Lecture Notes: Immunologic Diseases PDF

**Lecture Notes: Immunologic Diseases** **A) Review of Structure and Function** 1. **Immunity** - Resistance to or protection from an individual's environment Adaptive immune system - Internal chemical system whose purpose is to enhance specific reactivity to materials foreign to the b...

**Lecture Notes: Immunologic Diseases** **A) Review of Structure and Function** 1. **Immunity** - Resistance to or protection from an individual's environment Adaptive immune system - Internal chemical system whose purpose is to enhance specific reactivity to materials foreign to the body Antigen - Material recognized as foreign by the body - Antibodies bind to antigens at an epitope - Antigens can have several epitopes - Most antigens are introduced from outside the body, but some are native or altered endogenous materials treated as if they were foreign Antigens may be complete or incomplete - - Antibodies produced by plasma cells are released into the blood - Circulate freely as part of the gamma globulin fraction of serum proteins - Known as immunoglobulins B lymphocytes (B cells) - Lymphocytes capable of developing into plasma cells to produce immunoglobulins T lymphocytes (T cells) - Production programmed by thymus Both can recognize specific epitopes on antigens T cells have several known functions - Subtypes are named to reflect their function a. Some T-helper cells: - Deliver information about antigens to B cells - Aid macrophages in carrying out delayed hypersensitivity functions b. T-suppressor cells - Suppress other T cells to down-regulate the immune response - Suppress B cells to prevent production of excess antibody - Prevent production of antibodies to body's own tissues c. Cytotoxic T cells - Directly kill other cells that process foreign or altered antigens d. Natural killer (NK) cells - Destroy other cells in the absence of any known antigenic stimulation Antigens are usually processed and presented to T cells by: - Macrophages - Dendritic cells - Antigen-presenting cells (APCs) T cells cannot recognize an antigen unless it is presented in conjunction with HLA molecules - Known as MHC restriction or dual recognition T cell with specific receptor may: - Help program B cells to produce antibody - Suppress antibody production - Directly kill the foreign cell Antibodies become detectable about 10 days after the first encounter with an antigen - Secondary response involves more rapid production of antibodies - Certain lymphocytes serve as memory cells 2. **Immunoglobulins** are divided into five classes based on their biologic properties and major differences in protein structure - IgA, IgG, IgD, IgM, and IgE - IgG and IgM are most common **IgG** - Most abundant immunoglobulin - Can combine with antigens to neutralize activity or adhere to antigens to promote phagocytosis - Particularly important for infants - Transmitted across placenta from mother to fetus - Sometimes employs complement activation **IgM** - Noteworthy for their large size - Do not readily pass into tissues or across placenta - Develop more quickly than IgG antibodies following antigenic stimulation - Important in controlling: - Bacteria that enter the bloodstream - Agglutination of large foreign substances **IgA** - Secreted into body fluids to interact with antigens before they can enter body tissues **IgE** - Attaches to basophils in bloodstream and mast cells in tissues and releases vasoactive substances - Antigen receptor on surface of mature B cells - Precipitate or neutralize chemical action of small foreign materials - Initiate an acute inflammatory reaction to control spread of and destroy certain foreign agents - Combine with foreign substances on body surfaces to prevent their entry into body **MHC** - Genetically controls expression of HLA self antigens on cell surfaces of most cells - Important in tissue and organ transplantation **B) Classification of Immunologic Diseases** II. [Allergy or hypersensitivity reactions] - Too much or inappropriate response to foreign agents III. [Immune deficiency diseases] - Too little response to foreign agents - Immune deficiency diseases are subdivided into: - Inherited and acquired forms - Deficiencies of T-cell and B-cell immune systems, or both - IV. [Autoimmune Disease:] hypersensitivity reactions to the body's own components mediated by lymphocytes and/or antibodies 1. **Allergy or hypersensitivity reactions** a. **Major types of hypersensitivity** - Anaphylactic-atopic allergy - Includes reactions mediated by IgE antibody - Involves release of vasoactive chemicals - Occurs within minutes - Cytotoxic-type hypersensitivity - Involves destruction of host cells by agglutination and phagocytosis or by lysis of the cell membrane as a consequence of complement fixation - Reaction may be immediate or prolonged - Immune complex--type hypersensitivity - Complement-mediated reaction to precipitates of antigen and antibody - May take several days or longer - Delayed hypersensitivity or cell-mediated hypersensitivity - Harmful destruction of tissue by T lymphocytes and macrophages - Usually requires 1 to 2 days to reach a peak [Principal criteria separating hypersensitive and non-immune reactions] - Delayed reaction in allergic disease - Reaction time for non-immune responses is constant - Many hypersensitivity diseases occur only in selected susceptible individuals - Non-immune reactions affect people without bias - Often a poor relationship between dose of antigen and severity of hypersensitivity reaction - Dose--injury relationship