Exam 4 Flashcards
(160 cards)
1
Q
Define:
- -hypersensitivity
- -autoimmunity
- -immunodeficiency
A
o Hypersensitivity—Any immune response against a foreign antigen exaggerated beyond the norm (allergies)
o Autoimmunity—When one’s own immune system attacks its own tissues
o Immunodeficiency— An inadequate immune response (Including HIV/AIDS)
2
Q
Describe the 4 types of sensitivity reactions.
A
• Type I—Anaphylactic Reactions: immediate hypersensitivity, release of histamine in response to allergen; combining of IgE antibodies to antigens (IgE binds to eosinophils, mast cells, basophils and they release histamine); localized or systemic anaphylaxis
- Type II—Cytotoxic Reactions: cells are destroyed by an immune response; the combination of IgG or IgM to an antigenic cell activates complement
* Affected cell could be a foreign cell or a self cell that carries a non-self antigen on its surface (ex: blood transfusion reactions) - Type III—hypersensitivity where complex triggers complement and complex is destroyed via phagocytosis; excessive complex production (ex: Rheumatoid arthritis, lupus)
- Type IV—Delayed cell-mediated reactions (12-24 hours); T cells become sensitized to an antigen and produce cytokines, attracts macrophages, cause tissue damage, cells become sensitized to an antigen which results in cytolysis. (ex: graft rejection)
3
Q
What is systemic vs localized anaphylaxis of (IV reaction)
A
Systemic: allergen is picked up by the blood and the reaction occurs throughout the body (ex: insect stings, drugs like penicillin)
Localized anaphylaxis: allergen is found localized in the mucous membranes or skin (ex: pollen, fungal spores, animal dander)
4
Q
What is “desensitization”? How does it work?
A
Desensitization is reducing the sensitivity to an allergen
Severity may be reduced by desensitization shots (allergy shots).
• It is thought that when very dilute allergen is given by injection, it stimulates the production of IgG and IgA.
• IgG and IgA then act as blocking antibodies to bind and neutralize much of the allergen in secretions before it can bind to the deeper cell-bound IgE’s on the mast cells
• The shots also appear to suppress production of IgE by inducing tolerance
5
Q
Describe the ABO and Rh blood group system. For each of the 8 blood types (A +, B+, etc.), describe the antigens and antibodies that are produced. Make sure you understand its importance in transfusions.
A
Type A: Anti B antibodies, A antigen, A/O compatibility
Type B: Anti-A antibodies, B antigen, B/O compatibility
Type AB: no antibodies in plasma, A and B antigens, A,B,AB, O, AB+ is universal recipient
Type O: Anti-A and Anti-B antibodies, no antigens in RBC, O compatibility
6
Q
Who is the universal donor? Universal recipient? Why?
A
Universal donor: O type blood
Universal recipient: AB+ type blood
7
Q
What are the ABO blood group systems?
A
Depends on the presence of carbohydrate antigens on the surface of red blood cells (RBCs)
• An individual has A, B, both, or neither
• The plasma of an individual with a given blood type has antibodies against the alternative blood type
8
Q
Why do people with blood type A have anti-B antibodies in their plasma (and vice versa)?
A
Early in our lives, we are exposed to the A and B antigens by the foods we eat and the microbes we are exposed to; we then form the antibodies to the antigens that are foreign
9
Q
What is the Rh factor? What is HDN? How and why does it occur?
A
Rhesus (Rh) factor is an inherited protein found on the surface of red blood cells. If your blood has the protein, you’re Rh positive. If your blood lacks the protein, you’re Rh negative. Rh positive is the most common blood type
10
Q
Discuss the various types of grafts (4). Which type(s) is rejection a non-issue? Which type(s) is rejection an issue?
A
o Autograft: Use of one’s own tissue; moved from one place to another
• No rejection
o Isograft: Use of identical twin’s tissue.
• No rejection
o Allograft: Use of tissue from another genetically dissimilar person
• Major rejection issues
• Tissue typing plays an important role in finding donor match
o Xenographs product (xenographs)
• Use of non-human tissue
• Major rejection issues
• Perhaps…the use of a genetically modified pig!
11
Q
What is graft-versus-host disease?
