IMMUNOPATHOLOGY

IMMUNOPATHOLOGY

Some Definitions

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Oct 2014

* Nonspecific & Specific
Body Defense Mechanism

Oct 2014

* Nonspecific immune reaction (inflammation)

Second Line Defense Specific immune responses consist of:

1. Recognition of antigen by specific lymphocytes 2. Activation of lymphocytes (consisting of their proliferation and differentiation into effector cells), and 3. Elimination of antigen. The response declines as antigen is eliminated, and most of the antigen-stimulated lymphocytes die by apoptosis. 4. Specific immunity has a memory
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(Specific immunity)
Specific response to the causative agent. Characterized by:Production of antibodies (soluble proteins that bind to foreign antigens) “humoral immunity”Cell-mediated responses in which specific cells recognize foreign pathogens and destroy them “ cell mediated immunity”. Oct 2014
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Oct 2014

* Non-specific Immunity
Specific Immunity
There is immediate maximal response
There is a lag time between exposure and maximal response
Not antigen-specific
Antigen-specific
Exposure results in no immunologic memory
Exposure results in immunologic memory
Differences between specific & non specific types of immunity

Immunologic memory

The antigen-specific cells that survive are responsible for memory. •Vaccines depend on the memory cells Oct 2014
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Antigen

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Antibody“Immunoglobulin (Ig)” Immunoglobulins are glycoprotein molecules produced by plasma cells in response to an antigen.
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* All immunoglobulins have 4 chain structure as their basic unit: 2 identical light chains & 2 identical heavy chains bound together by Disulfide bonds

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Through the identification of specific cellular components, using specific monoclonal or polyclonal antibodies
through direct Ag-Ab reaction using labeled Ab.
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Immunoglobulin typesAccording to the heavy chain:-

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Immunoglobulin typesAccording to the light chain:-

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GENERAL FUNCTIONS OF IMMUNOGLOBULINS

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Cells of immune system

T-lymphocytes B- lymphocytes Natural killer (NK) cells Macrophages
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TYPES OF SPECIFIC IMMUNITY

Humoral immunity Cell mediated immunity
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Humoral immunity

B-cell lymphocyte mediated via production of antibodies Often develops as a response to soluble antigens
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Cellular immunityT-lymphocyte mediated immunity

T-lymphocyte constitute 60 -70 % of peripheral lymphocytes. They are responsible for cellular immunity. Types of T-lymphocytes: CD4+ helper lymphocytes CD8+ suppressor lymphocytes: cytotoxic T-lymphocytes. Other cells included & very important in cell mediated immunity are Macrophages
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Macrophages

Function: Process and present Ag to competent (specific) T-lymphocyte (so called Ag-presenting cells). This is crucial for induction of cell-mediated immunity. Important as effector cells in certain forms of cell-mediated immunity such as the delayed hypersensitivity reaction. Production & secretion of chemical mediators (cytokines) Phagocytes microbes opsonized by IgG or C3b in innate (nonspecific) immunity.
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* Cytokines are chemical mediators secreted from effector cells & induce their function through autocrine, parakrine & endocrine effects

Hypersensitivity reaction (HSR)

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Types of HSR
The types are classified based on the mechanism by which the injury is caused. Type I HSR (Atopic/anaphylactic reaction) Type II HSR (Antibody dependant cytotoxicity) Type III HSR (Immune complex disease) Type IV HSR (Cell mediated HSR)
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Type I hypersensitivity (IgE) “Atopy, immediate HSR, or anaphylactic HSR” Type I HSR occurs in 10-20% of the population. Allergens induce the formation of antibodies of the IgE isotype. Atopic individuals thus exhibit elevated levels of serum IgE E.g. Bronchial asthma, hay fever, food allergies...
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Mechanism of HSR I

Oct 2014
Professor Intisar Salim Pity
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2- Cross linkage: On re-exposure to the allergen (it should be polyvalent antigen), it will cross link the IgE molecules on the surface of the mast cells or the basophils and this will lead to activation of the cells.
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3- Degranulation: mast cells and basophils will release the contents of their granules to the exterior. These granules are mediators.
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The mediators include histamine, cytokines, prostaglandins, and leukotrienes; they are responsible for the immediate features of atopy like vasodilatation, increased vascular permeability, increased glandular secretion and smooth muscle contraction.
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4- In some patients as those with bronchial asthma, after 2-6 hours, another set of mediators are synthesized. These together with the accumulated eosinophils are responsible for the late phase response.
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Clinical Examples of Type I HSR

The resulted reactions can be localized, i.e. affecting a single tissue or organ or systemic, i.e. affecting multiple organs or tissue (as in systemic anaphylaxis “anaphylactic shock”).Localized type I HSR: the commonest examples are hay fever and extrinsic asthma both tend to run in families and often preceded by atopic eczema in infancy or childhood. Oct 2014
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Patients with hay fever develop acute inflammation of the nasal & conjunctival mucosae with sneezing and hypersecretion minutes (immediate) after exposure to the allergen like the grass pollen, food.
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Similarly, patients with bronchial asthma develop wheezes & acute respiratory distress due to bronchospasm and increased mucus secretion after exposure to house dust or animal dander.
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Systemic type I HSR: this is called anaphylactic reaction, which may result in anaphylactic shock characterized by hypotension, wide spread urticaria and dyspnea. Such shock may be seen following injection of a drug (like penicillin) to a sensitive patient and constitutes a medical emergency, which may be fatal.
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