Pathology Week 3: Quiz 2: Diseases of the Immune System- Hypersensitivity and Autoimmune Disorders Flashcards
Immediate Hypersensitivity Disorder
Type 1 Hypersensitivity Disorder
Antibody Mediated Hypersensitivity Disorder
Type 2 Hypersensitivity Disorder
Immune Complex Mediated Hypersensitivity Disorder
Type 3 Hypersensitivity Disorder
T Cell Mediated (Delayed) Hypersensitivity Disorder
Type 4 Hypersensitivity Disorder
What occurs in Type 1 Hypersensitivity Disorder?
- IgE production 2. Mast cells/basophils immediately release vasoactive amines and other mediators 3. later-recruitment of inflammatory cells
How long after antigen is encountered does it take for a Type 1 Hypersensitivity reaction to occur?
within mins
Histamine Acetylcholine Adenosine Chemotactic mediators Serotonin Leukotrienes Prostaglandin
vasoactive amines/mediators released in a Type 1 reaction
How long is the initial phase of a Type 1 Hypersensitivity reaction?
15 mins
How long is the late phase of a Type 1 Hypersensitivity reaction?
4-6 hrs
Examples of a Type 1 Hypersensitivity reaction?
- Atopic eczema 2. hay fever 3. food allergies
Easily sensitized to allergens that cause a localized reaction when inhaled or ingested.
Local anaphylaxis (atopy)
What are examples of what Local anaphylaxis can produce?
- hay fever 2. hives 3. asthma
What are examples of Local anaphylaxis triggers?
- food allergies 2.hay fever
A severe reaction that occurs within minutes
Systemic anaphylaxis
S&S of Systemic anaphylaxis
- acute asthma 2. laryngeal edema 4. Diarrhea 5. Uticaria 6. Shock
What are examples of Local anaphylaxis triggers?
- pcn allergy 2. bee stings allergy
Prior sensitization has resulted in an immune response initially mediated what?
CD4 lymphocytes
The immediate vascular and smooth muscle reaction to allergen develops within minutes after challenge.
Immediate Phase of of a Type 1 Hypersensitivity reaction
Reaction that develops 2 to 24 hours after challenge.
Late Phase of a Type 1 Hypersensitivity reaction
Characterized by vasodilation, congestion, and edema.
Immediate Phase of of a Type 1 Hypersensitivity reaction
Characterized by an inflammatory infiltrate rich in eosinophils, neutrophils, and T cells.
Late Phase of a Type 1 Hypersensitivity reaction
Clinical symptoms of a Type 1 Hypersensitivity reaction.
- Pruritus 2. Conjunctivitis 3. Rhinitis 4. Laryngeal edema 5. Urticaria 6. Bronchospasm 7. Dysrhythmias 8. Gastrointestinal cramping and malabsorption 9. Angioedema 10. Hypotension
Systemic, usually life threatening reaction due to release of histamine and other anti-inflammatory mediators on receptors throughout the body
Anaphylaxis
Clinical symptoms of Anaphylaxis
- Wide spread edema 2. Hypotension due to widespread vasodilation 3. Vascular shock 4. Difficulty breathing
What phase does Anaphylaxis occur in a Type 1 Hypersensitivity reaction.
Both
Example of Anaphylaxis occuring in both phases of a Type 1 Hypersensitivity reaction.
ACE inhibitors: -angioedema and anaphylaxis -rash, itching, tongue, face or throat swelling years after last dose of the drug
What occurs in Type 2 Hypersensitivity Disorder?
- Antibodies bind to antigens on patient’s own cell surfaces (Intrinsic or extrinsic). 2. These cells are recognized by macrophages or dendritic cells (antigen-presenting cells) 3. Causes B cell response (against the antigen)
“self” antigen, innately part of the patient’s cells
Intrinsic Antibodies
Adsorbed onto the cells during exposure to some foreign antigen, possibly as part of infection with a pathogen
extrinsic Antibodies
Type 2 Hypersensitivity Disorder Mediators
IgG or IgM
Examples of Type 2 Hypersensitivity Disorder
- mismatched blood transfusion reactions or ABO or Rh incompatibility 2. Certain drug reactions 3. ITP 4. Autoimmune hemolytic anemia 5. myesthnia gravis
Explanation of mismatched blood transfusion reactions or ABO or Rh incompatibility causing a Type 2 Hypersensitivity Disorder
- RBCs have different antigens 2. Recognized as different 3. B cell proliferation 4. Antibodies to the foreign blood type are produced 5. IgG and IgM bind to antigens to form complexes 6. Classical pathway of complement activation to eliminate cells presenting foreign antigens.
