immunology of human diseases

8/12/2019 Immunology of Human Diseases

1/14

Clinical

Biochemistry

MPhil Biochemistry

1st

Semester

Muhammad Asad Bilal

IMMUNOLOGY OF HUMAN

DISEASES


2/14

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


3/14


4/14

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


5/14

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.


6/14

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.


7/14

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


8/14

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


9/14

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


10/14

CONGENITAL

PRIMARY

IMMUNO-

DEFICIENCYDISOERDERS


11/14

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


12/14

Pathogenesis of HIV-1 infection

Multiple effects of loss of CD4 + T cells as a result of HIV infection


13/14

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.


14/14

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.

immunology of human diseases

Documents