A
Graft-versus-host disease
• Transplant recipients may suffer graft-versus-host disease when donated bone marrow T cells recognize the recipient’s cells as foreign.
• For example: Radiation therapy destroys the recipient’s leukemia or lymphoma cell, and leukocytes, eliminating the immune response.
• Donated marrow restores the immune response but can produce disease.
• Donor and recipient differ in MHC class I molecules
o Grafted T cells attack all of the recipient’s tissues
• Donor and recipient differ in MHC class II molecules
o Grafted T cells attack the host’s antigen-presenting cells
• Physicians examine the white cells of potential graft (allograft) recipients by tissue typing to identify a donor whose MHC proteins closely match those of the recipient.
12
Q
How does tissue typing (MHC) typing work?
A
MHC typing used to find close matches between donor and recipient
• remember major histocompatibility complex is how the body recognizes “self” cells
• Compatibility between donor and recipient difficult due to high variability of the MHC
• The more closely related the donor/recipient, the smaller the differences in MHC
• How it’s done:
• take white blood cells from potential donor
• take antibodies from person that needs transplant
• do the antibodies attack the MHC on the donor’s white blood cells?
13
Q
Why are tissue/organ transplant recipients on immunosuppression? Describe how it works.
A
Recipients of allografts often receive treatments/medications to suppress cell-mediated immune response in order to prevent rejection
• So basically a person has no cell-mediated immunity
• Intact humoral immunity resists some microbial infections
14
Q
What is meant by an “autoimmune” disease? When/how does an autoimmune disease occur?
A
–An autoimmune disease is a condition in which your immune system mistakenly attacks your body. … Normally, the immune system can tell the difference between foreign cells and your own cells. In an autoimmune disease, the immune system mistakes part of your body, like your joints or skin, as foreign.
–Autoimmune disease results when there is a loss of “self tolerance”
o a person’s immune system begins attacking self cells
o Can be cytotoxic, immune complex, or cell-mediated (Type II, III, IV hypersensitivity)
15
Q
In what group(s) of people (age, sex) are autoimmune disorders more common? Why (what are some theories about the causes)?
A
Women are less susceptible to infectious diseases than men, but are more often prone to autoimmune diseases. This higher prevalence is partly attributable to the X chromosome, which has many genes relating to the immune system.
16
Q
What are the causes of autoimmunity?
A
o Estrogen may stimulate destruction of tissue by cytotoxic T cells
o Some maternal cells may cross the placenta, colonize the fetus, and trigger autoimmune disease later in life
o Fetal cells may cross the placenta and trigger autoimmunity in the mother
o Environmental factors such as viral infections
o Genetic factors such as certain MHC genes
o T cells may encounter self-antigens that are normally “hidden” and thus not destroyed during deletion
o Microorganisms may trigger autoimmunity due to molecular mimicry
• Mimic an autoantigen, and thus immune system responds to self as well as the specific foreign antigen
o Failure of the normal control mechanisms of the
immune system
17
Q
What is Graves disease?
A
Graves: Caused by cytotoxic autoimmune reactions (Type II) Involves antibodies produced in response to cell-surface antigens on thyroid cells, stimulates thyroid to produce excessive amounts of thyroid stimulating hormone (TSH), Thyroid becomes enlarged; goiter develops; bulging eyes; weight loss; anxiety
18
Q
What is Myasthenia Gravis?
A
Myasthenia Gravis: Caused by cytotoxic autoimmune reactions (Type II), Involves antibodies that coat the acetylcholine receptors an nerve-muscle junctions, Results in muscle weakness; some types lead to eventual diaphragm and respiratory failure
19
Q
what is Multiple Sclerosis?
A
Multiple Sclerosis:Type IV hypersensitivity, Neurological disorder in which where T-lymphocytes and macrophages attack and destroy the myelin sheath that insulates nerves, Disease onset usually occurs in young adults & is more common in women, Progresses slowly and symptoms vary with time (Usually begins with vision and speech deficits, Weakness and fatigue, May lead to paralysis)
20
Q
what is Type I diabetes?
A
Type I diabetes: insulin dependent, Type IV hypersensitivity, CTLs destroy insulin-producing cells in the pancreas, Certain types of MHC molecules may predisposition a person to Type I diabetes. Thus a Genetic component
21
Q
What is meant by immunodeficiency? Differentiate primary and acquired immunodeficiency.
