgantobecomelymphoid
Maximumsize-beforebirth
Continuesgrowth–12
th
year
Afterpuberty-Spontaneousinvolution
Functionbest-Earlylife

7. Located -upper part of sternum
Two lobes surrounded by fibrous capsule,
septa arising from capsule divides the gland
into lobules differentiated -outer cortex
and inner medulla
Cortex -Actively proliferating lymphocytes
Medulla -Epithelial cells, lymphocytes
Hassall’s corpuscles

8. Primary function -Thymic lymphocytes
Lymphocytes conditioned in thymus -
‘thymus dependent lymphocytes’ or T cells
Lymphocyte proliferation -Not dependant
on antigenic stimulation

9. Humans and mammals –Site of B cell origin
and development
Immature B cells –Lymphoid progenitors-
proliferate and differentiate
Lymphocytes originate in bone marrow
T lymphocytes –thymus
B lymphocytes –bone marrow

10. Lymph nodes -Placed along course of
lymphatic vessels surrounded by a fibrous
capsule from which trabeculae penetrate
into the nodes
Node is differentiated into outer cortex
inner medulla

11. Cortex -Accumulation of lymphocytes
(primary lymphoid follicle) within which
germinal centres (secondary follicles)
develop during antigenic stimulation
Follicle contains dendritic macrophages
which capture and process antigen

12. Medulla: Lymphocytes, plasma cells and
macrophages arranged as elongated
branching bands (medullary cords)
Cortical follicles and medullary cords contain
B lymphocytes
Between cortical follicles and medullary
cords, broad, ill-defined intermediate zone
(paracortical are) contains T lymphocytes

13. Diagrammatic section of lymph node (arrows
indicate the path of lymph flow)

14. Filter for lymph
Phagocytose foreign material
Help proliferation and circulation of T and B
cells, enlarge following local antigenic
stimulation

15. Largest lymphoid organ
Capsule from which trabeculae descend,
dividing the organ into interconnected
compartments

16. Schematic diagram of splenic architecture

17. Graveyard for effete blood cells
Reserve tank and settling bed for blood,
systemic filter -trapping bloodborne foreign
particles
Immunological function -Bloodborne
antigens

18. Children –splenectomy –increased
incidence of bacterial sepsis, Streptococcus
pneumoniae
Neisseria meningitidis
Haemophilus influenzae
Adults
Bacteremia

19. Mucosa lining -Alimentary, respiratory
genitourinary and other lumen
Constantly Exposed to antigens
Endowed with rich collection of lymphoid
cells -either specialised aggregates -Peyer’s
patches or scattered lymphoid follicles –
collectively MALT

20. GALT -Lymphoid tissue in gut, adenoids
and tonsils, follicles in colon
BALT -Respiratory tract bronchus
Contain Lymphoid cells and phagocytic cells
B + T cells predominantly lg A

21. Lymphocytes -Small round cells
Peripheral blood, lymph, lymphoid organ
peripheral blood –20-40% of leucocyte
population
10
12
lymphocytes
10
9
-Renewed daily 1% of total body
lymphocytes -blood

22. SizeSmall –5-8 m
Medium –8-12 m
Large –12-15 m
Classified Life span
-short lived -two weeks -immune response
-long lived -three years –immunological
memory

23. Central lymphoid organs
Differentiate, mature circulation
Peripheral lymphoid organs
Lymphocyte recirculation -Blood, lymph,
lymphatic organs, tissues
Antigen -any part -immune response
recirculating lymphocytes -T cells B cells -
sessile

24. Before encountering antigen -naïve cell
‘educated by central lymphoid organs’
Immunologically competent cell (ICC)
Functions -recognition of antigen
immunological memory
immune response

25. Antigen recognition mechanisms recognise
one antigen
Reaction -Immunocompetent cell either
‘tolerance’ or immune response
Stimulated ‘T’ cells -lymphokines induce CMI
‘B’ cells -divide and transform into plasma
cells-synthesise immunoglobulin

26. T cells -Bind sheep erythrocytes –rosettes
Demonstration of CD3 cells on Tcells and Ig
on B cells
SRBC or E rosette by CD
2antigen B cells do
not
B cells -Bind sheep erythrocyte coated with
antibody and complement forming EAC
rosettes -C
3receptor
T cells do not possess this

27. B cells have immunoglobulin on their
surface first to appear -monomeric lgM
Therefore -antigen recognition unit T cells
-no surface lg
T cell receptors -TCR

28. T cells -Thymus specific antigen
T cells -Blast transformation -on treatment
with mitogens
B cells -Blast transformation -with bacterial
endotoxins
Scanning EM -T cells are free of cytoplasmic
surface projections
B cells -Filamentous surface, microvilli

29. T cell precursors -Yolk sac, fetal liver, bone
marrow migrate to
Thymus
Earliest cells-CD
7
+
-Pro-T cell
Acquire CD
2in thymus
Synthesise CD
3in cytoplasm -Pre -T
TCR synthesis takes place

30. TCR -heterodimer
Association with CD3 -antigen recognition
TCR -Two pairs of glycoprotein chains
 αβor 
Pre -T -differentiate -αβor 
TCR chains -Four separately encoded regions
V -variable, D -diversity
J -joining, C -constant
Immunoglobulin supergene family -reassortment
-wide repertoire of antigen specificities

31. T cell maturation

32. Contact with self antigens-within thymus
Destruction of immature T cells carrying
corresponding TCR
Therefore -elimination of T cells capable of
reacting with autoantigens
Potentially harmful ‘forbidden clones’ deleted
by antigen -specific suppressor cells

