Overview Introduction Humoral immunity is based upon the production and activity of antibodies that defend against extracellular threats such as bacteria via opsonization of the surface of the pathogen leading to phagocytosis by innate immune cells like macrophages cytotoxicity by triggering release of toxic compounds by innate immune cells neutralization of pathogens and viruses by blocking interaction of pathogenic proteins with host receptors inactivating virulence factors expressed by pathogens activation of the complement cascade through the classical pathway The main effector cell of humoral immunity B-cell that is activated by displaying peptides to helper T-cells undergoes affinity maturation to make higher affinity antibodies undergoes class switching to develop new classes of antibodies differentiates into plasma cells that are specialized to produce antibodies Humoral immunity occurs in multiple phases including the primary response that occurs immediately after B-cell activation the secondary response after further differentiation of B-cells Activation of Humoral-Mediated Immunity Humoral immunity can be activated by two classes of antigens including thymus independent antigens that do not require T-cell help thymus dependent antigens that require T-cell help Activation of Humoral Mediated Immunity Feature Thymus Independent Thymus Dependent Function Detect conserved non-peptide antigens Identify pathogens that are missed by T-cells Detect peptide antigens Cooperate with T-cells to clear pathogens Activation steps Crosslinking of B-cell receptors by polymeric antigens Examples include bacterial cell wall or lipopolysaccharide Activation by mitogens to promote general B-cell activity Endocytosis of protein antigens that are detected by the B-cell receptor Processing of these antigens in endosomes and presentation on MHC class 2 Recognition of MHC complexes by activated helper T-cells Interaction of costimulatory CD40 on B-cells with CD40 ligand Differentiation after cytokine stimulation Limitations Does not lead to class switching or affinity maturation Does not produce immunological memory (require adjuvent) Requires peptide antigen Must have functional helper T-cells Affinity Maturation and Isotype Switching After B-cells are activated they can undergo two main processes including affinity maturation to increase receptor affinity isotype switching to produce different antibody isotypes Affinity maturation is a coordinated process with distinct stages including migration of B-cells to secondary lymphoid organs where B-cells proliferate in germinal centers to form a colony the B-cell receptor is randomly mutated in different cells selection of the cells with the highest affinity receptors within the colony by providing a limited number of survival signals allowing mutated B-cells to compete for these signals pruning less effective B-cells through apoptosis Isotype switching is stimulated after activation and occurs in germinal centers of secondary lymphoid organs is the process of irreversibly switching constant regions by DNA rearrangement with removal of μ (IgM) and δ (IgD) type constant regions addition of other constant regions making IgG, IgE, and IgA is controlled by stimulation with specific cytokines no specific IL required for IgG production IL-4 produces IgE IL-5 produces IgA Primary and Secondary Responses Upon activation distinct populations of B-cells will develop including effector B-cells that mediate the primary response by secreting antibodies secreting cytokines proliferating B-cells that mediate the secondary response after undergoing affinity maturation and class switching differentiating into plasma cells These responses differ in a variety of key aspects Primary versus Secondary Responses Feature Primary Response Secondary Response Function Immediately secrete antibodies Contain infection while secondary response develops Develop into a more effective response with higher affinity Clear infection after development Antibody type Low affinity IgM High affinity IgG IgA in mucosal infections IgE in parasitic infections Timing Early in infection Late in infection
QUESTIONS 1 of 5 1 2 3 4 5 Previous Next Lab Values Blood Hematologic Cerebrospinal Sweat, Urine, and BMI Blood, Plasma, Serum Reference Range ALT 8-20 U/L Amylase, serum 25-125 U/L AST 8-20 U/L Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL Calcium, serum (Ca2+) 8.4-10.2 mg/dL Cholesterol, serum Rec: < 200 mg/dL Cortisol, serum 0800 h: 5-23 μg/dL //1600 h: 3-15 μg/dL 2000 h: ≤ 50% of 0800 h Creatine kinase, serum Male: 25-90 U/LFemale: 10-70 U/L Creatinine, serum 0.6-1.2 mg/dL Electrolytes, serum Sodium (Na+) 136-145 mEq/L Chloride (Cl-) 95-105 mEq/L Potassium (K+) 3.5-5.0 mEq/L Bicarbonate (HCO3-) 22-28 mEq/L Magnesium (Mg2+) 1.5-2.0 mEq/L Estriol, total, serum (in pregnancy) 24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL 28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL Ferritin, serum Male: 15-200 ng/mLFemale: 12-150 ng/mL Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL Female: premenopause: 4-30 mIU/mL midcycle peak: 