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ATTA-UR-RAHMAN SCHOOL OF
APPLIED BIOSCIENCES (ASAB)
Clinical Immunology
Jasmina Makarevic
Fall Semester 2016
General
1. Essentials of Clinical Immunology by Helen Chapel, Mansel
Haeney, Siraj Misbah, Neil Snowden
Contact E-Mail address: [email protected]
Examination:
-
At least two quizzes
Two OHT‘s
One final examination
One power point presentation
Jasmina Makarevic
www.kgu.de/urologie
Recommanded Book:
Todays lecture
What do you still know about immunology?
Jasmina Makarevic
www.kgu.de/urologie
Repetition of basic immunology!
Definition: Basic Immunology
Studies the relationship between body system, pathogenes and immunology. It is a
combination of epidomeology and medicine.
The study of the molecular and cellular components that comprise the immune system,
including their function and interaction, is the central science of immunology. The
immune system has been divided into a more primitive innate immune system and, in
vertebrates, an acquired or adaptive immune system. The latter is further divided
into humoral (or antibody) and cell-mediated component.
Jasmina Makarevic
www.kgu.de/urologie
Basic Immunology:
Definition: Clinical Immunology
The study of diseases caused by disorders of the immune system (failure, aberrant action, and
malignant growth of the cellular elements of the system).
It also involves diseases of other systems, where immune reactions play a part in the pathology and
clinical features.
The diseases caused by disorders of the immune system fall into two broad categories:
• immunodeficiency, in which parts of the immune system fail to provide an adequate response
(examples include chronic granulomatous disease and primary immune diseases);
• autoimmunity, in which the immune system attacks its own host's body (examples include
systemic lupus erythematosus, rheumatoid arthritis, Hashimoto's disease and myasthenia
gravis).
Other immune system disorders include various hypersensitivities (such as in asthma and other
allergies) that respond inappropriately to otherwise harmless compounds.
The most well-known disease that affects the immune system itself is AIDS, an immunodeficiency
characterized by the suppression of CD4+ ("helper") T cells, dendritic cells and macrophages by
the Human Immunodeficiency Virus (HIV).
Clinical immunologists also study ways to prevent the immune system's attempts to destroy
allografts (transplant rejection).
Jasmina Makarevic
www.kgu.de/urologie
Clinical Immunology:
Immune response in five parts
2. An early innate (non-specific) response to this recognition
3. A slower specific response to a particular antigen, known as adaptive responses
4. Non-specific augmentation of this response
5. Memory of specific immune responses, providing a quicker and larger response
when that particular antigen is encounted the second time
Jasmina Makarevic
September 10th, 2015
www.kgu.de/urologie
1. Recognition of material- recognized as foreign and dangerous
The Bone Marrow is the source of the precursor cells „ the pluripotent
haemopoietic stem cells“ which give rise to the stell constituents of the
immune system as a component of haemopoisis.
Haemopoises is the process by which all cells that circulate in the blood arise
and mature.
• Granulocytes: They constitute 65% of all white cells ( Eosinophiles,
Basophils and Neutrophils)
*Mast Cells:
(also known as a mastocyte or a labrocyte)
is derived from the myeloid stem cell.
It is a part of the immune system and contains many granules rich in histamine
and heparin. Although best known for their role in allergy
and anaphylaxis, mast cells play an important protective role as well, being
intimately involved in wound healing, including angiogenesis, and defense
against pathogens.
Jasmina Makarevic
www.kgu.de/urologie
Cells of the Immune Systems
* Monocytes:
• 5-10% of the circulating white blood cells.
• Large mononuclear cells
• They have short half life, usually 24h and than they become resident
in tissues and become macrophages
* Dendritic cells:
They are antigen-presenting cells (also known as accessory cells)
of the mammalian immune system.
Their main function is to process antigen material 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.
* Lymphocytes:
• 25%-30% of white cells
• they are found in the blood, lymphoid organs, or tissues and at sites of chronic
inflammation.
