This document provides an overview of T cell interaction and function. It discusses the major components of the immune system including lymphoid organs and lymphocytes. It describes the different types of T cells including T helper cells, cytotoxic T cells, regulatory T cells, and memory T cells. It explains T cell receptors, the MHC complex, and CD markers. It also covers T cell differentiation, activation, and effector functions. Finally, it briefly discusses tolerance and how self-reactive T cells can lead to autoimmune diseases when tolerance is broken.

1. T CELL INTERACTION

2. UNDER GUIDANCE OF:
Dr. Anjali Kapoor
Sr . Professor and Head
Dr.Sharmistha Vijay
Asso. Prof
DR. Setu Mathur Dr.Shikha Gupta Dr.Neha Saini
Asst.Prof Asst.Prof Asst. Prof
Dr. Ratnesh Jaiswal Dr.Debopriya Chatterjee
Senior Demonstrator Senior Demonstrator

3. contents
PART -I
• INTRODUCTION
• IMMUNE SYSTEM
• MHC
• CLUSTER OF
DIFFERENTIATION
• TYPES OF T CELLS
• TOLERANCE
PART-II
• AUTOIMMUNE
DISEASES
• ROLE OF T CELL IN
PERIODONTAL DISEASES
• T CELL & HIV

4. INTRODUCTION
• The immune system is responsible for the
ability of a host to resist foreign invaders.
• It includes an array of cells and molecules
with specialized role in defending the host
against continuous onslaught of microbes,
toxins, and cancer cells.

6. Organs and Cells of Immune System
• Lymphoid Organs :-
∞Primary lymphoid organs :-
a. Thymus
b. Bone Marrow
∞ Secondary lymphoid organs:-
a) Lymph nodes
b) Spleen
c) MALT ( Mucosa associated lymphoid
tissue)/GALT/ PEYER’S patches,bronchial,
nasal lymphoid tissues.

8. Lymphocytes
• Master of immune system
• 3 types :-
• B –Lymphoytes (10-15 %)
• T- Lymphocytes (75-80 %)
• NK cells (5-10 %)

10. *Kumar, V., Abbas, A.K., & Aster, J.C. (2013). Robbins basic pathology (9th ed.).
Philadelphia, PA: Elsevier Saunders

11. T Cells
• T cell-mediated immunity is an adaptive
process of developing antigen (Ag)-specific T
lymphocytes to eliminate viral, bacterial, or
parasitic infections or malignant cells.
• T cell-mediated immunity can also involve
aberrant recognition of self-Ag, leading to
autoimmune inflammatory diseases.
• The Ag specificity of T lymphocytes is based on
recognition through the T cell receptor (TCR) of
unique antigenic peptides presented by MHC
molecules on Ag-presenting cells (APC).

12. • T cell-mediated immunity is the central element
of the adaptive immune system and includes a
primary response by naive T cells, effector
functions by activated T cells, and persistence
of Ag-specific memory T cells.
• T cell-mediated immunity is part of a complex
and coordinated immune response that
includes other effector cells such as
macrophages, natural killer cells, mast cells,
basophils, eosinophils, and neutrophils.

13. Naive T cells are those that haven’t previously
responded to a pathogen.
Effector T cells :- When Naive T cells recognize a
pathogen, they rapidly divide and express
molecules such as cytokine proteins that help to
fight infection.
These responding cells are called effector T cells
and they can migrate into inflamed tissues and
kill infected cells.

15. • T lymphocytes are divided into 2 major cell types—
T helper (TH) cells and
 T cytotoxic (TC) cells
• that can be distinguished from one another by the
presence of either CD4 or CD8 membrane
glycoproteins on their surfaces.
• T cells displaying CD4 generally function as TH
cells and recognize antigen in complex with MHC
class II,
• whereas those displaying CD8 generally function
as TC cells and recognize antigen in complex with
MHC class I.