33. T cells -develop -MHC restriction
CD
8+ -antigens presented with HLA class
I
CD
4+ -antigens presented with HLA class
II
Immature T cells -exhibit -CD
7,2,3,1,4,8and
TCR
Functional maturity -lose CDI
Two major subsets -CD
8-
4+
CD
4-
8+

34. Broadly classified -regulatory and effector
Based on surface markers, target cells and
functions -following T cell categories
Helper/inducer cell-TH cell with CD
4+ surface
marker MHC class
IIrestriction
Suppressor T cell (Ts)
Cytotoxic/cytolytic T cell (Tc) CD
8+ surface
marker
Memory cells (Tm)

35. CD4+ surface marker
MHC class
IIrestriction promoting growth of T
cells and macrophages
2 subsets -TH
1, TH
2
TH1, cells -produce -cytoknies
Interferon gamma (IFN-)
Interleukin 2 (IL-2)
Activate macrophage and T cell promote CM1
Kill intracellular microbes-tubercle, lepra bacilli

36. TH 2 –cytokines ,IL4,5 and 6-stimulate B
cells to form antibodies
TH 17 –cytokine IL 17, promotes
inflammation, autoimmune disease (SLE,
Rheumatoid Arthritis) and cancer

37. CD 4 + cells
Produce cytokine TGF beta
Immune response and tolerance to self-
reacting cells

38. CD8 surface master
MHC -class I restriction
Kill and lyse target cells
Including tumour, virus-infected cells
Memory cell (Tm)
CD4 and CD8 memory and anamnestic
response

39. B lymphocyte precursors -pro B cells
Develop -fetal liver -embryonic life bone
marrow -adult
Pre-B cells –synthesise cytoplasmic lgM
Immature -B cells -lg M cell surface
Migrate to periphery, undergo
immunoglobulin isotype switching
So cell expresses -lg D, lg M, lgG, lgE, lgA

40. Appropriate antigen -mature B cell, clonal
proliferation
Activated B cell -memory cell
Plasma cell
Plasma cell
Antibody secreting cell

41. Antibody secreting cell, oval, eccentrically
placed oval nucleus, large block of chromatin –
peripherally.
Structurally -immunoglobulin production
End cells
Short life span

42. Antibody of single specificity single
immunoglobulin class allotype
Single light chain type
B cells selected –germinal centre –high
affinity membrane IgG for antigen
B cells differentiate to plasma cells and
memory cells

43. B cell maturation

44. 5-10% of circulating lymphocytes lack
features of either T or B cells
Null cells -large granular lymphocyte
Indented nuclei, abundant cytoplasm
azurophilic granules, mitochondria,
ribosomes, endoplasmic reticulum, golgi
apparatus

45. Different functions and surface markers
Important member -Natural killer (NK) cell
Antigen dependent cytotoxic cell (ADCC)
Lymphokine activated killer (LAK)
Natural killer (NK) sometimes -common
name -all null cells

46. Spontaneous cytotoxicity not antibody
dependent/MHC restricted
NK activity -‘natural’ ‘non-immune’ does
not require sensitisation
Part of innate immunity
Active in ‘severe combined
immunodeficiency disease’
Where ‘B’ and ‘T’ cells absent
CD16 and CD56 on surface

47. Phylogenetically oldest defense mechanism
-removal of foreign particles -
mononuclear macrophages and
polymorphonucleor macrophages
Blood macrophages –monocytes(12-15µ)
Tissue macrophages –histiocytes(15-20µ)

48. Macrophage -Induction, execution of immune
response
Trap antigen -provide it -to lymphocytes
Processing + presentation of antigen to T cell -
requires both cells -possess surface determinants
coded for by same MHC genes

49. T cell can accept -processed antigen only if
presented by a macrophage carrying -self-
MHC antigen when macrophage -different
MHC antigen -it cannot cooperate with
T cells -MHC restriction

50. Activated by lymphokines, complement
components or interferon
Activated macrophage -secrete
Hydrolytic enzymes, binding proteins
(fibronectin, transferrin)
Tumour necrosis factor –(cachectin)
Colony stimulating factor –(CSF) and
interleukin 1

51. Actively phagocytic, predominant in acute
inflammation, non-specific
Eosinophilic leucocytes, allergic
inflammation, parasitic infection

52. Immune system -primary function -
recognition and elimination of foreign cells
and antigens
Gorer -1930s -antigens responsible for
allograft rejection -inbred mice -
discovery of major histocompatibility
complex

53. Complex of genes on a segment of one
chromosome pair coding for three different
classes of proteins
Class I protein -Determine
histocompatibility -acceptance/rejection-
allograft
Class II protein -Regulate immune response
Class III protein -Complement system

54. Major antigens -determining
histocompatibility in humans -alloantigens
-surface of leucocytes
Human MHC antigens therefore synonymous
with human leucocyte antigen
MHC complex synonymous with HLA
complex

55. Complex of genes located on short arm of
chromosome 6
Consists of three separate cluster of genes
•HLA class I -comprising A, B + C loci
•HLA class II or D region-DR, DQ + DC loci
•HLA class III or complement region

56. HLA complex loci on chromosome

57. Antigen -obtained -multiparous women
antibodies to HLA antigen -husband
sensitisation during pregnancy
Monoclonal antibodies -HLA antigens
developed

58. For more discriminating than blood grouping
compatibility -tissue transplantation
Disputed paternity
Anthropological studies
HLA types and diseases
Ankylosing spondylitis -HLA B
27
Rheumatoid arthritis -HLA -DR
4
Autoimmune conditions -HLA DR
3