for Undergraduate Medical Students (MBBS)

1. Disorders of ImmunityDisorders of Immunity
Dr.CSBR.Prasad, M.D.Dr.CSBR.Prasad, M.D.

2. Immune SystemImmune System
 AntigenAntigen
 Protein substance that stimulates AntibodyProtein substance that stimulates Antibody
productionproduction
 HaptenHapten – non-protein substance, Small mol.wt.– non-protein substance, Small mol.wt.
 AntibodyAntibody
 Protein substance produced as a result ofProtein substance produced as a result of
antigen stimulationantigen stimulation
 Circulating Ab are immunoglobulinsCirculating Ab are immunoglobulins

4. Can you name oneCan you name one
carbohydrate antigen?carbohydrate antigen?
Blood group antigensBlood group antigens
(ABO sys)(ABO sys)

7. Immune SystemImmune System
 Non- Specific Immunity (Innate immunity)Non- Specific Immunity (Innate immunity)--
first line of defence without antigenicfirst line of defence without antigenic
specificityspecificity
 Humoral – Complement systemHumoral – Complement system
 Cellular – Neutrophils, MØ, NK cellsCellular – Neutrophils, MØ, NK cells
 Specific Immunity (Adaptive immunity)Specific Immunity (Adaptive immunity)
 Humoral .I - Antibody produced by B cellsHumoral .I - Antibody produced by B cells
 Cell mediated .I – T cells - produce SensitizedCell mediated .I – T cells - produce Sensitized
cellscells

12. Immune SystemImmune System
 LymphocytesLymphocytes
 T lymphocytesT lymphocytes
 B lymphocytesB lymphocytes
 MacrophagesMacrophages
 Natural killer cells (NK cell)Natural killer cells (NK cell)
 Dendritic cellsDendritic cells
 CytokinesCytokines
 Complement systemComplement system

14. Immune SystemImmune System
LymphocytesLymphocytes
 T lymphocytesT lymphocytes
 60-70% peripheral lymphocytes60-70% peripheral lymphocytes
 Paracortical areas of lymph nodeParacortical areas of lymph node
 Perifollicular sheaths of spleenPerifollicular sheaths of spleen
 T cell Receptor (TCR) – recognizes specificT cell Receptor (TCR) – recognizes specific
cell bound antigencell bound antigen

16. T cell Receptor (TCR)T cell Receptor (TCR)
 95% of TCR is a disulfide linked95% of TCR is a disulfide linked
heterodimer consisting of alpha and betaheterodimer consisting of alpha and beta
polypeptide chainpolypeptide chain
 Gamma and delta polypeptide chains seenGamma and delta polypeptide chains seen
at epithelial surfaces eg. Respiratory / GITat epithelial surfaces eg. Respiratory / GIT
mucosamucosa
 CD3 proteins are involved in transduction ofCD3 proteins are involved in transduction of
signals into the T cells after it has bound tosignals into the T cells after it has bound to
antigenantigen

17. The T-cell receptor (TCR) complex.
A, Schematic illustration of TCRα and TCRβ chains linked to the CD3 complex.

18. The T-cell receptor (TCR) complex.
The T-cell receptor (TCR) complex:
B, Recognition of MHC-
associated peptide displayed on
an antigen-presenting cell (top)
by the TCR. Note that the TCR-
associated ζ chains and CD3
complex deliver signals (signal
1) upon antigen recognition, and
CD28 delivers signals (signal 2)
upon recognition of
costimulators (B7 molecules).

