Exam 3 Flashcards
Species resistance
Protects humans from the pathogens of other animals: -Form of Innate immunity
- We lack the correct receptors for attachment (polysaccharides
- Wrong Temperature (canine pathogens prefer 39.2 C)
- Wrong nutrients to support growth of certain organisms
Steps of the Compliment Pathway
C1
C4 –> C4a or
C4b
CP C3 (convertase)
C3b (fB or fD goes to…)
AP c3 convertase (back in to C3b via amplification or)
CP and AP C5 convertases (due to increasing C3b density)
C5B
C6-C9
MAC(membrane attack complex for cell lysis)
Three ways to start the compliment pathway
Classical Pathway
Alternative Pathway
Lectin Pathway
Basic Functions of complement pathways
- Opsonization: enhance phagocytosis of antigens
- Chemotaxis: attracts macrophages and neutrophils
- Cell Lysis: ruptures membranes of foreign cells
- Clumping of antigen-bearing agents
Classical Pathway
Activated by compliment proteins binding to antibodies (typically coats bacteria or invader). C1 is needed to bind antibodies and become active enzymatically
Alternative Pathway
Random cleavage of C3 to C3a and C3b. C3b is able to bind pathogens and form MACs (Membrane Attack Complexes) through normal progression of the Complement system.
Lectin Pathway
Lectins (sugars) bind to sugars on pathogen surfaces (specifically mannos sugars, which we don’t have). Body makes MBL / f-proteins that can bind to those sugars which are on the surface of the membrane. Triggers compliment by cleaving C2 and C4
Alternate start to Classical pathway
Why is it called the Complement System?
The system is a heat sensitive component of normal plasma that assists the opsonization of bacteria by antibodies. This “compliments” the antibacterial activity of the antibody.
Adaptive Immunity
Adaptive (or acquired) Immunity creates immunological memory after an initial response to a specific pathogen, leading to an enhanced response to subsequent encounters with that same pathogen. The basis of vaccination
What is inactivation in terms of the Complement system
All of our bodies cells contain a membrane bound protein which deactivates complement
Innate Immunity
The body has three layers of defenses
External: (physical + chemical, non-specific)
Internal: non-specific (cells and processes that inactivate or kill invaders)
Internal: specific (cells that inactivate and kill invaders)
Two layers of skin
Dermis: contains protein fibers (collagen) that give skin strength and pliability to resist abrasions.
Epidermis: barrier of multiple layers of tightly packed cells that shed to remove attached microbes (10 billion skin flakes per day)
Chemical defenses of the skin
Salt: dessication
Dermicidins: broad spectrym antibacterial/fungal
Lysozyme: destroy cell walls of bacteria
Sebum (oil): secreted by sebaceous glands to lower skin pH
Mucous Membranes
Line all body cavities open to the outside environment. The epithelium is thin, living, outer covering with many tightly packed membranes. Your body makes about a liter of mucous a day
Epitopes
Antigenic determinant
3-D regions of antigens whose shapes are recognized by the immune system
Endogenous vs Exogenous antigens
Endogenous are generated within a previously normal host cell. Fragments of the microbe are displayed on the surface of the cells. Endogenous antigens come from the outside
Autoantigen
Target of an autoimmune response (otherwise normal cell)
Antibodies
Proteins (adaptive immune system) with Antigen-Binding sites that bind to epitopes on antigens.
Leukocytes
Agranulocytes or granulocytes involved in defending the body against invaders
Granulocytes stain different colors and contain large granules.
Basophil
Granulocyte
inflammation (bi-tri-lobed)
Eosinophil
Granulocyte
Phagocytosis (bi-lobed)
Neutrophils
Granulocyte
Phagocytosis (multi-lobed)
Macrophages
Agranulocytes
phagocytosis (as a kind of blob-shaped cells)
Iron Sequestration
Humans lock their iron away in lactoferrin proteins to protect from pathogens (bacteria can still occasionally access with a sidepheron)
Interferons
Stimulate productions of Antiviral Proteins (AVP)
-RNASE: breaks down mRNA
-Protein Kinase: inhibits translation by ribosomes
Interferons shut down all protein production in a human cell for 3-4 days. Cause many symptoms associated with viral infections
B Lymphocytes
- Arise and mature in bone marrow
- Secrete antibodies
- BCR’s on them can recognize millions of different epitopes and generate appropriate antibodies
- Composed mostly of plasma cells.
