IMMUNE SYSTEM – GENERAL
CONCEPTS AND
HISTOCOMPATIBILITY ANTIGENS
Dr Sowmya Uthaiah
Dept Of Pathology
Yenepoya Medical College
THE NORMAL IMMUNE RESPONSE

1.
2.
Definition of immunity: protection from infectious
pathogens
Innate immunity (natural, or native, immunity)
Adaptive immunity (acquired, or specific, immunity)
INNATE IMMUNITY
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First line of defense
Mechanisms that are ready to
react to infections even before
they occur
recognize
and
combat
microbes and non-microbial
substances
COMPONENTS OF INNATE IMMUNITY
1.
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Epithelia of the skin and gastrointestinal and
respiratory tracts
mechanical barriers to the entry of microbes from the
external environment
produce antimicrobial molecules eg. defensins
lymphocytes located in the epithelia combat microbes
2. Monocytes and neutrophils
 phagocytes in the blood
 resident macrophages – phagocytose
3. Dendritic cells
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epithelia, lymphoid organs, and most tissues
Antigen presenting function
stimulate the secretion of cytokines
4. Natural killer cells
 viruses and intracellular bacteria
5. Mast cells
 Secrete mediators of inflammation
6. Proteins of the complement system
 plasma proteins that are activated by microbes
 the alternative and lectin pathways in innate immune
responses
 adaptive immunity it is activated by antibodies classical pathway.
CELLULAR RECEPTORS FOR MICROBES,
PRODUCTS OF DAMAGED CELLS, AND FOREIGN
SUBSTANCES

microbial structures - pathogen-associated
molecular patterns

Leukocytes recognize molecules released by
injured and necrotic cells - damage-associated
molecular patterns

the cellular receptors that recognize these
molecules - pattern recognition receptors.
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Pattern recognition receptors
plasma membrane receptors detect extracellular
microbes
endosomal receptors detect ingested microbes
cytosolic receptors detect microbes in the cytoplasm
TOLL-LIKE RECEPTORS
Recognise microbial molecules
 10 TLR s in mammals
 plasma membrane and endosomal vesicles

TLR…..
(1) NF-κB pathway
synthesis and secretion of cytokines
 expression of adhesion molecules

recruitment and activation of leukocytes
(2) Interferon regulatory factors (IRFs)

the production of the antiviral cytokines, type I
interferons
NOD-LIKE RECEPTORS AND THE
INFLAMMASOME
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cytosolic receptors
recognize products of necrotic cells (e.g., uric acid and
released ATP), ion disturbances (e.g., loss of K+)
microbial products
signal via a cytosolic multiprotein complex called the
inflammasome ----activates an enzyme (caspase-1) -----cleaves precursor form of the cytokine interleukin-1 to
generate the biologically active form
OTHER RECEPTORS FOR MICROBIAL PRODUCTS
C-type lectin receptors (CLRs) :
expressed on the plasma membrane of
macrophages and dendritic cells
 detect fungal glycans
 elicit inflammatory reactions to fungi

RIG-like receptors (RLRs) :
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cytosol of most cell types
detect nucleic acids of viruses that replicate in the
cytoplasm of infected cells
stimulate the production of antiviral cytokines
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G protein–coupled receptors
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neutrophils, macrophages
short bacterial peptides containing N-formylmethionyl
residues
Mannose receptors
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Recognize microbial sugars
phagocytosis of the microbe
REACTIONS OF INNATE IMMUNITY
1. Inflammation
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Cytokines and products of complement activation
Vascular and cellular components of inflammation
Recruits leukocyte – eliminates microbes
2. Antiviral defense
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Type I interferons
activate enzymes that degrade viral nucleic acids
inhibit viral replication
3. Stimulate the subsequent adaptive immune
response
ADAPTIVE IMMUNITY
Lymphocytes and their products, including
antibodies
 two types of adaptive immunity:

1.
Humoral immunity

extracellular microbes and their toxins
2. Cell-mediated (or cellular) immunity

intracellular microbes
CELLS OF THE IMMUNE SYSTEM
T Lymphocytes
Helper T lymphocytes stimulates B lymphocytes to
make antibodies and activate other leukocytes
(e.g., phagocytes) to destroy microbes
Cytotoxic T lymphocytes (CTLs) kill infected cells
Regulatory T lymphocytes limit immune responses
and prevent reactions against self antigens
CD4 T CELLS & CD8 T CELLS
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CD4+ T cells
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approx 60% of mature T cells
cytokine-secreting helper cells that assist macrophages
and B lymphocytes
CD8+ - 30%
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cytotoxic (killer) T lymphocytes
destroy host cells harboring microbes
CD4 and CD8 serve as co-receptors in T-cell
activation
CD4 molecules bind to class II MHC molecules
that are displaying antigen
 CD8 molecules bind to class I MHC molecules