16. • The ratio of CD4 to CD8 T cells is
approximately 2:1 in normal mouse and
human peripheral blood.
• A change in this ratio is often an
indicator of immunodeficiency disease
(e.g., HIV), autoimmune diseases, and
other disorders.

17. T CELL RECEPTORS (TCR)
• T cells respond to antigen
fragments presented in
MHC molecules through
specific T-cell receptor
(TCR) complexes on their
plasma membrane surface
• Each receptor complex is
composed of two parts:
ᾰ Alpha chain
ᾰ Beta chain
• Each chain is stabilized by
disulfide bonds.

18. • A small fraction of the T cells express
• γ(gamma)
• δ (delta) chains in TCR,
• These appear to be much less
heterogenic than αβTCR T cells,
• Mainly found in skin and certain
mucosal surfaces, and

19. • The cytoplasmic tails
of the receptors do
not contribute to
signal transduction
but rather associate
with the CD3
accessory
polypeptides .
• The accessory
molecules transduce
antigen binding
events into
intracellular signals

20. WHY TO NAME CD ????
• The cluster of differentiation (CD) nomenclature system
was conceived to classify antigens found on the surface
of leukocytes.
• Initially, surface antigens were named after the
monoclonal antibodies that bound to them.
• As there were often multiple monoclonal antibodies
raised against each antigen by different labs, the need
arose to adopt a consistent nomenclature.
• The current system was adopted in 1982, during the 1st
International Workshop and Conference on Human
Leukocyte Differentiation Antigens (HLDA) in Paris.

21. • Under the current naming system, antigens that are
well characterized are assigned an arbitrary number
(e.g. CD1, CD2 etc)
• whereas molecules that are recognised by just one
monoclonal antibody are given the provisional
designation “CDw”.

22. • Physiologically, CD antigens do not belong in any
particular class of molecules, with their functions
ranging from cell surface receptions to adhesion
molecules.
• Although initially used for just human leukocytes, the
CD molecule naming convention has now been
expanded to cover other species (e.g. mouse) as well
as other cell types.
• Human CD antigens are currently numbered up to
CD363

23. • CD4 is a 55 kDa monomeric
membrane glycoprotein that
contains four extracellular
immunoglobulin-like
domains (D1–D4), a
hydrophobic transmembrane
region, and a long
cytoplasmic tail containing
three serine residues that
can be phosphorylated.
• .

24. • CD8 takes the form of a
disulfide-linked heterodimer
or homodimer.
• Both the and chains of CD8
are small glycoproteins of
approximately 30 to 38 kDa.
• Each chain consists of a
single, extracellular,
immunoglobulin-like domain,
a stalk region, a
hydrophobic transmembrane
region, and a cytoplasmic
tail containing 25 to 27
residues, several of which
can be phosphorylated.

26. Major Histocompatibility Complex
(MHC)
• The major histocompatibility complex (MHC) is a
collection of genes that code for the self/nonself
recognition potential of an animal.
• The human version of MHC is located on chromosome
6 and is called the human leukocyte antigen (HLA)
complex.
• HLA molecules can be divided into three classes:
• class I molecules are found on all types of nucleated
body cells;
• class II molecules appear only on cells that can
process antigens and present them to other cells (i.e.,
NK cells ,macrophages, dendritic cells, and B cells);
and

27. • class III molecules include various
secreted proteins that have immune
functions.
• Class III molecules are not required for
the discrimination between self and
nonself

29. • The Membrane-
Bound Class I Major
Histocompatibility
Complex Molecules.
• is a heterodimer
composed of the
alpha protein, which
is divided into three
domains: α1, α2 ,α 3.
and the protein
β2 microglobulin

30. • The class II molecule
is a heterodimer
• composed of two
distinct proteins
called alpha and
beta. Each is divided
into two domains
• α1,α2,
• β 1, β2

