STRUCTURE AND FUNCTION OF
IMMUNE SYSTEM
14-2-15/16-2-15/18-2-15
Dr Muzafar
INTRODUCTION
• The immune system protects organisms
from infection with layered defenses of
increasing specificity. In simple terms, physical
barriers prevent pathogens such as
bacteria and viruses from entering the
organism.
• If a pathogen breaches these barriers,
the innate immune system provides an
immediate, but non-specific response.
• If pathogens successfully evade the innate
response, vertebrates possess a second layer
of protection, the adaptive immune system.
• This improved response is then retained after
the pathogen has been eliminated, in the form
of an immunological memory, and allows the
adaptive immune system to mount faster and
stronger attacks each time this pathogen is
encountered.
MECHANISM OF IMMUNE RESPONSE
• Microorganisms invade the body from the skin
when it is scraped after injury, e.g., when you
fall down, from the mucous membranes of the
respiratory tract when you passed by
someone who coughed, and from the
alimentary canal when the food you ate was
rotten.
• If these microorganisms destroy the
epithelium or its surface is damaged due to
other reasons, macrophages and dendritic
cells habitually residing between epithelial
cells or in connective tissues directly
underneath perceive their invasion and emit
danger signals . These cells possess a group of
recognition molecules called Toll-Like
Receptor (TLR) and sugar chain-recognizing
molecules called lectins, which transmit
danger signals in accordance with the
characteristics of invader molecules
• Transmitting danger signals means secreting
proteins
referred
to
as cytokines and chemokines that are
physiologically active even with a minute amount.
• By secreting inflammatory cytokines and
chemokines, macrophages mobilize neutrophils,
the cells with a strong ability to directly obliterate
microorganisms, from the blood to the tissues.
This stimulates the thermoregulatory center to
elevate the body temperature, thereby inducing
swelling of the infected sites.
• In general, the response up to this point is a part
of natural immunity and is important in the
activation itself of biological defense and
acquired immunity until the subsequent
processes of acquired immunity are activated in
earnest.
• Dendritic cells present the constituent proteins
of microorganisms to lymphocytes (antigen
presentation: to induce their proliferation and
activation. At this point, the lymphocytes are
expressing on their surfaces molecules (such as
antibodies) that can recognize the antigens
presented by the dendritic cells.
• Although these responses occur within one
day after the invasion of microorganisms, it
requires at least 2 to 3 days before antigenspecific lymphocytes proliferate to reach a
sufficient number.
• Some of the activated lymphocytes eventually
start producing antibodies that can bind to
microorganism-derived antigens in several
days.
• As a result of the series of immune response,
infection sources are wiped away in an
effective manner.
CENTRAL(PRIMARY) LYMPHOID
ORGANS
THYMUS:
• Anger ,heart, soul, desire, life.
• Lymphoepithelial structure derived from
epithelium of 3rd and 4th pharyngeal pouches
at about 6th week of intauterine life.
• The thymus is of a pinkish-gray color, soft, and
lobulated on its surfaces.
• At birth it is about 5 cm in length, 4 cm in
breadth, and about 6 mm in thickness. The
organ enlarges during childhood, and
atrophies at puberty.
• Primary function of thymus is production of
thymic lymphocytes.
• Each lobe of the thymus can be divided into a
central medulla and a peripheral cortex which
is surrounded by an outer capsule.
• The cortex and medulla play different roles in
the development of T-cells.
• Cells in the thymus can be divided into thymic
stromal cells and cells of hematopoietic origin
(derived
from
bone
marrow
resident hematopoietic stem cells).
• Developing T-cells are referred to as
thymocytes and are of hematopoietic origin.
• Stromal cells include epithelial cells of the
thymic cortex and medulla, and dendritic cells.
• Thymic stromal cells allow for the selection of
a functional and self-tolerant T cell repertoire.
Therefore, one of the most important roles of
the thymus is the induction of central
tolerance.
• Lymphocyte precursors( lymphoblasts) from
yolk sac, foetal liver and bone marrow migrate
into thymus by 8th week of intrauterine life.
