The immune system can be simplistically viewed as having two “lines of defense” innate immunity and adaptive immunity. The immune system refers to a collection of cells and proteins that function to protect the skin, respiratory passages, intestinal tract, and other areas from foreign antigens, such as microbes, viruses, cancer cells, and toxins.
2. Lesson Outcomes:
Immune system &Types
Immunopathology
Hypersensitivity &Autoimmunity
Autoinflammation & Immunodeficiency
Application or emerging areas
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3. Immune System
A complex network of cells, tissues, organs, and the substances they make that helps
the body fight infections and other diseases
Many cells and organs work together to protect the body
White blood cells, also called leukocytes that play an important role in the immune
system.
The main parts of the immune system are:
White blood cells
Antibodies
Complement system
Lymphatic system
Spleen
Bone marrow
Thymus
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5. Types of immune system
1. Innate immune system:
Everyone is born with innate or natural immunity, a type of general protection.
The innate immune system forms a fast first-line defense.
Skin acts as a barrier to block germs from entering the body, recognizes when certain
invaders are foreign and could be dangerous
The strength of the innate, general defense is to be able to take action very quickly. As
the innate immune response is not specialized for specific pathogens, it does not need a
long start-up phase
The innate defense consists of several elements:
The skin and all mucous membranes in the body openings, which form external barriers
Different defense cells from the white blood cell group (Leukocytes)
Various substances in the blood and in body fluids
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6. How the Innate Immune System works?
Innate immune responses consist of all the immune defense mechanisms that do not
require antigen-specific immunologic memory
Innate immune response preferentially focuses on a few highly conserved structures
present in a large variety of microorganisms.
Referred to as pathogen-associated molecular patterns, and the corresponding
receptors of the innate immune system are called pattern-recognition receptors.
Expressed on many effector cells, most importantly on macrophages, dendritic cells,
and B lymphocytes collectively termed professional antigen-presenting cells.
Approximately 1015 somatically generated immunoglobulins and T-cell receptors
(TCRs) of the adaptive (antigen-specific) immune response
Recent evidence shows that this recognition can mainly be attributed to the family of
TOLL-like receptors (TLRs)
Binding of pathogen-associated molecular patterns to TLRs induces the production
of reactive oxygen and nitrogen intermediates and the pro inflammatory cytokines,
and up regulates expression of co-stimulatory molecules, subsequently initiating
adaptive immunity
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7. 2. Adaptive immune system
Antigen-dependent and antigen-specific it has the capacity for memory, which
enables the host to mount a more rapid and efficient immune response upon
subsequent exposure to the antigen.
Adaptive immune system and its innate counterpart, and defects in either system can
provoke illness or disease, such as autoimmune diseases, immunodeficiency
disorders and hypersensitivity reactions.
There are two main mechanisms of immunity within the adaptive immune system –
Humoral immunity is antibody-mediated immunity. Antigens from pathogens that
are freely circulating, or outside the infected cells. Antibodies produced by the B
cells will bind to antigens, neutralizing them, or causing lysis (dissolution or
destruction of cells by a lysin) or phagocytosis.
Cellular immunity occurs inside infected cells and is mediated by T lymphocytes.
The pathogen's antigens are expressed on the cell surface or on an antigen-presenting
cell. Helper T cells release cytokines that help activated T cells bind to the infected
cells’ MHC-antigen complex and differentiate the T cell into a cytotoxic T cell. The
infected cell then undergoes lysis
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8. To eliminate pathogens that are inside the tissue, a cell-mediated immune response is necessary.
These parts of the adaptive defense include:
T lymphocytes
B lymphocytes
Antibodies
Cytokines
T lymphocytes are responsible for the special defense in the tissue, which is carried out by cells.
They recognize infected cells and are responsible for their destruction and elimination from the
body.
T lymphocytes belong to the group of white blood cells and are produced in the bone marrow. In
the thymus gland, they mature into cells that are capable of recognizing self from non-self cells.
T cells have characteristic structures on their surfaces that pathogens can bind to similar to a
lock that a specific key fits to a pathogen that exactly fits a T cell stimulates this T cell to
multiply quickly and to develop into specialized T cells.
At the same time, the great number of newly produced T cells triggers other defense reactions.
This leads to the pathogens being destroyed and eliminated from the body
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10. Blood components
The immune system includes certain types of white blood cells.
It also includes chemicals and proteins in the blood, such as antibodies, complement
proteins, and interferon.
There are B and T type lymphocytes.
B lymphocytes become cells that produce antibodies. Antibodies attach to a specific
antigen and make it easier for the immune cells to destroy the antigen.
T lymphocytes attack antigens directly and help control the immune response. They also
release chemicals, known as cytokines, which control the entire immune response
During the course of a defense reaction, T lymphocytes develop into specialized cells.
These include:
T helper cells
T killer cells or cytotoxic T cells
memory T cells
regulatory T cells
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11. Passive immunization refers to the transfer of active humoral immunity, in the form
of ready-made antibodies, from one individual to another.