32. T HELPER CELLS (Th Cells)
• When naïve CD4 T
recognize an MHC-
peptide complex,
they can become
activated and
proliferate and
differentiate into
one of a variety of
effector T cell
subsets

33. • T helper type 1 (TH1) cells regulate the immune
response to intracellular pathogens, and
• T helper type 2 (TH2) cells regulate the response to
many extracellular pathogens.
• T helper type 17 cells (TH17), so named because they
secrete IL-17, play an important role in cell-mediated
immunity and may help the defence against fungi.
• T follicular helper cells (TFH) play an important role in
humoral immunity and regulate B-cell development in
germinal centers.
• Treg cells has the unique capacity to inhibit an immune
response.

34. • Th -9 cells
• subset that develops under the influence of IL-
4 and TGF-β and
• Secrets :-IL-9

35. • Which helper subtype dominates a response depends
largely on what type of pathogen (intracellular versus
extracellular, viral, bacterial, fungal, helminth) has
infected an animal.
• Each of these CD4 T-cell subtypes produces a different set
of cytokines that enable or “help” the activation of B cells,
TC cells, macrophages, and various other cells that
participate in the immune response

37. Regulatory T cell (Tregs)
• Another type of CD4 T cell, the regulatory T cell
(TREG), has the unique capacity to inhibit an
immune response.
• Although the majority of Treg appears within the
CD4+ T cell set, suppressor activity was also
reported among CD8+ T cells.
• They are identified by the presence of CD4 and
CD25 on their surfaces, as well as the expression of
the internal transcription factor FoxP3
• TREG cells are critical in helping us to quell auto
reactive responses that have not been avoided via
other mechanisms.
Wing K, Sakaguchi S (2010) Regulatory T cells exert checksand balances on self tolerance and
autoimmunity. Nat Immunol 11: 7–13

38. • Foxp3 is essential in the development and function of
Treg.
• The absence of functional Foxp3 results in severe
systemic autoimmune diseases in man.
• Foxp3 inhibits IL-2 transcription and induces up-
regulation of Treg-associated molecules, such as CD25,
CTLA-4 and GITR
• That can down-regulate the immune response of
adjacent cells
Wing K, Sakaguchi S (2010) Regulatory T cells exert checksand balances on self tolerance and
autoimmunity. Nat Immunol 11: 7–13

39. • 2 types :-
nTREG(Natural )
iTREG(Induced)
• nTREG:-
• These cells arise during maturation in the
thymus from auto reactive cell .
• 10 % of total CD4 cells.
• Characterized by constitutive expression of the
α-chain of the IL-2 receptor (CD25) and the
transcription factor Foxp3
F.P. Nijkamp and M.J. Parnham (eds.), Principles of Immunopharmacology: 3rd revised and
extended edition,DOI 10.1007/978-3-0346-0136-8_2, © Springer Basel AG 2011

40. • iTREG cells:-
develop in the periphery from naive
CD4+ T cells in the presence of TGF-β and
IL-10, or
Tr cells depend on IL-10 for their
induction and their suppressive action,
F.P. Nijkamp and M.J. Parnham (eds.), Principles of Immunopharmacology: 3rd revised and
extended edition,DOI 10.1007/978-3-0346-0136-8_2, © Springer Basel AG 2011

41. • The inhibitory effect of all Treg primarily
requires stimulation of the TCR.
• Upon activation, cells may mediate their
function via :-
• Inhibitory cytokines – IL-10,TGF-β , IL-35
• Granenzymes A & B
• Cytokine deprivation by IL-2
• Direct cell to cell interaction via CTLA4
F.P. Nijkamp and M.J. Parnham (eds.), Principles of Immunopharmacology: 3rd revised and
extended edition,DOI 10.1007/978-3-0346-0136-8_2, © Springer Basel AG 2011

42. F.P. Nijkamp and M.J. Parnham (eds.), Principles of Immunopharmacology: 3rd revised and
extended edition,DOI 10.1007/978-3-0346-0136-8_2, © Springer Basel AG 2011

44. • Helper T-cell subsets often “cross-regulate”
each other.
• The cytokines they secrete typically enhance
their own differentiation and expansion
and inhibit commitment to other helper T-cell
lineages.
• This is particularly true of the TH1 and TH2
pair, as well as the TH17 and TREG pair.

