Micro exam 4

Ch 12, 13, 19

upper respiratory tract

nose, pharynx, middle ear, and eustachian tubes; saliva and tears protect mucosal surfaces

lower respiratory tract

trachea, bronchial tubes, and alveoli

pleura

double layered membrane enclosing the lungs

anatomical defenses against pathogens

nasal hair traps particles; cilia moves particles upwards toward the throat (ciliary escalator); mucus is a natural trap for invading microbes

second and third lines of defense against pathogens

complement, antimicrobial peptides, cytokines, macrophages, secretory IgA

respiratory tract and its defenses

healthy upper respiratory system harbors thousands of commensal microorganisms; lungs have a limited normal biota

pharyngitis

caused by irritation from prolonged shouting or drainage from the sinus cavity; same viruses that cause the common cold; most serious cases caused by Streptococcus pyogenes

pharyngitis signs and symptoms

pain, inflammation of the throat, reddened and/or swollen mucosa

streptococcal pharyngitis (strep throat)

transmitted by respiratory secretions; symptoms: local inflammation, fever, tonsillitis, enlarged lymph nodes, and often otitis media; rapid antigen tests for detection; treated with penicillin (may develop rheumatic fever without treatment)

scarlet fever

streptococcus pyogenes strain that produces an erythrogenic (reddening) toxin (toxin gene expressed from lysogenic phage; additional symptoms: pinkish-red skin rash, high fever, strawberry tongue that becomes very red and enlarged; mild illness but requires treatment to avoid rheumatic fever

rhinitis (the common cold)

the most prevalent human disease; over 200 different viral causes (rhinoviruses: 30-50%; coronaviruses: 10-15%); sneezing, nasal secretion, nasal congestion: can lead to laryngitis and otitis media, not accompanied by fever; antibiotics are of no use (relief via cough suppressants and antihistamines)

sinusitis

causative agents: various viruses, bacteria and fungi (less common); treatment: broad spectrum antibiotics for bacterial infection, antifungals and/or surgery for fungal infection

otitis media

infection of the middle ear; formation of pus puts pressure on the eardrum; causes: most common is streptococcus pneumoniae, other bacteria; common in childhood due to smaller auditory tube

bronchitis (bronchiolitis)

respiratory infections involving the bronchi

pneumonia

severe complications of bronchitis involving pulmonary alveoli; inflammatory condition of the lungs in which fluid fills the alveoli; wide variety can cause: have characteristics allowing penetration and survival in the lower respiratory tract, avoid phagocytosis od eath once inside microphage

community acquired pneumonia

develops in the general population

healthcare associated pneumonia

develops in a healthcare setting

lobar pneumonia

infects the lobes of the lungs

bronchopneumonia

infects the alveoli adjacent to the lungs

pleurisy

complication from pneumonia; pleural membranes inflamed

pneumococcal pneumonia

symptoms: infected alveoli fill with fluids and RBCs interferes with oxygen uptake, rust colored sputum, high fever, breathing difficulty, chest pain

legionellosis (legionnaires’ disease)

caused by Legionella; grows well in water and forms biofilms; transmitted by inhaling aerosols, not person to person (problematic for air conditions, humidifiers, decorative fountains); symptoms: high fever and cough

mycoplasmal pneumonia

also called primary atypical pneumonia or walking pneumonia; mild but persistant respiratory symptoms: low fever, cough, headache (common in children and young adults); “fried-egg” appearance on media

pneumocystis pneumonia

causes pneumonia in the immunocompromised (asymptomatic in the immunocompetent) - primary indicator of AIDS; founded in the lining of the alveoli (forms a cyst, cysts rupture, releasing offspring); fatal without treatment

healthcare-associated pneumonia

about 1% of hospitalized people experience pneumonia; often associated with mechanical ventilation, via an endotracheal or tracheostomy tube (labeled “ventilator-associated pneumonia” or VAP); most frequent causes: MRSA strains, and many are polymicrobial in origin; prevention/treatment: proper care of mechanical ventilators and respiratory therapy equipment, elevation of patients’ heads ro a 30 to 45 degree angle helps reduce aspiration of secretions, patient education on the importance of deep breathing, frequent coughing can reduce postoperative infection rates

influenza (flu)

chills, fever, headache, and muscle aches (no intestinal symptoms; 3,000 to 50,000 deaths in the US annually)

neuraminidase (NA) spikes - flu

help the virus separate from the infected cell

influenza A, B, C

influenza A identified by HA and NA; HA - 16 subtypes, NA - 9 subtypes

antigenic drift - flu

minor antigenic changes in HA and NA; allow the virus to elude some host immunity

antigenic shift - flu

changes great enough to evade most immunity, lead to pandemics, involve the reassortment of the eight RNA segments

pertussis (whooping cough)

caused by Bordetella pertusis; produces a capsule (allows attachment to ciliated cells in trachea; destroys ciliated cells and shuts down the ciliary escalator); two toxins (tracheal toxin damages ciliated cells; pertussis toxin enters bloodstream)