It can occur naturally by transplacental transfer of maternal antibodies to the
developing fetus or it can be induced artificially by injecting a recipient with
exogenous antibodies targeted to a specific pathogen or toxin.
The latter is used when there is a high risk of infection and insufficient time for the
body to develop its own immune response, or to reduce the symptoms of chronic or
immunosuppressive diseases.
Active immunization refers to the production of antibodies against a specific agent
after exposure to the antigen.
It can be acquired through either natural infection with a microbe or through
administration of a vaccine that can consist of attenuated (weakened) pathogens or
inactivated organisms
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13. Immunopathology
Defects or malfunctions in either the innate or adaptive immune response can provoke
illness or disease
caused by release of toxins and apoptosis of infected cell
Such disorders are generally caused:
- overactive immune response, hypersensitivity reactions,
- inappropriate reaction to self known as autoimmunity
- ineffective immune responses known as immunodeficiency
Hypersensitivity reaction or intolerance
- refers to undesirable reactions produced by the normal immune system
- including allergies and autoimmunity
Gell and Coombs distinguishes four types of immune response which result in
bystander tissue damage
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15. TYPE I: IMMEDIATE
These allergic reactions are systemic or localized, as in allergic dermatitis
- as anaphylactic reaction or allergy
Antigen cross-linking with membrane-bound IgE antibody of a mast cell or basophil
Histamine, serotonin, and lipid mediators are released during the anaphylactic reaction.
These released substances have the potential to cause tissue damage
Example of the inhaled antigen is ragweed pollen. Food allergens are also a common
cause of type I hypersensitivity reactions
TYPE II: CELL BOUND
Initiated by antibody reacting with antigen
IgG and IgM antibodies bind to cell-surface molecules,
- complexes that activate the complement system
Examples: Goodpasture's syndrome, erythroblastosis fetalis, and autoimmune anemia
Hemolytic transfusion reactions and hemolytic disease of newborns are type II reactions
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16. TYPE III: IMMUNE COMPLEX
IgG and IgM antibodies bind to soluble proteins forming immune complexes that can deposit in
tissues, leading to complement activation, inflammation, and mast cell degranulation
These activate complement, which results in PMN chemotaxis and activation. PMNs then
release tissue damaging enzymes.
Serum sickness and rheumatoid arthritis are examples of type III reactions
TYPE IV: DELAYED
Cell-mediated reactions are initiated by T-lymphocytes and by effector T-cells and
macrophages. This involves the interaction of antigens with the surface of lymphocytes.
Sensitized lymphocytes can produce cytokines, which are biologically active substances that
affect the functions of other cells.
Many chronic infectious diseases, including tuberculosis and fungal infections, exhibit delayed
hypersensitivity.
Tuberculin reactions, chronic asthma, and contact dermatitis are examples of type IV reactions.
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17. Autoimmunity
Involve loss of normal immune homeostasis such that the organism produces an
abnormal response to its own tissue.
- occurs when an adaptive immune response attacks our own tissues
- specific antigens by T-cell receptors and B cell receptors
Paul Ehrlich, proposed the concept of horror autotoxicus
- body's innate aversion to immunological self-destruction
Autoimmune disorder may result in:
- destruction of body tissue,
- abnormal growth of an organ,
- changes in organ function
Autoimmune diseases can be broadly divided into:
Localized autoimmune disorder, immune response is directed toward antigens in a
single organ
Systemic and organ-specific immune system attacks self antigens in several organs
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18. There are two situations.
A sudden change in a tissue. This might be an infection that kills cells or an accident
that causes local damage. This tissue damage releases signals that trigger an immune
response against itself.
The second is when antigens derived from the tissue and those produced by an
infection are very similar and the host has a TCR that can recognize both.
Both of these processes can be demonstrated in animal models of autoimmune disease.
However, in human disease,Infections that contain cross-reactive antigens probably
also always cause tissue damage, and an accident that is bad enough to damage tissue
is often accompanied by broken skin and the possibility of infection
Localized autoimmune diseases are
- Addison’s disease, Grave’s disease , Type 1diabetes, Crohn’s disease
Systemic autoimmune diseases are :
- Rheumatoid arthritis, Multiple sclerosis, Systemic lupus erythematosus,
Scleroderma 18
19. An Allergic reaction occurs
- hypersensitive to certain substances
- causes inflammation and irritation.
Allergic responses can arise to a very broad range of different stimuli
- BeNatural, such as the pollens that cause hay fever
- Or they may be drugs, such as the antibiotic penicillin.