45. Cytotoxic T lymphocyte (CTL).
• Naïve CD8+ T cells browse
the surfaces of antigen
presenting cells with their
T-cell receptors.
• If and when they bind to
an MHC-peptide complex,
they become activated,
proliferate, and
differentiate into an
effector cell called a
cytotoxic T lymphocyte
(CTL). .

46. • The CTL has a vital function in monitoring the cells of
the body and eliminating any cells that display
foreign antigen complexed with class I MHC, such as
virus-infected cells, tumor cells, and cells of a foreign
tissue graft .
• To proliferate and differentiate optimally, naïve CD8
T cells also need help from mature CD4 T cells

47. • Once activated, CTLs kill target cells in at
least two ways:
1) Cytolytic pathway, using perforins and
granulysins, that is similar to complement-
mediated lysis; and
2) Apoptotic (programmed cell death)
pathways triggered by CD95-Fas-FasL
(ligand) or by granzymes and perforins.
• The cellular signaling that results in one
pathway over the other is not known.
However, use of the right killing pathway is
critical.

48. F.P. Nijkamp and M.J. Parnham (eds.), Principles of Immunopharmacology: 3rd revised and
extended edition,DOI 10.1007/978-3-0346-0136-8_2, © Springer Basel AG 2011

49. • By inducing target-cell apoptosis,
rather than cell lysis, both the perforin/
granzyme and the CD95 pathways
stimulate membrane changes that are
thought to trigger phagocytosis and
destruction of the apoptotic cell by
macrophages.

50. MEMORY T CELLS
• When T Cells recognize a pathogen, they rapidly divide
and express molecules such as cytokine proteins that help
to fight infection.
• These responding cells are called effector T cells and they
can migrate into inflamed tissues and kill infected cells.
• Once the pathogen is eliminated, most effector cells die,
but a small pool of long-lived memory cells remains that is
poised to respond rapidly if reinfection occurs.
• Which cells give rise to memory T cells has been
extensively investigated.
Transcriptional control of effector and memory CD8+ T cell differentiation. Nat Rev
Immunol. 2012 Nov;12(11):749-61.

51. Two general possibilities have been
proposed
1) The cells arise descend directly
from naive T cells, which could, as
early as their first cell division,
give rise to cells with effector-T-cell
or memory-T-cell potential.
2) A subset of effector cells gives rise
to memory T cells.
Transcriptional control of effector and memory CD8+ T cell differentiation. Nat Rev
Immunol. 2012 Nov;12(11):749-61.

52. Transcriptional control of effector and memory CD8+ T cell differentiation. Nat Rev
Immunol. 2012 Nov;12(11):749-61.

53. Tolerance
• An essential part of T cell-mediated
immunity is the development of non-
responsiveness toward naturally occurring
self-Ag, while mounting effective immune
responses against “foreign” Ag .
• Breakdown of self-tolerance will result in
the development of autoimmune diseases.
• Self-reactive T cells, both CD4 & CD8 cells
are responsible for initiating and
mediating tissue damage in organ-specific
autoimmunity.
F.P. Nijkamp and M.J. Parnham (eds.), Principles of Immunopharmacology: 3rd revised and
extended edition,DOI 10.1007/978-3-0346-0136-8_2, © Springer Basel AG 2011

54. • Immunological tolerance
• Peripheral tolerance
F.P. Nijkamp and M.J. Parnham (eds.), Principles of Immunopharmacology: 3rd revised and
extended edition,DOI 10.1007/978-3-0346-0136-8_2, © Springer Basel AG 2011

