5. Innate
immunity
Introductio
n
Components
• Epithelia
• Neutrophils and
monocytes
• Dendritic cells
• NK cells
• Mast cells
• Complement system
Receptors of innate immunity (Pattern recognition
receptors)
• Toll like receptors
• NOD like receptors
• C lectin type receptors
• RIG like receptors
• G protein coupled receptors
• Mannose receptors
Reactions of innate
immunity
• Inflammation
• Anti viral defense
• Stimulate adaptive immunity
7. Introduction
• Innate immunity is always
present, ready to provide
defence against microbes and
to eliminate damaged cells
• Does not have memory or
fine antigen specificity
• Innate immunity uses about
100 different receptors to
recognize 1,000 molecular
patterns
• In contrast, adaptive immunity
uses two types of receptors
(antibodies and T-cell receptors,
described later), each with
millions of variations, to
recognize millions of antigens.
10. Epithelia
• Provide mechanical barriers to the
entry of microbes
• Also produce antimicrobial molecules
such as defensins
11. Neutrophils
and
monocytes
• Monocytes and neutrophils are
phagocytes in the blood
• All tissues contain resident macrophages,
the professional phagocytes of the body
12. Dendritic
cells
• Dendritic cells are
involved in the
initiation of innate
immune responses,
but, unlike
macrophages, they
are not key
participants in the
destruction of
microbes
• Present in
epithelia,
lymphoid organs
• They capture protein
antigens and display
peptides for
recognition by T
lymphocytes
17. Tolllike
receptors • All these receptors signal by a common
pathway that culminates in the activation of
two sets of transcription factors:
• NF-κB – critical for the recruitment
and activation of leukocytes
through
• synthesis and secretion of cytokines
• expression of adhesion molecules
• Interferon regulatory factors (IRFs) -
antiviral cytokines
19. Reactionsof innate immunity
The innate immune system provides host defence by
• Inflammation
• Vascular and cellular components of inflammation
• Stimulate adaptive immunity
23. INTRODUCTION – TYPESOFADAPTIVE IMMUNITY
Humoral immunity
Mediated by Blymphocytes by secreting
antibodies
Protect against extracellular microbes and their
toxins
Cell mediated immunity
Mediated by Tlymphocytes
Protect against intracellular pathogens
26. T
Lymphocytes Type
s
Helper T cells
(CD4)
-stimulate B
lymphocytes
to make antibodies
and activate other
leukocytes (e.g.,
phagocytes) to
destroy microbes
-60% of all T cells
Cytotoxic T cells
(CD8)
- kill infected
cells
- 30% of all T
cells
Regulator T
cells
- limit immune
responses and
prevent reactions
against self antigens
Mature T cells are found in the
blood, where they constitute 60%
to 70% of lymphocytes, and in T-
cell zones of peripheral lymphoid
organs
28. Introduction
• Also called Human leukocyte antigens
(HLA) because they were initially
detected on leukocytes
• Clustered on a small
segment of chromosome 6
• MHC molecules are
• Fundamental to the recognition
of antigens by T cells; display
peptide fragments of protein
antigens
29. T
ypes
• Class I MHC
• Display peptides
from viral and
tumour antigens;
that are located in
the cytoplasm;
recognized by CD8+
T lymphocytes
• Class II MHC
• Present antigens
that are internalized
into vesicles,
typically derived
from extracellular
microbes and
soluble proteins;
recognized by
CD4+ T cells
30. Roleof MHC
antigens
• Organ transplantation
• MHC system is highly polymorphic, meaning that there
are many alleles of MHC genes (in the thousands) in
humans and each individual’s alleles differ from those
inherited by most other individuals in the population.