• Lymphoid
stem
cells
become
immunocompetent under action of peptide
•
•
•
•
hormones
viz
thymulin,
thymosin,
thymopoietin.
Proliferation of lymphocytes in thymus is
antigen independent.
As T cells migrate from cortex to medulla,
undergoes a series of differentation acquiring
numerous antigen receptors called cluster of
differentation.
About 98% precursor T cells die in thymus.
2% leave as mature T cells and migrate to
the secondry lymphoid organs.
• Immunologically competent T cells comprise
75% of circulating lymphocytes.
BONE MARROW:
• Some lymphoid stem cells from yolk sac,
foetal liver, bone marrow develop within bone
marrow into Ig producing lymphocytes called
as B lymphocytes.
• Site for stem cell proliferation, origin of pre-B
cells and maturation into function B- cells.
• Maturation and differentation is supported by
IL-7 secreated by stromal cells.
• About 75% are killed in bone marrow.
• 25% will survive and go further maturation.
• Mature B cells are called virgin as they have
not yet been exposed to Ag.
• Before they migrate to spleen and lymph
nodes...blood phase will last for about an hour
expressing IgM and IgD on surface.
PERIPHERAL( SECONDRY) LYMPHOID
ORGANS
LYMPH NODE:
• 2-10 mm in size.
• Act as filters of fluid that passes from
intercellular spaces into lymphatics.
• Surrounded by fibrous capsule.
• Consists of outer cortex, inner medulla and a
paracortical zone.
• Cortex contains lymphoid follicles...primary
and secondry.
• T and B lymphocytes are largely seperated
into different anatomical compartments.
1. Cortex.........B cells and macrophages, which
capture and process Ag.
2. Paracortex.....T cells and interdigitating
cells.
3.Medulla.....B and T cells, Ab producing
plasma cells, interdigitating cells arranged as
elongated branching bands(medullary cords).
• B and T cells migrate to sinusoidal spaces of
medulla and pass into blood via efferent
lymphatics.
• Exchange of cells occurs between various
areas.
• Lymph nodes act as filters.
• Dendritic macrophages capture and process
antigen which helps in proliferation.
Spleen:
• Largest lymphovascular organ but without
lymphatic supply.
• Processes material directly from blood.
• Spleen filters antigens, encapsulated bacteria
and platelets.
• Spleen has two distinct areas----------white
pulp and red pulp.
• Central arterioles are devoid of adventitia,
surrounded by sheath of lymphoid tissue.
• Periarterial lymphoid collections in white pulp
are known as Malpighian corpuscles or
follicles
• T and B cells are segerrated in spleen......
B cell area...Perifollicular region, germinal
center and marginal zone.
T cell area.....Periarteriolar lymphatic sheath.
• Red pulp is a storage site for blood cells, site
for turnover of RBC’s and platelets.
• Graveyard for effete blood cells..
MUCOSA ASSOCIATED LYMPHOID TISSUE(MALT):
• Subepithelial accumulations of lymphoid
tissue guard immunologically the mucosa of
alimentary, respiratory and genitourinary
tracts.
• Lung and Lamina propria......present as diffuse
collections of lymphocytes, plasma cells and
macrophages.
• MALT contains both B and T cells, phagocytes.
• Forms interconnected secretory system of
IgA and IgE producing cells.
• B cells predominate in gut associated
lymphoid tissue.
• In blood about 70% lymphocytes are T cells,
20% B cells and 10% killer cells.
CELLS OF IMMUNE RESPONSE
1.Structural cells........reticulum cells, endothelial
cells and fibroblasts.
2.Immunologically competent cells lymphocytes,
plasma cells and macrophages.
LYMPHOCYTES:
• Ehrlich 1879.....staining of blood cells and
described lymphocytes.
• Small round cells present in peripheral blood
lymph, lymphoid organs.
• Size..........Small:5-8µm,,,Medium:8-12µm and
Big:12-15µm.
