Immunobiology
The role of the
immune system
The defence against:
(1) pathogenic organisms (viruses, bacteria, fungi, unicellular organisms, worms)
(2) Tumor cells
Malfunctioning:
Autoimmune disease (e.g. rheumatoid arthritis
type 1 diabetes)
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2
Two subdivisions of the
immune system
IMMUNE SYSTEM
1. Innate (nonspecific)
2. Adaptive (specific)
1st line of defence
2nd line of defence
Cellular
components
Humoral
components
Cellular
components
Humoral
components
Two subdivisions of the immune system
Innate immune responses are activated directly by pathogens and defend all multicellular organisms against infection. In
vertebrates, pathogens, together with the innate immune responses they activate, stimulate adaptive immune responses,
which then work together with innate immune responses to help fight the infection.
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4
Two subdivisions of the
immune system
Features
Innate immune system
Adaptive immune system
Response is antigen-independent
Response is antigen-dependent
There is immediate maximal response
There is a lag time between exposure and
maximal response
Not antigen-specific
Antigen-specific
Exposure results in no immunologic memory
Exposure results in immunologic memory
Cells of immune system
Neutrophils
Granulocytic
Basophils
Eosinophils
Myeloid cells
Macrophages
Monocytic
Kupfer cells
Dendritic cells
IMMUNE
SYSTEM
Helper cells
T cells
Suppressor cells
Cytotoxic cells
Lymphoid cells
B cells
NK cells
Plasma cells
Memory cells
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I. Innate Immune System
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Innate Immune System
A. Anatomical barriers
Membrane-attack
complex
Mechanical factors: skin, cilia, mucus, peristaltics, flushing of tear and saliva
Chemical factors: low pH in the stomach and sweat
Biological factors: natural flora of skin and intestines
B. Humoral barriers
Complement system
Coagulation system
Others: lactoferrin, interferon, lyozyme, defensin
C. Cellular barriers
Neutrophil and eosinophil granulocytes
Macrophages
Natural killer (NK) cells
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Inhibition of host complement factors by viruses
X
Inflammation
Splinter
Skin
Bacteria
introduced
by splinter
Mast cell
Blood
capillary
Damaged tissues attract
mast cells which release
histamine, which diffuses into
the capillaries.
X
Inflammation
Complement
proteins
Phagocyte
Histamine causes the
capillaries to dilate and
become leaky; complement
proteins leave the
capillaries and attract
phagocytes.
Blood plasma and
phagocytes move
into infected tissue
from the capillaries.
X
Inflammation
Signaling molecules stimulate
endothelial cell division, healing the
wound.
Dead
phagocyte
Phagocytes engulf
bacteria and dead
cells.
Histamine and complement
signaling cease; phagocytes are no
longer attracted.
II. Adaptive Immune System
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Adaptive immune responses
2 main classes:
LIMPHOCYTES
(1) Humoral immune response (= antibody response, B cell-mediated response)
(2) Cellular immune response (=T cell-mediated immune response)
virus
Against extracelluláris parasites
The antibodies…
(1) block the ability of viruses to bind to receptors
(2) block the effect of toxins by masking them
(3) mark pathogens for destruction
Against intracelluláris parasites
The T cells …
(1) induce apoptosis?
(2) activate macrophages  phagocytosis
(3) activate B cells  antibody production
B cell
T cell
Cellular
response
antibody
Humoral response
virus-infected cell
Human lymphoid organs
2x1012 lymphocyte in the body
nasopharyngeal tonsil
(adenoid)
thymus
tonsil
lymphatic vessels
lymphatic nodes
Peyer’s patches
in small intestines
appendix
bone marrow
spleen
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The innate and adaptive immune system work together
Pathogen-associated molecular patterns (PAMPs)

pattern recognition receptors
Pattern recognition receptors:
(1) Located on the surface of phagocytes
(2) Secreted receptors (marking the pathogens through binding them)
(3) Located on the surface of e.g. dendritic cells (Toll-like receptors),
which activate intracellular signal molecules that lead to the secretion of extracellular signal
molecules that promote inflammation and help activate adaptive immune responses
Dendrytic
cell
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The innate and adaptive immune system work together
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5.