19. T - lymphocytesT - lymphocytes
 Expresses non polymorphous functionExpresses non polymorphous function
associated molecules – CD4, CD8 andassociated molecules – CD4, CD8 and
accessory molecules – CD2,CD9, CD28 andaccessory molecules – CD2,CD9, CD28 and
CD40 ligandCD40 ligand
 CD4 is expressed on 60% of T cells (HelperCD4 is expressed on 60% of T cells (Helper
T cell)T cell)
 CD8 is expressed on 30% of T cellsCD8 is expressed on 30% of T cells
(cytotoxic T cell)(cytotoxic T cell)

20. Markers for B & T cellsMarkers for B & T cells
 T cell markers are unidigits (Eg: CD3)T cell markers are unidigits (Eg: CD3)
 B cell markers are double digits (Eg: CD20)B cell markers are double digits (Eg: CD20)

21. T - lymphocytesT - lymphocytes
 CD4 binds to Class II MHC moleculeCD4 binds to Class II MHC molecule
expressed on APCexpressed on APC
 CD8 binds to Class I MHC moleculeCD8 binds to Class I MHC molecule
 CD4+ T cellCD4+ T cell - Master regulator- Master regulator
 Influences the function of other T cells, B cells,Influences the function of other T cells, B cells,
macrophages & NK cellsmacrophages & NK cells

22. The T-cell receptor (TCR) complex.
The T-cell receptor (TCR) complex:
B, Recognition of MHC-
associated peptide displayed on
an antigen-presenting cell (top)
by the TCR. Note that the TCR-
associated ζ chains and CD3
complex deliver signals (signal
1) upon antigen recognition, and
CD28 delivers signals (signal 2)
upon recognition of
costimulators (B7 molecules).

23. T - lymphocytesT - lymphocytes
 T Helper- 1 (TH1) subsetT Helper- 1 (TH1) subset
 Secretes IL-2 and gamma IFNSecretes IL-2 and gamma IFN
 Involved in delayed hypersensitivityInvolved in delayed hypersensitivity
 Macrophage activation and synthesis of IgG antibodyMacrophage activation and synthesis of IgG antibody
 T Helper- 2 (TH2) subsetT Helper- 2 (TH2) subset
 Secretes IL4 and IL5Secretes IL4 and IL5
 Involved in the synthesis of IgE antibodyInvolved in the synthesis of IgE antibody
 CD8 T lymphocytesCD8 T lymphocytes
 secretes IL-2 and gamma IFNsecretes IL-2 and gamma IFN
 Act as cytotoxic cellsAct as cytotoxic cells

24. B - lymphocytesB - lymphocytes
 10-20 % of circulating lymphocytes10-20 % of circulating lymphocytes
 Present in BM, germinal centre ofPresent in BM, germinal centre of
lymphnode and white pulp of spleenlymphnode and white pulp of spleen
 Activation of B- lymphocytes – plasma cellsActivation of B- lymphocytes – plasma cells
– secretes Ig (humoral Immunity)– secretes Ig (humoral Immunity)
 IgM present on all B cells form the antigenIgM present on all B cells form the antigen
binding component of B cell receptorbinding component of B cell receptor

25. MacrophagesMacrophages
 Part of Mononuclear phagocytic systemPart of Mononuclear phagocytic system
 Process and present antigen toProcess and present antigen to
immunocompetent T cellsimmunocompetent T cells
 Important for delayed hypersensitivityImportant for delayed hypersensitivity
reaction. Gamma IFN secreted by T Helper-reaction. Gamma IFN secreted by T Helper-
1 (TH1) subset enhances microcidal1 (TH1) subset enhances microcidal
properties of macrophageproperties of macrophage
 Phagocyte the microbes that are opsonizedPhagocyte the microbes that are opsonized
by IgG or C3bby IgG or C3b

26. Dendritic CellsDendritic Cells
 Interdigitating dendritic cellsInterdigitating dendritic cells
 Present in lymphoid cells, interstitium of heart and lungPresent in lymphoid cells, interstitium of heart and lung
 Epidermis – Langerhans cellEpidermis – Langerhans cell
 Expresses MHC class II molecule and act as APC for TExpresses MHC class II molecule and act as APC for T
cellscells
 Follicular dendritic cellsFollicular dendritic cells
 Germinal centre of lymphoid follicle in spleen andGerminal centre of lymphoid follicle in spleen and
lymphnodelymphnode
 Bear Fc receptor for IgG and hence can trap antigenBear Fc receptor for IgG and hence can trap antigen
bound to antibodybound to antibody

27. The morphology and
functions of dendritic cells
(DC).
A, The morphology of
cultured dendritic cells.
B, The location of dendritic
cells (Langerhans cells) in the
epidermis.
C, The role of dendritic cells
in capturing microbial
antigens from epithelia and
transporting them to regional
lymph nodes.

