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Immunology II Adaptive immunology, Foreign invasion, Bone Marrow,…
Immunology II
Adaptive immunology
The origins of B and T lymphocytes, the concept of adaptive immunity, and its 4 main features: specificity, diversity, memory, and tolerance.
B cells
are derived from
lymphocytes
that matured and differentiated in the
bone marrow
Lymphocytes
Bone Marrow
T cells
are
derived from
lymphocytes
that
originated in the
bone marrow
but
matured and differentiated in the
thymus
.
Lymphocytes
Bone marrow
Thymus
After early childhood, new B and T cells are produced primarily by colonies of B and T cells established in
peripheral lymphoid tissues
during fetal life and early childhood.
B cells and antibody-mediated immunity.
Antibody-Mediated Immunity
Antigens stimulate B cells to convert into plasma cells that produce antibodies (immunoglobulins – Ig).
Five Antibody Classes: IgM, IgG, IgA, IgE, and IgD. Antibodies are Y shaped and classified according to properties of their tail portion.
Physical hindrance of pathogens from infecting the host.
Neutralize microbial toxins (eg tetanus). Amplification of innate immune responses, such as complements.
Immune complex disease – ie vasculitis, inflammation of blood vessels.
4 Actions
Neutralisation
Clumping of antigenic cells to eliminate bacteria
Activation of Complement system
Coating of bacterium with antibodies specific to it
Inactivate C1 complement molecule activated by antigen-attached antibody
Formation of C5-C9
Forms holes in foreign cells
Lysis of cells
Enhancement of phagocytosis
Phagocyte attached to bacterium via the antibody
Phagocyte will then ingest bacterium
Stimulation of Natural Killer Cells
NK cells bind to antigen via antibodies
Lysis of foreign antigens occurs
5 Different Antibody Classes
IgG
Usually comes after IgM
80%
of all antibodies in blood
Found in
blood, lymph and intestines
Monomer
structure
Protects against
bacteria
and
viruses
by enhancing
phagocytosis
,
neutralizing toxins
and triggering
complement systems
Only class of antibody to cross
placenta
from mother to
foetus
IgA
10-15%
of all antibodies
Found in
sweat
,
tears
,
saliva
mucus,
breast milk
and
GI secretions
Small quantities in
blood
and
lymph
Monomers and dimers
Levels increase during stress, lowering resistance to infections
Provides localised protection of mucous membranes against bacteria and viruses
IgM
5-10%
of all antibodies in
blood
Found in
lymph
Occurs as
pentamers
First antibody class
to be secreted by plasma cells
Activates
complement
and causes
agglutination
and
lysis
of microbes
Present as monomers on B cells, as antigen receptors
They are the anti-A and anti-B antibodies of
ABO blood group
.
IgD
Found on surface of B cells
as antigen receptors, where it occurs as monomers
IgE
Less in 0.1% of antibodies in blood
Located on
mast cells and basophils
Involved in
allergic
and
hypersensitivity
reactions
Protection against
parasitic worms
Summary
Ancestral Origin
B: Bone Marrow
T: Bone Marrow
Site of maturational processing
B: Bone Marrow
T: Thymus
Receptors for antigen
B: Antibodies inserted in the plasma membrane. Highly specific
T: Not the same as antibodies
Bind with
B: Extracellular antigens such as bacteria and free viruses, other circulating foreign material
T: Foreign antigen in association with self-antigen such as virus-infected cells
Types of active cells
B: Plasma cells
T: Cytotoxic, helper, regulatory T cells
Formulation of memory cells
B: Yes
T: Yes
Type of Immunity
B: Antibody-mediated
T: Cell-mediated
Secretory product
B: Antibodies
T: cytokines
Functions
B: Helps eliminate free foreign invaders by enhancing innate immune responses against them
T: Lyse virus infected cells and cancer cells; aid B cells in antibody production; modulate immune responses
Life Span
B: Short
T: Long
T cells, cell-mediated immunity and antigen presentation.
The three types of T cells are
Cytotoxic,
Helper,
Regulatory T cells
Differentiated based on both cellular functions and surface protein expression, known as Cluster of Differentiation (CD).
Cytotoxic cells (CD3+CD8+) destroy host cells harboring anything foreign.
Helper T cells (CD3+CD4+) modulate activities of other immune cells.
Regulatory T cells are small subset of CD4+CD25+ cells, regulatory immune response.
Antigen Recognition
T cells respond only to antigens that are bound to
glycoproteins
in cell membranes, and presented to them by
antigen-presenting cells (APCs)
.
Major histocompatibility complex (MHC)
are membrane glycoproteins that bind to antigens. Two classes of MHCs:
Class I
: found in membranes of
all nucleated cells
. Pick up small peptides inside the cell and carry them to the surface (viral/tumour proteins).
Class II: found in
membranes of APCs
(dendritic cells in lymph nodes/spleen, tissue macrophages (alveolar), kupffers cells (liver), langerhans cells (skin), microglia (CNS), extracellular peptides from pathogens.
Class I MHC (Intracellular)
Viral or bacterial infection within the c
ell membrane
Abnormal peptides
go into endoplasmic reticulum
Class I MHC proteins
incorporate
abnormal peptides
The MHC proteins are then
transported
to cell membrane
Abnormal peptides are
displayed
on cell membrane
Activation of T Cells
Class I MHC molecules found on
surface
Recognised
only
by
cytotoxic (CD8+) T cells
CD8 coreceptor
links the two cells together
Cytotoxic T cells
destroy
body cells if invaded by foreign antigen
Class II MHC (Extracellular)
Pathogen phagocytised by antigen presenting cell (APC)
Lysosome action produces antigenic fragments from pathogen
Antigenic fragments bound to Class II MHC proteins, which are produced from endoplasmic reticulum
Antigenic fragments are transported to membrane and displayed by Class II MHC proteins.