A
Absence of a sufficient immune response
• Can be congenital (primary) or acquired (secondary)
• Primary:
o Congenital: due to defective or missing genes
o Develops in infants and young children
o Examples: DiGeorge’s syndrome:
• Recessive disorder that results in the lack of thymus gland (and thus, a lack of cell mediated immunity)
• Acquired: develop during an individual’s life
o Drugs (e.g., anti-cancer chemotherapies)
o Pathogens (e.g., HIV/AIDS)
o Malnutrition and environmental factors
o Some cancers
22
Q
What does AIDS stand for? What does HIV stand for? How is HIV thought to have arisen?
A
Thought to arisen from a mutation of SIV (simian immunodeficiency virus) that affects monkeys/chimps in Central/West Africa
o Virus jumped hosts in the 1930s (estimated)
• Due to close association with monkeys
o Virus spread as the area became more urbanized
• Highway transportation, sexual promiscuity, etc.
o In 1959, first reported death due to AIDS in the Democratic Republic of Congo
23
Q
What is the structure of HIV?
A
o Genus Lentivirus
• Retrovirus
o Enveloped virus, with 2 antigenic glycoproteins
• Gp120
• These gp120 spikes bind with CD4 receptor sites
• Gp41
• Promotes fusion of viral envelope to target cell
o Each copy of the virus contains 2 identical strands of RNA and 2 reverse transcriptase molecules
• Also carries enzymes integrase and protease
24
Q
Contrast the 2 types of HIV. Which type and clade is most common in the United States?
A
2 types of HIV
o HIV-1
• More virulent and easily transmitted
• Clade B most common in the United States and the Western world
• Clade C most common in sub-Saharan Africa
• Clade E most common is Far East and Asia
• Note: Clades may vary by 30+%
o HIV-1
• Primarily in western Africa; rare elsewhere
• Less transmittable
25
Briefly describe the replication cycle of HIV. Be sure to describe how the virus can be latent or active.
• Attachment: Gp120 attach to CD4 receptors
o On Helper T-cells, macrophages, dendritic cells
• Entry: HIV capsid enters cell by fusion
• Uncoating of capsid: releases the 2 viral RNA molecules and the reverse transcriptases (and other enzymes)
• Reverse transcriptase transcribes viral RNA to produce double stranded DNA
• DsDNA enters the nucleus
o The viral DNA is then integrated into host cell chromosome as a provirus by viral integrase
o There, the provirus can be active or latent
• Active vs. Latent
o Active: transcription of the provirus produces new viral genomes and translation produces viral capsids; release of virus by budding
o Latent: provirus remains in host’s chromosome not actively producing new HIV
26
Describe several ways that HIV evades the immune system
o Attacks immune system CD4 sites (Helper T cells)
o Incorporates self into host chromosome
• Remains latent in vacuoles within T cells
o Some infected cells become memory cells
o Allows a reservoir of the virus to persist for decades
• high mutation rate
o reverse transcriptase makes lots of mistakes with no proofreading
27
What are the 3 stages of HIV infection?
Briefly describe the 3 stages of HIV infection. When does AIDS develop?
An initial 6-weeks period of flu-like disease before specific immunity brings the infection under control
Steady-state period during which viral replication is kept more-or-less under control
o until the growth of newly arising virus variants is no longer successfully brought back under immune-system control
o with some break outs of viral replication as immune-system evading virus variants arise
o steady state can persist over many years (usually <10) and even longer with anti-viral cocktail of drugs
A gradual decline in immune system resilience and functioning
o The progression of HIV to AIDS takes about 10 years (global average)
• Up to 25-30 years with a strict drug regiment (at about $30,000 a year)
• Progession to AIDS is 5 years in sub-Saharan Africa
o AIDS is not a single disease but a syndrome
• A group of signs, symptoms, and diseases associated with a common pathology
o AIDS is actually only the end-product of a long decline in immune system functioning
o Clinical AIDS
• includes Candida albicans infections of esophagus, bronchi, and lungs; eye infections; TB; pneumonia; toxoplasmosis of brain; Kaposi’s sarcoma
• TH numbers < 200/µl of blood (normal = 800-1000/mm3)
28
Describe the ELISA test for the HIV virus. What are some limitations of the test?
