Blueprint w3: Immunity and Infection Flashcards
Staphylococcus Aureus
-bacterial
-Gram +
-Cellulitis, toxic shock syndrome, food poisoning, impetigo, wound and medical device infections
‒Major cause of hospital-acquired (nosocomial) infections and antibiotic resistance
-β-lactamase, an enzyme that destroys penicillin; more recently, bacteria developed a resistance to methicillin, called methicillin-resistant S. aureus (MRSA)
-staph is an infection of the skin –> portal of entry from a skin agent that enters a broken skin area
Rheumatoid Arthritis
-Autoimmune d/o Affects Joints and Collagen
-Probable Self-Antigen: immunoglobulin G (IgG)
-T cells against type II collagen (a protein present in joint tissues) contribute to the destruction of joints in rheumatoid arthritis
-Rheumatoid arthritis causes damage mediated by cytokines, chemokines, and metalloproteases.
-DX: specific clinical, lab, & imaging
-TX: DS-modifying antirheumatic meds, physical measures (pt/ot), surgery
-Incidence-1%; F 2-3x M
-Onset: 35-50 years, but can be childhood
**Signaling Molecules for WBCs
check this info
-Hormones: send regulatory msgs throughout the body in ECF (endocrine signaling)
-Local regulators: adjacent cells/near to secretion
-Neurotransmitters
-Cytokines and growth factors
-Nitric Oxide
-Prostaglandin: reg. aggregation of Plts
-Paracrine Signaling
-Autocrine signaling
-Neurotransmitters/neurohormones
-Neuroendocrine signaling
-Synaptic signaling
-Pheromones
Stages of Infection: Incubation, Prodromal, Invasion (acute illness), Convalescence
-Incubation period: The period from initial exposure to the infectious agent and the onset of the first symptoms; during this time, the microorganisms have entered the individual, undergone initial colonization, and begun multiplying but are at insufficient numbers to cause symptoms. This period may last from several hours to years. The time between exposure and symptoms is often termed clinical latency. With some infections (e.g., HIV and varicella zoster infection), there is an acute symptomatic phase, followed by a latency period that can last months or even years.
-Prodromal stage: The occurrence of initial symptoms, which are often mild and include a feeling of discomfort and tiredness; pathogens continue to multiply during this stage.
-Invasion or acute illness period: The pathogen is multiplying rapidly, invading farther and affecting the tissues at the site of initial colonization as well as other areas; the immune and inflammatory responses have been triggered; symptoms may be specifically related to the pathogen or to the inflammatory response.
-Convalescence: In most instances, the individual’s immune and inflammatory systems successfully remove the infectious agent and symptoms decline; alternatively, the disease may be fatal or enter a latency phase with resolution of symptoms until pathogen reactivation at a later time.
Hypersensitivity Reactions (general)
-It is an altered immunologic response to an antigen that results in disease or damage to the individual.
-Types I, II, and III hypersensitivity reactions are mediated by antibodies, whereas type IV hypersensitivity reactions are mediated by T lymphocytes and do not involve antibodies
Hypersensitivity-Type 1 (IgE-exagerated response
Are mediated by antigen-specific IgE and the products of tissue mast cells
The most common allergic reactions are type I reactions against environmental antigens (e.g., pollen, bee venom, nuts, medications).
-Generate an inappropriate IgE-mediated response to what would otherwise be an innocuous exposure.
-Most commonly, the term allergy indicates IgE-mediated reactions.
-The immediate reaction, occurs within minutes
Ex: Anaphylaxis, acute rhinitis, food allergy
S/s: mild, local (urticaria, rhinorrhea, itch) to life-threat (arrhythmias, shock, bronchospams, laryngeal obs.)
DX: skin testing or EOSINOPHILIA, hx of s/s, freq, triggers
TX: symptom based- anthistamines (H1 blockers), corticosteroids, epinephrine
Hypersensitivity-Type 2 (IgM or IgG)
-immune reactions against a specific cell or tissue
-Environmental antigens (e.g., drugs or their metabolites) may bind to the plasma membranes of specific cells and function as haptens, making them targets of type II reactions.
ex: hemolytic ds, rheumatic fever, bullous pemphigoid (abd/groin blistering), Goodpasture syndrome (soa, hemoptysis, hematuria), Guillian-barre syndrome (ascending paralysis), MG (weakness, ptosis, diplopia, dysphagia), Graves (tremor, insomnia, irritable, wt loss, tachy), Pernicious anemia
labs: coombs test (abo compatibility); RBC antigen, immunohistochem., diffuse radioactive iodine uptake
tx: steriods, plasmapheresis, immunosuppression
Mechanisms of type II, tissue-specific reactions
Complement-mediated lysis occurs when antibodies (IgM or IgG) bound to tissue-specific antigens cause activation of the complement cascade through the classical pathway. Formation of the membrane attack complex (C5-9) damages the membrane and results in lysis of the cell. For example, erythrocytes are destroyed by complement-mediated lysis in individuals who have received mismatched transfused blood cells (see the section on Alloimmunity).