3 stages of pertusis

catarrhal stage (like the common cold), paroxysmal stage (violent coughing, gasping for air), convalescence stage (may last for months); prevented by DTaP vaccine

respiratory syncytial virus (RSV)

most common viral respiratory disease in infants (almost all children are infected by age 2); life threatening pneumonia in older adults (14,000 deaths annually); causes cell fusion (syncytium) in cell culture; coughing and wheezing for more than a week

tuberculosis

caused by Mycobacterium tuberculosis; 20-hour generation time; lipids in cell wall make it resistant to drying and antimicrobials; mycobacterium avium-intracellulare complex: infects people with late stage HIV infection

tuberculosis pathogenesis

inhaled bacteria are phagocytized by alveolar macrophages (healthy individuals typically destroy bacteria at this stage); bacteria multiply in macrophages (mycolic acids, cell wall, stimulate inflammatory response; chemotaxis of macrophages to infection site); organisms are isolated in the walled-off tubercle (inner macrophages die; caseous center - cheeselike; bacteria remain viable but do not grow well, latent, noninfectious TB); tubercle breaks down, releasing bacteria into the lungs (military TB: disseminated infection)

TB symptoms

chest pain, coughing, bloodstained sputum; as defense becomes overwhelmed: weight loss, loss of vigor, fatal hemorrhaging)

TB traditional diagnosis

skin test: purified protein from TB bacterium injected cutaneously, positive reaction means a current or previous infection, or exposure to the bacterium); followed by X-ray or CT scan, sputum staining, and bacterial culture

TB treatment

minimum of 6 months of drug therapy (due to slow growth and dormancy of bacteria); first line drugs: may cure disease, resistance often develops due to patients not following long schedule; second line drugs: fro resistant strains, often less effective with toxic side effects; multi drug resistant strains: resistant to first line drugs; extensively drug resistant strains: resistant to second line drugs (very difficult to treat and emerging globally)

susceptibility

lack of resistance to a disease

immunity

ability to ward off disease

1st line of defense

skin, mucous membranes, antimicrobial substances; keep pathogens on the outside or neutralize them before infection begins

2nd line of defense

inflammation, fever, phagocytes; slow or contain infections when 1st line defenses fail

3rd line of defense

humoral and cellular immunity; target specific pathogens for destruction when the second line defenses don’t contain infections; includes a memory component that allows the body to more effectively respond to that same pathogen in the future

innate immunity

defenses against any pathogen; rapid, present at birth; link between innate and adaptive immunity

adaptive immunity

immunity or resistance to a specific pathogen; slower to respond, has memory component

toll-like receptors (TLRs)

on host defensive cells attach to pathogen associated molecular patterns (PAMPs); ones bound to PAMPs induce the release of cytokines from the host defensive cells (innate system)

pathogen associated molecular patterns (PAMPs)

molecular structures common to pathogens: LPS outer membrane of gram-neg bacteria, peptidoglycan cell wall in gram-pos bacteria, flagellin (protein) in flagella, DNA and RNA of viruses

cytokines

small signaling proteins; regulate the intensity and duration of immune responses; innate- recruit defensive cells to isolate and destroy microbes as part of inflammatory response

skin

epidermis and dermis; shedding and dryness of skin inhibits microbial growth

epidermis

outer portion of skin made of tightly packed epithelial cells containing keratin, a protective protein

dermis

inner portion of skin made of connective tissue

mucous membranes

epithelial layer that lines the GI, respiratory, and genitourinary tracts; mucus: viscous glycoproteins that trap microbes and prevent tracts from drying out; ciliary escalator transports microbes trapped in mucous away from the lungs, propels them upwards towards the throat