Easier to detect antibodies for HIV than for the virus itself
• e.g., ELISA test (enzyme-linked immunosorbent assay)
• Blood is added to a solution containing antigen from the virus and a color change indicator
• If somebody has HIV, then they will have antibodies for that antigen
• If antibody is present, it will form antigen-antibody complex
• A change in color indicates antigen-antibody complexes, mean the person is infected with HIV
o Some issues with ELISA
• Takes several days
• Few come back for results
• The window of time between infection of HIV and antibody production can be up to 3 months
• Thus, antibody tests may give a false negative
o Newer tests have either been able to detect a lower concentration of antibodies or test for the presence of the virus
• This has narrowed the window to about 21-25 days
29
What is the viral load test for HIV? What are its advantages over ELISA? When (or for who) is the test used?
Plasma viral load tests
• Detect HIV circulating in blood
• Costly and still take up to 3 days to complete
• Used on infants
• Used to tract effectiveness of drugs
• Red Cross uses it to test blood donations for HIV
30
How is HIV transmitted?
```
o Sexual contact
o Breast milk
o Transplacental infection of a fetus
o Contaminated needles
o Organ transplants
o Blood transfusion
```
31
What is the current drug treatment for HIV?
Prevention includes the use of Condoms and Sterile needles; Education; testing blood donations, etc.
o Treatment directed at “cocktails” of drugs
• HAART (highly active antiretroviral therapy)…often called ART
• Combination of reverse transcriptase inhibitors and protease inhibitors
• Target any of the steps of infection (attachment, integration, etc.)
o Does not cure, but slows progression of AIDS
o Drug resistant strains
o Cost…not everybody gets it!
32
Why is an HIV vaccine not likely?
—Vaccine not likely anytime soon
• Viruses mutates very quickly
• Various clades
• Cost
33
What are the 2 layers of the skin? What are some functions of the skin?
—2 Layers: Epidermis and dermis.
—Functions: Prevents excessive water loss, Regulates temperature, Involved in sensory phenomena, Assists in vitamin D formation, Barrier against microbial invaders
34
What are some of the first lines of defense used the skin and eyes to prevent infection? How do microbes gain access to the skin?
—First line of defense: Keratinized epidermis, Salt (from perspiration) creates a hypertonic environment, Secretions are acidic (pH = 3-5), Lysozyme hydrolyzes peptidoglycan, Fatty acids inhibit some pathogens, Defensins secreted by skin are antimicrobial peptides, Microbial antagonism (by normal flora)
35
Describe the normal flora of the skin.
—Microbes that are normal residents of the skin need to be resistant to dessication and tolerant of salt
o Mainly gram positive
o staphylococcus epidermidis= 90% of normal flora of skin
o Diptheroids (rods)
• e.g., Propionibacterium acnes in sebaceous glands produce propionic acid; linked to acne
o Includes various fungi as well
• e.g., Malassezia furfur causes dandruff
• e.g., Candida albicans
36
Describe some differences between Staphylococcus aureus and Staphyloccocus epidermidis.
taphylococcus epidermidis
o Coagulase negative (does not form fibrin clots)
o Normal flora that can become opportunistic pathogens
o E.g. endocarditis; infections due to catheters
• Staphylococcus aureus
o Most pathogenic Staphylococcus species
o Coagulase positive (forms clots) prevents phagocytosis and other defenses; helps form abcess
o Produces several exotoxins
• exfoliative exotoxin
• Staphylococcal food poisoning (enterotoxin)
• Toxic shock toxin
o In general, reistant to penicillin
• MRSA…methicillin resistant
o Also foundin nasal passages (where it is easily transferred to skin)
o Opportunistic pathogen
37
Describe some virulence factors (such as specific enzymes and toxins) produced by Staph. Aureus.
Produces several exotoxins
• exfoliative exotoxin
• Staphylococcal food poisoning (enterotoxin)
• Toxic shock toxin
38
What are the 3 types of hemolysis? What group does S. pyogenes belong to? Describe some virulence factors of S. pyogenes.