B- LYMPHOCYTES
Produces antibodies
 mediators of humoral immunity
 develop from precursors in the bone marrow
 Mature B cells - 10% to 20% of the circulating
peripheral lymphocyte population
 present in peripheral lymphoid tissues such as
lymph nodes, spleen, and mucosa-associated
lymphoid tissues
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DENDRITIC CELLS
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Interdigitating dendritic cells
Antigen-presenting cells
Initiates t-cell responses against protein antigens
Located under epithelia and interstitial tissues
Immature dendritic cells within the epidermis langerhans cells
Follicular dendritic cell - germinal centers of lymphoid
follicles in the spleen and lymph nodes
MACROPHAGES
mononuclear phagocyte system
 APC - phagocytosed microbes and protein
antigens process the antigens and present
peptide fragments to T cells
 cell-mediated immunity-T cells activate
macrophages and enhance their ability to kill
ingested microbes
 effector phase of humoral immunity

NATURAL KILLER CELLS
destroy irreversibly stressed and abnormal cells
- virus-infected cells and tumor cells.
 5% to 10% of peripheral blood lymphocytes
 do not express TCRs or Ig, do not need prior
exposure or activation
 Larger than small lymphocytes
 contain abundant azurophilic granules
 Two cell surface molecules, CD16 and CD56
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NK cells also secrete cytokines such as interferon-γ
(IFN-γ)- activates macrophages
IL-2 and IL-15 stimulate proliferation of NK cells
IL-12 activates killing and secretion of IFN-γ
TISSUES OF THE IMMUNE SYSTEM
Generative Lymphoid Organs
 Thymus - T cells
 Bone marrow - B lymphocytes
Peripheral Lymphoid Organs
 lymph nodes
 spleen
 mucosal and cutaneous lymphoid tissues
MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)
MOLECULES: THE PEPTIDE DISPLAY SYSTEM OF
ADAPTIVE IMMUNITY
Display peptide fragments of protein antigens
for recognition by antigen specific T cells
 many alleles of MHC genes

CLASS I MHC MOLECULES
all nucleated cells and platelets
 heterodimers consisting of a polymorphic α, or
heavy, chain (44-kD) linked noncovalently to a
smaller (12-kD) nonpolymorphic protein called β2microglobulin.
 The α chains are encoded by three genes,
designated HLA-A, HLA-B, and HLA-C
 The extracellular region of the α chain is divided
into three domains: α1, α2, and α3.
 The α1 and α2 domains form a cleft, or groove,
where peptides bind.

display peptides that are derived from proteins,
such as viral and tumor antigens, that are
located in the cytoplasm and usually produced
in the cell
 are recognized by CD8+ T lymphocytes
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CLASS II MHC MOLECULES
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encoded in a region called HLA-D, which has three
subregions: HLA-DP, HLA-DQ, and HLA-DR
class II molecule is a heterodimer consisting of a
noncovalently associated α chain and β chain, both of
which are polymorphic
Extracellular portions of the α and β chains both have
two domains designated α1 and α2, and β1 and β2
peptide-binding clefts formed by an interaction
of the α1 and β1 domains
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Class II MHC molecules present antigens that
are internalized into vesicles – derived from
extracellular microbes and soluble proteins
CYTOKINES: MESSENGER MOLECULES
OF THE IMMUNE SYSTEM
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cellular interactions and functions of leukocytes are
mediated by secreted proteins called cytokines
Interleukins -mediate communications between
leukocytes
cytokines act on the cells that produce them (autocrine
actions) or on neighboring cells (paracrine) and rarely
at a distance (endocrine)

Innate immune response -TNF, IL-1, IL-12, type I IFNs,
IFN-γ, and chemokines
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produced rapidly after encounter with microbes and other
stimuli
induce inflammation and inhibit virus replication
sources are macrophages, dendritic cells, and NK cells,
endothelial and epithelial cells
Adaptive immune response - IL-2, IL-4, IL-5, IL-17, and
IFN-γ
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Produced by CD4+ T lymphocytes
promote lymphocyte proliferation and differentiation and to
activate effector cells