• Adults have 10 9lymphocytes.
• Lymphocytes have have thin rim of pale blue
cytoplasm and spherical nucleus.
• Small lymphocytes are most numerous.
• According to life span lymphocytes are of 2 types
short lived(10-20 days) and long lived (100-200 days).
• Constitute about 25-45% of leucocytes in blood.
• Lymphocytes are predominant 90% cell types
in lymph and lymphoid organs.
Identification of lymphocytes:
Monoclonal antibodies....these identify a
number of surface antigens or markers.When
cluster of monoclonal antibodies was found to
react with particular antigen the marker was
indicated by a separate number and given a
CD number (cluster of differentiation).
• Based on immunological function and cell
membrane components, lymphocytes are
broadly divided into B-cells, T-cells and Null
cells.
• Naïve/ unprimed lymphocytes....Mature B and
T cells which have not engaged
in
immunological cell response but fully
competent to respond to Ag.
• Ag stimulates the naïve cell to form a
lymphoblast.
• Lymphoblast proliferate and differentiate into
effector cells and memory cells.
Differentation of T cell and B cell can be done
by their surface markers such as
demonstration of Ig on B cell surface and CD3
on T cell.
CD2 present on T cell bind to sheep
erythrocytes forming rossets. B cell show no
such effect.
T cells posses thymus specific Ag which are
lacking in B cells.
B cells have microvilli on its surface.
• Lymphocytic recirculation.
Time taken for recirculation.....1-2 days.
• T cell maturation.
TYPES OF LYMPHOCYTES
T cells are classified on basis of surface Ag and
function:
A. According to surface Ag marker.......
• T cells are defined with help of specific
antibodies to their cell surface molecules.
• Some of these are systemically named by
CD(cluster of differentation) protein.
• More than 150 types of CD’S are identified by
monoclonal antibodies.
• CD1: Cortical thymocyte marker.
Found in earlier stages of maturation in
thymus.
Disappears in later stages.
• CD2:Early Ag .
Acts as receptor for sheep red blood cells
Cell adherence.
T cell activation.
Persists in all mature T cells.
• CD3:Present in all T cells.
Closely associated with T cell receptor.
Transmitis signal to interior of cell
following Ag binding.
T cell activation, production of IL-2.
• CD4:Present on 65% of circulating T cells.
Indicates helper function.
Also found on macrophages and
monocytes.
CD4 molecule acts as receptor for HIV.
Recognises Ag by MHC class II molecules.
T cells possessing CD4 lack CD8 molecule.
• CD5:Present in majority of T cells from stage
of maturation.
Function uncertain.
• CD8:Present on suppressor and cytotoxic T
cells.
Recognise Ag by MHC class I molecules.
B. According to functions.......
1. Regulatory T cells:
These include T Helper(CD4) and Suppressor
T(CD8) cells.
• Helper T cells(CD4)....have two subsets TH1
and TH2.
TH1....mainly produce cytokines--- interferon
gamma and IL-2, resulting in activation of
macrophages, promotion of cell mediated
immunity, destruction of target cell.
killing of intracellular organisms(T.B and
Leprae)
TH2 cells produce IL-4,5 and 6....results in
stumilation of B cells thus production of
immunoglobulins.
• Suppressor T cells(CD8):
Down regulate immune response
Keeps check on over stimulation of B cells
Overactivity of T cells and decreased activity
of suppressor T cells leads to autoimmunity.
Decreased activity of helper and increased
suppressor
cell
activity
results
in
immunodeficiency states.
2. Effector T cells:
Cytotoxic, DTH, MLR cells.
• Cytotoxic/Cytolytic T cells....contain CD8
marker and MHC I.
Kill and lyse target cells carrying new or
foreign Ag’s including virally infected cells,
tumour cells and allograft.
• Delayed type hypersensitivity (DTH) cells:
Cause delayed type IV hypersensitivity.
Possess CD4 markers.
Secrete IFN-gamma and cytokines responsible
for DTH.