- Cells are short lived and die within a few days of activation. Persist through their antibodies and progeny
Memory B cells
- Do not generate antibodies
- Have BCR’s complimentary to specific antigens that triggered their production
- Divide only a few times and persist in the lymphoid tissue
T lymphocytes
- Circulate in lymph and blood
- Have TCR’s that bind to antigens
- Act directly against antigens (no antibody secretion)
Cytotoxic Cells
(Tc)
Directly kill infected human cells
Secrete Perforin and Granzyme (induce apoptosis within virus-infected cells)
Helper T Cells
(Th)
Help activity of other immune cells by releasing cytokines
Essential b cell antibody class switching and in maximizing bactericidal activity of phagocytes
Types of acquired immunity
Natural: antigens encountered daily
Artificial: vaccination
Active: administration of vaccine to mount a protective immune response. slower
Passive: Antiserum used. Transfer of immune antibodies from a protected individual. Immediate, but short lived
Vaccine Types
Live / Attenuated:
Inactivated: whole and deactivated subunits or live (no contact immunity)
Toxoid (inactivated toxin): chemically or thermically modified toxins used to stimulate active immunity (unable to make some answers to certain pathogens, allergic reactions, risk in development discourages new ones)
Conjugate / Subunit:
Adjuvents
Chemicals that enhance antigenicity (such as aluminum hydroxide)
Staphylococcus (genus)
Gram-positive
Coccus (clearly)
nonmotile
bacteria
Staphylococcus epidermidis
Normal microbiota of human skin Cells occur in grape-like clusters Tolerant of salt and dessication survive on fomites produce catalase (ID) Opportunistic pathogen in immunocompromised patients or when transferred to the body via catheters and prosthetics Causes Endocarditis, UTI's, and Sepsis
Staphylococcus aureus
Normal microbiota of human skin (for about 20% of people)
Found on moist portions of skin
Beta-hemolytic (organism’s secretions break down RBC’s)
Variety of diseases based on strain and the infection site
Noninvasive Staphylococcus aureus
Caused by secreted Enterotoxin: intestinal muscle contractions, nausea, vomiting.
Food must remain at room temp for hours while the bacteria multiply and excrete enterotoxin
Toxin is heat stable (100C for 30 minutes)
Impetido
Cutaneous Staphylococcus aureus
Red patches that develop into encrusted blisters (opaque pus). Blisters are more crusty and scabbed over (direct result of bacteria instead of toxin)
Scalded Skin Syndrome
Cutaneous Staphylococcus aureus
Large blisters with clear pus and peeling of the outer layer of skin
Result of a toxin (clear pus is also due to toxins)
Skin damage leads to high potential for secondary infections
Folliculitis
Cutaneous Staphylococcus aureus
Infection of traumatized hair follicles
Furuncles
Cutaneous Staphylococcus aureus
Extension of folliculitis into surrounding tissue (a boil)
Carbuncles
Cutaneous Staphylococcus aureus
Coalesced furuncles that extend deep into the skin
Toxic Shock Syndrome
Systemic Staphylococcus aureus
The toxin TSST-1 enters the blood via a wound or abraded vagina (80’s epidemic caused by super-absorbent tampons)
Fever, vomiting, rash, peeling skin, low blood pressure (shock)
Pneumonia
Systemic Staphylococcus aureus
Alveoli and bronchioles fill with fluid
Staphylococcus aureus Pathogenicity: Structure
Protein A: coats cell surface -interferes with antibody binding -inhibits complement system Capsule -Sticky layer of polysaccharides -inhibits phagocytosis -Fascilitates attachment
Endocarditis
Systemic Staphylococcus aureus or Streptococcus Pneumoniae attacks the heart
Osteomyelitis
Systemic Staphylococcus aureus causes inflammation of the bone
Staphylococcus aureus: diagnosis and treatment
Diagnosis:
-Catalase test: differentiates the genus Staph (if positive) from strep.
-Coagulase test: differentiates staph aureus from other staph species
Treatment: Methicillin is drug of choice
Penicillin: 95% of staph species carry a gene that codes for
Staphylococcus aureus Pathogenicity: enzymes
Coagulase: forms blood clots from fibrin in human blood that staph hides in
Staphylokinase: dissolves fibrin threads in blood clots to allow escape
Hyaluronidase: allows spread between host cells
Lipase
Beta-lactamase
Staphylococcus aureus Pathogenicity: toxins
Entertoxins
Toxic Shock Syndrome Toxin
Cytolytic Toxins: disrupts cytoplasmic membrane
Leukocidin: lyses WBC’s
Exfoliative Toxins: causes the patient’s skin cells to separate from each other and peel off the body.
MRSA
Appeared in US in 1980
First signs are bumps resemnling pimples, bites, or folliculitis
May be accompanied by fever or rashes
becomes more furuncle / boil like within 72 hours and then open into a large, painful, deep, pus-filled carbuncle
can become systemic
Vancomycin is used, but with decreasing effectiveness (VRSA)
Streptococcus (genus)
Gram-positive, coccus, nonmotile, bacterium
Lancefield Classification
Divides Strep sepcies into groups based on polysaccharide antigens on their surface.