is more linear and predictable with non-immune injury Most Frequent and Serious Problems 1. Type I hypersensitivity reactions - Atopic allergies - Allergic asthma - Anaphylactic reactions 2. Cytotoxic (type II) hypersensitivity reactions - Transfusion reactions 3. Immune complex hypersensitivities (type III) - Drug reactions - Some types of glomerulonephritis 4. Delayed hypersensitivity (type IV) reactions - Allergic contact dermatitis - Graft rejection b. **Immune deficiencies** - Inherited immune deficiencies are rare - Acquired immune deficiencies are more common - Vary in severity and cause - Acquired immune deficiency syndrome (AIDS) - Frequent result of T-helper cell immunodeficiency caused by HIV infection **Laboratory Tests** a. *Electrophoresis of serum* - Measures amount of gamma globulin in blood - Nephelometry or ELISA assays - Measures immunoglobulin, immunoglobulin class, and complement levels b. *Skin tests* - Diagnosis of type I anaphylactic-atopic allergies - Used to evaluate delayed (cell-mediated) hypersensitivity to microorganisms c. *Direct Coombs test* - Demonstrates cytotoxic antibodies on erythrocytes d. *Indirect Coombs test* - Detects serum antibodies having the potential to react with erythrocytes e. *Immunofluorescence* - Deposition of antigen, antibodies, and complement in tissues may be tested for by immunofluorescence f. *Immunohistochemistry* - Used for testing antigens g. *Antinuclear antibody (ANA) test* - Detects antibodies against nuclei of tissue cells found in serum of patients with certain autoimmune disease h. *Rheumatoid Factor* - antobody i. *Lymphocytes* - Can be tested for subtypes when necessary **C) Specific Diseases** 1. **Immune Deficiency Diseases** - Manifest as increased susceptibility to infections - Immunoglobulin deficiency - Infections such as pneumonia occur - Cell-mediated immune deficiency - Infections produced by weak, opportunistic pathogens occur - Immune Deficiency Diseases - Inherited deficiency of immunoglobulin system - Can be substantiated by finding very low levels of serum gamma globulin - Acquired deficiency of immunoglobulin system - Levels are not usually as low - Immune Deficiency Diseases - Deficiencies of T-cell immune system - Demonstrated by absence of skin reactivity to substances that commonly cause a delayed hypersensitivity reaction - Can adversely affect antibody production if the deficiency involves T-helper cells - Acquired Immune Deficiency Syndrome - AIDS - Now most important and severe form of acquired immune deficiency 2. **Anaphylactic-Atopic Allergies (Type I)** - Caused by release of vasoactive amines, producing: - Contraction of most nonvascular smooth muscle - Vasodilation - Increased vascular permeability - Stimulation of secretory activity of some glands - Increase in eosinophils in blood or tissue - Increase in IgE in plasma - Potential atopic allergens may be evaluated by skin testing **[Asthma and Allergic Rhinitis (Hay Fever)]** a. Asthma - Involves bronchi and produces three effects: - Bronchoconstriction - Edema - Increased bronchial secretion of thick, tenacious mucoid material - Chief mechanical difficulty is increased resistance to air flow manifested by wheezing - Attacks are generally episodic, but status asthmaticus can also occur - Prolonged and unresponsive asthmatic distress b. Allergic rhinitis - Short, seasonal form is called hay fever - Allergens are seasonal plant pollens - Ubiquitous allergens may produce a chronic condition lasting year-round - May be aggravated by factors such as high humidity, irritating vapors, and upper respiratory tract infections - Marked by edema and hypersecretion by mucosal lining of nasopharyngeal cavities - Secondary infection and inflammation of sinuses and middle ear may result - Allergic nasal polyps may develop after many years - Urticaria (Hives) and Angioedema **[Urticaria]** - Type I hypersensitivity reaction - Produces slightly raised, flat, well-demarcated, edematous patches with congested border - Develops rapidly after exposure to allergen - Associated with pruritus - Urticaria (Hives) and Angioedema - May be caused by: - Anaphylactic reaction in skin to allergens introduced into skin - Allergens that have been ingested and distributed throughout the body - Urticaria (Hives) and Angioedema **[Angioedema]** - More extreme skin manifestation of immediate hypersensitivity - More widespread edematous eruption - Involves deep dermis - Often affects lips, tongue, face, or pharynx - Causes are similar to those of urticaria **[Systemic Anaphylaxis]** - True medical emergency - Patient feels itching of scalp, tongue, and throat very quickly after exposure to allergen - Breathing becomes difficult and blood pressure and body temperature drop - Shock and loss of consciousness occur within a short time - Train of events can lead to death from shock within 15 minutes of exposure if early reversal is not instituted - Treatment - Immediate subcutaneous administration of epinephrine **[Gastrointestinal Food Allergies]** - Primary allergic reactions in GI tract are less common than skin reactions - Reaction begins shortly after eating specific foods to which person is allergic - Symptoms include diarrhea, vomiting, and cramps 3. **Cytotoxic Hypersensitivities (Type II)** - Usually manifested by low levels of specific types of blood cells - Antibodies may form against red blood cells, platelets, or white blood cells - May produce anemia, thrombocytopenia, or leukopenia - Direct Coombs test is used to detect antibodies on the surface of red blood cells **[Erythroblastosis Fetalis]** - Hemolytic disorder of newborns - Caused by immunologic incompatibility between mother and child - Usually involves Rh antigen - First pregnancy with Rh-incompatible fetus is uncomplicated - Subsequent pregnancies with Rh-incompatible child causes continuous hemolysis and jaundice at birth - Condition can be prevented by injecting mothers with human gamma globulin containing anti-Rh antibodies within 72 hours after delivery of first and subsequent Rh-positive children **[Blood Transfusion Reactions]** - Rh-negative individual does not have anti-Rh antibodies unless previously sensitized - Persons with A antigen on red blood cells have anti-B antibody - Persons with group B have anti-A antibodies - Persons with O have anti-A and anti-B - Persons with AB have neither antibody Transfused blood with ABO incompatibility will produce immediate hemolysis of transfused red blood cells - Prevented by typing and cross-matching of blood before transfusion **[Autoimmune Hemolytic Anemia and Thrombocytopenia]** - Many are cytotoxic-type hypersensitivity reactions, which may be mild - Splenectomy may control disease in mild types - Autoimmune hemolytic anemias can be detected by direct Coombs test - Drugs sometimes attach to cell surface and become part of the antigen - Drug is a hapten 4. **Immune Complex Hypersensitivities (Type III)** - Produce vasculitis - Renal glomeruli involvement associated with: - Loss of protein and red blood cells in urine - Variable degrees of renal failure - Involvement of joint leads to joint swelling - More severe form results in generalized vasculitis **[Arthus Reaction]** - Prototype of immune complex hypersensitivity reactions - Experimental reaction, not natural disease - Shows evidence of: - Cell necrosis - Infiltration with neutrophils - Vasculitis **[Serum Sickness]** - Prototype of systemic Arthus type or immune complex reaction - Classically occurred after injection of horse serum - Antibodies began to develop after about 10 days - Horse serum is rarely used anymore - Same reaction can be seen with drugs such as penicillin - Symptoms: - Fever - Painful joints - Enlarged lymph nodes and spleen - Allergic urticaria - Patient usually recovers after suspending administration of offending material **[Glomerulonephritis]** - Some forms are mediated by immune complex reactions resulting from lodging of antigen--antibody complexes in basement membrane of glomeruli - Poststreptococcal glomerulonephritis - Develops in association with immune response to infection by group A streptococci - Renal disturbance first seen in 1 to 4 weeks after apparent recovery from acute infection - Predominantly affects children - Recovery is the rule **[Polyarteritis Nodosa]** - Severe but rare form of immune complex reaction - Produces widespread, multifocal, necrotizing vasculitis most often in medium-sized arteries - Usually leads to organ failure - Antigen usually not identified 5. **Delayed, or Cell-Mediated Hypersensitivities (Type IV)** - Manifest as subacute or chronic inflammation with infiltration of tissues by lymphocytes and macrophages and variable degrees of necrosis - Tuberculin skin test - Example of typical subacute reaction - Poison ivy - Example of chronic reaction - Delayed, or Cell-Mediated Hypersensitivities (Type IV) - Internal delayed hypersensitivity reactions - Variable in appearance - All are characterized by a chronic inflammatory cell reaction, with predominance of lymphocytes and with variable degrees of tissue destruction **[Contact Dermatitis]** - Acute or chronic delayed-type hypersensitive response to allergens on skin surface - Can be caused by large range of agents - Lesion varies from simple erythema to edematous, pruritic, vesicular dermatitis - May be difficult to discover or remove allergen - Treatment - Removal of allergen - Topical hydrocortisone creams to reduce inflammation - Systemic steroids may be used for very severe reactions **[Infections Manifested Primarily as Delayed Hypersensitivity Reactions]** - Some microorganisms stimulate cell-mediated immunity - Marshalling of sensitized T lymphocytes and macrophages into infected tissue produces chronic or granulomatous inflammation - Delayed hypersensitivity reactions may play a role in manifestations of viral infections **[Graft Rejection]** - Caused by antibodies rejecting tissue and delayed hypersensitivity reaction - Naturally occurring tissue antigens in graft cause development of sensitized lymphocytes of recipient - Histocompatibility antigens must be matched between donor and recipient 6. **Autoimmune Diseases** - Occur when sensitized lymphocytes or antibodies develop against self-antigens - Most common types appear to be immune complex (type III) and hypersensitivity (type IV) **[Systemic Lupus Erythematosus]** - May affect multiple organ systems - Characterized by butterfly rash on face - Skin is generally photosensitive - Joints may also be involved - Muscles may become weak and atrophic - Kidneys may develop glomerulonephritis - Blood may show hypergammaglobulinemia, anemia, leukopenia, and thrombocytopenia - Predominantly affects young to middle-aged women - Has protracted but variable course - Can end with renal insufficiency, bacterial endocarditis, cardiac failure, sepsis, or pneumonia - Neurologic problems can occur - Primary tissue damage likely caused by: - Cytotoxic antibodies - Immune complexes - Delayed hypersensitivity - Infiltrates of chronic inflammatory cells are found in many organs - Antinuclear antibodies provide basis for ANA test