28. Natural Killer (NK) cellNatural Killer (NK) cell
 10-15% of peripheral blood lymphocyte10-15% of peripheral blood lymphocyte
 Larger than small lymphocyte and containLarger than small lymphocyte and contain
azurophilic granulesazurophilic granules
 Large granular lymphocyteLarge granular lymphocyte
 First line of defence against tumour cells, viralFirst line of defence against tumour cells, viral
infected cellsinfected cells
 CD16 and CD56 positiveCD16 and CD56 positive
 Secretes gamma InterferonSecretes gamma Interferon
 Antibody Dependent Cell mediated CytotoxicityAntibody Dependent Cell mediated Cytotoxicity
(ADCC)(ADCC)

30. CytokinesCytokines
 Messenger molecule of immune systemMessenger molecule of immune system
 Short acting soluble mediators, involved inShort acting soluble mediators, involved in
the induction and regulation of immunethe induction and regulation of immune
responseresponse

31. CytokinesCytokines
Five groupsFive groups
1.1. MediateMediate naturalnatural immunityimmunity
 IL-1, IL-6, TNF- alphaIL-1, IL-6, TNF- alpha
2.2. RegulateRegulate lymphocytelymphocyte growth, activation and differentiationgrowth, activation and differentiation
 IL-2 & IL-4 – favours lymphocyte growth and Diff.IL-2 & IL-4 – favours lymphocyte growth and Diff.
 IL-10 & TGF-beta – downregulate immune responseIL-10 & TGF-beta – downregulate immune response
3.3. Activation ofActivation of inflammatory cellsinflammatory cells
 Gamma interferon, TNF alpha, lymphotoxin (TNF- beta), MIFGamma interferon, TNF alpha, lymphotoxin (TNF- beta), MIF
4.4. ChemokinesChemokines –– leukocyte movementleukocyte movement
5.5. Stimulation ofStimulation of hematopoiesishematopoiesis
 GM-CSF & G-CSF act on committed progenitor cellsGM-CSF & G-CSF act on committed progenitor cells

32. CytokinesCytokines
 Produced by different cell typesProduced by different cell types
 IL-1, TNF - alphaIL-1, TNF - alpha
 Act on many cell typesAct on many cell types
 IL-2 act on T cell, B cell and NK cellIL-2 act on T cell, B cell and NK cell
 Act in 3 waysAct in 3 ways
 Autocrine effect – IL-2Autocrine effect – IL-2
 Paracrine effect - IL- 7 BM stromal cellsParacrine effect - IL- 7 BM stromal cells
 Endocrine effect - IL-1, TNF – alpha (acuteEndocrine effect - IL-1, TNF – alpha (acute
phase reactant)phase reactant)

33. CytokinesCytokines
 Cytokines mediate their effect by binding toCytokines mediate their effect by binding to
specific high affinity receptorsspecific high affinity receptors
 Useful in therapyUseful in therapy
 Control the harmful effect of inflammation/Control the harmful effect of inflammation/
tissue damaging immune responsetissue damaging immune response
 Enhances immunity against cancer/microbialEnhances immunity against cancer/microbial
infectionsinfections

34. Histo-compatibilityHisto-compatibility
Antigens -Antigens - HLAHLA
Chromosome # 6
Identity of SELF

35. Histo-compatibility AntigenHisto-compatibility Antigen
 Antigens that evoke rejection of transplantedAntigens that evoke rejection of transplanted
organsorgans
 Principal function is to bind peptidePrincipal function is to bind peptide
fragments of foreign protein for presentationfragments of foreign protein for presentation
to appropriate antigen specific T cellsto appropriate antigen specific T cells
 MHC antigens – Human LeukocyticMHC antigens – Human Leukocytic
Antigen (HLA)Antigen (HLA)
 MHC antigens and corresponding genes areMHC antigens and corresponding genes are
complex in structurecomplex in structure