How long does a Type 2 Hypersensitivity Disorder reaction caused by mismatched blood transfusion reactions or ABO or Rh incompatibility last?
Hours to a day
Examples of Type 2 Hypersensitivity Disorder reaction affecting healthy cells
- RBCs in autoimmune hemolytic anemia 2. Acetylcholine receptors in myesthnia gravis
Explanation of a Type 2 Hypersensitivity Disorder causing Hemolytic anemia.
- Antibody drug RBC interaction 2. Alters the RBC membrane 3. uncovers an antigen 4. Induces autoantibody production
What occurs in Type 3 Hypersensitivity Disorder?
- excess of soluble antigens antigen not bound to cell surfaces (as opposed to those in type II) 2. immune complexes form that fix complement 3. not cleared from the circulation 4. antigens bind antibodies 5. Large complexes can be cleared by macrophages but macrophages have difficulty in the disposal of small immune complexes 6. Small immune complexes lodge into small blood vessels, joints, and glomeruli 7. Cause damage 8. Inflammatory Response
What are the mediators in Type 3 Hypersensitivity Disorder?
Insoluble antigen-antibody complexes
Examples of Type 3 Hypersensitivity Disorders?
- SLE 2. Post-streptococcal glomerulonephritis
What occurs in Type 4 Hypersensitivity Disorder?
- CD4+ Th1 helper T cells recognize foreign antigen in a complex with the MHC class II major histocompatibility complex on the surface of antigen-presenting cells. 2. These can be macrophages that secrete IL-12 3. Stimulates the proliferation of further CD4+ Th1 cells 4. CD4+ T cells secrete IL-2 and interferon gamma 5. Induces further release of other Th1 cytokines 6. mediating the immune response.
Type 4 hypersensitivity is often called delayed type hypersensitivity as the reaction takes how long to develop?
several days
Examples of Type 4 hypersensitivity reaction.
- Contact dermatitis 2. Diabetes type 1 3. Inflammatory bowel disease 4. multiple sclerosis
What are the mediators in a Type 4 hypersensitivity reaction?
T lymphocytes
SLE
Systemic Lupus Erythematous (SLE): is an autoimmune disease that involves multiple organs and involves autoantibodies specifically antinuclear antibodies (ANA). This injury is caused by the binding of ANA’s to various cells in the cells and tissues. They also have other autoantibodies. Anti-phosphopholipids antibodies are present in 30-40% of patients. Antibodies bind to phospholipids may prolong the partial thromboplastin time, these antibodies show delay in clotting times and are related to hypercoagulable states in those with Lupus. Clinical Features of Lupus include butterfly rash on the face, fever, pain without deformity in the joints, pleuritic chest pain, and photosensitivity. Renal involvement may include hematuria, proteinuria, red blood cell casts, and nephrotic syndrome.
Sjogren syndrome
Chronic disease characterized by immunologically mediated destruction of the lacrimal and salivary glands. Usually associated with other autoimmune diseases, i.e. Rheumatoid arthritis or SLE. Sjogren syndrome is thought to be caused by an abnormal reaction from the lymphocytes that protect the body from infection and cancer, see them as being foreign and attack the glands that produce tears and saliva causing inflammation and damage. Clinical symptoms include eye pain, blurred vision resulting from damage to the cornea. Do to lack of saliva production patients can suffer from persistent dry eye, mouth (can lead to tooth decay), higher risk of developing interstitial pneumonitis, interstitial nephritis and thyroid gland abnormalities, vasculitis (inflammation of the blood vessels)
Pediatric Considerations
Neonates have depressed inflammatory and immune function: neutrophils and monocytes may not be capable of efficient chemotaxis. This is normal for an infant. Cell mediated function is active, but antibody production is deficient, some IgM, some IgA in utero, but no significant IgG. Maternal antibodies are transferred into fetus through fetal circulation, these levels drop to their lowest at 5-6 months old as the fetal IgG is increasing. Neonates are partially deficient in complement, especially alternative pathway: develop severe and overwhelming sepsis and meningitis when infected with bacteria with no maternal antibody protection
Geriatric Considerations
Immune function decreases in old age due to decreased lymphocyte function and populations Decrease T cell activity and T cell function Decreased antibody production in response to antigenic challenges Increases in circulating immune complexes and autoantibodies Decrease in circulating memory B cells Higher risk of wounds due to changes in skin, subcutaneous fat loss, change in collagen/elastin Decrease perfusion causes more risk on wound beds Innate resistance cellular components are deficient, or are less active/effective
Definitions
Host: provides nutritional and physical growth requirements of another Infection: the presence and multiplication within a host with injury to the host Colonization: establishment of a presence in a host can be infectious, or can be commensal Virulence: disease producing potential of an organism Pathogens: microorganisms that are typical causing disease in humans Opportunistic pathogens: produce infectious disease when host has been weakened by illness, malnutrition or medical therapy
Chain of infection
Microbes enter the host through breaches in the skin, by inhalation or ingestion or by sexual transmission. These bacteria need a mode of entry and can disseminate by different routes. Skin serves as a natural barrier. Cutaneous infections are typically acquired by entry of microbes through breaks in the skin including through wounds or through surgical incisions, burns or diabetic pressure ulcers. Needle sticks can also expose the recipient to infected blood with hepatitis B or hepatitis C or HIV. The infection then spreads through the lymphatic system and blood stream then to distant organs.