—Secrete exotoxins called hemolysis, which lyse RBCs (and most other cells)
• Alpha-hemolytic
• Partial hemolysis; part of normal flora
• Results in a “greenish” cloudy zone on media
• Beta-hemolytic
• Complete hemolysis; most pathogenic
• Produces “clear” zone on media
• Gamma-hemolytic
• No hemolysis; part of normal flora
• No change on media
— Streptococcus pyrogenes
• Streptococcus pyogenes produces over 90% of all Strep. infections
• However, it is still susceptible to penicillin and bacitracin!
• Virulence due to:
• M-proteins, which prevents activation of complement and escapes phagocytosis by neutrophils
• Produces hyaluronidase (spreading factor)
• Produces streptokinase (dissolves blood clots)
• Forms capsules
• Produces pyrogenic toxins
39
Describe similarities and differences Staphylococcus and Streptococcus. Include things like shape and arrangement, catalase reactions, and general diseases they cause.
—Streptococcus is gram positive, cocci chains, catalase negative, secrete hemolysis exotoxins, cause impetigo, toxic-shock syndrome, necrotizing fasciitis
—Staphylococcus is gram positive, cocci clusters, catalase positive, opportunistic pathogens that can cause impetigo, toxic shock, folliculitis, scalded skin syndrome
40
What are some characteristics of Pseudomonas? What makes it the epitome of an opportunistic pathogen? What color pigment does it produce? Describe 2 infections caused by Pseudomonas aeruginosa.
```
• Gram-negative rod
• inhabitant of water and soil
• Produces a blue-green pigment called pyocyanin
• Common in soil and water
```
41
Impetigo
caused by staph aureus, Superficial skin infection, Small red patches, some pus filled, Can lead to Erysipelas if spread to lymph nodes
42
Folliculitis
Staph. infection of a hair follicle, causing it to beome red, swollen, and pus filled, Results in pimples, boils, sty (if on eyelid)
43
Scalded Skin Syndrome
About 5% of S. aureus strains produce exfoliative toxin, Cells of outer epidermis peel off, Transmission: person to person via contact with cut/abrasion
44
Necrotizing fasciitis
Commonly called flesh-eating bacteria, caused by streptococcus pyogenes, Exotoxin A and streptolysin S damage cells and tissues, Enters through break in skin, Characterized by: (Sunburn-like rash, Pain and swelling, Bacterial digestion of the muscl fascia and adipose tissue, Toxemia, Leading to organ failure and death in 20% of cases), Treated typically with clindamycin and penicillin, Hard to diagnose early since symptoms are nonspecific
45
Cutaneous anthrax
caused by Bacillus anthracis, Results when bacillus endospores enter a wound in the skin, makes Endspores often shed from an infected animal, producing a sold skin nodule, spreads to form a painless black ulcer called an eschar, Treatment with oral antimicrobial drugs is usually successful, Prevention in livestock by vaccination is effective in preventing human disease.
46
Gas Gangrene
caused by Clostridium perfringens, Gram-negative endospore-forming bacilli, Anaerobic, Found in soil, water, sewage, causes Ischemia (loss of blood flow to a tissue) can cause tissue to die and become anaerobic and releases toxin to spread, Blackening of infected muscle and skin, Foul smelling drainage, Presence of gas bubbles (hydrogen and carbon dioxide), Shock, kidney failure, death within a week if not treated, 40% mortality rate; Treatment: remove dead tissue, oxygenate, intravenous antibiotics—penicillin
47
Warts
Benign skin growths caused by papillomavirus (plantars warts), Some papillomavirus strains are oncogenic in host chromosomes, Transmitted via by direct contact and fomites, Warts usually regress on their own by cell-mediated immunity, but pain and ugliness may necessitate treatment, Treatment: liquid nitrogen (cryotherapy), burning with acids, laser, some topical treatments, Virus can remain latent in neighboring cells and produce new warts at a later time
48
Small pox
variola pox virus, DNA virus, Closely related viruses include coxpox and monkeypox, Humans only reservoir of the small pox virus, First vaccine developed was for small pox by Edward Jenner in 1796, Transmitted via respiratory route, Travels to blood and lymph, becoming systemic, Travels to skin after infecting internal organs (12 days incubation), maculopapular rash, including on palms and soles of feet
49
Chicken pox
Caused by varicella-zoster virus (a herpes virus) (VZV), respiratory tansmission, pusfilled vesicles, rupture and scab, Prodromal: fever, headache, swollen glands, and other flu-like symptoms
50
Shingles