1.
2.
3.
4.
(1) Dendritic cells ingest invading microbes or their products at the site of an infection. (2) The microbial PAMPs activate the dendritic cells
(through toll-like receptors) to express co-stimulatory proteins on their surface and (3) to migrate in lymphatic vessels to a nearby lymph node,
where (4) the activated dendritic cells activate the small fraction of T cells that express a receptor for the microbial antigens displayed on the
dendritic cell surface. (5) These T cells proliferate and some then migrate to the site of infection, where they help eliminate the microbes, by
either helping to activate macrophages or killing infected cells .
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HUMORAL IMMUNE RESPONSE
ACTIVATION PHASE
Class II MHC
protein
Interleukin-1 (a cytokine)
activates a TH cell.
Antigen
Macrophage
Helper
T cell
(TH)
The antigen is
taken up by
phagocytosis and
degraded in a
lysosome.
A T cell receptor recognizes an
antigenic fragment bound to a
class II MHC protein on the
macrophage.
T cell
receptor
Cytokines released by the
TH cell stimulate
it to proliferate.
Y
HUMORAL IMMUNE RESPONSE
The TH cell
proliferates
and forms
a clone.
Y
HUMORAL IMMUNE RESPONSE
EFFECTOR PHASE
Cytokines activate
B cell proliferation.
B cell
TH cell
The binding of antigen to a specific IgM
receptor triggers endocytosis,
degradation, and display of the
processed antigen.
A T cell receptor recognizes an
antigenic fragment bound to a class II
MHC protein on a B cell.
Y
HUMORAL IMMUNE RESPONSE
Memory cell
B cells proliferate
and differentiate.
Plasma cell
The plasma cell
produces antibodies.
Y
CELLULAR IMMUNE RESPONSE
ACTIVATION PHASE
Class I MHC
protein
T cell
receptor
Infected
cell
Antigen
A viral protein made in an
infected cell is degraded
into fragments and picked
up by a class I MHC protein.
Cytotoxic
T cell
(TC)
A T cell receptor recognizes
an antigenic fragment bound
to a class I MHC protein on
an infected cell.
Y
CELLULAR IMMUNE RESPONSE
The TC cell
proliferates
and forms
a clone.
Y
CELLULAR IMMUNE RESPONSE
EFFECTOR PHASE
Infected cell
(one of many)
A T cell receptor again recognizes
an antigenic fragment bound to a class I
MHC protein.
The T cell
releases
perforin…
Y
CELLULAR IMMUNE RESPONSE
…which lyses
the infected cell before
the viruses can multiply.
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The development of T and B cells
1. central lymphoid organs
hematopoetic tissues
thymus
common lymphoid
progenitor cell
2. peripheral lymphoid organs
T cell
thymocyte
hematopoetic
stem cell
ANTIGEN
T cell-mediated
immune response
B cells can act over long distances by
Secreting antibodies that are widely
distributed by the bloodstream
T cells can migrate to distant sites, but,
once there, they act only locally on
neighboring cells
Antibody response
B cell
common lymphoid
progenitor cell
developing B cell
maturation
effector cells
B cells  plasma cells:
- make antibodies
- make memory cells
T cells  (1) cytotoxic T cells:
 (2) helper T cells:
- directly kill infected host cells
- secret cytokines thereby activate macrophages,
dendritic cells, B cells, and cytotoxic T cells
- inhibit the function of helper T cells,
cytotoxic T cells, and dendritic cells
 (3) regulatory T cells:
Hematopoesis
Development of blood cells
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Hematopoesis
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transcription factors
PU.1
Ikaros, Aiolos, Helios
TRANSCRIPTION
FACTORS GATA-1
GROWTH FACTORS
Names are not needed to study!
