student.LECTURE.Immunity.Hematology.pdf

Immunity and Hematology  Tell me what you know… ► Cytokines ► are signaling proteins that help control inflammation in your body. They allow your immune system to mount a defense if germs or other substances that can make you sick enter your body. Too many cytokin...

Immunity and Hematology  Tell me what you know… ► Cytokines ► are signaling proteins that help control inflammation in your body. They allow your immune system to mount a defense if germs or other substances that can make you sick enter your body. Too many cytokines can lead to excess inflammation ► Natural Killer Cells ► Monocytes-Macrophages ► B and T Lymphocytes ► CD4 (HIV takes out the CD4 cells) and CD8 Cells ► Antigen Presenting Cells ► Plasma ► Immunoglobulins  Overview of the Immune System Concept Characteristic Immune System: Two Innate- born with it/mucus components membranes/skin Adaptive- we were introduced with it-vaccine, we now have the antigen Recognize “self” vs Antigens: “non-self” substances, target “non-self” of immune response Immunodeficiency Weakened immune system Autoimmunity Attack “self” cells Hypersensitivity Overreactive immune system -asthma-  Innate Immunity (continued_2) ► Cytokines- What is it ► Chemical signals produced by WBC s’ ► Regulate/coordinate immune system ► Inflammation regulation ► The cytokines cause an inflammatory response in a case of an asthma ► Natural killer cells (NK cells) ► Granular lymphocytes ► Destroy tumor and virus-infected cells  Adaptive Immunity ► Acquired, specific, memory response ► T and B cells (lymphocytes) ► T cells: cell-mediated immunity ► B cells: antibody-mediated immunity ► Also known as humoral immunity ► Recognize self vs non-self ► MHC: major histocompatibility complex ► Also known as HLA: human leukocyte antigen Cell Types ► Antigen-presentin g cells (APCs) ’ ► Macrophages and dendritic cells ► Present antigento activate T cells ► CD4 and CD8 cells ► CD4: helper T cell ► CD8: cytotoxic T cell ► HIV damages CD4 cells  Plasma Cells ► B cell ► Activated by specific antigen ► B cell becomes plasma cell ► Produces antibodies (immunoglobulins, Igs) ► First antibody-mediated response takes time ► Activated B cell ► Also forms memory cell ► Quicker and stronger response with next antigen encounter  B Cell Activation There different types of Igs and there are a  Immunoglobulins (Igs) ► Produced by B cells ► Bind to specific antigens ► Five subtypes: KNow that there are different types of IGs ► IgM: Earliest Ig response ► IgG: Most abundant Ig ► IgA: Mucosal secretions: Breast milk, sweat, saliva, tears ► IgD: Hypersensitivity reaction; GI tract, skin, respiratory tract ► IgE: Involved in allergies  Immunoglobulins (Igs) (continued_2) ► Primary response ► First exposure to antigen ► Lag time before Ig levels increase ► IgM first antibody type formed ► Secondary response ► Any exposure after the first ► IgG levels increase rapidly ► Due memory cell response ► Antigen neutralized before disease signs and symptoms  Active Acquired vs Passive Acquired Immunity ► Active acquired ► Exposure to antigen activates immune system ► Infection ► Vaccine ► Antibodies, memory cells produced ► Passive acquired ► Receive premade antibodies ► Short-term duration of response ► Examples: hepatitis B immunoglobulin (HBIg) or antibodies transferred in breast milk  Vaccines (General) ► Specific formulation ► Either viral or bacterial components ► Most viral vaccines consist of live virus ► Virus has been inactivated ► Goal: ► Exposure to antigen (non-disease causing) ► Provoke immune response ► Produce memory cells WITHOUT disease manifestation  Vaccines (General) (continued_2) ► Primary response to vaccine is long lasting ► Booster: help to obtain full immunity- when the vaccine is low in the body ► Vaccine administration: ► Some given in series ► Others require routine boosters ► Tetanus  mRNA Vaccines ► mRNA created encoding viral pathogen ► mRNA administered to patient ► Patient’s body manufactures viral antigen ► Spike protein ► Synthesized viral antigen