• Mixed lymphocyte reactivity(MLR) cells:
These cells undergo rapid proliferation in
mixed lymphocyte reactivity.
T cell receptor(TCR)
• TCR in association with CD3 acts as
recognition unit and is known as TCR complex.
• TCR is analogous to Ig on surface of B
lypmhocytes but differs from Ig.
B cell :
• Primary function is to produce antibodies.
• Also internalise Ag and present Ag to T cells
either to initiate or enhance the immune
response and memory cells.
Immature B cell
Pro-B cell expresses on its surface following
markers.....Igα and Igβ, CD19,CD24,CD43.
• B cells develop in foetal liver during embryonic
life and in blood there after.
• Pro-B cell differentiates into Pre-B cell in
bonemarrow.
• In pre-B cell stage translation of heavy chain
genes begins.
• The µ chain is usually synthesized first
accumulating in cytoplasm.
• No light chains are synthesized.
• Smaller peptides not light chains are
synthesized during later part of pre-B cell
stage. Which complex with µ chains and this
complex is expressed on cell membrane.
• B cell which express this complex proceed
further development.
• Pre-b cell divides 32-64 times producing large
clone of immature B cells.
• CD25 expression stops and Pre-B cell receptor
disappears.
• Immature B cell is committed to one antigenic
specificity IgM.
• Immature B cell also express CD21---a
receptor for complement component C3d.
Mature B cell
• Mature B cell expresses both Ig M and Ig D on
cell surface.
• Mature B cells also called naïve or virgin cells
migrate to peripheral lymphoid tissue and
undergoes Ig isotype switching by series of
gene arrangement.
• By reassortment of Ig genes, B cells can
produce Ig molecules against all possible
epitopes so that cell expresses on its surface
IgM, IgG, IgA or IgE.
• By process of allelic exclusion, each B
lymphocyte becomes programmed to produce
only one class of Ig.
• In peripheral lymphoid organs, naïve B cells
encounter Ag and becomes activated.
• Activated B cell undergoes blastoid
transformation to lymphoblast, clonal
expansion and terminally differentiate into 2
types of effector cells.
Plasma cells................Antibody production.
Memory cells..............responsible for recall
phenomena on subsequent contact with same
ag with heightened secondary immune
response.
B cell receptor complex
• Analogous to TCR receptor complex.
• Composed of
Cell surface immunoglobins
Class II MHC molecules
Receptors for C3b and C3d products of
complement cascade(CR1, CR2).
•
•
•
•
•
•
Plasma cell
It is Ab secreting differentiated B cell.
Oval, twice size of small lymphocyte.
Small eccentrically placed nucleus, large
cytoplasm.
Nucleus has cartwheel appearance because of
radially arranged chromatin.
Cytoplasm contains golgi apparatus, abundant
endoplasmic reticulum.
Russell
body..localised
immunoglobin
aggregates
• Plasma cell can only synthesise an antibody of
single specificity, exception is primary immune
response---producing IgM initially---may later
switch over to synthesis of IgG.
• One plasma cell secretes 2000 molecules of
immunoglobins per second.
• Mature plasma cell survive for 2-3 days.
• Neoplastic or myeloma plasma cells are
capable of unlimited number of cell divisions.
• Plasma cells are present in germinal centers of
lymph nodes, spleen, diffuse lymphoid tissue
of alimentary and respiratory tracts.
• Lymphoblasts and transitional cells may
produce immunoglobins to certain extent.
•
•
•
•
•
•
NULL CELLS
5-10% of lymphocytes lack features of B and T
cells........called as null cells.
Also called as large granular lymphocytes.
Derived from bonemarrow but do not mature
in thymus.
Double the size of lymphocyte.
Abundant cytoplasm with large azurophilic
granules.
Contain mitochondria,ribosomes,E.R,G.A.
• Null cells are heterogenous group of cells
having differences in their functional
properties and surface markings, include NK,
ADCC and LAK.
Natural killer..........
• Spontaneous cytolytic for certain tumours,
virally transferred target cells, involved in
allograft rejection.