55. • Immunological tolerance is achieved by
different mechanisms at different stages.
• Initially, potential self-reactive T
lymphocytes are deleted during T cell
development in the thymus.
• T cells with TCR of low to moderate affinity
to self-Ag escape from the thymus and
migrate to the periphery.
• These T cells are normally “ignorant” to
self-Ag or develop tolerance after initial
activation
F.P. Nijkamp and M.J. Parnham (eds.), Principles of Immunopharmacology: 3rd revised and
extended edition,DOI 10.1007/978-3-0346-0136-8_2, © Springer Basel AG 2011

56. • Peripheral tolerance can also be controlled by
immune cytokine divergence and by Treg cells.
• Both natural and adaptive CD4+ regulatory
cells have been implicated in the regulation of
the autoimmune response.
• Thymus-derived CD25+ nTreg cells suppress
other types of cell activation by largely
unknown mechanisms.
• They require strong costimulatory signals for
induction and maintenance, with Foxp3
expression.
F.P. Nijkamp and M.J. Parnham (eds.), Principles of Immunopharmacology: 3rd revised and
extended edition,DOI 10.1007/978-3-0346-0136-8_2, © Springer Basel AG 2011

57. Introduction
• In 1965, Kraus demonstratedthe presence of
immunoglobulin-producingplasma cells in thegingival
tissues of patientswith periodontal disease.
• This was thefirst direct evidence thatadaptive immune
mechanismsplay a role in thepathogenesisof periodontal
inflammation
• The study by Ivanyi and Lehner (1970) was thefirst to report
possible suppression ofcell-mediatedimmunityin advanced
periodontitis subjects.

58. Th Cells AndPeriodontalDisease
• Studies ofhumanperiodontaltissues suggestedthattheratioof
Th1 toTh2cellsingingival tissuecontributestothedevelopment
andpathogenesisofperiodontitis.
• Th1 cytokineswere foundin almostallperiodontitisgingival
tissuesandwere thereforeassociatedwith asusceptible
individual,whereasTh2 cytokineswerefoundless frequently
(Seymour et al.,1993).
• The T cellsin diseasedgingivaltissueswere reportedto
predominantlyexpress thechemokinereceptors CCR5 and
CXCR3,which arecharacteristicofTh1 cells (Gamonaletal.,
2001).

59. • It has been proposedthat
Stable periodontal lesions
resemble a Delayed type
hypersensitivity lesion and
• Progressive lesion involves
large number of B cells, these
lesions may be mediated by
Th1 and Th2 cells,
respectively
Gemmel E, Seymour GJ. Immunoregulatory control of Th1/Th2 cytokine profiles in periodontal
disease. Periodontol 2000. 2004;35:21–4

60. • Mice withA.actinomycetemcomitans-inducedperiodontitis
demonstratedupregulationofTh1 cytokines(IFN-γand IL-12)in
theearly stageand
• Th2 cytokines(IL-4andIL-10)inthe latestage,indicatingthe
involvementof each Tcellsubsetin differentdiseasestages.
• It hasbeen shown thata strong innateresponse leadsto aTh1
response under theinfluence ofIL-12,IL-2and
IFN-γwhile
• a weakinnateresponse leads toa Th2 response under the
influenceof IL-4cytokines.

61. Yamazaki K, Yoshie H, Seymour GJ. T cell regulation of the immune response to
infection in periodontal diseases: a review. Histology and Histopathology 2003;18: 889–
896.

62. • In a stable lesion,IFN-γenhances the phagocytic activityofboth neutrophils
and macrophages and hence contains the infection.
• In case ofa poor innate immune response andminimal IL-12production, a
weak Th1response may not contain infection.
• Mastcell stimulationand the subsequent production of IL-4would encourage a
Th2response, B-cellactivation and antibody production.
• If these antibodies areprotective and clearinfection, the disease willnot
progressbut iftheyarenot protective, as incase ofIgG2, the lesion willpersist.
• ContinuedB-cell activationmay resultin largeamounts ofIL-1and hence
tissue destruction.