lacrimal apparatus

drains tears; washes eye

•Compete with pathogens via microbial antagonism - normal microbiota

Competitive advantage for space and nutrients; Produce substances harmful to pathogens; Alter conditions that affect pathogen survival

formed elements found in blood (WBCs)

erythrocytes (RBCs), leukocyte (WBCs), platelets; created in red bone marrow stem cells by hematopoiesis

hematopoiesis

creation of cellular components of blood (all blood cells arise from stem cells)

leukocytes

divided by appearance under microscope: granulocytes visible granules in cytoplasm (neutrophils, eosinophils, basophils), agranulocytes: granules in cytoplasm are not visible under light microscope (monocytes, dendritic cells, lymphocytes)

neutrophils

phagocytic; work in early stages of infection; can leave blood and enter infected site

basophils

release histamine; mediate inflammation and allergic responses

eosinophils

phagocytic; toxic against parasites and helminths; can leave blood

monocytes

leave blood, enter body tissues, and mature into macrophages (become phagocytic)

dendritic cells

found in the skin, mucus membranes, and thymus; phagocytic, initiate adaptive response

lymphocytes

T cells, B cells, and NK cells; play a role in adaptive immunity

differential WBC counts

measure leukocytes in the blood (% per 100 counted cells); leukocytosis vs leukopenia

high WBC count

leukocytosis: may indicate bacterial infections, autoimmune diseases or side effects of medications

low WBC count

leukopenia: may indicate viral infections, pneumonia, autoimmune diseases, or cancers

lymphatic system (components and basic functions)

lymph (fluid), lymphatic vessels (vessels, similar to circulatory systems), lymphoid tissues (structures and organs - ex: thymus and lymph nodes), red bone marrow (hematopoiesis)

lymphoid tissue: structures and organs

Scattered throughout mucous membranes that line GI, respiratory, urinary, and reproductive tracts; Specific organs and aggregations of lymphoid tissues:spleen, thymus, tonsils, Peyer's patches (in small intestine)

overview of lymphatic system

Interstitial fluid (fluid between cells in tissues) flows into lymphatic capillaries (small lymphatic vessels); Fluid (now called lymph) flows in one direction and enters lymphatic vessels; At intervals along system, lymph flows through lymph nodes – nodes contain fibers to trap microbes, and defense cells to kill them by phagocytosis; Eventually all lymph passes through lymphatic ducts and enters bloodstream (lymph is now blood plasma); Blood plasma moves through cardiovascular system and eventually becomes interstitial fluid again

phagocytes

specialized WBCs that protect body by engulfing and digesting harmful organs particles; phagocytosis

phagocytsosis

the ingestion of microbes or other substances by a cell – performed by phagocytes; At start of infection, granulocytes (mostly neutrophils) and monocytes move to infected area; Neutrophils dominate initial response; Monocytes mature into macrophages; Fixed macrophages are residents in tissues and organs; free (wandering) microphages roam tissues and gather at sites of of infection; As infection progresses, macrophages become predominant cell

mechanism of phagocytosis (4 steps)

chemotaxis, adherence, ingestion, digestion

chemotaxis

chemical signals attract phagocytes to microorganisms

adherence

attachment of phagocyte to microbe surface (TLRs and PAMPs); Enhanced by opsonization: microbial antigens are marked with serum proteins (ex: antibodies)

ingestion

pseudopods (plasma membrane extensions) engulf microbe; pseudopods fuse and form phagosome; phagosome pinches off membrane and enters cytoplasm

digestion

phagosome fuses with lysosome (contains digestive enzymes and bactericidal substances; forms phagolysosome); phagolysosome digests microorganism; phagolysosome releases indigestible material outside cell

inflammation

local defensive response triggered by injury to body tissue; Destroys injurious agent; removes it and by products, or Limits its effects on the body; walling off/isolating it and by products, Repairs and replaces tissue damaged by the injurious agent and by products; types: acute and chronic

signs and symptoms of inflammation (PRISH)

pain- release of chemicals, redness- increased blood flow, immobility- loss of function, swelling- fluid accumulation, heat- increased blood flow

actue inflammation

rapid development of signs and symptoms; last days to weeks; mild and self limiting; primarily neutrophils (ex: appendicitis, cold, flu, sore throat, minor cuts/scratches); Begins when TLRs on phagocytes (neutrophils and macrophages) recognize PAMPs and release cytokines; liver responds to cytokines in blood and activates acute phase proteins (these serum proteins increase or decrease in concentration by >25% in response to cytokines)

chronic inflammation

slow development of signs and symptoms, last months to years; more severe and progressive; primarily monocytes and macrophages (ex: peptic ulcers, TB, rheumatoid arthritis)

mechanism of inflammation (3 steps)

