Pathophysiology - Immunity and Abnormal Responses PDF

Pathophysiology (1) (MBS 213) lecture 3: immunity and abnormal responses Textbook ;Pathophysiology for the Health Professions, 4th edition, 2011 Chapter 3, P.39-67  Purpose of the immune system: The Immune System's Role: Protects the body from infections and diseases. Re...

Pathophysiology (1) (MBS 213) lecture 3: immunity and abnormal responses Textbook ;Pathophysiology for the Health Professions, 4th edition, 2011 Chapter 3, P.39-67  Purpose of the immune system: The Immune System's Role: Protects the body from infections and diseases. Recognizes and attacks foreign invaders (like bacteria and viruses). Can also help identify and destroy abnormal cells, such as cancer cells. Key Features: Distinguishes "self" from "non-self": Identifies and attacks foreign substances while leaving healthy body cells alone. Memory: Remembers past encounters with invaders for faster responses in the future Regulation: Has built-in controls to prevent excessive or harmful reactions. Cancer and the Immune System: A strong immune system can help prevent cancer by recognizing and destroying abnormal cells. A weakened immune system can increase the risk of cancer development. However, some cancer cells can evade the immune system's detection. Major Components of the Immune System and Their Functions: Component Function Lymph nodes Filter lymph fluid and remove foreign substances Filters blood and removes old or damaged red blood cells; stores white Spleen blood cells Tonsils Trap and remove pathogens entering the throat Intestinal lymphoid tissue Protect against pathogens in the digestive tract Network of vessels that carry lymph fluid, immune cells, and waste Lymphatic circulation products Produces stem cells that develop into various blood cells, including Bone marrow immune cells Thymus Site of T cell maturation and development Macrophages Engulf and destroy pathogens; present antigens to T cells T lymphocytes (T cells) Directly attack and destroy infected cells, cancer cells, and foreign cells B lymphocytes (B cells) Produce antibodies that neutralize pathogens Antibodies Proteins that bind to and neutralize pathogens  Tissue And Organ Transplant Rejection Transplantation of organs is now very successful, with increasing frequency for kidneys, hearts, and lungs. But there is a major complication: the recipient's body often rejects the transplanted organ, recognizing it as foreign. This rejection occurs because our bodies have unique markers, known as HLA, which identify our cells as "self." When a foreign organ with different HLA markers is introduced, the immune system attacks it, trying to destroy it. This is the reason for searching for a close matching donor and recipient to ensure transplantation works well. HLA means Human Leukocyte Antigen. HLA are proteins found on the surface of most cells in your body. They act like unique identity tags that enable your immune system to recognize your "self" cells from "non-self".  Types of transplant rejection One type of rejection occurs when the host, or recipient’s, immune system rejects the graft (host-versus-graft disease [HVGD]), a possibility with kidney transplants. Sometimes the graft tissue contains T cells that attack the host cells (graft-versus-host disease [GVHD]), as may occur in bone marrow transplants. Rejection may occur at any time: Hyperacute rejection occurs immediately after transplantation as circulation to the site is re-established. This is a greater risk in patients who have preexisting antibodies, perhaps from prior blood transfusions. The blood vessels are affected, resulting in lack of blood flow to the transplanted tissue. Acute rejection develops after several weeks when unmatched antigens cause a reaction. Chronic or late rejection occurs after months or years, with gradual degeneration of the blood vessel  Immunosuppressive Drugs Medications like cyclosporine, azathioprine, and prednisone are used to suppress the immune system and prevent organ rejection. These drugs must be taken continuously and require careful monitoring to avoid side effects. Risks of Immunosuppression: Increased Infection Risk: Weakened immune systems make individuals more susceptible to infections, particularly from opportunistic microorganisms. Cancer Risk: Increased risk of certain cancers, including lymphomas, skin cancers, and some internal cancers. Dental Considerations: Patients on cyclosporine may experience gingival hyperplasia, an overgrowth of gum tissue. Dental professionals should be aware of this potential side effect. In some cases, babies can receive heart transplants from donors that aren't a perfect match because their immature immune systems may not strongly reject the new heart.  