63. • Despite its simplicity, theTh1/Th2 modeldoes not adequately
explainmany findingswithrespect to T-cell-mediated
immuneresponses.
• Various studies have reported discrepancies withregard to
predominance of Th1 or Th2 response or theinvolvement of
both Th1 and Th2 cells in diseased tissue

64. Th17
• It has become apparent that the pathogenesis of
periodontitis cannot be fully explained through the
prism of the Th1/Th2 paradigm; therefore, the
discovery of Th17 has been expected to clarify the
complex pathogenesis of periodontitis.
• Studies have shown an elevated level of IL-17 in
gingival tissues or gingival crevicular fluid from
periodontitis lesions compared with healthy sites .
The Role of Distinct T Cell Subsets in Periodontitis—Studies
from Humans and Rodent Models, Curr Oral Health Rep (2014) 1:114–123

65. • These reports also demonstrated the association of
other Th17-related cytokines (eg, IL-1β, IL-6, IL-21, and
IL-23) with periodontitis.
• It was demonstrated that Porphyromonas
gingivalis outer membrane protein induced a
significant increase in the production of IL-17.
• IL-17 has been shown to stimulate epithelial,
endothelial and fibroblastic cells to produce IL-6, IL-
8 and PGE2.
• In addition, IL-17 induces receptor activator of
nuclear factor-κ B ligand (RANKL) production by
osteoblasts[and thus influence osteoclastic bone
resorption

68. • The serum concentration of IL-17 was
dramatically increased in aggressive
periodontitis patients compared with healthy
subjects .
• Zhao et al reported that nonsurgical
periodontal therapy reduced the proportion of
IL-17+ cells in peripheral blood CD4+ T cells.
Evidence of the presence of T helper type 17 cells in chronic lesions of human periodontal
disease.Cardoso CR, Garlet GP, Crippa GE, Rosa AL, Júnior WM, Rossi MA, Silva JS
Oral Microbiol Immunol. 2009 Feb; 24(1):1-6.

69. • Collectively, humanand animal studiessuggest thatT-helper
17 subset possibly hasbeneficialand detrimentalaspects in
thepathogenesisof periodontal disease;
• thereby, an appropriate balance between thefunctionally
differentsubsets may be important to eliminateinfectionand
abrogate tissuedestruction.
Evidence of the presence of T helper type 17 cells in chronic lesions of human periodontal
disease.Cardoso CR, Garlet GP, Crippa GE, Rosa AL, Júnior WM, Rossi MA, Silva JS
Oral Microbiol Immunol. 2009 Feb; 24(1):1-6.

70. TREGS CELLSINPERIODONTAL DISEASE
• EvidenceregardingtheexactroleplayedbyTregcellinmediatingperiodontal
diseasecontinuestobecontroversial.
• Nakajima[2005]andCardoson[2008]demonstratedthatperiodontitispatients
showedan increasedpercentageofTregcellsingingivalconnectivetissue
comparedtogingivitispatients.
• Itwas concludedthatTregslevelswereupregulatedinchronicperiodontitis
lesionsas protectionagainstself-antigenssuchas collagen-1.
• Ernst[2007]demonstratedthatTregcellsdownregulatedRANKLexpressionin
periodontaldisease.
Ebersole JL, Dawson DR, Morford LA, Peyyala R, Miller CS, Gonzaléz OA. Periodontal disease
immunology: “Double indemnity” in protecting the host. Periodontol 2000 (2013) 62:163–202.
doi:10.1111/prd.12005

