TUTORIAL PRESENTATION

IMMUNOLOGY OF LEPROSY
PRESENTER:-DR.BHAGWAN DASS
INTRODUCTION
Leprosy bacilli obtained from patients wit dff. Types
of disease, and living different parts of world, all
produce identical histo-pathological changes when
transmitted to the foot pad of mice, and this strongly
suggests that human leprosy is produce by one
strain of bacillus, and that clinical patterns of the
disease are determined by different host response ,
i.e.by immunilogical factors in the host

Leprosy is influenced by genetic factors
host , environmental factors such as the state
nutritional , BCG vaccination and exposure rate
to M. leprae or other response micobacterias.
immune response is crucial for the defense of
body upon exposure to the bacillus .
Leprosy characterized by high infectivity and low
pathogenicity, and the majority of the population , more
95% of individuals are naturally immune
In leprosy , alteration of the immune response is
associated with the development of different clinical
forms ,
where the predominant cellular response is
related to milder clinical form of the disease
( tuberculoid ) and absence , and the clinical form more
severe ( lepromatous )
In the course of the disease or many times after
initiation
treatment , some patients may have
calls or reactional leprosy reactions ,
secondary to acute inflammatory processes
release of antigens and hypersensitivity reactions
The types of reactions are the most important
reaction
type 1 or reversal reaction ( RR ) and type 2 reaction
or ENL
CLASSIFICATION HANSEN disease
The clinical forms of leprosy present distribution
spectrum that is associated with immunological changes
the host.
The classification of Ridley & Jopling is the most
recommended in immunological studies ; is based on
histological criteria and suggests the possibility of
oscillating in the spectrum of Forms
disease , sometimes to the pole of resistance (
tuberculoid )
prays pole susceptibility ( lepromatous)
Subtypes are TT ( tuberculoid ) , BT ( borderline
tuberculoid )
BB ( borderline borderline ) , BL ( borderline lepromatous
)
and LL ( lepromatous )
Initially patients were treated According to the
histopathological classification of Ridley & Jopling ,
however, due to the need for expansion of leprosy
elimination campaign was proposed OMS12 by a
classification based on the operating counting the
number of skin lesions . Patients are classified into
paucibacillary ( PB ) or multibacillary (MB ) are presented
one to five lesions or more than five lesions ,
respectively. It destacarum recent study in which we
compared the two ratings for treatment of leprosy , which
concluded that , in areas where the frequency of patients
MB is high , the smear should be performed and skin
biopsy to properly classify the patient , in order to avoid
its undertreatment . 13 In Brazil , the Madrid classification
( Congress International , 1953) is used to work field , but
do not take into account the evaluation Histological which
has a strong correlation with the
immunological aspects of the disease.
DEVELOPMENT OF IMMUNE RESPONSE
The immune response can be divided schematically
in innate and acquired . An immune response
Innate effective in combination with low virulence
M. leprae is associated with resistance to development
The hansenase.2 the innate immune response has
characteristic of being non-specific defense mechanism ,
with general action on microorganisms , independent
of his nature . The first line of interaction
between M. leprae and is mediated by the Man
host cell receptors that recognize
molecular patterns of mycobacteria , called
pattern recognition receptors
( PRR ) . An example of this type of receivers , the receivers
Toll - like receptors (TLRs ) are essential for the recognition
pathogens by macrophages and cells
dendritic cells during innate immune response .
Ten TLRs have been identified , including heterodimers
TLR2 - TLR1 , TLR2 and TLR4 homodimers
seem to be important for the recognition of
micobactrias.
TLR receptors , especially the TLR- 2 are
activated by lipoproteins of M. leprae , and the ability
starting the protective response is directly
related to the secretion and the differentiation IL-12/23
dendrticas.15 cells and macrophages , latter 16
present the antigen and cause the activation of
naive T cells through IL- 12.17 This
process can lead to expansion and differentiation
Th1 cells produce interferon (IFN- ), which
induces the elements of the immune response responsible
the Elimination of bacillus thereby controlling the evolution
's disease. In some studies with M.
tuberculosis , TLRs have been identified as necessary
for optimal production of IL- 12, 14 proinflammatory cytokine
responsible for the induction of immunity
cellular (Th1 ) and TNF- , cytokine involved 18
in cell activation and granuloma formation , which
is also related to tissue destruction
associated with outbreaks of hansenase.19 reaction , 20
The adaptive immune response characterized by
provide mechanisms that are based on the recognition
specific antigens mediated by recep-tors present in the membranes of T and B
lymphocytes
Classically adaptive immune response can be
categorized into type 1 or cellular , and humoral or
type 2 . The ability for helper lymphocytes
(CD4 +) , also known as helper T lymphocytes
( Th ) in inducing humoral and cellular responses are
related to the types of cytokines, and
provide the development of the already known
Th1 or Th2 cells. The predominant response
humoral or cellular immune , front bacillus infection ,
can influence the evolution of the disease and be associated
at least in part, to the clinical
observed in patients with forms
TT and VV , respectively.3
The leprosy patients of
TT so have vigorous cellular immune response
against mycobacteria , which would limit the disease a few
and well-defined skin lesions and nerve trunks .


