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Immunity
and Abnormal Responses
Bio 375 Pathophysiology
Immune System
The immune system is a major component of the body’s defenses It is a SPECIFIC defense, responding to particular substances: Cells Toxins Proteins Other substances that are perceived as foreign to the body
The Normal Immune
Response
Unique antigens (usually proteins) on the cell surface enable a persons immune system to distinguish self from nonself (foreign) and thus detect and destroy unknown material This involves: Recognition of a specific foreign invader Developing a specific response to that antigen Storing that specific response in memory for future reference should the invader return
Pathogenesis of Measles
Remember:
Prior exposure necessary to prime the immune system for this defense to be effective Immune system is aided by general defense mechanisms such as phagocytosis and the inflammatory response By removing the foreign material, the immune system plays a role in preparing the area for healing
Components
of the Immune System
Lymphoid structures Immune cells Tissues concerned with immune cell development Chemical mediators
Cells of the Immune System
Macrophages develop from monocytes Dendritic cells form in red bone marrow These large, phagocytic cells, located throughout the body, intercept and engulf foreign material and present antigens to the lymphocytes Lymphocytes: T-cells produce cell mediated immunity B-cell produce antibody mediated immunity
Development
of Cellular
and
Humoral
immunity
T-cells are most effective against virus- infected cells, fungal and protozoan infections, cancer cells and foreign cells such as transplanted tissues B-cells are most effective against bacteria and viruses that are outside of cells as well as toxins produced by bacteria and parasites Natural killer (NK) cells require no prior exposure or sensitization and kill cancer cells and cells infected with viruses with perforin and granzyme causing apoptosis
Antibodies or
Immunoglobulins
The basic Y-structure is formed from two pairs of polypeptide chains called light and heavy Each antibody molecule has a region common to most antibodies called the constant region and a unique region called the variable region The variable regions form the antigen binding site
Structure of Basic Antibody
Types of Antibody Molecules
Adaptive Immunity
Adaptive immunity requires prior exposure; the response consists of two steps: A primary immune response which occurs on first exposure to a foreign antigen A secondary immune response which results when a repeat exposure to the same antigen occurs; due to memory cells
Lymphocyte Specificity
Each T- and B-cell expresses receptors for only one antigen Millions of different naïve lymphocytes When activated by an appropriate antigen, an activated lymphocyte undergoes rapid cell division to produce clone of similar lymphocytes
Types of Acquired Immunity
Active natural immunity Active artificial immunity Passive natural immunity Passive artificial immunity
Tissue and Organ
Transplantaton
Tissue Rejection
One type of rejection involves the host immune system rejecting the donated tissue or organ (host-versus-graft disease) or HVGD Sometimes the grafted tissue contains T-cells that attack the host tissues (graft-versus-host disease) or GVHD
Immunosuppression
Immunosuppressive techniques are used to reduce the immune response and prevent rejection Commonly, this involves drugs like cyclosporine, Imuran and prednisone Immunosuppressive drugs have been successful in reducing the risk of rejection, but dosage must be carefully monitored because of the high risk of infection
Side Effects of
Immunosuppression
Suppressing the immune system not only reduces it ability to reject grafts, but reduces it ability to: Fight infection Prevent cancers Cyclosporine can also cause gingival hyperplasia
Hypersensitivity Reactions
HR or allergic reactions are unusual and perhaps damaging immune responses to normally harmless substances. There are four basic types: Type I Hypersensitivity- Allergy Type II – Cytotoxic Hypersensitivity Type III – Immune Complex Hypersensitivity Type IV – Cell-mediated or Delayed Hypersensitivity
Type I: Allergy
Allergies are very common and appear to be increasing in incidence and severity A tendency toward allergic conditions is inherited Allergic reactions can take many forms: Skin rashes hay fever anaphylaxis
Allergens
The causative antigen is called an allergen; It may be a food like shellfish, nuts, strawberries Chemical pollen like ragweed Drugs like aspirin, penicillin, sulfa
An example
would the
response to
an incompatible
blood transfusion
Type III- Immune Complex HR
Antigen combines with antibody, forming a complex The complex is then deposited in tissue, often in blood vessel walls Complement is activated Causes inflammation and tissue destruction Glomerulonephritis and rheumatoid arthritis are examples
Immune complex reaction
Type IV-Cell-Mediated or
Delayed HR
This is a delayed response by sensitized T-cells to antigens, resulting in the release of lymphokines or other chemical mediators that cause an inflammatory response and destruction of the antigen Contact dermatitis or an allergic skin rash is caused by Type IV reaction to direct contact with the chemical
Type IV
The cause may be: Cosmetics Dyes Soaps Metals like nickel Rubber or latex Plant toxins like poison ivy, oak, summac Organ transplant rejection
Contact Dermatitis
Autoimmunity
Localized examples: Hashimoto’s thyroiditis- antibodies are produced that cause destruction of thyroid tissue leading to hypothyroidism Myasthenia gravis- a chronic autoimmune disease mediated by anti-acetylcholine receptor antibodies at myoneural junctions Systemic example: Systemic Lupus Erythematosus (SLE)
SLE
Effects primarily women Manifests between ages 20- 40 Familial occurrence Named for “butterfly” facial rash Chronic inflammatory disease that affects multiple systems Progressive disease with remissions and exacerbations
SLE
Characterized by antibodies against DNA, platelets, erythrocytes, nucleic acids, and sometimes others Immune complexes, especially those with DNA, are deposited everywhere in the body, activating complement and causing inflammation and necrosis Vasculitis (inflammation of blood vessels) develops in many organs impairing blood flow (ischemia) to many organs
Common Manifestations of SLE
Clinical Findings Used to
Assess SLE
- Facial rash confined to the checks
- Discoid rash
- Photosensitivity caused rash
- Oral or nasopharyngeal ulcers
- Nonerosive arthritis of at least 2 peripheral joints
- Serositis (pleurisy, pericarditis)
- Renal disorder (proteinuria or casts)
- Neurological disorders (seizures/psychosis)
- Hematologic disorders (hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia)
- Immunologic disorders: anti-double stranded DNA antibodies, false positive test for syphilis, antiphospholipid antibodies, etc)
- Presence of antinuclear antibody (ANA)
Secondary Deficiencies
Caused by infection Splenectomy Malnutrition Liver disease Use of immunosuppressive drugs Radiation and chemotherapy Stress, physical and emotional AIDS which affects helper T-cells (CD4)
HIV Infection of CD-4 Cells
Using the immune system to attack melanoma cells