71. • However, their capacityto provide immunoregulatory function in
periodontal disease has been questioned.
• Dutzan[2009] suggested that Treg cells may not have a regulatory
function due to lack of CTLA-4 expression that is required for cell-cell
contact inhibition of T-cellproliferation. Further,
• Okui[2007] suggested that Treg cells in gingival tissues may not have
similar functions as that in circulation due to differences in Foxp3
expression in the two.
• To summarize, although the exact nature of the role (protective vs. non-
protective) played by Treg cells is not known, these cells exert important
influences on the overall T-cell response
Ebersole JL, Dawson DR, Morford LA, Peyyala R, Miller CS, Gonzaléz OA. Periodontal disease
immunology: “Double indemnity” in protecting the host. Periodontol 2000 (2013) 62:163–202.
doi:10.1111/prd.12005

72. CD8+ TCells in Chronic periodontitis
• The role of CD8+ T cells in chronic periodontitis is less obvious,
• most studies have consistently shown that despite being more
abundant in gingival tissues of periodontitis patients than in patients
with gingivitis or healthy controls, CD8+ T cells are not involved in
gingival tissue pathology .
• Similar conclusions were drawn from mice studies byBaker et al.
(1999),
Cardoso EM and Arosa FA (2017) CD8+ T Cells in Chronic Periodontitis: Roles and Rules. Front.
Immunol. 8:145. doi: 10.3389/fimmu.2017.00145

73. Memory T cells& PeriodontalDiseases
• Studies demonstratedthatin both healthyand PD gingival
samples,CD45RO+memorycellspredominateandfewCD45RA+
naïvecells comprise thetissue.
• The memorycells were presumedto bespecificforcommensal
bacteriapresent inoral plaquebiofilms.
• Gemmellet al.,1992documented thatmemoryT cellsare evident
in gingival tissueirrespectiveofperiodontitis,yettherole ofthese
cells in both healthanddiseaseremainsan enigma.
• MemoryT cellstatusof micewithexperimentalPD alsoremains
completelyunknown.
.T cells, teeth and tissue destruction - what do t cells do in periodontal disease? Campbell L et
al. Molecular oral microbiology. 31(6):445-456

74. T Cells And Osteoimmunology
• Binding ofRANKLto RANKexpressed on the surfaceof pre-
osteoclastsinduces differentiationtomatureosteoclasts.
• RANKL-inducedosteoclastogenesisis responsibleforthe alveolar
bone destruction in periodontaldiseasesand
• RANKLexpressionhas beenidentifiedon T cells(Kawaietal.,
2006,).
• Therefore,it is plausiblethatT cells are directly involved in bone
resorptionofPD (BelibasakisandBostanci,2012).

75. Gonzales JR (2015) T- and B-cell subsets in periodontitis. Periodontol 2000 69:181–200

76. AUTOIMMUNITYAND PERIODONTALDISEASES
B),on theotherhand,theautoimmune
responsestimulatesscavengercells totakeup the
degeneratedself-componentsresultingin accelerationof
thetissuerepairprocess.Thesemechanismsmaybe well
controlledby regulatoryT cells.Consequently,tissue
integrityismaintainedandthestablelesioncanbe seen
.In susceptiblepatients(A), infectionand
subsequentinflammationresultin theup-regulationof
auto-antigenssuch asheat-shockprotein60 andcollagen
typeI andtheactivationofauto-reactiveT andBcells
specifictothoseantigens.AlthoughregulatoryTcells are
induced in thelesion,theirnumberandfunctionmaynot
besufficienttocontrolimmunepathology.In non-susceptible
patients(

77. T cellImmunodeficiency
• T cell immunodeficiencycan occur as one of a group of
primary disorders or develop secondary to chronic infection,
illness or drug therapy.
• Primary T celldisorders..
• Secondary T celldeficiency
T cell immunodeficiency ;J D M Edgar; J Clin Pathol 2008;61:988–993.
doi:10.1136/jcp.2007.051144

78. • Primary immunodeficiency syndromes are usuallytheresult
of single genedisorders or other maturationalabnormalities
thattypically result in a defective immunesystem from early
in life.
• Specific T celldisorders account for approximately 11% of
primary immunodeficiencies