chicken pox Remains latent in peripheral nerves (for decades), and later causes Shingles (herpes zoster), Occurs in 15-20% of people who have had chickenpox, Localized vesicles in distinct areas, usually around the waist, Expressed “differently” than chicken pox, because person now has partial immunity to the virus, Vaccine available for those 60+ who have had chickenpox or have those who have not been vaccinated
51
Herpes
Herpes simplex virus, type 1, HSV-1, is cold sores/fever blisters, Subclinical in 90% of population, Reoccurence of lesions is characteristics, Remains latent in nerve cells that communicate with the face, Reactivated by sunlight, hormones, stress, fever, Transmitted via skin contact with active lesions, HSV-2 is transmitted thru sexual contact leads to genital herpes, Also associated with neonatal herpes
52
Measles
Rubeola, Single stranded RNA virus, Produces a fusion protein that allows the virus to spread cell-to-cell, avoding antibodies, Most contagious and most serious childhood disease, 1-5% mortality rate, Humans are only reservoir, Spread by respiratory route, 10-12 days later, fever, sore throat, cough, followed by a facial rash that spreads to trunk and extremities, Include Koplik’s spots: lesions in the mouth, vaccination given at 1 year old, booster at 4 or 5, Nearly eliminated in the United States but reemergence from non vaxers,
53
Rubella
Caused by the rubivirus, Single stranded RNA virus, in general, milder than Rubeola (measles), Spread by respiratory route, Swollen lymphs and small red spots and light fever 2-3 weeks later, Maternal infection during first trimester can cause severe birth defects, Congenital rubella syndrome (deafness, eye cataracts, heart defects, retardation)
54
Fifth Disease (Eruthema Infectiosum)
Viral Diseases of the skin: Erythema Infectiosum, Called Fifth disease, because it was the fifth rash on a list that doctors used in the 1900s, Caused by the Erythrovirus, Manifests itself as reddening of the skin, beginning on cheeks and spreading to arms, thighs, buttocks
55
Roseola
Caused by a herpesvirus Roseolovirus (called human herpesvirus 6 (HHV-6), Characterized by sore throat, enarged lymph nodes, faint pink rash on face, neck, trunk, and thighs
56
Ringworm
dermatophytoses, looks like a rings, Not actually a worm!!! Caused by various fungal species, Includes athlete’s foot and jock itch
57
Candidiasis
Candida albicans, Fungal infection of the mucous membranes, Opportunistic pathogen, AIDS patients, diabetic, Causes thrush (in the mouth); vaginal yeast infections
58
Pityriasis versicolor
caused by Malassezia furfur interferes with melanin production causing hypo- or hyper- pigmented skin
59
Leishmaniasis
disease of the skin and oral mucous membranes caused by an intracellular parasitic protozoan, causes lesions in infected tissue, Zoonotic: carried in dogs and rodents, and is spread to humans via sand flies, the flies deposit the protozoa into the body where macrophages attempt to attack them, the protozoa can then move into macrophages and multiply, There are three clinical forms of this disease, cutaneous leishmaniasis, ulcers occur around the infection site on the skin, mucocutaneous leishmaniasis, lesions enlarge to incorporate the mucous membranes of the mouth/nose, visceral leishmaniasis, macrophages spread the parasite to internal organs, fatal if untreated
60
Scabies
insect, Sarcopes scabiei mite that burrows under the skin to lay its eggs, Triggers inflammation and Type IV hypersensitivity, intense itching, Transmitted by intimate contact
61
Lice
caused by pediculus humanus, lots of itching, which can lead to secondary bacterial infections
62
Describe the 2 divisions of the central nervous system.
* CNS
* Brain and spinal cord
* Picks up sensory information from the environment, interprets the information, and sends impulses that coordinate the body’s activities
* PNS
* The nerves that branch off from the brain and spinal cord
* Lines of communication between the CNS, various parts of the body, and the external environment
63
What are meninges? Describe them and their function.
—Membranes that cover the brain and spinal cord
• 3 layers cover the brain and spinal cord
• Dura mater, arachnoid mater, and pia mater
• Cerebrospinal fluid circulates between the inner 2 layers (subarachnoid space)
• Acts as a shock absorber, provides nutrients and oxygen to the CNS, and removes waste
• CFS has low levels of complement, antibodies, and phagocytic cells
• Thus, theoretically it should be an easy location for infection to occur!