recognized as foreign ► Patient develops antibody to viral antigen ► Provides protection if encounter infectious agent When giving vaccines we are looking at how that body will respond in the system  Anergy Panel ► Immunocompetence test ► Inject common antigens (mumps, candida) intradermally ► Positive skin reaction indicates immune response ► Lack of response may indicate immunodeficiency We want some form of a reaction in the body like a TB on the skin  Antibody Screening and Titer ► Antibody titers ► Presence and level of antibodies ► Antibody presence indicates exposure to disease/antigen (as in vaccines) ► Can be used to indicate immunity ► Example: antibodies to rubella following vaccination for rubella  Allergy Testing ► Skin test ► Scratch or inject small amount of antigen into skin ► Assess reaction to allergen ► Serology testing ► IgE levels in response to antigens  Basic Immune Disorders: Overreaction ► Hypersensitivity: 4 types ► Type I: Immediate (allergies) ► Type II: Cytotoxic ► Type III: Immune complex ► Type IV: Delayed ► Autoimmune disorders  Basic Immune Disorders: Underreaction ► Immunodeficiency ► Primary (congenital) ► Present at birth ► Genetic defect ► Secondary (acquired) ► Develops due to infection, chemotherapy (kills everything not just chemo cells), immunosuppressive drugs, etc.  Type I: Immediate Hypersensitivity ► Known as allergy or atopic disorder ► Process ► Antigen (allergen) interacts with APC (antigen-presenting cell) ► APC, with specific antigen, activates B cells ► B cells produce IgEs ► IgEs bind to mast cells ► Mast cells degranulation (release chemicals) ► Chemicals induce allergy symptoms  Allergy Response DOn’t need to know that  Type I Hypersensitivity ► Local or systemic response ► Hives (urticaria); nasal discharge- because they have that allergen that comes into their body; bronchial asthma; allergic gastroenteritis (nasal congestion) ► Allergic rhinitis ► 50% of U.S. population test positively ► Allergen causes release of histamines (give antihistamines), prostaglandins, leukotrienes ► Mucus hypersecretion, bronchiole constriction, pale nasal mucosa, watery eyes, sneezing  Anaphylaxis- if not treated immediately, they will die! ► Severe, life-threatening response ► Death can happen within minutes ► Overwhelming response to allergy mediators ► Urticaria, bronchoconstriction, laryngeal edema, angioedema (swelling of facial area) ► Medical emergency ► EpiPen (epinephrine) ► Used to counteract response to allergen ► Maintain patient until further medical care available  Type II Hypersensitivity: Cytotoxic ► Igs attack antigens on cell ► Cell lysis results ► Example: ► Blood transfusion reaction Hypersensitivity is seen within the first 15 minutes Type III Hypersensitivity: Immune Complex ► Antigen-antibody complex deposited in tissues ► Known as “immune complex” ► Damage to tissue ► Presentation: ► Systemic (lupus) ► Localized (rheumatoid arthritis)  Type IV Hypersensitivity: Delayed ► T-cell mediated ► Other hypersensitivities B-cell mediated ► Previous exposure to antigen primes the T cells ► T cell attack does not occur until days later ► Example: poison ivy, transplant rejection ► Mantoux test for tuberculosis ► Demonstrates a Type IV hypersensitivity  Autoimmune Disorder Overview ► Attack “self” cells ► Ig-mediated (autoantibodies) and/or ► T-cell ► Organ-specific or systemic ► Underlying etiology is unknown ► Molecular mimicry ► Body’s antigens resemble infectious agent ► Example: rheumatic fever ► Antistreptococcal antibodies attack heart valves Molecular Mimicry  Systemic Lupus Erythematosus (SLE) ► Multisystem disease ► Antinuclear antibodies (ANA s) present ’ ► Antibody complexes deposited in tissues ► Hormonal and environmental factors triggers ► Estrogen ► Genetics (X chromosome) ► EBV infection (especially African American) ► Drugs: hydralazine, procainamide, quinidine, phenytoin, isoniazid, and penicillamine ► Ultraviolet (UV) light ► Tobacco smoking ► Exposure to silica dust Remember what the patient looks like  Systemic Lupus Erythematosus (SLE) (continued_2) ► Clinical presentation ► Skin rash (butterfly rash across cheeks) ► Joint inflammation ► Kidney damage ► Vasculitis ► Raynaud’s phenomenon ► Remission and exacerbations Systemic Lupus Erythematosus (SLE) (continued_4) ► Raynaud’s Phenomenon When it gets super cold, the hands get so white, and turn purple- not enough circulation  Systemic Lupus Erythematosus (SLE) (continued_5) ► Clinical manifestations ► Pericarditis, endocarditis, and coronary artery disease ► Anemia, lymphopenia, and thrombocytopenia ► Peritonitis, intestinal perforation ► Sicca syndrome (dry eye disease), conjunctivitis, retinal vasculitis, and optic neuritis  Systemic Lupus Erythematosus (SLE) (continued_7) ► Pharmacological treatment ► Hydroxychloroquine or chloroquine ► NSAIDs (advil/ ► Corticosteroids (short-term) ► Immunosuppressive agents ► Azathioprine, methotrexate, cyclophosphamide ► Biological agents (monoclonal antibodies) ► Belimumab and anifrolumab  Systemic Lupus Erythematosus (SLE) (continued_8) ► Nonpharmacological therapy ► Avoid prolonged exposure sunlight/UV ► Supplement vitamin D ► Smoking cessation ► Avoid sulfonamide and tetracycline ► Pregnancy should be avoided in active disease ► Up-to-date immunizations ► Avoid live virus vaccines in persons on immunosuppressive  Rheumatoid Arthritis (RA) ► Chronic joint inflammation ► May have systemic effects ► Specific criteria for diagnosis of this disorder ► Symmetric polyarthritis with possible systemic manifestations: ► Fatigue, peripheral neuropathy, vasculitis, pericarditis, lung involvement Rheumatoid Arthritis (RA) (continued_2) Overused joints  Rheumatoid Arthritis (RA) (continued_3) ► Cause unknown- they don’t know what triggers it ► Autoimmune mechanisms ► Genetic factors (50% of risk) ► Example: allelic variation in the HLA-DRB1 ► Epigenetic changes ► Environmental factors: smoking, hormonal (female more at risk), immunological, and infectious factors (EBV)  Rheumatoid Arthritis (RA) (continued_4) ► Progression ► Unknown, initial antigenic stimulus provokes APC ► APCs activate T cells ► T cells secrete cytokines, recruit other WBCs ► Inflammatory response continues ► Reactivated T cells and proinflammatory cytokines attract WBCs to joint space ► B cells secrete Igs (autoantibody: RF, rheumatoid factor) It goes to the joints  Rheumatoid Arthritis (RA) (continued_5) ► Progression (continued_1) ► Continual inflammation causes synovial hypertrophy: pannus ► Bone erosions ► Joint deformity ► Approximately 40% of RA cases affect additional tissues: skin, lung, heart, blood vessels, nervous system  Rheumatoid Arthritis (RA) (continued_6) Microphages- eats it up  Rheumatoid Arthritis (RA) (continued_8) ► Treatment ► NSAIDs- prolonged intake leads to bleeding, methotrexate ► DMARDs ► Disease-modifying antirheumatic drugs ► Immunosuppressants  Sarcoidosis ► Chronic, multi-system disorder ► Asymptomatic to severe ► Accumulation of T cells, and macrophages in organs ► Chronic inflammation causes granulomas () ► Lungs most frequent place of involvement ► Skin and eyes also  Sarcoidosis (continued_2) ► Erythema nodosum (EN) ► Tender, erythematous nodules on anterior legs ► Lupus pernio ► Maculopapular rash around eyes and nose, on back and extremities ► Löfgren’s syndrome (LS) ► Clinically distinct syndrome in sarcoidosis ► Acute disease onset with fever, bilateral hilar lymphadenopathy, arthritis, and EN  Sarcoidosis (continued_3) ► Fever, fatigue, malaise, anorexia ► Lung involvement: coughing, wheezing due to impaired gas exchange as some areas of the lungs are not working as they should ► Parotid gland, lymph node, eye involvement ► Anemia ► Lymphopenia: lympohcytes sequestered in granulomas ► Neuritis  Sarcoidosis (continued_4) ► Diagnosis ► Three major criteria: ► Clinical presentation ► Nonnecrotizing granulomatous inflammation in one or more tissue samples ► Exclusion of alternative causes of granulomatous disease ► Treatment ► Glucocorticoids, immunosuppressive agents ► Disease clears spontaneously in many patients  Sjögren's Syndrome- dry mucus membrane ► Dry eyes (keratoconjunctivitis sicca) ► Dry mouth (xerostomia) ► Immunological destruction of lacrimal and salivary glands ► Women more commonly affected, may also suffer from RA ► Diagnosis ► ANAs ’ ► anti-Ro/SSA and anti-La/SSB ► Treatment ► Symptom relief and limit damage due to dry eye and mouth  Scleroderma ► AKA systemic sclerosis ► Abnormal accumulation of fibrous tissue in skin and organs ► Associated with several gene mutations ► Inflammatory reaction with injury to endothelium ► Most noticeable change is “tightening” of skin- shiny, stretched ► Skin appears smooth, shiny, and stretched ► Contractures of fingers may occur  Scleroderma (continued_2) ► Three major pathological mechanisms: ► Widespread microangiopathy ► Inflammation and autoimmunity ► Visceral and vascular fibrosis: multiple organs ► Presentation ► Diffuse, widespread disease or ► Localized disease limited to skin on face, arms, hands, and fingers  Scleroderma (continued_3) ► Extracutaneous scleroderma: ► Lungs ► Interstitial fibrosis ► Pulmonary hypertension ► GI system (particularly the esophagus) ► Kidneys ► Musculoskeletal system ► Heart  Scleroderma (continued_4) ► CREST ► Type of scleroderma ► Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia ► Diagnosis ► Elevated ANAs ’ ► “Ground glass” appearance in lungs ► Treatment ► NSAIDs, corticosteroids, immunosuppressants ’  Immunodeficiency Disorders ► Primary ► Congenital ► Genetic defect ► Secondary ► Acquired (HIV, chemotherapy, radiation, etc.)  Selective IgA Deficiency (sIgAD) ► One of most common primary immune deficiencies ► May be asymptomatic ► Normal IgG and IgM ► Increased risk for atopic and autoimmune diseases ► Risks ► Some medications ► Some infections ► Monthly injections of Igs can be used for treatment if needed  Human Immunodeficiency Virus (HIV) ► Virus that infects CD4 cells (T helper cells)- cell-mediated immunity 1. Affects our body’s 2 important immunity (CD4 and T helper cells) ► Infection has three stages 1. Acute 2. Chronic 3. AIDS ► Acquired Immunodeficiency Syndrome Human Immunodeficiency Virus (HIV) (continued_2) ► Routes of transmission ► High-risk individuals ► Sexual activity; semen ► Participate in unsafe and vaginal secretions sex ► Blood ► MSM ► Transplacental ► Men who have sex with men ► Breast milk ► Young Black/African ► Organ transplants American gay and ► Saliva (into open mouth bisexual men are most wounds) affected ► IV drug abusers  Human Immunodeficiency Virus (HIV) (continued_3) ► Retrovirus- Goes back and changes what CD4 cell does and makes itself host/ in charge of it so it makes more of itself ► RNA virus ► Reverse transcriptase ► Enzyme converts HIV RNA into DNA ► Targets cells that express CD4 receptors and chemokine receptor CCR5 ► Those without CCR5 are resistant to HIV  Human Immunodeficiency Virus (HIV) (continued_4) ► HIV infection ► Initial infection leads to flulike symptoms, which resolve, and patient becomes asymptomatic ► HIV still present ► Can remain dormant in inactive CD4 cell ► Macrophages serve as reservoir for HIV ► Infected CD4 cells are unable to function ► Risk of opportunistic infection increases ► Severe immunodeficiency eventually develops Human Immunodeficie ncy Virus (HIV) (continued_5)  Human Immunodeficiency Virus (HIV) (continued_6) ► Following initial infection, detectable antibody levels develop in 2 weeks to 6 months ► Seroconversion ► Early in disease, asymptomatic, but can infect others ► “Latent period” ► Over time, CD4 levels fall, as HIV RNA levels increase ► 140 bpm No urine output  Anemia Caused by Chronic Blood Loss ► Causes ► GI bleeding ► Menstrual blood loss ► Medications ► NSAIDs may lead to GI bleeding ’ ► Signs and symptoms ► Blood loss is slow ► Patient may report no noticeable changes but they will overtime  Hemolytic Anemias ► Erythrocyte destruction: Outpaces replacement ► Causes: ► Hemoglobinopathies ► Inherited disorder of Hgb ► Autoimmune disorders ► Warm (IgG) and cold (IgM) agglutinin syndrome ► Alloimmune hemolysis ► Blood transfusion reactions ► Hemolytic disease of the