79. T cell immunodeficiency ;J D M Edgar; J Clin Pathol 2008;61:988–993.
doi:10.1136/jcp.2007.051144

80. X LinkedImmune DeficiencyWith Associated
HyperIgM
• Hyper IgM syndrome describes a group of conditions in which low
serum IgG is typically andparadoxicallyassociated with high serum IgM.
• These disorders reflect a failure of ‘‘class switching’’ of the humoral
immune response
• In response to infectious stimuli, IgM is produced normally; however this
does not progress to the normal production of antigen-specific IgG.
• Switching to IgA and IgE production is also usually defective.
• The most common underlying defect is abnormal expression of the Tcell
surface antigen CD40 ligand

81. Severe combinedimmune deficiency(SCID)
• Severe combinedimmunedeficiency(SCID) comprises a group of
disorders characterisedbysevere Tcelldeficiency,
• withor withoutabnormalB celldifferentiation.
• SCID maybe caused by reticulardysgenesisin which both
myeloidand lymphoidcelllines are affected,
• or itmaybe caused by specificdeficienciesaffectinglymphocytes
(eg,XlinkedSCID;).
• Mostof theseaffectthedevelopmentoflymphoidstemcellsinto
pre Tcells.

82. DiGeorgeSyndrome
• DiGeorgesyndrome isassociated witha developmental abnormality ofthe
thirdand fourth branchial arches.
• The clinical featuresofthe fullyexpressed syndrome consist of:-
i. Abnormal facies withlow-setears,‘‘fish-shaped’’ mouth, hypertelorism,
notched ear pinnae, micrognathia and a downward slant ofthe eyes;
ii. Hypoparathyroidism (oftenpresenting withneonatal hypocalcaemic tetany);
iii. congenital heart disease (particularlyaortic archdefects: truncus arteriosus,
interruptedarchorFallot’stetralogy);and
iv. cellularimmune deficiency

83. • Peripheral bloodT cellcounts fallprogressively,
• The thymus isoftenmarkedlyhypoplasticand T cellcytotoxicityis
impaired.
• The clinicalmanifestationof immunedeficiency is usuallymild
andsomepatientsrequire no preventativetherapy.
• However manywillrequire immunoglobulinreplacementand
someprophylactic antiviraland fungalagents.
• Patientsultimatelydevelop lymphoidleukaemia/lymphomain
thesecond andthird decades and this,withprogressive combined
immunedeficiency,is theusual cause ofdeath

84. SecondaryImmunodeficiency
• Secondary immunodeficiencyis amuch more common
phenomenonthan primaryimmunodeficiency.
• Common causes ofsecondary immunodeficiencyinclude :-
 Drugs (eg,corticosteroids,cytotoxics,etc),
 Infection(HIV, EBV,malariaetc),
Malignancy,(lymphoproliferativedisease),
Malnutrition,and
Systemic disease(diabetes,liver/renalfailure).

86. HIV
• HIV-1and-2expressthe surface proteingp120, which specifically
binds tocellsurface CD4 and thus HIV specificallyinfectsand
depletesT helper cellsandmacrophages/monocytes(which also
express CD4).
• As CD4 cells are lost,a profound immunodeficiencyresults with
particular susceptibilitytoviral, fungalandother opportunistic
pathogens.
• The relationshipbetweenthe CD4 cellcount and susceptibilityto
particular micro-organismsis welldefined.

87. Investigationof T cell
• Investigation of T cell numbers and function
• WBC with differential: will give total lymphocyte number.
• Flow cytometry: to detect the absolute CD4+ and CD8+ T cell numbers.
• Functional assessment of T cells:
• T cell proliferative capacitywhen stimulated with antigen: by flow
cytometry
• T cell cytokine responses to antigens: by ELISpot and flow cytometry •
• T cell surface markers: by flowcytometry
• Delayed type hypersensitivity reactions

88. THNAK YOU
HAVE A GOOD DAY