The clonal selection theory
precursor cell
McFarlene
Burnet
PROLIFERATION AND DIVERSIFICATION
IN BONE MARROW
different resting cells
antigen
ANTIGEN BINDING TO SPECIFIC B CELL
(B) IN PERIPHERAL LYMPHOID ORGAN
PROLIFERATION (CLONAL EXPANSION)
AND DIFFERENTIATION OF B CELLS
antibody-secreting
effective B cells
secreted antibodies
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Epitopes
antigen-binding site
Epitopes
antibody A
(antigenic determinants)
antigen
antibody B
antibody C
Epitopes: those parts of an antigen that bind to the antigen-binding site on either an antibody
molecule or a lymphocyte receptor
Immunodominant epitopes: epitopes producing a greater immune response than others
Both B and T cells
naive cell
1st exposure to antigen
memory cells
effector cells
Primary immune response
Immunological memory
memory cells
effector cells
Secondary immune response
2ndexposure to antigen
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Immunological tolerance to self antigens
Lymphocyte with
altered specificity
RECEPTOR
EDITING
Self antigens
Immature
lymphocytes
Mature naive
CLONAL
lymphocytes
DELETION
Dead lymphocyte
Effector or memory
lymphocytes
Foreign antigen
Co-stimulatory signal
Foreign antigen
CLONAL
DELETION
Self antigen
Central lymphoid organ
CLONAL
INACTIVATION
CLONAL
SUPPRESSION
Effector or memory
lymphocytes
Dead lymphocyte
Inactivated
lymphocyte
Suppressed
lymphocyte
Regulatory T cell
Peripheral lymphoid organ
David Nemazee
Martin Weigert  receptor editing
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Autoimmune diseases – 2 examples
Myasthenia gravis: immune reaction against acetylcholine receptor
Diabetes type 1: immune reaction against insulin-secreting cells in the pancreas
The membrane-bound and secreted antibodies
made by a B cell clone
antigen
antigen receptor
resting cell
PROLIFERATION
AND
DIFFERENTIATION
effector B cells
secreted antibodies
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Antibodies
antigen-binding site
antigen-binding site
variable
constant
Heavy chain
hinge region
light chain
heavy chain
light chain
heavy chain
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Antibody–antigen interactions
The 5 classes of antibodies
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The main stages in B cell development
Plasma cell
Memory cell
ANTIGEN
EFFECT
A pentameric IgM molecule
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IgG: antibody-activated phagocytosis
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Dimeric IgA molecule
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The role of IgE in histamine secretion by mast cells
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Antigen binding to antibody
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Molecules with multiple antigenic determinants
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Heavy and light chains
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Constant and variable regions of immunoglobulin chains
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Antibody hypervariable regions
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Immunoglobulin domains
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The organization of the DNA sequences that encode the constant
region of an antibody heavy chain, such as that found in IgG
Immunogenetics
Human antibody
genes
 Light chain
 Light chain
Heavy chain
Z
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The V–J joining process involved in making a human k light chain
Primary antibody repertoire
The heavy-chain VDJ recombination
The human heavy-chain locus
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The role of recombination signal sequences in
RAG-mediated gene segment joining
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Allelic exclusion: Selection of antibody loci
during B cell development in the bone marrow
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Some ways in which AID can cause mutations during
somatic hypermutation
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An example of the DNA rearrangement
that occurs in class switch recombination
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The main mechanisms of antibody
diversification in mice and humans
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A T cell receptor (TCR) heterodimer
 chain: VJ régió
 chain: VDJ régió
No somatic hypermutation
Three types of proteins on the surface of an
activated dendritic cell involved in activating a T cell
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Two strategies by which effector
cytotoxic T cells kill their target cells
Differentiation of naive helper T cells into either TH1 or TH2
effector helper cells in a peripheral lymphoid organ
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Recognition by T cells of foreign peptides bound
to MHC proteins
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Class I and class II MHC proteins
MHC-I
protein
MHC-II
protein
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Human MHC genes
The interaction of a T cell receptor with a viral peptide bound to a
class I MHC protein
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CD4 and CD8 co-receptors on the surface of T cells
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The processing of a viral protein for
presentation to cytotoxic T cells – MHC-I system
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Some effects of interferon-g (IFNg) on virus-infected cells
The processing of an extracellular protein antigen by
a dendritic cell for presentation to a helper T cell –
MHC-II system
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Selection of T cells
1.
2.