Group a: S. Pyogenes
Group b: S. agalactiae
Group c-h: mostly found in animals
Streptococcus pyogenes
Normal microbiota of the respiratory tract in 15% of humans
Some purely pathogenic strains exist
Pharyngitis
Streptococcus pyogenes
strep throat
do not confuse with viral equivalent
Scarlet Fever
Streptococcus pyogenes
often accompanies pharyngitis
Necrotizing Fasciitis
Streptococcus pyogenes
Toxin production destroys skin, and eventually muscle and fat tissue
Spreads along and destroys the fascia
Pyoderma
Streptococcus pyogenes
Confined, pus-producing lesion that usually occurs on the face, arms, or legs
spread from person to person
Rheumatic Fever
Streptococcus pyogenes
Stimulates autoimmune response in body
Glomerulonephritis
Streptococcus pyogenes
Antigens and antibodies accumulate in kidneys
Streptococcus pyogenes Pathogenicity: structures
Protein M: destabilizes complement proteins and interferes with optimization and lysis
Hyaluronic Acid Capsule: camouflages bacteria
Streptococcus pyogenes Pathogenicity: Enzymes
Streptokinases: break down blood clots
Streptolysins: lyse blood clots
Streptococcus pyogenes treatment
Antibiotics are usually effective
Tissue removal sometimes necessary depending on disease
Human memory B cells provide long term protection against future infections of pyogenes, but only if same strain
Streptococcus agalactiae
Normal microbiota of lower GI tract
Easily transfered to genitals and urinary tract
Leading cause of neonatal morbidity and mortality: septicemia, meningitis, and pneumonia in newborns
Antibiotics still usually effective
Preventative penicillin given at birth.
Immunization of women against B strep to protect future infection
Streptococcus pneumoniae
Normal microbiota of mouth and pharynx, but can cause disease if travels elsewhere
Virulent strains exist
No group specific polysaccharide (no lancefield group)
Alpha-hemolytic (anaerobic incubation produces beta-hemolytic colonies) only partial destruction (green color here when clear in O2 free environment)
Pneumococcal Pneumonia
Streptococcus pneumoniae
bacteria multiply in alveoli, causes damage, and stimulates inflammation
Sinusitis
Streptococcus pneumoniae
Bacterial invasion of the sinuses. Common cause of death for the elderly.
Otitis Media
Streptococcus pneumoniae
Bacterial invasion of the middle ear. Common cause of death for the elderly.
Pneumococcal Meningitis
Streptococcus pneumoniae
Streptococcus pneumoniae Pathogenicity
Phosphorylcholine: stimulates cells to phagocytize the pneumonia. It’s capsule protects it from lysis
Adhesin binds epithelial cells of the pharynx
igA protease destroys antibodies
Pnuemolysin lyses epithelial cells
Streptococcus pneumoniae treatment
Antibiotics still usually viable
Vaccines from the capsule are available
Streptococcus Diagnosis
S. pyogenes are differentiated by their strong hemolysis and sensitivity to the antibiotic Bacitracin.
S. agalactiae is differentiated by production of CAMP
factor
S. Pneumoniae is sensitive to alpha-hemolysis and optochin
Enterococcus (genus)
Gram-Positive, non-motile, coccus, bacteria
Arranged in short chains or pairs
Usually non or alpha hemolytic
Typically resistant to antimicrobials
Enterococcus diagnosis
Very similar to streptococcus, but growth on a Bile-Esculin agar can differentiate the two
Bacillus (genus)
Gram-Positive, rod, single, pairs or chains
Varied motility
Bacillus anthracis
Causes Anthrax
Contracted from Inhalation, Inoculation of endospores through skin breaks, or ingestion
Large colonies with irregular edges (Medusa Colonies)
Forms endospores
Forms a capsule when grown in presence of CO2
Anthrax
3 types (capsule made of glutamic acid)
Inhalation: (rare for humans
- endospores germinate in lungs and secrete toxins which are absorbed into blood. 80% lethal
Gastrointestinal:
-Ingested. Diarrhea followed by intestinal hemorrhaging and eventually death (80% leath)
Cutaneous
-Most common. Produces an eschar (ulcer) and toxemia. 5-10% lethal
Anthax Treatment and Prevention
Many antibiotics are still effective against Bacillus anthracis
Control of the disease in animals can prevent spread
A vaccine is available, but requires multiple doses and annual boosters. (6 doses over 18 months)
Clostridium (genus)
Gram-Positive, non-motile, tapered rod, anaerobic
Form endospores (terminal)
Ubiquitous in nature
Widely distributed in soil and frequent in intestinal tracts
Clostridium perfringens
Gas Gangrene: endospores introduced into the body via trauma germinate, bacteria reproduce and secrete necrotic toxins
Bacterial wastes smell awful
