immunology of human diseases
TRANSCRIPT
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Clinical
Biochemistry
MPhil Biochemistry
1st
Semester
Muhammad Asad Bilal
IMMUNOLOGY OF HUMAN
DISEASES
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Immunity is defined as resistance to disease, specifically infectious disease. It has the ability
to differentiate between the individual`s own cells and harmful invading organisms.
Active immunityis the immunity induced in an individual by infection or vaccination.
Passive immunity is the immunity conferred on an individual by transfer of antibodies or
lymphocytes from an actively immunized individual.
Immune Systemis the collection of cells, tissues, and molecules that mediate resistance to
infections(prevent infections and to eradicate established infections)
The coordinated reaction of these cells and molecules to infectious microbes is the Immune
Response.
Immunologyis the study of the physiological functioning of the immune system in states of
health, diseases and malfunctions of the immune system in immunological disorders
(Autoimmunity & Immunodeficiency).
The Primary lymphoid organsof the immune system are thethymus andbone marrow.
The secondary lymphatic tissuesincludespleen,tonsils,lymph vessels,lymph
nodes,adenoids,andskin and liver.
http://en.wikipedia.org/wiki/Thymushttp://en.wikipedia.org/wiki/Bone_marrowhttp://en.wikipedia.org/wiki/Spleenhttp://en.wikipedia.org/wiki/Tonsilhttp://en.wikipedia.org/wiki/Lymphatic_systemhttp://en.wikipedia.org/wiki/Lymph_nodehttp://en.wikipedia.org/wiki/Lymph_nodehttp://en.wikipedia.org/wiki/Adenoidhttp://en.wikipedia.org/wiki/Skinhttp://en.wikipedia.org/wiki/Skinhttp://en.wikipedia.org/wiki/Adenoidhttp://en.wikipedia.org/wiki/Lymph_nodehttp://en.wikipedia.org/wiki/Lymph_nodehttp://en.wikipedia.org/wiki/Lymphatic_systemhttp://en.wikipedia.org/wiki/Tonsilhttp://en.wikipedia.org/wiki/Spleenhttp://en.wikipedia.org/wiki/Bone_marrowhttp://en.wikipedia.org/wiki/Thymus -
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Comparison between Innate & Adaptive Immunity
Innate (Natural, Native or Non-Specific) Immunity Adaptive (Acquired, Adaptive or Specific) Immunity
1. 1st
line of defense
2. Rapid, immediate response
3. Limited specificity, same response for a variety of
agents
4. Limited diversity & specificity
5. No memory cell
6. Recognise and react against microbes only
7. Self/non-self discrimination is perfect
8. Soluble components of blood or tissue fluids
include many antimicrobial peptides & proteins
9. Major cells include Phagocytes (monocytes,
macrophages, neutrophils), natural killer (NK) cells,
dendritic cells
1. 2nd
line of defense
2. Delayed, response takes at least few days
3. Highly Specific for microbes & Antigen (can
differentiate Antigen)
4. Extensive diversity, resulting in wide range of
antigen receptors
5. Has memory cell which remember microbes and
induce amplified responses on re-exposure
6. Recognise and react against microbial and non-
microbial antigens
7.Self/nonself discrimination is very good but
occasional failure result in autoimmune disease
8. Soluble components of blood or tissue fluids
include antibodies
9. Major cells include T cells, B cells & antigen-
presenting cells
Mechanism & Comparison of Humoral & Cellular Immunity
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CELLS OF IMMUNE SYSTEM
Disorders of the Immune System
The immune system in general responds appropriately to the presence of foreign antigens.
However, there are certain diseases that arise from either a defective or over responsive
immune system on the part of the host. Two major therapeutic approaches are possible;
either immunesuppression or immunepotentiation of the immune system.
Immune system diseases can be mainly divided into four major categories
1. Hypersensitivity reactions (Too much response)
2. Autoimmune diseases (Misdirected response)3. Immunodeficiency (Too little response)
4. Amyloidosis
Hypersensitivity reactions:
These diseases result from normal immune responses and not because of excessive or
Hyper responses. Both exogenous and endogenous antigens may elicit hypersensitivity
reactions. The development of hypersensitivity diseases is often associated with the
inheritance of particular susceptibility genes.