Portal of Entry
The process by which a pathogen enters the body, gains access to susceptible tissues, and causes disease Penetration Direct contact Ingestion inhalation Lets talk more about the portals of entry. Skin is the dense ,keratinized outer layer of skin which is a natural barrier to infection. The skin’s low ph and fatty acids inhibit growth of microorganisms other than normal bacteria and fungi. Normal skin flora such as Staph Aureus and Candida albicans. Gastrointestinal pathogens are transmitted by food or drink contaminated with fecal material. Acidic gastric secretions are important defenses and are lethal for many GI pathogens. Shigella and Giardia cysts are resistant to gastric acids, so fewer than 100 organisms can cause illness.There are four other defences within the GI tract that assist in the defense against organisms including the layer of viscous mucousthat covers the intestinal epithelium, lytic pancreatic enzymes and bile, mucosal anti-microbial peptides, defensins and normal flora, and IgA antibodies made from the plasma cells located in mucosa associated lymphoid tissue (MALT) as previous learned. Infection of the GI tract will occur when the defenses are weakened or the organism is able to develop strategies to overcome these defenses. Respiratory tract sees large numbers of microorganisms that are inhaled daily through dust or aerosols. Large particles get trapped in the mucocilary that lines the nose and the upper respiratory tract. Microorganisms get trapped in the mucus secreted by the goblet cells then transported by ciliary action to the back of the throat where they are then swallowed or coughed out. Some bacteria respiratory pathogens can release toxins that paralyze cilia which include H. influenza and mycoplasma pneumoniae.While other respiratory pathogens avoid phagocytosis or destruction after phagocytosis which include M. tuberculosis. Fungi infections infect the lungs when cellular immunity is depressed or when leukocytes are reduced which can be seen in those patients receiving chemotherapy for cancer or those who underwent a bone marrow transplant. The urogenital tract is mostly invaded from the exterior by way of the urethra. Urine in the bladder is normally sterile. Women have more urinary tract infections due to their anatomy as the distance between the urinary bladder and skin is in close proximetry.
Acquired immunodeficiency syndrome
Caused by the retrovirus human immunodeficiency virus (HIV) Profound immunosuppression that leads to infections and secondary neoplasms and neurologic manifestations Transmission by sexual, parenteral, mother to infant Mechanism of immune deficiency: loss of CD+T cells: T cell death during viral replication and budding, apoptosis occurring as a result of chronic stimulation, decreased thymic output, defective macrophage function and destruction of lymphoid tissue
Acquired immunodeficiency syndrome
The initial infection with HIV infection begins in the mucosal tissue, involving the memory CD4+T-cells and dendritic cells then spreading to the lymph nodes. Viral replication leads to viremia and widespread seeding of lymphoid tissue. Viremia is controlled by the host immune response, and the patient then enters a phase of clinical latency. During this phase, viral replication in both T cells and macrophages continues with some immune containment of the virus. A gradual erosion of CD4+ cells continues and ultimately, CD4+ T-cell numbers decline and the patient develops clinical symptoms of full blown AIDS. Cancers can occur during times of low CD4+counts. Control the HIV infection with antivirals with improved CD4+ counts and treatment with chemotherapy can place patient in remission from cancer.