When an allergic reaction occurs, allergens bind to antibodies that the body produces
called IgE
- mast cells will release chemicals
- Histamine causes the muscles in the airways and
- walls of the blood vessels to tighten
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20. Auto-inflammation
When innate immune cells become activated, due to dysregulated secretion of
pro-inflammatory cytokines and consequent damage to host tissues, it is
termed Auto inflammation
In 1970,defects in innate immunity, in complement pathways were identified
Inflammasome an intra-cytoplasmic structure that assembles from several
proteins when the cell detects danger
Subunits of the inflammasome come together and activate an enzyme that then
releases inflammation promoting cytokines can cause sickness and fever
Inflammasome activation is triggered by changes in the environment that cause
the subunits to assemble
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21. Gout disease, follows the deposition of crystals in small joints depends on
inflammasome activation by these crystals, which lead to inflammation
Although mutation in a molecular pathway that is part of the innate
immune system, large-scale and persistent inflammation can, in time, lead
to the development of autoimmunity
Number of conditions included is increasing
as molecular and genetic studies reveal disease mechanisms
Dysregulation of the inflammasome and progression of several
autoinflammatory and autoimmune diseases, including:
- Cryopyrin-associated periodic syndrome
- Familial Mediterranean Fever (FMF)
- Rheumatoid arthritis (RA)
- Systemic lupus erythematosus
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22. Auto inflammatory diseases are caused by changes in genes that
regulate the innate immune system and also called periodic fever
Symptoms include inflammation of muscles, joints, skin, the
gastrointestinal tract and internal organs
Mutation leading to abnormal behaviour of activity of IL-beta
processing inflammasome complex have been found in several
autoinflammatory syndrome
If not properly controlled, repeated inflammation can lead to
potentially fatal deposits of amyloid protein in vital organs like the
kidney
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23. Immunodeficiency
Immunodeficiency refers to a state in which the immune system’s ability to fight
infectious disease is compromised or entirely absent
- involve B cell, T cell, Phagocytes and complement system
Two types of immunodeficiency disorders:
- Primary immunodeficiency
- Secondary immunodeficiency
Immunodeficiency disorders result in a full or partial impairment of the immune
system
- Being unable to effectively resolve infections or disease
Primary immune deficiencies are the result of genetic defects, and
Secondary immune deficiencies are caused by environmental factors, such as
HIV/AIDS or malnutrition
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24. Immunosuppression may be profound when patients have received
transplanted organs or bone marrow.
For example targeting specific cytokines such as tumour necrosis
factor (TNF) and interleukin (IL)-17 or targeting molecules that regulate
how immune cells migrate around the body
For example, drugs used to treat multiple sclerosis, which inhibit T-cell
trafficking into the brain, are effective in reducing autoimmune disease, but
occasionally lead to the re-emergence of previously suppressed infection
Therapies that neutralize TNF give great relief to patients with rheumatoid
arthritis, but, in some cases, this promotes the re-emergence of tuberculosis
These immunodeficiencies arising because of infection or therapy in adults
indicate that an active immune response remains an important guardian of
health throughout life
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25. Primary immunodeficiency(PID) inherited conditions sometimes caused by single-
gene mutations, by Genetic defects.
PIDs are categorized based on the part of the immune system that is disrupted
Examples of primary immunodeficiency disorders are:
- B cell immune deficiencies
- T cell immune deficiencies
- Severe combined immune deficiencies
- Phagocyte disorders
- Complement defects
Secondary immune deficiency are more common and are the result of a primary
illness, such as HIV or other external factor such as malnutrition or some drug
regimen.
Examples of secondary immunodeficiency disorders:
- Malnutrition – Protein-calorie malnutrition
- Chronic infections
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27. Vaccinations
“A method of inducing artificial immunity by exposing the individual
to some portion or form of the pathogen.”
• Triggers an adaptive immune response resulting in the production of
memory T and B cells specific for antigens from the pathogen.
• A secondary exposure will result in a potent and immediate immune
response to the specific pathogen due to the memory cells.
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28. Polyclonal Vs MonoclonalAntibodies
Polyclonal Antibodies
Collection of antibodies (Ab’s) produced by many B cells specific for
the same antigen (i.e., from many B cell “clones”).
1) Immunize animal (usually.. rabbit, goat, chicken)
whole or desired antigen (protein or whole pathogen)
2) Collect blood serum from immunized animal
(full of Ab’s that bind various epitopes on antigen)
3) Use for testing
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29. Monoclonal Antibodies
A monoclonal Ab(mAb) is a collection of identical Ab’s from a single B
cell clone.
Sometimes monoclonal Ab’s are preferable to polyclonal Ab’s:
Much “cleaner” than polyclonal serum, can give cleaner, more precise
results
Recognize only 1 epitope on the antigen
Preferable when greater target specificity is needed
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33. Diagnostic Immunology
The diagnostic uses of immunology include all the
immunological phenomena and devices that may be contrived to
aid the understanding of individual clinical problems.
Diagnostic immunology involves using antibodies to acquire
clinical data using procedures such as:
1. Precipitation Reactions:
The formation of insoluble Ab: Ag complexes
2. Agglutination:
The formation of visible Ab: Ag aggregates
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34. Diagnostic Immunology
3. Neutralization Reactions:
Inhibition of cytopathic effects due to antibody binding
4. Fluorescent Antibody Staining:
Reveal the presence of specific pathogens
5. ELISA:
Automated technique revealing presence of Ab or Ag
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