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Mechanism:It occurs when an already sensitized individual is re-exposed to the same
foreign substance. Hypersensitivity reflects an imbalance between the effector mechanisms
of immune responses and the control mechanisms that serve to normally limit such
responses. These reactions result in tissue injury or other pathophysiological changes. The
response may be immediate or delayed depending upon the type of reaction involved.
Types & related mechanisms of hypersensitivity diseases:
In 1964, Gell and Coombs classified four types of immunologically mediated hypersensitivity
states.
*Type I represents allergic reactions, while Type IIIV belongs to autoimmune diseases.
Autoimmune diseases:
Autoimmune diseases are a group of disorders in which tissue injury is caused (due to
misrecognition of bodysown constituent parts (healthy body tissues) as non self) by
humoral (by auto-antibodies) or cell mediated immune response (by auto-reactive T cells) to
self antigens.
Autoimmunity can be caused by immunological, genetic (HLA gene is the most importantautoimmune susceptibility gene), viral, drug-induced, and hormonal factors.
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General Features of Autoimmune diseases:
Epitope spreading:Autoimmune reactions initiated against self antigen that injure
tissues may result in the release and alterations of other tissue antigens, activation
of lymphocytes specific for these other antigens, and exacerbation of the disease.
Once induced it tends to be progressive, sometimes with sporadic relapses and
remissions, and the damage becomes inexorable.
The clinical and pathologic manifestations of an autoimmune disease are determined
by the nature of the underlying immune response.
Some autoimmune diseases may have a genetic component and are triggered by
external factors (e.g., infection) or injury. Others are probably strictly caused by
external factors (e.g., infection) or injury.
Possible Mechanisms of infections break tolerance:
Mechanism Effect ExampleDisruption of cell or
tissue barrier
Release of sequestered self antigen;
activation of nontolerized cells
Sympathetic
opthalmia
Infection of antigen-
presenting cell
Induction of co-stimulatory activity on
antigen-presenting cells
Effect of adjuvants
in induction EAE
Binding of pathogen
to self protein
Pathogen acts as carrier to allow anti-self
response
interstitial
nephritis
Molecular mimicry Production of cross-reactive antibodies or T
cells
Rheumatic fever
Diabetes
Multiple sclerosis
Superantigen Polyclonal activation of autoreactive T cells Rheumatoidarthrirtis
Types of Autoimmune Diseases:
1. Haemolytic Autoimmune Diseases
This can be any clinical disorder causing destructions of blood components. Auto Ab are
formed against ones own RBCs, Platelets or Leucocytes, e.g. Haemolytic anaemia,
Leucopenia, Thrombocytopenia, etc
2. Organ-Specific Autoimmune Diseases
A particular organ is affected due to auto Abs.
Type of Immune
Response
Autoimmune Disease Target of Immune Response
Antibody to
receptors
Myasthenia gravis
Graves disease
Acetylcholine receptor
TSH receptor
Antibody to cell
components
other than
receptors
Pernicious anemia
Goodpastures synd.
IDDM
Addisons disease
Male infertility
Pemphigus
Hashimotosthyroiditis
Primary myxedema
Intrinsic factor and parietal cells
BM of kidney & lung
Islet cell
Adrenal cortex
Sperm
Desmoglein in tight junctions of skin
Thyroglobulin
Thyroid peroxidase
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Hashimotos thyroiditis
Hypothyroidism & destruction of thyroid cells.
Characterised by Goitre, enlarged thyroid gland.
Characterized by Type IV hypersensitive reactions.
It is a T-cell associated auto immune disease.
Myasthenia Gravis
Caused by auto antibody against muscle antigen & acetylcholine receptor antigen.
Characterized by muscular weakness
Eventually death from respiratory failure.
Neuromuscular junction is severely affected
3. Multisystem or Non-Organ Specific Autoimmune Diseases
Immune complexes accumulate in many tissues and cause inflammation and damage.