There are two subtypes: B- and T-Lymphocytes in a ratio 1:5!
Jasmina Makarevic
www.kgu.de/urologie
Cells of the Immune Systems
Cells of the Immune Systems
•They recognize macromolecules „antigenes“ through surface receptors
„antibodies“
• They mature into plasmacelles and become fixed in tissues to secrete
antibodies.
*T-lymphocytes: „Thymus- dependent“
• They aquire the ability to recognize and destinguish self from non self foreign
tissues and infections agents.
•They are not capable of antibody production
•They can be identified by special glycoprotein on their surface CD
„Cluster of diffentiation“
* Natural Killer Cells (NK):
•They resemble T-Cells, but remain distant
•They have the ability to kill lysis of Virus cells and tumour cells.
•They have specialized surface glycoproteins
•They do not need the thymus to mature
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*B- cells: „antibody forming, bursa derived B-Cells“
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B- and T-Cells
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Innate immunity
• Non specific, is present at birth and will not change in intensity (memory)
• It is the first line of protecting the body of invading organisme like bacteria,
funghi, worms.
Acts immediatly, but it is not specific!
Granylocytes: especially,
• Neutrophils are the key player, a specialiced
microbial phagocyte activated by the complement system, Cytokines…They
are abundant in bone marrow and blood.
• Eosinophils: mainly located in tissue and against parasites.They also are
invilved in Allergetic reactions
• Mastcells and Basofils:
Share many features together. They have histamine granules and high affinity
receptors for IgGE
Such responses are normally accompanied by inflamation and occure within
few hours of stimulation!
Jasmina Makarevic
www.kgu.de/urologie
Innative Immunity:
Adaptive immunity
• divided into humoral and cellular responses
•Humoral responses result in generation of Antibodies (Immunoglobulins-Ig),
reactive with a particular antigen. Igs can be transfered passevily to another
individiual by injection of serum.
•Cellular immunity can only be transfered by cells (Lymphoid cells).
Antibody producing lymphpcytes, which are dependent on the bone marrow
are known as B-cells. In response to antigene stimulation , B cells will mature
to antibody secreting plasma cells.
•T-cells: Thymus-dependent cells
Jasmina Makarevic
www.kgu.de/urologie
Adaptive Immunity:
Features
Innate
Adaptive
Foreign molecules
recognized
Structure shared by
microbes, recognized as
patterns PAMPs (pathogen
accociate molecular
patterns)
Wide range of very
particular molecules or
fragments of molecules on
all types of extrinsic and
modified self structures
Nature of recognition
receptors
Germline encode – limited
PRRs (Pattern recognition
receptors)
Somatic mutation results in
wide range of specifities
and affinities
Speed of response
Immediate
Time for cell movement
and interaction between
cell types
Memory
None
Efficient
Humoral components
Complement components
Antibodies
Cellular components
Dendritic cells, neutrophils,
macrophages, NK cells,
NKT cells, B1 cells,
epithelial cells, mast cells
Lymphocytes – T (Th1,
Th2, T regs) B
Jasmina Makarevic
www.kgu.de/urologie
Components of innate and adaptive immunity
Recognitation phase: Classical dentritic cells, that recognize general pathogene
features or specific antigenic molecules, process the antigenes and present them to
The other cells of immune syste,
Effector phase: neutrophils and macrophages (innate immunity) and antibodies and
effector T lymphocytes (adaptive immunity) eliminate antigen. Effector mechanisms
are often dependeent on messages from initiating or regulating clls; soluble
Mediators: Interleukins, Cytokines, Chemokines
Jasmina Makarevic
www.kgu.de/urologie
Innate and adaptive immunity: in common
Found on:
•Macrophages
•Dentritic cells
•Neutrophils
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www.kgu.de/urologie
Pattern recognition receptors (PRRs) such as Toll-Like receptors,
chemotactic receptors and phagocytotic receptors
Antigenic epitopes
Having been processed
By denritic cells, will be
Recognited by specific
T-Or B cells
Jasmina Makarevic
www.kgu.de/urologie
T-Cell receptor
Major histocompatibility complex molecules (MHC)
MHC restriction: MHC molecule restricts the
ability of T –cells to recognize antigene. T cell specific to a
particular peptide and a particular MHC allele.
