Immune system Bone marrow Produces erythrocytes, leukocytes & platelets; specific leukocytes play a vital part within the immune system Thymus The site where t-cells mature which are important in adaptive immunity Lymph nodes Secondary lymphoid organs in the body & it cleanses the lymph Spleen Stores breakdown of erythrocytes (the iron) for future usage Myeloid cells - innate (1st line of defense Monocytes / macrophages • monocytes (baby cells) • macrophages (engulf/ kill) • live for a long time Granulocytes 1. Neutrophils - 1st responder/ first line of defense 2. Basophils - increase as infection increases 3. Eosinophils - increase when having an allergic reaction Dendritic cells - key antigen producing cell • intermediate (middle) - b/w innate & adaptive immunity ! Lymphoid cells - adaptive (2nd line of defense) B - cells (mature in bone marrow) • won't function until mature • baby cells until exposed to antigen T - cells (mature in thymus) • CD4 - helper • CD8 - cytotoxic Natural killer cells (INNATE) • lymphocytes • not adaptive ! Innate immunity • 1st line of defense • composed of natural anatomic barriers - skin, mucosa, nasal cavity, saliva, WBC & enzymes • cellular barriers: phagocytic cells (non specific) - macrophages • NK cells • natural enzymes PPP When a foreign invader attempts to enter these systems what happens? Respiratory system? • cough/ sneeze GI tract? • vomiting/ pooping Eyes? • tears/ cry Skin? • sweat/ itching GU (urinary)? • urine cleans urethra Adaptive immunity • 2nd line of defense • ability to recognize self from non-self antigens • develops memory • humoral immunity: B - cell (antibodies) • cell-mediated immunity: T cell (thymus) ! Adaptive immunity cont'd CD4 - helper • influence other cells to do their jobs (macrophages, T & B cells) ! Immunoglobulins IgG - General • bloodstream (abundant)/ body fluids CD8 - cytotoxic • directly attack antigens IgA - Active • mucosal secretion (breast milk, sweat, tears) Antigen presenting cells • dendritic cells IgM - Made early • earliest to respond to antigen Active acquired • exposure to antigen • vaccination • long lasting IgE - (Ewww) allergies • elevated w/ certain parasitic infections • triggers histamine Passive acquired • given fully formed antibodies against antigen • immediate, short term, not long lasting; ex. flu IgD - Defense (nonspecific) • found on surface of B - cell • acts as a shield CC Which innate cells are considered antigen presenting cells, meaning they help initiate the adaptive response? • dendritic Which adaptive cells produce specific receptors for antigens & are primary mediators of adaptive immunity? • B & T cells A patient w/ a bone marrow disease that is destroying the function of the marrow is @ increased risk for infection….. WHY? • w/o B cells there is no immunity (increased risk for infection) A child is born w/ hypoplasia of the thymus. What is significant about this condition as it relates to the immune system? • NO thymus NO T - cells; no cell mediated immunity ! Immune response in the elderly Immunesenescence (confused when sick) • NK cells less functional • T - cells have decreased ability to recognize and attack More susceptible to infection • innate & adaptive immunity decrease in strength & efficiency • don't show normal signs & symptoms of infection ! Hypersensitivity • excessive or inappropriate activation of our immune response • body damaged by overactive response rather than by the antigen itself • in cell-mediated or antibody mediated immune mechanisms Type 1 - immediate hypersensitivity • allergic reaction • immediate response • binds to mast cells in respiratory, nasal & conjunctiva • allergens: dust, pollen, food, pet hair • histamine - vasodilator of arterioles & venuoles • anaphylactic reaction - edema, difficulty breathing, vascular shock due to vasodilation Antigen enters → IgE responds to allergen by binding to mast cell → releases histamine Type 2 - cytotoxic hypersensitivity • tissue specific • ex. mismatched blood transfusion & drug interactions Antigen attaches to a cell → antibodies Ig go specifically to that antigen → destroys antigen & cell