Type of Immune
Response
Autoimmune Disease Target of Immune Response
Antibody to cellcomponents
other than
receptors
Rheumatoid arthritisSLE
Sjogrens syndrome (Sicca
syndrome)
Guillain-Barre synd.
IgG in jointsdsDNA, histones
RNP antigens (SS-A/Ro and SS-B/La)
Myelin protein
Systemic Lupus Erythematosus (SLE)
Multisystem disease: Skin, kidneys, serosal surfaces, joints, CNS & heart
Unknown etiology, genetic & non-genetic factors (drugs, UV light, estrogen enhance,
androgen decrease)
Pathogenesis: Due to the production of antinuclear factor (ANF). In these patients, LE cell (a mature neutrophil) appears in blood & bone marrow
FunctionPhagocytosis in the presence of ANF.
Rheumatoid Arthritis
Disease of the joints.
Caused by the auto Antibody of IgM type, called as rheumatoid factors.
Activation of T-helper cellscytokinesactivate B cellsAbsNon-suppurative
proliferative synovitis (destruction of articular cartilage & progressive disabling
arthritis)
Marked by inflammatory changes in the synovial membrane.
In later stage, deformity develops.
Rheumatoid
Arthritis:
Morphology
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Immunodeficiency Disorders:These are of two main types of immunodeficiencies;
Primary: Almost always genetically determined. Affect the humoral and/or cellular arms of
adaptive immunity or the defense mechanisms of innate immunity.
Secondary: May arise as complications of cancers, infections, malnutrition, or side-effects of
immunosuppressive drugs, irradiation, or chemotherapy for cancer and other diseases.
Simplified scheme of lymphocyte development and sites of block in primary immunodeficiency diseases
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CONGENITAL
PRIMARY
IMMUNO-
DEFICIENCYDISOERDERS
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ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) & HUMAN
IMMUNODEFICIENCY VIRUS (HIV):
AIDS is aretroviral disease characterized by profound immunosuppression that leads to
opportunistic infections, secondary neoplasms, and neurologic manifestations.
Important Facts:
It is the 2nd
leading cause of death in men 25-44 years old 3rd
leading cause of death
in women.
HIV virus was discovered independently by Luc Montagnier of France and Robert
Gallo of the US in 1983-1984.
3 major routes of transmission include sexual transmission75%, parenteral
transmission (drug users, hemophiliacs, BT) and mother-to-infant transmission.
Two main types include HIV-1most common type associated with AIDS in the US,
Europe, and Central Africa & HIV-2West Africa and India.
The pattern of disease progression:
Following infection, the virus hones to and infects cells with CD4 receptorsbattle
between the immune response with production of new CD4+ cells and the dying (apoptotic)
HIV-infected CD4 cells (individual may be asymptomatic for many years)eventually, the
host immune system deteriorates, and the individual succumbs to the complications
secondary to loss of the cellular immune system.
Life cycle of HIV, showing the steps from viral entry to production of infectious virions
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Pathogenesis of HIV-1 infection
Multiple effects of loss of CD4 + T cells as a result of HIV infection
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Amyloidosis:Amyloid is a pathologic proteinaceous substance, deposited in between cells in various
tissues and organs of the body in a wide variety of clinical settings. It appears as an
amorphous, extracellular substance that, with progressive accumulation, encroaches on andproduces pressure atrophy of adjacent cells. Affected organs are often enlarged and firm
and have a waxy appearance.
Chemical Nature:
95% consist of fibril proteins, 5% P component and other glycoproteins.
3 most common amyloid proteins
1. AL (amyloid light chain)derived from plasma cells and contains Ig light chains.
2. AA (amyloid-associated)non-Ig protein synthesized by the liver.
3. Aamyloidfound in Alzheimer disease.
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Proposed mechanisms in the pathogenesis of amyloidosis
Organs mostly affected by amyloidosis:
Kidney, spleen, liver and heart are the key organs affected with amyloidosis. Other organs
may include adrenal, thyroid and pituitary glands, GIT, tongue, respiratory tract and brain.