36. Histo-compatibility AntigenHisto-compatibility Antigen
 Base on structure, distribution and functionBase on structure, distribution and function
of MHC gene productsof MHC gene products
 Class I MHC antigensClass I MHC antigens have loci as HLA- A,have loci as HLA- A,
HLA – B and HLA – CHLA – B and HLA – C
 Class II MHC antigensClass II MHC antigens have single locushave single locus
HLA – D . It has 3 subregions – HLA- DP,HLA – D . It has 3 subregions – HLA- DP,
HLA-DQ and HLA- DRHLA-DQ and HLA- DR
 Class III genesClass III genes - complement- complement

38. Class I MHC antigensClass I MHC antigens
 Expressed on all nucleated cells & plateletExpressed on all nucleated cells & platelet
 It binds to peptides that are derived fromIt binds to peptides that are derived from
proteins such as viral antigensproteins such as viral antigens
 Cells process the antigen and transported toCells process the antigen and transported to
cell surface for presentation to CD8cell surface for presentation to CD8
cytotoxic T lymphocytescytotoxic T lymphocytes

39. Figure 6-10 Antigen
processing and recognition.
The sequence of events in
the processing of a
cytoplasmic protein antigen
and its display by class I
MHC molecules are shown
at the top. The recognition
of this MHC-displayed
peptide by a CD8+ T cell is
shown at the bottom.

40. Class II MHC antigensClass II MHC antigens
 Present only on APC – Macrophages,Present only on APC – Macrophages,
Dendritic cells & B cellsDendritic cells & B cells
 It binds to exogenous antigens (microbes,It binds to exogenous antigens (microbes,
soluble proteins) that are first internalisedsoluble proteins) that are first internalised
and processed in endosomes / lysosomesand processed in endosomes / lysosomes
 Peptide - MHC complex is transported toPeptide - MHC complex is transported to
the cell surface, where it is recognized bythe cell surface, where it is recognized by
CD4 helper T cellsCD4 helper T cells

41. The T-cell receptor (TCR) complex.
The T-cell receptor (TCR) complex:
B, Recognition of MHC-
associated peptide displayed on
an antigen-presenting cell (top)
by the TCR. Note that the TCR-
associated ζ chains and CD3
complex deliver signals (signal
1) upon antigen recognition, and
CD28 delivers signals (signal 2)
upon recognition of
costimulators (B7 molecules).

42. HLA & Disease associationHLA & Disease association
 InflammatoryInflammatory
 Myesthenia gravis – HLA B8Myesthenia gravis – HLA B8
 Ankylosing spondylitis- HLA B27Ankylosing spondylitis- HLA B27
 Polygonococcal arthritis – HLA B27Polygonococcal arthritis – HLA B27
 Salmonella arthritis – HLA B27Salmonella arthritis – HLA B27
 Rheumatoid arthritis – HLA DR4Rheumatoid arthritis – HLA DR4
 Chronic active hepatitis – HLA DR3Chronic active hepatitis – HLA DR3
 Grave’s disease – HLA DR3Grave’s disease – HLA DR3
 Inherited errors of metabolismInherited errors of metabolism
 21 hydroxylase deficiency – HLA BW4721 hydroxylase deficiency – HLA BW47
 AutoimmunityAutoimmunity
 Insulin dependent diabetis – HLA DR4 &DR3Insulin dependent diabetis – HLA DR4 &DR3

43. OverviewOverview
 HI --- Ab synthesisHI --- Ab synthesis
 CMI --- Sensitized cellsCMI --- Sensitized cells
 TH1 is associated with IgG elaborationTH1 is associated with IgG elaboration
 TH2 is associated with IgE elaborationTH2 is associated with IgE elaboration
 NK cells are non-specific in their actionNK cells are non-specific in their action
 HLA-B27, HLA-DR3 & 4 are moreHLA-B27, HLA-DR3 & 4 are more
commonly associated with diseasescommonly associated with diseases
 CytokinesCytokines

44. E N DE N D