1.vasodilation and increased permeability of blood vessels (Occurs immediately following tissue damage); Vasodilation: dilation of blood vessels, Causes redness (erythema) and heat, Increased permeability, Causes fluid accumulation (edema), Caused by vasoactive mediators: chemicals that promote inflammation, after chemical release, blood clots form, Prevents spread of microbes or toxins, Abscess forms: cavity created by breakdown of tissue, Contains pus: mixture of dead cells and body fluids

2.Phagocyte migration and phagocytosis: Margination occurs: as blood flow decreases, phagocytes (neutrophils and monocytes) stick to inner surface of blood vessel, Diapedesis then occurs: phagocytes squeeze between endothelial cells of blood vessels, Then phagocytosis of microbes

3.Tissue repair: Begins during active inflammation but cannot be completed until all harmful substances are removed or neutralized, Tissue is repaired when stroma or parenchyma produce new cells, Parenchyma is the functioning part of the tissue, Stroma is the supporting connective tissue, Repair involving only parenchymal cells = near perfect repair, Repair involving stromal cells = scar tissue

Fibrosis

accumulation of connective tissue resulting in scar tissue

increased permeability

defensive substances can leave blood vessels and enter injured area

fever

typically caused by bacterial or viral infection; high temp maintained until cytokines are eliminated; released cytokines cause hypothalamus to (body’s thermostat) to reset to higher temperature

complement system

>30 proteins produced by the liver that circulate in blood serum and body tissues; aids and enhances immune systems ability to destroy microbes; activation: proteins act in a cascade, one reaction triggers another: 3 activation pathways resulting in activation of C3: classical (initiated when antibodies bind antigens), alternative (activated by contact between complement proteins and microbe), lectin (initiated when lectins bind CHOs on microbe surface – proteins that bind carbohydrates); outcome: cytolysis, opsonization, and inflammation

cytolysis

activated complement create a membrane attack (MAC); MAC creates hole in plasma membrane; fluid inflow bursts cell; more effect against gram-neg bacteria

opsonization

complement proteins bind microbes; promotes attachment of phagocytes to microbe

inflammation (complement system outcome)

activated complement proteins bind to mast cells, releasing histamine

regulation of complement

regulatory proteins readily break down complement proteins, minimizing host cell destruction; lack of complement proteins causes susceptibility to infections

interferons (IFNs)

class of cytokines with antibacterial and antiviral activity; great variation between types; 3 primary types: IFN-a, IFN-b (produced by cells in response to viral infections; cause neighboring cells to produce proteins that inhibit viral replication), IFN-y (causes neutrophils and macrophages to kill bacteria)

iron binding proteins

iron is essential for survival of humans and pathogens; concentration of free iron in body is low (due to competition between pathogens and human cells); human iron binding proteins: transferrin, lactoferrin, ferritin, hemoglobin; bacteria produce siderophores to compete with iron binding proteins

transferrin

found in blood and tissue fluids

lactoferrin

found in milk, saliva, and mucus

ferritin

found in the liver, spleen, and mucus

hemoglobin

located in RBCs

antimicrobial peptides

short peptides produced in response to protein and sugar molecules on microbes; possess a broad spectrum of activity: work against bacteria, viruses, fungi, and eukaryotic parasites, inhibit cell wall synthesis, form pores in the plasma membranes, destroy DNA and RNA

humoral immunity

fights invaders and threats outside cells: extracellular bacteria and toxins, viruses before they enter a host cell; takes place in extracellular fluids; performed by protective molecules termed antibodies; antibody = immunoglobin (Ig); antibodies recognize and combat foreign molecules called antigens

B cells (B lymphocytes)

lymphocytes with antibodies to specific antigens on their surface: binding of surface antibodies to antigens activates B cells, plasma cells (a type of activated B cell) secrete antibodies against that particular antigen

cellular immunity (cell mediated immunity)

attacks antigens that have already entered cells: viruses and some intracellular bacteria; focuses on antigens that have entered cells; based on T cells; T cells and T cell receptors, intracellular antigens

T cells and T cell receptors

T cells have TCRs on their surface that recognize antigenic peptides produced by phagocytic cells (APC in picture)