Antibody-dependent cell-mediated cytotoxicity (ADCC) occurs when antibodies bound to tissue-specific antigens activate macrophages, neutrophils, and natural killer (NK) cells, which attack the target cells. When antibodies activate complement, there is the deposition of C3b on the target cell surface. Receptors on macrophages and neutrophils recognize and bind these opsonins (antibody plus C3b) and increase phagocytosis of the target cell. Toxic products produced by neutrophils (lysozymes and toxic oxygen radicals) also cause tissue damage. ADCC also involves NK cells. Antibodies on the target cell are recognized by Fc receptors on NK cells, which release toxic substances that destroy the target cell. Examples of ADCC include autoimmune conditions in which autoantibodies are made against antigens on platelets or red blood cells, causing them to be removed by phagocytes in the spleen.
Antireceptor antibodies do not destroy the target cell but rather cause the cell to malfunction. These autoantibodies change the function of the target receptor by blocking, overstimulating, or destroying it. For example, in Graves disease, autoantibodies called thyroid-stimulating immunoglobulins (TSIs) bind to and activate receptors for thyroid-stimulating hormone (TSH) on thyroid gland cells. TSH normally stimulates thyroid hormone secretion but is under the control of feedback mechanisms. When TSIs bind to the TSH receptors, they stimulate the thyroid cells to overproduce thyroxine, thus producing symptoms of hyperthyroidism
Hypersensitivity-Type 3 (IgG)
Disease reactions are caused by antigen-antibody (immune) complexes that are formed in the circulation and are deposited in vessel walls or other tissues
The primary difference between type II and type III mechanisms is that in type II hypersensitivity, antibodies bind to antigen on the cell surface, whereas in type III, antibodies bind to soluble antigen that was released into blood or body fluids.
Mechanisms: Serum Sickness (Raynauds) or Arthrus reaction-vasculitis d/t repeated local exposure (celiac ds, allergic alveolitis or Farmers lungs ds/pigeon breeders ds), post-strep glomerulonephritis
s/s: fever, fatigue, rash/uticaria, protienuria, arthralgias, ulcers, pleuritis, pericarditis
labs: antibody testing, histopath,
Hypersensitivity Type 4 (T Lymphocytes, no antibodies) Delayed reaction
Tc cells directly kill target cells. Macrophages release soluble factors, such as lysosomal enzymes and toxic reactive oxygen species. Together, these responses cause tissue damage.
The response is delayed, 24 to 72 hours after antigen reexposure b/c of the time it takes for sensitized T cells to travel to the site of antigen reexposure and the time needed to produce cytokines that activate other cells including macrophages (delayed hypersensitivity).
CD4 (helper) Tcells, CD8 (cytotoxic/killer) Tcells
Ex: Graft Rejection, TB skin test reaction, poison ivy
-component may be present in autoimmune ex Rheum. arthritis; T1DM, hashimotos, MS, Celiac ds,
IgE: –> ALLERGY RESPONSES !!!!
igE inserts itself into mast cells and eosinophils
Is the least concentrated of the immunoglobulin classes in the circulation
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Acts as a mediator of many common allergic responses.
Defends against parasites.
??Antigens Vs. Antibodies
Antigens (anything that can produce an immune response AGAINST) have haptin and epitope (epitope that is recognized on the cell by the B or T cells; rest of antigen is HAPTEN!!!)-
🡪 multivalent (some cells have more than one epitope on them) proteins are recognized by other t or B cells)
Antibodies
Innate (resistance) vs Adaptive Immunity (acquired) AKA: Lines of Defense
- Inate: present at birth, and include the surface barriers skin and mucous membranes; Biochemical barriers; prevent damage from enviorn. and infection; epithelial cells on skin, GI/GU and resp.
–Normal flora - Inflammation: activated with injury or infectious disease. aka: first responder
-Complement system; Clotting, Kinen
-Mast Cells-degranulation;
-Macrophages: tumor-necrosis factor-a; ILL, IFN, antiinflamm cytokines - Adaptive: specific to particular antigens, and has memory.
-lymphocytes and antibodies (serum proteins)
-process starts after external barriers and inflam. activated
-slowly augments initial defenses and promote processes against re-infection
Innate Immunity (non-specific)
-1st line of defense
-Immediate response (0-96hrs)
-Cells: Natural Killer cells, macrophages, neutrophils, dendritic cells, Mast cells, basophils, and eosinophils
-Independent from antigen
-ex: Skin, hair, cough, mucous membranes, phagocytes, granulocytes
Adaptive Immunity (specific)
-2nd/3rd line of defense
-Long-term response >96 hrs
-Cells: T/B Lymphocytes
-Dependent on antigens
-ex: Pus, swelling, redness, pain, T and B lymphocyte response
Immunocompromised Patients and Infectious Risks
-A suppressed immune system is weakened to the point that it leaves an individual vulnerable to infections.
-C/b: diseases, medications, and lifestyle factors
-most common: autoimmune diseases, such as lupus, rheumatoid arthritis, or type 1 diabetes.
Dx: exam, labs (CBC)
Tx: monitoring for infections, practicing lifestyle behaviors that boost the immune system, and taking medications to treat the associated symptoms and underlying causes.
High-level Risk:
-primary combined immunodef
-rec. chemotherapy
-within 2 months organ transplant
-HIV w/ CD4<200
-daily steroid w/ dose >20mg longer than 14 days
-Biologic immune modulators: tumor necrosis factor-a (RNF-a) blocker or rituximab
Low Risk
-asymtomatic HIV w/ CD4>200
-lower daily dose of corticosteroids
-methotrexate <0.4/kg/we
-azathioprine <3mg/kg/day
-mercaptopurine <1.5mg/kg/day