• Cytotoxicity is not MHC restricted but is
natural.
• Do not require prior sensitisation by Ag hence
form part of innate immunity.
• Do not need Ab for cytotoxicity.
• Can recognise altered surface structure of
target cells.
• Found in spleen and peripheral blood.
• Possess CD16 and CD56 on their surface.
• Bind to glycoprotein receptors on surface of
autologous and allogenic target cells, release
granule contents into space between target
and effector cells.
• Perforin molecules released causes pores in
target cell through which cytotoxic factors e.g,
TNF-β enter and destroy it by apoptysis.
• Interferon and other agents that activate
macrophages (BCG VACCINE) enhance activity
of NK cells.
• NK cells play important role in controlling
development of neoplastic cells(anti tumour
immunity) and viral replication(anti viral imu).
Antibody dependent cell mediated cytotoxic cell
• Contains surface receptors for Fc portion of
IgG.
• Capable of killing target cells sensitised with
IgG Ab’s.
• Do not require complement for killing or lysis.
• Differs from cytotoxic T cells which is
independent of antibody.
Lymohokine activated killer cells(LAK)
• When NK cells are treated with IL-2 get
converted to cytotoxic cells with wide range of
cytotoxic effect on tumour cells.
• In animal trials therapy with autologous LAK
cells along with high IL-2 conc, has yielded
results.
• In human trials LAK cells have shown
promising results in treatment of some
tumours such as renal cell carcinoma.
• Serious side effects with IL-2 is problem.
•
•
•
•
•
PHAGOCYTIC CELLS
Phagocytic cells include polymorphonuclear
microphages and mononuclear macrophages.
Microphages include nueutrophil, eosinophil
and basophil.
Neutrophil:
Size 10-12 µm.
Multilobed nucleus.
Contain small granules in cytoplasm.
• Constitute 50-70% of circulating leucocytes.
• Remains in circulation for 7-10 hrs, there after
migrate to tissues.
• Life span 3-4 days.
• Important role in acute inflammation by
locating,migrating and engulfing the offending
agent.
• Neutrophil do not play role in immune
response.
• During infection...rise in neutrophil count incld
•
•
•
•
•
precursor forms(band forms),termed as left
shift.
Eosinophils :
Size 11-15 µm.
Bilobed nucleus.
Cytoplasm
contains
large
orange-red
eosinophilic granules.
Granules contain various hydrolytic enzymes.
Kills parasites which are too large to be
phagocytosed by neutrophils.
• Eosinophilia occurs in certain allergic
condition , parasitic conditions and diseases
with formation of Ag-Ab complexes.
Basophil:
• Present in very small numbers 0.2%.
• These are not phagocytes.
• Basophilic
granules
contain
heparin,
histamine, serotonin and other hydrolytic
enzymes.
• Possess plasma membrane receptors for Fc
portion of IgE and cross linking of this
immunoglobin by Ag leads to release of
pharmacological mediators in anaphylaxis and
atopic allergy.
MACROPHAGES
• Includes monocytes of blood and cells derived
from monocytes which are found in tissues as
free or wandering in lung, peritoneum and
inflammatory granulomas; fixed or resident
macrophages integrated in tissues.
Kupffer’s cells----------Liver
Microglial cells-----------Brain
Langerhan’s cells--------Skin
Dendritic cells -----------L.node, tissue
Histiocytes-----------------Connective tissue
• Blood monocytes measure 12-15µm.
• Nucleus....... Single-lobed or bean shaped.
• Cytoplasm..... Stains sky blue, containing few
azurophilic granules.
• Monocytes constitutes 2-8% of leucocytes.
• Macrophages contains lysosomes.
• Functions..............
1. Phagocytoses.
2. Antigen processing and presentation to T
cells.
3. Secretion of lymphokines
IL-1, IL-6, IL-12 and TNF-α.......to activate and
promote immune and inflammatory response.
IL-1.....endogenous pyrogen, induces synthesis
of IL-2 by T-cells which inturn facilitates T cell
activation.