• This constitutes a formidable barrier in organ
transplantation
and graft rejection
• Autoimmune diseases
• Number of autoimmune diseases are associated
with the inheritance of particular HLA alleles
• Immune response
• Individual mounts an immune response against a
protein antigen only if he or she inherits the genes for
those MHC molecules that can bind peptides derived
from the antigen and present it to T cells
• By segregating cytoplasmic and internalized antigens,
MHC molecules ensure that the correct immune
response is mounted against different microbes
• Allergic reactions
• If the antigen is a peptide from ragweed pollen, the
individual who expresses class II molecules capable
of binding the antigen would be genetically prone to
allergic reactions against pollen
32. Introduction
• All adaptive immune responses
develop in steps, consisting of:
• Antigen recognition, activation of
specific lymphocytes
• Differentiation into effector and
memory cells
• Elimination of the antigen
• Decline of the response, with memory
cells
being the long-lived survivors
36. Humoral
immunity
• Each plasma cell is derived from an
antigen- stimulated B cell and secretes
antibodies that recognize the same
antigen that was bound to the BCR and
initiated the response
• T cell dependent response –
• B cells ingest protein antigens into
vesicles, degrade them, and display
peptides bound to class II MHC
molecules for recognition by helper T
cells
• T-dependent responses show features
such as immunoglobulin isotype
switching and affinity maturation
• T cell independent response –
• Many polysaccharide and lipid antigens
are able to engage receptor molecules
on B cell and initiate the process of B-
39. Hypersensitivity
General features
And Classification
Type I
• Localised reaction
• Immediate reaction
• Activation of TH2
Cells and
Production of IgE
Antibody
• Sensitization
and Activation
of Mast Cells
• Mediators of
Immediate
Hypersensitivit
y
• Late-Phase Reaction
• Allergy
• Systemic Anaphylaxis
• CLINICAL
MANIFESTATIO
NS
Type II
• Introduction
• Mechanisms
• Opsonization
and
Phagocytosis
• Inflammation
• Cellular dysfunction
• Examples
Type III
• Introduction
• Immune complex
diseases
• Systemic
Immune
Complex
Disease
• Acute
• Chronic
• Morphology
• Local Immune
Complex
Disease
(Arthus
Reaction)
Type IV
• Introduction
• CD4+ T Cell–Mediated
Inflammation
• Responses of
Differentiated
Effector T Cells
• Clinical Examples of
CD4+ T Cell–
Mediated
Inflammatory
Reactions
• CD8+ T Cell–Mediated
Cytotoxicity
41. General
features
• Hypersensitivity implies an excessive or
harmful
reaction to
antigen
• Can be elicited by
• Exogenous environmental antigens –
Allergy
• Dust, pollens, foods, drugs, microbes,
and various chemicals
• Immune responses to such antigens
range from itching of the skin, to
potentially fatal diseases, such as
bronchial asthma and anaphylaxis
• Endogenous self antigens – Autoimmune
diseases
• Results from an imbalance between the
effector mechanisms of immune responses
and the control mechanisms that serve to
normally limit such responses
• Often associated with the inheritance of
particular susceptibility genes
Hypersensitivit
y
42. Classification
• TYPE I – Immediate hypersensitivity
• Caused by TH2 cells, IgE
antibodies, and mast cells and
other leukocytes
• TYPE II – Antibody mediated disorders
• Secreted IgG and IgM antibodies injure
cells
by promoting their phagocytosis or lysis
• TYPE III – Immune complex mediated
diseases
• IgG and IgM antibodies bind antigens
usually in the circulation, and the
antigen- antibody complexes deposit
in tissues and induce inflammation
• TYPE IV – Cell mediated immune
Hypersensitivit
y
45. Immediate reaction
• Vasodilation, vascular leakage,
and depending on the location,
smooth muscle spasm or
glandular secretions
• Within minutes after exposure to
an allergen
• Subside in a few hours
46. Late-phase reaction
• Sets in 2 to 24 hours later
• Without additional exposure to
antigen
• May last for several days
• Characterized by infiltration of tissues
with eosinophils, neutrophils,
basophils, monocytes, and CD4+ T
cells, as well as tissue destruction,
typically in the form of mucosal
epithelial cell damage
48. 1.Activation of TH2
Cellsand Production
of IgEAntibody
• Presentation of the
antigen to naive CD4+
helper T cells by
dendritic cells
• T cells differentiate into
TH2
cells
• TH2 cells produce IL4
acts on B cells to
stimulate class
switching to IgE
52. LATE PHASE REACTION
• In the late-phase reaction, eosinophils that are recruited
amplify and sustain the inflammatory response without
additional exposure to the triggering antigen
• TH2 cytokine IL-5 is the most potent eosinophil-activating
cytokine known
• Late-phase reaction is a major cause of symptoms allergic
asthma
• Treatment of these diseases requires the use of steroids,
rather than anti-histamine drugs, which are of benefit in the