Clostridium perfringens treatment
Fatal if untreated
Must remove dead tissue and administer large doses of antitoxin and penicillin or
Place patient / limb in an oxygenated hyperbaric chamber (increases pressure)
Clostridium botulinum
Produces botulism toxin
stable at low pH
tightly binds to cytoplasmic membranes of neurons
Toxin causes flaccid paralysis that starts at face and goes down. Fatal when it reaches the diaphragm
Clostridium botulinum diagnosis and treatment
Symptoms of botulism are diagnosed by themselves. Confirm diagnosis by culture
You can treat with administration of antibodies against botulism toxin to neutralize then administer anti-microbial drugs
1ng / kg of weight is lethal
Clostridium Tetani
Tetanus: spasms and contraction that can result in death because patients can’t exhale
Results when the bacterial endospores germinate and produce tetanus toxin (tetanospasms)
Toxin blocks the release of NTs responsible for muscle relaxation. Rigid paralysis
Rarely isolated because slow growing O2 sensitive bacteria
Treatment: clean wound, antibodies for toxin
Listeria Monocytogenes
Gram-Positive, motile, rod
Found in soil, water, mammals, birds, fish, and insects
Enters body via contaminated food and drink
Virulence not due to toxin but the bacteria’s ability to live within cells
Listeriosis
Primarily a GI illness
Can spread to nervous system
infection during pregnancy can lead to miscarriage
Listeriosis Diagnosis and Treatment
Look for organism in blood, feces, CSF, and amniotic fluid
Immunofluorescence of CSF: rarely seen by gram-staining because few listeria cells are required to produce disease
Umbrella motility
Sensitive to meds, prevention can be difficult because of ubiquitous nature of organism
Corynebacterium diptheriae
Gram-positive, club-shaped, rods arranged in K’s, V’s, or W’s
Form metachromatic granules (phosphate inclusions)
Diptheria
Transmitted from person to person via respiratory
Toxin responsible for signs and symptoms
Gene for toxin is carried by a bacteriophage
Toxin inhibits protein synth which leads to cell death
Severe respiratory infections in non-immune patients
Thick fluid covers and adheres to respiratory track
Pseudomembrane can completely block respiratory passage
Propionibacterium acnes
small, gram-positive, rod, prefers anaerobic, normal flora of the skin
causes most acne
antimicrobials for treatment
Mycobacterium (genus)
Gram-positive rod, grows slowly
Mycolic acid (waxy lipid) in cell wall
Protection from lysis after phagocytosis
Resists: gram staining, detergents, many antimicrobials, and desiccation (can survive the dry for 8 months)
Mycobacterium avium-intracellulare (not discussed)
Mycobacterium leprae
Cases are relatively rare
Person to person contact. Progressive and non forms
Non-progressive disease that is characterized by loss of sensation in regions of the skin
Progressive: causes gradual tissue destruction
Loss of facial features, digits, and other body structures
Treatment: combo of antimicrobial drugs, lifelong treatment sometime needed
Prevention: primarily prevented by limiting exposure to pathogen.
Mycobacterium ulcerans
(not clinically relevant)
Commonly found in swampy areas
Produces a necrotic toxin that destroys fat and muscle cells
Buruli Ulcer (visual manifestation): nodule formation at a break in the skin followed by swelling
Mycobacterium tuberculosis
Fundamentally a respiratory disease. Cases are declining in the US but is endemic in other parts of the world. About 5% of infected develop disease, 50% mortality rate for those untreated
Primary, Secondary, and Disseminated forms
Mycobacterium tuberculosis primary
Occurs soon after infection. A stalemate occurs between tuberculosis and immune system. Your body slowly begins to win while mycobacterium is slowly removed from body Ghon Complex appears when your body wins.
Mycobacterium tuberculosis secondary
Reestablishment of an active infection after a period of dormancy. Occurs when host-pathogen stalemate is broken by rupture of tubercle. Common occurrence in immunocompromised patients
Mycobacterium tuberculosis disseminated
Final stage when infected macrophages carry infection throughout the body. End up in spine, spleen, and brain
Mycobacterium tuberculosis diagnosis and treatment
Chest x-rays can ID the disease and a positive TB test can show patients who have fought it at some point.
Difficult to treat with antimicrobials because of the slow growing nature of the organism.
Prevention via prophylactic use of antibacterials for patients who test positive on the skin test or with known exposure