Macrophages also secrete GMCF.
4. Activated macrophages secrete a number of
other biologically active substances such as.....
hydrolytic
enzymes,
binding
proteins(
fibronectin, transferrin), TNF etc.
Surface receptors and Ag’s of macrophages
• Surface receptors..... Macrophages express
receptors for Fc of IgG and C3b product of
complement. These receptors facilitate
phagocytoses of Ag, bacteria, viruses with IgG
proteins.
• Surface antigens........ Macrophages express
class II MHC antigen, which allows these cells
to present Ag to Helper T cells which have
same surface antigen.
DENDRITIC CELLS
• Dendritic cells (DCs) are antigen-presenting
cells (also known as accessory cells) of
the immune system.
• Their
main
function
is
to
process antigen and present it on the cell
surface to the T cells of the immune system.
• They
act
as
messengers
between
the innate and the adaptive immune systems.
• Dendritic cells are present in those tissues
that are in contact with the external
environment, such as the skin(where there is a
specialized dendritic cell type called
the Langerhans cell) and the inner lining of
the nose, lungs, stomachand intestines.
• They can also be found in an immature state
in the blood
• Once activated, they migrate to the lymph
nodes where they interact with T cellsand B
cells to initiate and shape the adaptive
immune response.
• Most similar to monocytes. MDC are made up
of
at
least
two
subsets:
• (1) the more common mDC-1, which is a
major
stimulator
of
T
cells
• (2) the extremely rare mDC-2, which may have
a function in fighting wound infection
• Dendritic cells are derived from hematopoietic
bone marrow progenitor cells.
• These progenitor cells initially transform into
immature dendritic cells.
• These cells are characterized by high
endocytic activity and low T-cell activation
potential.
• Immature dendritic cells constantly sample
the surrounding environment for pathogens
such as viruses and bacteria.
• This is done through pattern recognition
receptors (PRRs) such as the toll-like
receptors (TLRs).
• TLRs recognize specific chemical signatures
found on subsets of pathogens.
• Once they have come into contact with a
presentable antigen, they become activated
into mature dendritic cells and begin to
migrate to the lymph node.
• Immature dendritic cells phagocytose
pathogens and degrade their proteins into
small pieces and upon maturation present
those fragments at their cell surface
using MHC molecules.
• Simultaneously, they upregulate cell-surface
receptors that act as co-receptors in T-cell
activation
such
asCD80,
CD86,
and CD40 greatly enhancing their ability to
activate T-cells.
• They also upregulate CCR7, a chemotactic
receptor that induces the dendritic cell to
travel through the blood stream to
the spleen or through the lymphatic system to
alymph node.
• Here they act as antigen-presenting cells:
they activate helper T-cells andkiller T-cells as
well as B-cells by presenting them with
antigens derived from the pathogen,
alongside non-antigen specific costimulatory
signals.
• Every helper T-cell is specific to one particular
antigen. Only professional antigen-presenting
cells (macrophages, B lymphocytes, and
dendritic cells) are able to activate a resting
helper T-cell when the matching antigen is
presented.
MAJOR HISTOCOMPATIBILITY COMPLEX
• The major histocompatibility complex(MHC)
is a set of cell surface molecules encoded by a
large gene family which controls a major part
of the immune system.
• The major function of MHCs is to bind to
peptide fragments derived from pathogens
and display them on the cell surface for
recognition by the appropriate T-cells.
• MHC molecules mediate interactions of
leukocytes, also called white blood
cells(WBCs), which are immune cells, with
other leukocytes or with body cells.
• The MHC determines compatibility of donors
for organ transplant as well as one's
susceptibility to an autoimmune disease via
crossreacting immunization
• In humans, the MHC is also called the human
leukocyte antigen (HLA).
• HLA complex is located in three regions on
short arm of chromosome 6.
• Two complementary chromosome strands
one maternal and one paternal are inherited.
• Each strand provides an MHC haplotype thus a
string of genes are linked together on same
chromosome.