its attached to Type 3 - immune complex hypersensitivity • Damage occurs primarily b/c of complement activation • body responds w/ inflammation mediators that lead to damage results • ex. lupus (flare ups b/c of immune complex) Antigen + Ig = immune complex → immune complex deposits into vessel lining/ tissues → damage to tissues & organ dysfunction Type 4 - delayed hypersensitivity • Examples of delayed reactions: 1. Exposure to poison ins 2. TB test Initiated by sensitized (seen before & understands what to do) T lymphocytes → do not attack antigen until days after exposure → inflammatory reaction is delayed Inflammation & infectious diseases ! Functions of the inflammatory process Aims of inflammation • wall of area of injury • prevent spread of injurious agent • bring body's defenses to the region under attack Inflammatory response • multistage process that involves vascular & cellular changes Most efficient • rids body of injury • enhances healing process • resolves problem • Is inflammation beneficial or harmful? Both! inflammation can be acute or chronic Types of inflammation Acute inflammation • triggered by infections, physical injury, surgery, cancer, foreign bodies, etc. • 3 main stages 1. Vascular permeability 2. Cellular chemotaxis 3. Systemic responses ! Vascular permeability Mediators: 1. Histamine 2. Bradykinin ! • • • 1. 2. 3. 4. WBC, fluids & platelets are allowed to travel to site of injury vasodilation of arterioles inflamed area: Red Warm Congested Swollen Classic signs of inflammation Five signs 1. Rubor - redness 2. Tumor - swelling 3. Calor - heat 4. Dolor - pain 5. Functio laesa - loss of function Types of inflammatory contents • Purulent exudate aka Pus (infection/ dead cells) • Abscess - localized pus underskin • Transudate aka blister litter to no protein/ fluid • Effusion - accumulation of fluid in a cavity Cellular chemotaxis Leukocytosis • chemical signals from WBCs & endothelial cells attract platelets to site of injury • increased # of WBC (leukocytosis) ! Mediators of inflammation Substances that promote/ inhibit inflammatory reactions • cytokines • chemokines • acute phase proteins Table 9-1 Tumor necrosis factor-alpha fever, lack of appetite Interleukins - fever, platelet production, fatigue Histamine - vasodilation, increase vascular permeability Kinins - pain, hypotension Platelet-activating factor vasodilation, angiogenesis Prostaglandins - pain, fever Substance P - hypotension, pain CC Discuss labs seen in patients w/ inflammation C-reactive protein (CRP) • released from liver Erythrocyte sedimentation rate (ESR) • active inflammation marker • will be elevated White blood cell count (WBC) Will be elevated w/ inflammation • neutrophil count • lymphocyte count • apart of CBC Types of white blood cells • • Neutrophils, basophils, eosinophils = Granulocytes Phagocytosis Systemic responses • fever • headache • fatigue • chills • pale skin • sweat ! What are the physiologic behaviors/ signs & symptoms that occur during the development of fever? • flushed skin • dehydration - risk of fever (loosing fluids via sweat) Thermoregulation and fever in elderly • elderly pop. have a lower baseline temp • fever is 1.1 degree over normal basal temp • more susceptible for infection due to decreased immune response Systemic responses • Lymphadenopathy enlargement of lymph nodes • histamine release - (increase permeability) inflammatory mediator - basophils Acute inflammation will result in one of three 1. Complete resolution 2. Healing by connective tissue 3. Chronic inflammation ! Chronic inflammation Causes/ etiologies • persistent infection • hypersensitivity disorders • prolong exposure to toxins Consequence of chronic inflammation on body tissues • tissue damage • delayed healing, granuloma (collection of WBCs left over after healing process) • connective tissue replaces injured cells ! PPPAcute Key differences b/w acute & chronic inflammation Chronic Cause triggered by infections, physical injury, surgery, cancer, foreign bodies, etc Major cells involved Neutrophils Onset Minutes or hours During the transition from acute inflammation to tissue