Hypersensitivity Reactions Hypersensitivity or allergic reactions are unusual and perhaps damaging immune responses to normally harmless substances. These reactions stimulate an inflammatory response. There are four basic types of hypersensitivities, which differ in the mechanism causing tissue injury: Type I Hypersensitivity: Allergic Reactions Type II : Cytotoxic Hypersensitivity Type III: Immune Complex Hypersensitivity Type IV: Cell-mediated Or Delayed Hypersensitivity  Type I Hypersensitivity: Allergic Reactions This is an allergic reaction mediated by IgE antibodies. When first exposed to an allergen, the body produces IgE antibodies that attach to mast cells. Upon re-exposure, it binds to the IgE antibodies on mast cells, triggering the release of chemicals like histamine, leading to symptoms like: Redness, swelling, vesicles or blisters, Intense itching (pruritus) examples: Hay Fever (Allergic Rhinitis): Sneezing, runny nose, itchy eyes, and congestion. Often seasonal but can occur year-round due to various allergens. Food Allergies: Nausea, vomiting, diarrhea, and skin rashes (hives).Severe cases can cause airway obstruction. Atopic Dermatitis (Eczema):Chronic skin condition common in children. Itchy rashes on the face, trunk, and extremities. Often associated with food allergies, irritants, and dry skin. Asthma: Allergic reactions in the airways can trigger asthma, causing difficulty breathing. Often occurs in families with a history of hay fever and eczema.  Anaphylaxis: A severe, life-threatening allergic reaction causing a sudden drop in blood pressure, airway obstruction, and lack of oxygen. Triggers: Common triggers include insect stings, food allergies (nuts, shellfish), medications (penicillin, latex) Pathophysiology: The release of large amounts of chemicals from mast cells causes widespread vasodilation (blood vessel widening) and airway constriction. Symptoms: Itching, coughing, difficulty breathing, dizziness, fainting, weakness, fear, swelling (eyes, lips, tongue), loss of consciousness Treatment: Epinephrine (adrenaline) injection: Immediate treatment is crucial. Antihistamines: block the effects of histamine. Corticosteroids: reduce inflammation and stabilize the vascular system. Diagnosis: Skin tests to identify specific allergens. Careful observation of triggers and symptoms. Prevention: Avoiding known allergens is the best way to prevent anaphylaxis.  Type II : Cytotoxic Hypersensitivity In type II hypersensitivity, often called cytotoxic hypersensitivity, the antigen is present on the cell membrane The antigen may be a normal body component or foreign. Circulating IgG antibodies react with the antigen, causing destruction of the cell by phagocytosis or by releasing cytolytic enzymes related to complement activation. An example of this reaction is the response to an incompatible blood transfusion. A person with type A blood has A antigens on his red blood cells and anti-B antibodies in his blood. A person with type B blood has anti-A antibodies. If type B blood from a donor is added to the recipient’s type A blood, the antigen-antibody reaction will destroy the red blood cells (hemolysis) in the type A blood. Another type of blood incompatibility involves the Rh factor.  Type III: Immune Complex Hypersensitivity In this type of reaction, the antigen combines with the antibody, forming a complex, which is then deposited in tissue, often in blood vessel walls, and also activates complement. This process causes inflammation and tissue destruction. A number of diseases are now thought to be caused by immune complexes, including glomerulonephritis and rheumatoid arthritis. Serum sickness refers to the systemic reaction that occurs when immune complex deposits occur in many tissues. With reduced use of animal serum for passive immunization, serum sickness is much less common today. An Arthus reaction is a localized inflammatory and tissue necrosis that results when an immune complex lodges in the blood vessel wall, causing vasculitis. One example is “farmer’s lung,” a reaction to molds inhaled when an individual handles moldy hay.  