newborn (HDN) ► Hereditary spherocytosis ► Lead poisoning  Hemolytic Anemias (continued_2) ► Signs and symptoms ► Typical anemia signs PLUS jaundice, dark urine (urobilinogen), enlarged spleen due to elevated RBC breakdown ► Diagnosis ► Elevated reticulocytes to replace lost cells, peripheral smear will show misshapen and damaged RBCs ’ ► Treatment ► Depends on underlying causes Enough saline so that the body starts to dilute when there is a reaction occurring  Hemoglobinopathy ► Inherited disorder ► Abnormal structure of the Hgb molecule ► Cannot carry oxygen efficiently ► Leads to destruction of RBC ► Examples: ► Sickle cell anemia (SCA) ► Thalassemia  Sickle Cell Anemia (SCA) ► Autosomal hemoglobinopathy ► Homozygous and heterozygous forms (HbS) ► Homozygous form more severe ► Carrier state ► Distorts shape of RBC (exposure to hypoxia, dehydration, stress) ► Signs do not appear until fetal Hgb levels decline ► Malaria: ► SCA provides increased resistance to malaria ► Genetic expression has remained high  Sickle Cell Anemia (SCA) (continued_2) ► Peripheral blood smear ► RBC misshapen, sickle-cell appearance ► Abnormal RBCs ’ ► Lifespan of 10 to 20 days ► Reticulocytosis  Sickle Cell Anemia (SCA) (continued_3) ► Vasco-occlusive crises ► Misshaped RBC ► Lodge in capillaries ► Causing tissue hypoxia ► Very painful ► Chronic damage to liver, spleen, kidneys, and eyes ► Spleen may become damaged, requiring removal  Sickle Cell Anemia (SCA) (continued_4) ► Clinical presentation ► Typical anemia signs, hyperbilirubinemia and enlarge spleen may be present ► Vaso-occlusive crisis ► Diagnosis: Electrophoresis revealing HbS ► Treatment ► Avoid triggers of vaso-occlusive crises ► Folic acid supplement to assist in RBC synthesis ► Blood transfusions to replace lost cells (watch that iron levels do not elevate too much) ► Bone marrow transplant  Blood Transfusion Reactions ► Known as hemolytic transfusion reactions ► Recipient blood-type antibodies attack transfused cells ► Type and crossmatch ► Mandatory that two clinicians double check donor-recipient blood types ► If transfusion reaction suspected, stop transfusion  Blood Transfusion Reactions (continued_2) ► Presentation ► Nonhemolytic febrile reactions and mild allergies ► Anaphylactic reactions ► Manifestations ► Fever, chills, flushing, burning at IV line, joint pain, tachycardia ► Severe cases ► Hypotension, oozing from the IV site, diffuse bleeding, oliguria, shock, and renal failure  Vitamin B12 Deficiency Factor Characteristic Prevalence Unknown vitamin B12 deficiency Pernicious anemia Autoimmune disease disrupting intrinsic factor Intrinsic factor needed for vitamin B12 absorption Common cause of anemia worldwide Neurological component Needed for RBC synthesis DNA synthesis Myelin sheath formation At risk Those suffering malnutrition Vegan diet Elderly Food–cobalamin malabsorption syndrome Achlorhydria (frequent use proton-pump inhibitors) Bariatric surgery Pernicious Anemia The body is not breaking it down as it should  Vitamin B12 Deficiency (continued_2) ► Needed for folic acid metabolism and RBC DNA ► Megaloblastic anemia ► Neurological system ► Typical signs of anemia along with glossitis, numbness and tingling, unsteady gate ► Diagnosis ► CBC, peripheral blood smear reveals large cells ► Folate, homocysteine, and methylmalonic acid levels should be examined  Lack of Bone Marrow Production of RBCs ’ ► Erythropoietin (EPO) lack- made in the bone marrow ► Usually due to kidney failure ► Hypothyroidism may also decrease EPO ► Recombinant EPO can be given  Primary Polycythemia ► AKA: polycythemia (overproliferation of all blood cells in bone marrow) vera ► Hyperproliferation of all blood cells ► Increased clot risk ► CBC may show HCt >60% ► Etiology unknown, may be chromosomal abnormality ► Rare ► EPO level is low  Secondary Polycythemia ► AKA: erythrocytosis ► More common than primary form ► Caused by prolonged hypoxia, i.e., COPD ► Correct underlying hypoxia will reverse condition ► Signs and symptoms develop slowly ► Spleen may enlarge ► EPO levels are HIGH