repair Duration Few Days Several months to years Outcome Complete resolution, healing by connective tissue, chronic inflammation persistent infection, hypersensitivity disorders, prolong exposure to toxins Lymphocytes & macrophages Damage healthy cells, tissues & organs during inflammation process Acute vs. Chronic inflammation Acute inflammation • allergic reaction • chemical irritants • infection • trauma injury • burns • laceration, cuts, wounds • frostbite Chronic inflammation • cardiovascular disease • neurological disease • autoimmune disease • rheumatoid arthritis • cancer • lupus • fibromyalgia • chronic fatigue syndrome Tissue repair & wound healing 4 phases of normal wound healing • homeostasis - just after injury & stops bleeding via clots • inflammation - increased permeability (vasodilation); chemotaxis (attracts platelets) • proliferation (aka granulation phase) - granuloma tissue formation; fibroblast - make collagen • remodeling - 3 weeks after injury/ scar tissue formed ! Factors affecting wound healing What role do these nutrients play in wound healing? Protein - cellular regeneration; best source of N; synthesis of CT Carbohydrates - energy; spare protein sources for tissue healing Fats - cell membranes; synthesized during healing process Vitamin A & C - build protein; increase collagen strength Vitamin K - enables coagulation factors & clotting Vitamin B12 - cell replication; growth of RBC; healthy nervous system If these nutrients were deficient, what is the impact on wound healing? Protein - no cellular regeneration; no synthesis of CT Carbohydrates - lack of energy & tissue healing Fats - no synthesis in healing process; cell membranes not formed properly Vitamin A & C - no protein; lack of collagen strength Vitamin K - lack of clotting & coagulation Vitamin B12 - no cell replication; no RBC; no healthy nervous system Factors affecting wound healing cont'd Blood flow & oxygen delivery • predisposes person to ischemia • w/o O2 WBC cannot function & kill infection; collagen growth less efficient • O2 needed for neutrophil phagocytosis & collagen synthesis & WBC function Immune strength • delay wound healing & predispose to infection Contamination • foreign bodies present in wound; diminish healing ability • ex. foreign bodies: sutures that remain overtime; surgically placed devices, ex. pacemaker Mechanical factors • localized pressure to body ex. torsion, twist; turning on extremity Age • regeneration process; elderly have slow healing process Dysfunctional wound healing What patients are at risk for dysfunctional wound healing? • immunocompromized • diabetes • heart problems • circulation problems POSSIBLE COMPLICATIONS Wound rupture • dehiscence - opening @ suture line • evisceration - opening of a wound w/ excretion of organs & tissue Keloid - hyperplasia of scar tissue; ex. ear or leg Contractures - inflexible shrinkage of wound tissue from edge to center Fistula - abnormal connection b/ w 2 epithelial lined organs that should not connect; ex. trachealosophageal fistula Adhesions - internal scar tissue b/w tissue & organs; cause tissue to connect/ adhere to bone Stricture - abnormal narrowing of a tubular body passage from formation of scar tissue Infections diseases Normal flora vs. Pathogens • NF - don't cause infection when remained in anatomical area of the body • P - bacteria in/ on body that will harm the patient; ex. staff, e. coli Incidence vs. Prevalence • I - # of new cases of infection w/i a population • P - # of active cases going on @ any time Epidemic vs. Pandemic • E - abrupt increase in disease in a geographical region • P - global spread of disease Immunocompetent vs. immunosuppression • IC - ability to protect against many organisms • IS - immune system affected; increased risk for infection Types of microorganisms Bacteria - free living microorganism w/i any environment that can be adventitious/ harmful • human body colonized w/ normal flora Viruses - depend on host cell to survive • consist of DNA & RNA genomes w/ protein coat • can initiate cancer cell growth • resistant to antibiotics Fungi - mold like; can live on human tissue & cause infections diseases Parasites - enter through GU or GI tract & come through contaminated water, food or insects Mechanisms of infection DRY, CLEAN & INTACT SKIN PREVENT MOST INFECTIONS PORTS OF ENTRY Skin - any breaks can allow microorganisms to enter Respiratory - droplets from sneezing/ coughing • mucous & nose hairs are protection GI - poor hygiene from fecal-oral route GU - e. coli may adhere to bladder & cause UTIs & STIs • urine flushes urethra - protective mechanism Blood - blood transfusions (most common method) • exposure through needlestick/ lacerating injuries CC What are common manifestations of a patient w/ infection? (what are they going to present with) • fever • malaise • myalgia • lethargic • anorexia (inability to eat) Discuss the role of these lab tests in the Dx of infection? Gram stain or acid fast stain • classify bacteria based on how membrane absorbs the dye Culture • identity organism & guide treatment Biopsy • examine tissue cells under a microscope for signs of inflammation & identifies organism responsible Antibody titer • level of measurement that measures antibody in bloodstream • look at IgG & IgM levels Immune disorders Autoimmune disease Autoimmune disease happens when the body develops Igs against its own tissues aka antibodies • T - cells or Igs cannot make a distinction b/w non-antigenic cell surface markers and antigenic surface markers • The body's own immune system: 1. Intolerant to its own cells 2. Attacks its own tissues 3. Renders organ dysfunctional • Examples: 1. Organic specific: type 1 diabetes, rheumatoid arthritis 2. Generalized: systemic lupus erythematosus (SLE) Systemic lupus erythematosus (lupus) • chronic disorder • characterized by autoantibodies (antinuclear antibodies aka ANAs) • periods of remissions & exacerbations (they are moments when they are ok & moments when they are not) • exacerbations include fever, skin rash, joint inflammation, damage to kidneys and lungs & serosal membranes • demographic: women of child bearing age, African-American women are 2X more likely to develop • causes: unknown • risk factors: genetic, hormonal, environmental, medications • PATHO: antibodies form immune complexes deposited in organs & tissues • main area: lupus nephritis Systemic lupus erythematosus (lupus) cont'd • Signs & symptoms: butterfly rash, nephrotic syndrome, Raynaud’s phenomenon (tri-colored change in fingers from cyanosis/ blue to palor/ pale to rubor/ red due to exposure to cold • common in lupus patients - episodic vasospasm of arteries that supply the fingers of blood • Dx: based on combination of clinical findings 1. Butterfly rash 2. Mouth sores 3. Arthritis 4. Lung or heart inflammation 5. Kidney problems 6. Neurological problems 7. Abnormal blood tests Scleroderma • aka systemic sclerosis • chronic autoimmune disorder • cause/ etiology: unknown • characterized by: abnormal accumulation of fibrous tissue in skin/ organs; also in GI tract, kidneys, muscles & lungs • demographic: women 30-50 & African-Americans • PATHO: an inflammation reaction w/ injury to endothelial lining of blood vessels; extensive deposition of collagen occurs resulting in fibrosis in the skin very noticeable; skin is shiny, smooth, stretched in appearance • complications: kidney, heart, vessel damage, MI, musculoskeletal pain & swelling • clinical presentation: CREST syndrome • Dx: clinical presentation and physical exam, CXR, EKG, ANAs elevated CREST syndrome Calcinosis - calcium deposits in the skin Raynaud's phenomenon Esophageal dysfunction acid reflux & decrease in motility of esophagus Sclerodactyly - thickening & tightening of skin (shiny & smooth) on the & hands Telangiectasis - dilation of capillaries causing red marks on surface of the skin Rheumatoid Arthritis • chronic autoimmune disease • demographic: 2-3X more common in women • cause/ etiology: unknown; genetic factors account for 50% • PATHO: body's immune system attacks its own synovial tissues • stimulate inflammation & destruction of cartilage, bone, tendon & ligaments @ those spaces • APCs activate T - cells; key role in destruction of joint components • symptoms: symmetrical, tender, swollen joints, fingers, wrist, knees, hips, feet • characteristic deformities: 1. Boutonnière - deformity of thumb (late stage) 2. Swan neck - deformity of fingertips • Dx: clinical criteria & elevated serum RF, ESR, CRP & X-ray • In RA there is bone erosion, cartilage wears away & reduced joint space Immunodeficiency disorders Primary (Genetic) • manifest b/w 6 months & 2 years • X-linked disorders; mostly in males • B - cell deficiency more common than T - cell • IgA deficiency most common Secondary (Acquired) • HIV (SCID) Severe combined immunedeficiency disease • • • • • SCID, genetically distinct syndrome defects of both antibodymediated & cell-mediated immune response malfunction of T & B - cells (lose immune response affects infants @ 3months susceptible to recurrent & severe infections Selective IgA deficiency • Most common - primary immune deficiencies • cause: genetic cause, 50X more likely from 1st degree relative • PATHO: cells that produce IgA are dysfunctional • signs & symptoms: sinus & pulmonary infections in adults • ear infections & sinus in children • demographic: person w/ absent IgA; can present w/ respiratory tract infections include: 1. Swelling 2. Pain 3. Tenderness upon palpation of sinuses & ear infections 4. Fever Hypgammaglobalinema • demographic: have impaired antibody response • B - cells have to mature to work • PATHO: decreased # of Igs related to a defect in B - cell development & maturation • cause: genetic or acquired • susceptible to infections • Dx: come out having recurring infections involving: 1. Ear 2. Eyes 3. Sinuses 4. Nose • can be viral • may have enlarged lymph modes PPP What significant role does immunodeficiency have on an individual? Increase risk for infection What is the first clinical clue of a primary immunodeficiency disease in children? History of infection that is persistent (difficult to treat); they keep getting it (recurrent) HIV infection • a retrovirus (RNA as genetic material; comes equipt w/ its very own enzyme called reverse transcriptase - converts RNA into DNA) w/ a long latency period & slowly progressing disease course • The host cell uses DNA for instruction to manufacture more viruses - replication • attacking CD4 cells allows virus to destroy immune mechanisms of the body • demographic: AfricanAmerican, Hispanic men & IV drug users • PATHO: HIV targets cells that express CD4 receptor & the chemokine receptors • cells: T - cells, macrophages in the lymph nodes, spleen & bone marrow • after HIV uses the CD4 cell for replication it destroys these cells & moves on • • • • • • protease - HIV enzyme that assists in the assembly of protein components to construct brand new viruses hallmark sign: progressive depletion of CD4 T - cells (800-1200 per ml3), leading to immunodeficiency complications: opportunistic infections - illness caused by pathogen that takes advantage of the lack of immune defenses within the host cell immunological impairment is significant when CD4 count goes below 500 - becomes susceptible to opportunistic infections when CD4 count is below 200 there is an existence of an opportunistic infection a Dx of AIDS is made Dx: CD4 count (accurate), HIV viral load, HIV drug resistance testing; candidiasis (thrush), Hep A, B & C, CMV, HPV, TB, Herpes, shingles CC A young pregnant woman with HIV asks you if her unborn baby will have HIV too. • what should you tell the patient? There is a chance the baby will have HIV - most cases transmitted @ time of delivery when the baby is exposed to the mothers blood via birth canal • what can be done to prevent the spread of HIV to the infant? Scheduled C-section avoids cross contamination & minimizes risk; breastfeeding not recommended b/c HIV is spread through body fluids/ breast milk When the baby is born, its initial antibody test is positive for HIV. • does this mean the baby is infected? Not necessarily b/c mom passively passes an antibody to the baby that may be present in the baby's blood for months. Must know 1. Etiology 2. Epidemiology/ demographic 3. Pathophysiology - what is happening at the cellular level 4. Diagnosis