• HLA complex of 8 genetic loci grouped in three
separate clusters of genes:
1. HLA class I.......A, B , C loci.
2. HLA class II...... Or the D region consisting of
DR, DQ and DP loci.
3. HLA class III.....or the complement region
contains the genes for compliment
components C2 and C4( classical pathway) as
well as properdin factor B( alternate
pathway).
HLA MOLECULES
MHC proteins have immunoglobulin-like
structure.
CLASS I HLA ANTIGENS:
• MHC I occurs as an α chain composed of three
domains—α1, α2, and α3. The α1 rests upon a
unit of the non-MHC molecule β2
microglobulin.
• The α3 subunit is transmembrane, anchoring
the MHC class I molecule to the cell
membrane.
• The peptide being presented is held by the
floor of thepeptide-binding groove, in the
central region of the α1/α2 heterodimer (a
molecule composed of two nonidentical
subunits).
• The genetically encoded and expressed
sequence of amino acids, the sequence of
residues, of the peptide-binding groove's floor
determines which particular peptide residues
it binds.
Dristribution:
• Found on surface of all nucleated cells.
• Abundant on lymphoid cells.
• Sparsely on cells of liver, lung and kidney.
• CD8 T-cells are specific for HLA(MHC) class I
antigens.
Functions:
• These are principle antigens responsible for
allotypic differences between individuals that
cause graft rejection and cell mediated
cytolysis( e.g,destruction of viral infected
cells).
Class I molecules may function as components
of hormone receptors.
HLA CLASS II:
• MHC class II is formed of two chains, α and β,
each having two domains—α1 and α2 and β1
and β2—each chain having a transmembrane
domain, α2 and β2, respectively, anchoring
the MHC class II molecule to the cell
membrane.
• The peptide-binding groove is formed of the
heterodimer of α1 and β1.
• MHC class II molecules in humans have five to
six isotypes. Classic molecules present
peptides to CD4+ lymphocytes. Nonclassic
molecules, accessories, with intracellular
functions, are not exposed on cell
membranes, but in internal membranes
in lysosomes, normally loading the antigenic
peptides onto classic MHC class II molecules.
Distribution of class II molecules...
• Limited cellular distribution, mostly limited to
antigen presenting cells.
• Principally found on surface of macrophages,
monocytes, B lymphocytes and CD4- T
lymphocytes.
FUNCTIONS:
• Significant role in Graft versus Host response,
mixed lymphocytic reaction.
• Immune response genes are identical to MHC
II genes in man.
CLASS III HLA ANTIGENS:
• Class III molecules have physiologic roles
unlike classes I and II, but are encoded
between them in the short arm of human
chromosome 6.
• Class III molecules include several secreted
proteins with immune functions: components
of the complement system (such as C2, C4,
and B factor), cytokines (such as TNF-α, LTA,
and LTB), and heat shock proteins.
INDICATIONS OF HLA TYPING:
• HLA system is very useful in tissue typing and
matching prior to transplantation.
• Paternity determination, anthropological
survey.
• Establishing association between HLA and
disease susceptibility.
• HLA-B 27 is associated with ankylosing
spondylitis.
• Other diseases showing strong association
with HLA.......Reiter’s syndrome, Juvenile
rheumatoid arthritis, acute anterior uveitis,
coeliac disease and grave’s disease
Inteference with expression of MHC molecules
on membrane of infected cells diminishes
recognition of infected cell by immune system.
•
•
•
•
MHC RESTRICTION:
Macrophages or other Ag presenting cells
present processed antigen to T cells.
T cell respond to processed antigen only when
both cells must possess same MHC antigen for
successful immune response.
Cytotoxic T(CD8) cell respond to Ag in
association with Class I Ag.
Helper T cells(CD4) recognise Class II antigens.
QUESTIONS:
• Write a short note on lymph node and draw a
diagram?
• How do T-cells differ from B-cells?
• What is MHA complex and what are
indications of HLA typing?
• Write a short note on lymphocytes?
• Describe the development(maturation) of T
cell and B cell?