10-90 mIU/mL postmenopause: 40-250 pH 7.35-7.45 PCO2 33-45 mmHg PO2 75-105 mmHg Glucose, serum Fasting: 70-110 mg/dL2-h postprandial:<120 mg/dL Growth hormone - arginine stimulation Fasting: <5 ng/mLProvocative stimuli: > 7ng/mL Immunoglobulins, serum IgA 76-390 mg/dL IgE 0-380 IU/mL IgG 650-1500 mg/dL IgM 40-345 mg/dL Iron 50-170 μg/dL Lactate dehydrogenase, serum 45-90 U/L Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL Female: follicular phase: 5-30 mIU/mL midcycle: 75-150 mIU/mL postmenopause 30-200 mIU/mL Osmolality, serum 275-295 mOsmol/kd H2O Parathyroid hormone, serume, N-terminal 230-630 pg/mL Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L Phosphorus (inorganic), serum 3.0-4.5 mg/dL Prolactin, serum (hPRL) < 20 ng/mL Proteins, serum Total (recumbent) 6.0-7.8 g/dL Albumin 3.5-5.5 g/dL Globulin 2.3-3.5 g/dL Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h Thyroxine (T4), serum 5-12 μg/dL Triglycerides, serum 35-160 mg/dL Triiodothyronine (T3), serum (RIA) 115-190 ng/dL Triiodothyronine (T3) resin uptake 25%-35% Urea nitrogen, serum 7-18 mg/dL Uric acid, serum 3.0-8.2 mg/dL Hematologic Reference Range Bleeding time 2-7 minutes Erythrocyte count Male: 4.3-5.9 million/mm3Female: 3.5-5.5 million mm3 Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/hFemale: 0-20 mm/h Hematocrit Male: 41%-53%Female: 36%-46% Hemoglobin A1c ≤ 6 % Hemoglobin, blood Male: 13.5-17.5 g/dLFemale: 12.0-16.0 g/dL Hemoglobin, plasma 1-4 mg/dL Leukocyte count and differential Leukocyte count 4,500-11,000/mm3 Segmented neutrophils 54%-62% Bands 3%-5% Eosinophils 1%-3% Basophils 0%-0.75% Lymphocytes 25%-33% Monocytes 3%-7% Mean corpuscular hemoglobin 25.4-34.6 pg/cell Mean corpuscular hemoglobin concentration 31%-36% Hb/cell Mean corpuscular volume 80-100 μm3 Partial thromboplastin time (activated) 25-40 seconds Platelet count 150,000-400,000/mm3 Prothrombin time 11-15 seconds Reticulocyte count 0.5%-1.5% of red cells Thrombin time < 2 seconds deviation from control Volume Plasma Male: 25-43 mL/kgFemale: 28-45 mL/kg Red cell Male: 20-36 mL/kgFemale: 19-31 mL/kg Cerebrospinal Fluid Reference Range Cell count 0-5/mm3 Chloride 118-132 mEq/L Gamma globulin 3%-12% total proteins Glucose 40-70 mg/dL Pressure 70-180 mm H2O Proteins, total < 40 mg/dL Sweat Reference Range Chloride 0-35 mmol/L Urine Calcium 100-300 mg/24 h Chloride Varies with intake Creatinine clearance Male: 97-137 mL/minFemale: 88-128 mL/min Estriol, total (in pregnancy) 30 wks 6-18 mg/24 h 35 wks 9-28 mg/24 h 40 wks 13-42 mg/24 h 17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 hFemale: 2.0-8.0 mg/24 h 17-Ketosteroids, total Male: 8-20 mg/24 hFemale: 6-15 mg/24 h Osmolality 50-1400 mOsmol/kg H2O Oxalate 8-40 μg/mL Potassium Varies with diet Proteins, total < 150 mg/24 h Sodium Varies with diet Uric acid Varies with diet Body Mass Index (BMI) Adult: 19-25 kg/m2 Calculator ( ) xy AC 7 8 9 ÷ 4 5 6 × 1 2 3 - 0 . = + Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.IM.73) The only immunoglobulin found as a dimer has what primary function? Review Topic QID: 100589 1 Protect against invasive helminth infection 8% (3/36) 2 Protect against viral infections 0% (0/36) 3 Provide an initial humoral immune response to newly presenting bacterial antigens 8% (3/36) 4 Inhibiting bacterial adherance and colonization of mucous membranes 67% (24/36) 5 Provides the most specific recognition to circulating antigens in the bloodstream 11% (4/36) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 4 (M1.IM.66) Which of the following events is likely to occur in the germinal center? Review Topic QID: 100487 1 Development of early pro-B cells 24% (10/42) 2 Development of immature B cells 24% (10/42) 3 T-cell negative selection 7% (3/42) 4 Isotype switching 33% (14/42) 5 Formation of double-positive T cells 5% (2/42) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 4 (M1.IM.56) A 12-year-old African American is exposed to pollen while playing outside. The allergen stimulates TH2 cells of his immune system to secrete a factor that leads to B-cell class switching to IgE. What factor is secreted by the TH2 cell? Review Topic QID: 100477 1 IFN-gamma 5% (1/22) 2 IL-4 91% (20/22) 3 IL-17 5% (1/22) 4 TGF-beta 0% (0/22) 5 IL-22 0% (0/22) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 2 (M1.IM.36) Immunology researchers attempt to characterize the role of several cytokines in a 5-year-old male’s allergic reaction to peanuts. Months after initial exposure to peanuts, the child was brought to the ER with symptoms of anaphylaxis that resolved following epinephrine injection and supportive therapy. Which of the following best describes the role of IL-4 in the child’s response: Review Topic QID: 100457 1 B cell class switching 62% (50/81) 2 Stimulates IgA production 4% (3/81) 3 Macrophage and Th1 cell activation 15% (12/81) 4 Neutrophil chemotaxis 11% (9/81) 5 Growth of cytotoxic T cells 2% (2/81) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 1
Humoral-Mediated Immunity Immunology - Humoral-Mediated Immunity - Treatment Consult This video describes humoral-mediated immunity. 2/16/2015 69 views