T CELL INTERACTINS WITH PERIODNTAL DISEASES

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

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

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.

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.

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

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

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).

• 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.

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.

• 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.

• 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.

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.

• 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

• 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

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.

• 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”.

• 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

• 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.
• .

• 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.

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

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

• 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

• 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

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

• 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.

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

• 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

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

• 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

• 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

• 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,

• 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

• 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.

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). .

• 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

• 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.

• 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.

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.

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.
Immunol. 2012 Nov;12(11):749-61.

Immunol. 2012 Nov;12(11):749-61.

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.

• Immunological tolerance
• Peripheral tolerance

• 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

• 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.

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.

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).

• 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

• 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.

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.

• 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.

• 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

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

• 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

• 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.

• 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.

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

• 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

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

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

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).

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

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(

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

• 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

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

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

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.

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

• 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

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).

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.

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

T CELL INTERACTINS WITH PERIODNTAL DISEASES

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