Activation of T Cells
Class II MHC molecules are found on surface of
immune cells
with which helper T cells interact.
Dendritic cells
Macrophages
B cells
The molecules are recognised only by
helper (CD4+) T cells
CD4 coreceptor
links the 2 cells together
To be activated, helper T cells must bind with
Class II MHC-bearing APC
(dendritic cell or macrophage)
To activate B cells (and combat the foreign antigen), helper T cell must bind with a class II MHC-bearing B cell with
displayed foreign antigen
.
Unlike the situation with Class I, the APCs are not destroyed, as they are doing the job of bringing the foreign pathogens to the surface.
Interaction between innate and adaptive immune system.
See slide 51
Diseases of the immune system: autoimmunity & allergy.
Disorders
A malfunction of the immune system that recognizes and treats “normal (self) tissue” as foreign antigens.
Activated B cells make autoantibodies (auto-Abs) against body cells.
Thyroiditis: release of auto-Abs against thyroglobulin, a precursor of the thyroid hormones. - Rheumatoid arthritis: auto-Abs form immune complexes within connective tissues around the joints.
T cells play a simpler role by releasing cytokines.
Innate immunity being activated by the adaptive immune response to these normal tissue antigens.
Allergies
Inappropriate or excessive immune responses to antigens. Allergens: antigens that trigger allergic reactions.
Type 4
Delayed hypersensitivity
TH1
Soluble antigen
Macrophage activation
TH2
Soluble antigen
IgE production, eosinophil activation, Mastocytosis
CTL
Cell-associated antigen
Cytotoxicity
Contact sensitising agent penetrates skin and binds to self proteins, which are taken up by Langerhans' cells
Langerhans' cells present self peptides haptenated with the contact sensitising agent to TH1 cells, which secrete IFN and other cytokines
Activated keratinocytes secrete cytokines
Products of keratinocytes and TH1 cells activate macrophages to secrete mediators of inflammation
Type 1
Immediate hypersensitivity (IgE)
A rapid and severe response to the presence of an antigen, usually after multiple exposures.
Most commonly recognized type of allergy.
Includes allergic rhinitis (environmental allergies), pollens, pets.
In Singapore, food: Bird’s nest, Seafood (shellfish), Egg, Cow’s milk.
Radio-contrast agents such as organic iodinated media.
If left unattended can be fatal 30-120 minutes – anaphylaxis.
Smooth muscles of respiratory system contract: make breathing difficult.
Peripheral vasodilatation: can cause circulatory collapse (anaphylactic shock).
Antigen: Soluble
Effector mechanism: Mast-cell activation
Food ingested
Wheeze/Breathlessness
Angioedema
Urticaria (some rash)
Hypotension
Anaphylaxis
Skin
Cardiovascular
Respiratory
GI
Treatment
Adrenaline
Anti histamine
Oxygen
Salbutamol (broncodilation)
Fluids
Mast Cell and Histamine
Mast cell activation and granule release
GI Tract
Increased fluid secretion
Increased peristalsis
Expulsion of GI tract contents
Airways
Decreased diameter
Increased mucous secretion
Congestion and blockage of aiways
Swelling and mucous secretion in nasl passages
Blood vessels
Increased blood flow
Increased permeability
Increased fluid in tissues causing increased flow to lymph nodes
Increased cells and protein in tissues
Increased effector response in tissues
Treatment
Epinephrine
Anti histamine
Oxygen
Fluids
Steroids
General Concepts
Adaptive immune responses include
Antibody-mediated immunity (B cells),
Cell-mediated immunity (T cells).
Specificity
Each T or B lymphocyte responds to only one specific antigen.
Diversity
The body produces many T and B lymphocytes, each recognize a different type of antigen, hence developing multiple active lymphocytes to combat a specific pathogen which posses many different antigenic sites (ie. Hepatitis B virus).
Memory
The ability of the immune system to respond more rapidly and effectively to pathogens that have been encountered previously (think of C-19 vaccination).
Activated lymphocytes (memory cells) stay in circulation for years in order provide to immunity against new exposure
Tolerance
Immune system ignores “self” antigens in order to prevent autoimmunity. ie Blood group A has anti-B antibodies, but not anti-A.
Primary vs Secondary Immune Response
Occur in
both
antibody-mediated and cell-mediated immunity.
First exposure: produces
initial response
;
Next exposure: triggers
secondary response
, is more
extensive
and
prolonged
as memory cells are already primed.
Primary –
takes time
to develop: antigens activate B cells differentiate into Plasma cells. Antibody titer
slowly
rises, can take
2 weeks
to develop and declines rapidly.
IgM is produced faster than IgG
.
Secondary – activates memory
B cells
to secrete antibodies in massive qualities.
IgG
: rises
fast
(within 10days) can remain
elevated for extended time
.
Hep B vaccination – 3 doses.
Primary and Secondary Immune Response
Primary response, which takes roughly
2 weeks
to develop peak antibody concentrations.
Both IgM and IgG levels
do not remain elevated
.
Secondary response, characterized by
rapid increase in IgG
, to levels much higher than those of the primary response, and
remains elevated
period (weeks/months) after the second exposure to the antigen.
Hence, booster shoots – Covid-19 Vaccination x 3 injections
Foreign invasion
Bone Marrow
Thymus
T cells
Cell-mediated immune response
B cells
Antibody-mediated immune response
Peripheral lymphoid tissues
T cells
B cells
+
+
+
+
Fetal and early childhood
After early childhood