immediate reaction
55. General
features
• Caused by antibodies that react
with antigens present on cell
surfaces or in the extracellular
matrix
• Cause disease by destroying these
cells, triggering inflammation, or
interfering with normal functions
• The antibodies may be
• Specific for normal cell or tissue
antigens (autoantibodies)
• Specific to exogenous antigens, such
as chemical or microbial proteins, that
bind to a cell surface or tissue matrix
58. 1. Opsonization and Phagocytosis
Antibody dependent cellular cytotoxicity - ADCC
• Contribution of ADCC to common hypersensitivity diseases is uncertain
• Occur in the following situations
• Transfusion reactions, in which cells from an incompatible donor react with
and are opsonized by preformed antibody in the host
• Hemolytic disease of the newborn (erythroblastosis fetalis), in which
there is an antigenic difference between the mother and the fetus, and
IgG antierythrocyte antibodies from the mother cross the placenta and
cause destruction of fetal red cells
• Autoimmune hemolytic anemia, agranulocytosis, and
thrombocytopenia, in which individuals produce antibodies to their own
blood cells, which are then destroyed
• Drug reactions, in which adrug acts asa“hapten” by attaching to plasma
membrane proteins of red cells and antibodies are produced against the
60. 2. Inflammation
• When antibodies deposit in fixed tissues,
such as basement membranes and
extracellular matrix, the resultant injury is
due to inflammation
67. INTRODUCTION
Immune complexes may
be formed when
• Antigen combines with antibody in
the circulation and deposits in
vessel walls
• Complexes may be formed at sites
where antigen hasbeen “planted”
previously (called in situ immune
complexes)
Antigens that form
immune
complexes may be
• exogenous, such as a foreign protein
that is injected or produced by an
infectious microbe
• endogenous, if the individual
produces antibody against self
antigens (autoimmunity)
68. Systemicimmune
complex disorders
(Acute)
Pathogenesis
• Complement protein C3
plays an active role in
Type III reaction
• Serum C3 levels can be
used to monitor disease
activity
• Protein antigen triggers an
immune response that
results in the formation of
antibodies, typically about
a week after the injection
of the protein.
• These antibodies are
secreted into the blood,
where they react with the
antigen still present in the
circulation and form
antigen-antibody
complexes
• The circulating antigen-
antibody complexes are
deposited in various
tissues
• Organs where blood is
filtered at high pressure
to form other fluids, like
urine and synovial fluid,
are sites where immune
complexes become
concentrated and tend
to deposit; hence,
immune complex
disease often affects
glomeruli and joints.
• Once immune complexes
are deposited in the
tissues, they initiate an
acute inflammatory
reaction
• During this phase
(approximately 10 days after
antigen administration),
clinical features such as
fever, urticaria, joint pains
(arthralgias), lymph node
enlargement, and
proteinuria appear
• Resultant inflammatory lesion
is termed vasculitis if it
occurs in blood vessels,
glomerulonephritis
• if it occurs in renal glomeruli,
arthritis if it occurs in the
joints
69. Acute vasculitis
• Necrosis of the
vessel wall and
intense neutrophilic
infiltration
• The necrotic tissue
and deposits of
immune complexes,
complement, and
plasma protein
appear as a smudgy
eosinophilic area of
tissue destruction,
termed fibrinoid
necrosis
74. CD4+T Cell–Mediated Inflammation
(Delayed type Hypersensitivity -DTH)
• DTH is a tissue reaction to in immune individuals
• In this reaction, an antigen administered into the
skin of a previously immunized individual results in
a detectable cutaneous reaction within 24 to 48
hours (hence the term delayed, in contrast to
immediate hypersensitivity)
• Both TH1 and TH17 cells contribute to organ-
specific diseases
• The inflammatory reaction associated with TH1 cells
is dominated by activated macrophages, and that
triggered by TH17 cells has a greater neutrophil
component
75. Stagesof CD4+TCell–MediatedInflammation
APCs produce
1. IL6 – TH1 cells
2. IL1/6/23 – TH17
cells
TH1 cells
Secrete IFN-γ, augments
the ability of
macrophages to kill
microorganisms
TH17 cells
secrete IL-17, IL-22 -
recruit neutrophils and
monocytes to the
reaction
77. Tuberculin reaction
(Mantoux test)
• Used to check whether
the individual has been
previously exposed to
tuberculous antigen
• Intracutaneous injection
of purified protein
derivative (PPD, also
called tuberculin), is
given
• In a previously sensitized
individual, reddening and
induration of the site
appear in 8 to 12 hours,
reach a peak in 24 to 72
hours, and thereafter
slowly subside
• Morphologically,
characterized by the
accumulation of
mononuclear cells,
mainly CD4+ T cells
and macrophages,
around venules,
producing perivascular