Type IV: Cell-mediated Or Delayed Hypersensitivity This type of hypersensitivity is a delayed response by sensitized T lymphocytes to antigens, resulting in release of lymphokines or other chemical mediators that cause an inflammatory response and destruction of the antigen. The tuberculin test uses this mechanism to check for prior exposure to the organism causing tuberculosis. Once in the body, this mycobacterium has the unusual characteristic of causing a hypersensitivity reaction in the lungs, even when an active infection does not develop. When a small amount of antigen is injected into the skin of a previously sensitized person, an area of inflammation develops, indicating a positive test. This positive reaction does not necessarily indicate active infection, but it does indicate exposure of the body to the tuberculosis organism at some prior time. An x-ray and sputum culture will determine the absence or presence of active tuberculosis. Contact dermatitis, or an allergic skin rash, is caused by a type IV reaction to direct contact with a chemical like cosmetics, dyes, soaps, and metals. These skin reactions usually do not occur immediately after contact.  Autoimmune Disorders Autoimmune Disorders occur when the immune system mistakenly attacks the body's own tissues. Autoantibodies: Antibodies that mistakenly target the body's own cells. Causes: Loss of Self-Tolerance: The immune system fails to distinguish between "self" and "foreign" cells. Genetic Predisposition: Increased risk in individuals with a family history of autoimmune diseases. Examples: Hashimoto's thyroiditis, Systemic Lupus Erythematosus, rheumatoid arthritis, myasthenia gravis, scleroderma, pernicious anemia, Graves' disease.  Example: Systemic Lupus Erythematosus Systemic lupus erythematosus (SLE) is an autoimmune disease where the immune system attacks the body's own tissues. It can affect various organs and is often characterized by a distinctive rash across the cheeks and nose. While the exact cause is unknown, it likely involves a combination of genetic, hormonal, and environmental factors. Early diagnosis and treatment are crucial for managing the condition. Pathophysiology of SLE: The body produces autoantibodies against its own DNA, cells, and other nuclear components. These autoantibodies form immune complexes that deposit in various tissues. This triggers inflammation, blood vessel inflammation (vasculitis), and tissue damage due to reduced blood flow (ischemia). Commonly Affected Organs: Kidneys, lungs, heart, brain, skin, joints, and digestive tract. Diagnosis: Based on the presence of multiple system involvement and the detection of autoantibodies in laboratory tests.  Common Symptoms: Skin rash (butterfly rash), Joint inflammation, Lung and kidney involvement Disease Course: SLE typically follows a fluctuating course with periods of remission (improvement) and exacerbation (worsening). Treatment of SLE: Medications: Glucocorticoids (like prednisone): To reduce inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs): To relieve pain and inflammation. Antimalarial drugs (like hydroxychloroquine): To reduce disease activity. Disease-Modifying Anti-Rheumatic Drugs (DMARDs): May be used in some cases. Immunosuppressive Drugs: In severe cases, medications to suppress the immune system may be necessary. Lifestyle Modifications: Sun avoidance to minimize flare-ups, stress management to reduce the impact of stress on the disease.  Immunodeficiency Immunodeficiency: A condition where the immune system is weakened, increasing susceptibility to infections and cancer. Primary Immunodeficiency: Inherited or congenital defects in the immune system. Examples: Defects in bone marrow function. Problems with thymus development. Inability to produce antibodies. Secondary Immunodeficiency: Acquired later in life due to various factors: Infections (especially viral infections), Splenectomy, Malnutrition, Liver disease, Severe stress, Immunosuppressive medications (used in transplant recipients and cancer treatment), Radiation and chemotherapy, HIV/AIDS  Effects Of Immunodeficiency: 1. Increased Risk of Infection: People with immunodeficiency are highly susceptible to infections caused by microorganisms that are normally harmless in healthy individuals. 2. Complications of Procedures: Invasive procedures (like dental extractions) can increase the risk of infection in immunocompromised individuals. 3. Increased Cancer Risk: Weakened immune systems may increase the risk of developing cancer due to the body's decreased ability to detect and destroy malignant cells. Prophylactic antibiotics may be given to prevent infections before invasive procedures in immunocompromised individuals. Treatment Replacement therapy for antibodies using gamma globulin may be helpful. Depending on the cause, bone marrow or thymus transplants are possible, but success with these has been limited.  