21 Patients with leprosy fashion
VV present absence of cellular immune response
specific ( anergy ) against mycobacteria , occurring
proliferation of M. leprae , with the presence of many
extensive infiltration and damage to the skin and nervos.22
In the TT form of the disease , interferon IFN- , IL -2, and
are secreted lymphotoxin - lesions , resulting in
phagocytic activity intensa.9 , 23,24 Macrophages under
influence of these cytokines along with lymphocytes,
form the granuloma.25 , 26 CD4 + lymphocytes are
mostly found within the granuloma , and
The CD8 + cells are found in the outer area
envolvem.27 28
The way VV is characterized by poor training
the granuloma . The production of predominantly
IL- 4, IL -5 and IL- 10.29 , 30 has been described which
IL-4 decreases the expression of TLR2 and in moncitos14
that IL -10 suppresses production of IL -12 which is 31
associated with the predominance of CD8 + lesions virchowianas.28 After
recognition by cells of the bacillus dendritic subsequent local cytokine and
chemokines regulates the inflammatory process and directs the course of
adaptive immunity mediated by Th1 cells or Th2 responses in response to
M. leprae.32 -34 Langerhans cells are subtypes Dendritic cells that initiate
the immune response the skin. VV patients have few cells Langerhans cells
of the skin , whether biopsy samples healthy skin or lesion compared to
uninfected controls or patients TT.35 , 36 In contrast , TT patients have an
increased number Langerhans cells in the lesions , suggesting infiltration
these cells in the active site. Also found in biopsy material of leprosy patients
, increased receptor expression in monocytes TLR1 and TLR2 and dendritic
cells tuberculous lesions compared virchowianas.35 with injuries , 37 was
also detected mutation of TLR2 in the clinical VV . 38.39 Upon stimulation of
cells with the mutation bacilli or antigens of M. leprae was found
a failure of activation of the transcription factor NF - kB , relevant to the
production of inflammatory cytokines , determining decreased production of
IL-2 , IL-12 , IFN- and TNF- , and increased production of IL-10 , 40,41 in

compared with cells lacking the mutation.
By immunohistochemical techniques ,
has been shown to exhibit tuberculous lesions
more CD4 + cells with the CD4 + / CD8 +
of 1.9:1 , in contrast , lesions exhibit virchowianas
the CD4 + / CD8 + of 0.6:1.27,42 was still observed
the cells present were primarily CD4 +
phenotype and nave CD8 + T phenotype were
suppressor , may act by suppressing the response
clula.43 mediated immune However , the role of
T regulatory cells (CD4 + CD25 +) in various forms
clinical leprosy should be further
clarified .
The borderline forms of leprosy spectrum
are immunologically dynamic oscillation occurring
between the two polar forms . Patients BT ,
BB and BV , the progressive reduction of the response mediated
per cell shape to form BT BV is accompanied
by skin lesions and nerves more numerous ,
increased bacterial load and antibody levels
(Figure 1) .10,22 Humoral immunity is present in the
forms VV and BV , and displays high titers of antibodies
specific against one phenolic glycolipid ( PGL -1)
specific antigen of M. leprae , without give
significant protection , since the individual has spread
bacilar.10