The major histocompatibility complex (MHC) is a set of cell
surface proteins essential for the acquired immune system to
recognize foreign molecules in vertebrates, which in turn
determines histocompatibility. The main function of MHC
molecules is to bind to peptide fragments derived from
pathogens and display them on the cell surface for recognition
by the appropriate T-cells.
Jasmina Makarevic
www.kgu.de/urologie
Fundemantal role in immunity by presenting
Antigenic peptides to T Cells!
Isotype
Main function
IgM
Neutralization
and
Opsonization
IgG1
Opsonization
IgG2
IgG3
Opsonization
IgG4
IgA1
Neutralizatin at
mucosal surface
IgA2
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IgD
Lymphocyte
membrane
receptor
IgE
Mast cell
attachment
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Antigene receptors on B-cells (BCR-s) are surface bound
immunglobulin molecules
Immunglobulin molecules isotypes and their significance
IgM has five complement binding sites, which results in excellent activation of the classical
complement system
IgG: is smaller and penetrates in tissues easily. It is the only immunoglobulin to provide immune
protection to the neonate as IgG is activated transported across the placenta. There are four
subclasses.
IgA: is the major mucosal immunglobulin.
IgD: is synthesized by antigene sensitive B lymphocytes, is not secreted, acting as a cell-surface
receptor for activation of these cells by specific antigene relating to the BCR; it is essential for
activation of antigen responsive B cells.
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IgM: is phylogenetically the oldest class of IG. It is a large molecule and penetrates poorly into tissues.
IgE: is produced by plasma cells but is taken up by specific IgE receptors on mast cells and basophils.
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Cytokines and chemokines
• Their half-lieves are short
•They are rapidly degraded as another method of regulation and thus difficult to measure in circulation
•Most act locally within the cell‘s microenvironment, which confines their action to a particular site.
•Some act on the cell of production itself, promoting self-activation and differntiation through
high-affinity celll surface receptors
•Many cytokines are pleotropic in their biological effects
•Most exhibit biologically overlapping functions, illustrating the reundance of the group.
Def: Cytokines are soluable mediators secreted by macrophages or monocytes or lymphocytes.
These mediators act as stimulatory or inhibitory signals between cells. (Interleukines, those
between cells of the Immune system)
Def. Chemokines:
Cytokines that induce chemotaxis of leucocytes are referred to as chemokines (something chemical
To help movement). Chemokines are structural similar proteins of small molecular size (8-10kDa),
Which are able to diffuse from the site of productionto form a local concentration gradient along
Which granulocytes and lymphocytes can migrate towards the stimulus.
Jasmina Makarevic
www.kgu.de/urologie
Common features of cytokines:
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Receptors of mononuclear phagocytic cells
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Antigene-presenting cells
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Key function:
Opsonization of microorganisms by
Covering their surface, so that they
Can be recognized for phagocytosis.
Some fragments of the
complementsystems also function
As chemokines to activate
Other reactions of the immune
System.
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Function of the complement pathway
Def.:The complement system is a
part of the immune system that
enhances (complements) the ability
of antibodies and phagocytic cells to
clear microbes and damaged cells
from an organism, promotes
inflammation, and attacks membrane.
It is part of the innate immune system,
which is not adaptable and does not
change over the course of an
individual's lifetime.
However, it can be recruited and
brought into action by the
adaptive immune system.
Jasmina Makarevic
www.kgu.de/urologie
Function of the complememnt pathway
Jasmina Makarevic
www.kgu.de/urologie
Thank You for Your Attention!
Jasmina Makarevic