Example: AIDS (Acquired Immunodeficiency Syndrome) AIDS is a serious disease caused by the HIV virus. HIV attacks the immune system, making it difficult for the body to fight off infections. There can be a long period between HIV infection and the development of AIDS. The presence of certain infections or cancers can be a sign that someone may have HIV. HIV Transmission: Primarily through bodily fluids: Blood, semen, vaginal secretions. Risk factors: 1-Unprotected sexual intercourse, 2-Intravenous drug use (sharing needles) 3-Mother-to-child transmission (during pregnancy, childbirth, or breastfeeding) Not transmitted by: Casual contact, sneezing, coughing, sharing food or utensils, insect bites. Prevention: 1-Safe sex practices (condom use), 2-Needle exchange programs, 3-Antiretroviral therapy for pregnant women to reduce transmission to their babies, 4-Blood screening for HIV  Clinical signs and symptoms: HIV/AIDS: A Complex Disease Stages: Acute Infection: Initial infection with flu-like symptoms. Latent Phase: Virus is present, but symptoms may be minimal or absent. AIDS: Advanced stage with significant immune system damage, opportunistic infections, and cancers. Symptoms: Generalized: Fatigue, weakness, lymphadenopathy (swollen lymph nodes). Gastrointestinal: Diarrhea, vomiting, ulcers, weight loss, muscle wasting. Neurological: Encephalopathy (brain dysfunction), cognitive impairment, seizures. Opportunistic Infections: Pneumocystis pneumonia, tuberculosis, herpes, Candida infections. Cancers: Kaposi's sarcoma, lymphomas. Diagnostic Tests: HIV infection is diagnosed through blood tests that detect the presence of antibodies against the virus or the virus itself. These tests include ELISA, Western blot, and PCR. AIDS is diagnosed based on a significant decrease in a type of white blood cell (CD4+ T- cells) and the presence of certain infections or cancers that are uncommon in people with healthy immune systems. Treatment: Antiretroviral Therapy (ART): Combines multiple drugs to suppress viral replication. Goal: To reduce viral load, increase CD4+ cell counts, and prevent opportunistic infections. Challenges: Drug resistance, side effects, access to treatment. Prognosis: Improved significantly with the advent of effective antiretroviral therapies. People with HIV can now live longer and healthier lives.  Infection What is Infection? Infection occurs when the body is invaded and colonized by pathogenic microorganisms (bacteria, viruses, fungi, parasites). These microorganisms can disrupt normal bodily functions and cause a range of symptoms and diseases. Transmission: Direct Contact: Touching infected lesions, sexual intercourse. Indirect Contact: Contaminated objects (fomites), food, water. Droplet Transmission: Inhaling respiratory secretions. Aerosol Transmission: Inhaling airborne particles containing microorganisms. Vector-borne Transmission: Transmission through insects or animals. Reservoirs of Infection: Infected individuals (symptomatic or asymptomatic). Animals. Contaminated environments (water, soil, food). Nosocomial Infections: Infections acquired in healthcare settings (hospitals, clinics). Common causes: *Poor hand hygiene. *Contaminated equipment. *Weakened immune systems in patients. *Antibiotic-resistant bacteria (e.g., MRSA, C. difficile). Host Resistance: This refers to how well your body can fight off infections. Factors that weaken resistance: Age (very young or old), genetic factors, weakened immune system (like in HIV/AIDS), poor nutrition, chronic diseases, stress, injuries to the skin, and long-term use of certain medications like steroids.  Pathogenicity refers to the capacity of microbes to cause disease. Virulence is the degree of pathogenicity of a specific microbe, based on: 1. Invasive qualities, allowing it to directly damage host cells and tissues and spread 2. Toxic qualities, including production of enzymes, exotoxins, and endotoxins that damage host cells or interfere with a host function such as nerve conduction 3. Adherence to tissue by pili, fimbriae, or specific membrane receptor sites. 4. Ability to avoid host defenses (e.g., the presence of a capsule or mutation with altered antigenicity). Microorganisms undergo frequent mutation. Slight changes in the organism may occur spontaneously or in response to environmental conditions, including the presence of drugs. When bacteria or viruses mutate, antibodies that matched the earlier form are no longer effective, so the individual is no longer protected. Vaccines or drugs are unlikely to be effective against the new form. This is why a new influenza vaccine must be developed and administered each year. -Virulence is often expressed in the case fatality rate, the percentage of deaths occurring in the number of persons who develop the disease. Thank you