• However the blood vessels that supply the CNS are composed of tightly joined cells which typically prevents microbes and other large molecule from passing through
• Called the Blood-Brain-Barrier (BBB)
64
Describe the blood-brain barrier. Why is it important?
* A series selectively-permeable capillaries leading to the brain
* permit essential nutrients to pass from the blood into the brain but restrict potentially harmful substances
* Lipid soluble molecules move easily (e.g., caffeine, barbituates)
* Water soluble molecules require specialized transporters
* Large molecules/substance not allowed to cross
* Functions
* Protects the brain from foreign substances, such as pathogenic microbes and their toxins, in the blood
* Protects the brain from hormones and neurotransmitters in the rest of the body
65
Describe the normal flora of the brain? How do microbes invade the nervous system?
```
—CNS is axenic
• No normal flora
—Pathogens enter via:
• Skull or backbone fractures
• Breaks/tears in meninges
• Medical procedures
• Can travel along the peripheral nerves (PNS)
• Blood or lymph
• Inflammation can also stretch the cells of the BBB and make them more permeable for pathogens to squeeze through
```
66
Define:
• Meningitis
• Encephalitis
• Meningoencephalitis
* Meningitis— inflammation of the meninges
* Encephalitis—inflammation of the brain itself
* Meningoencephalitis—inflammation of both
67
Bacterial meningitis
—Inflammatory bacterial infection of the meninges
• Most commonly the pia and arachnoid mater
• Characterized by an increased number of white blood cells in the CSF
• Causative agents:
• Not only a bacterial disease (bacteria, virus, protozoa, etc.)
• Viral typically more mild
• More than 50 species of bacteria can cause meningitis
• Many are opportunistic pathogens of the normal flora
• 3 bacterial species cause 70%+ cases
• Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis
• Note: all possess capsules that prevent phagocytosis
• Signs/symptoms:
• Fever, headache, and stiff neck, followed by nausea and vomiting
• Eventually progresses to convulsions and coma (if not treated)
• Death from bacterial meningitis often can occur quickly (due to shock)
• Treated with cephalosporins
• Able to cross BBB
• Vancomycin: broad spectrum (before causative agent is identified)
• Diagnosis:
• Spinal tap (ouch!); Gram stain
68
Listeriosis
Causative agent: listeria monocytogenes
• Gram positive rod
• Reproduce within monocytes (hence its name)
• Excreted in animal feces (including humans)
o Found widely in soil and water
• Rarely pathogen in healthy adults
o Increasingly important infection of pregnant women
can cause abortion/stillbirth or lead to meningitis of newborn
o Often causes meningitis in immuno-suppressed patients (AIDS, diabetes, cancer)
• Outbreaks are usually food-borne
o Dairy foods, uncooked meats and vegetables, etc.
o Can grow at refrigerator temperatures
• Not spread among humans
69
Leprosy (Hansen’s disease)
Causative agent: Mycobacterium leprae
• Acid-fast rod
• Diagnosis is based on the signs and symptoms
• Confirmed by presence of acid-fast bacilli in samples
• Virulence factors
• Mycolic acid in the cell wall is responsible for several characteristics of the bacterium
• Slow growth rate
• Protection from phagocytic lysis
• Can live inside cells for years
• Growth within phagocytes
• Resistance to many antimicrobial drugs
• Treatment:
• multiple drugs for a minimum of 2 years
• some effectiveness of BCG vaccine to treat TB
• Grows in peripheral nervous system and skin cells.
• Cell-mediated response damages nerves
• Person to person transmission
• However, transmission requires prolonged contact with an infected person.
• Tuberculoid:
• Non progressive; high cell mediated response
• Loss of sensation in certain areas of skin
• Lepromatous:
• Low cell mediated response, so progresses
• Disfiguring nodules over body
• deformation of hands and nose
• necrosis of tissue
70
Botulism
Caused by clostridium botulinum
• Anaerobic, endospore-forming gram-positive rod
• Common in soil and water
• Often not an infection, but an intoxication (exposure to toxin/not the bacteria)
• Produces the most potent exotoxin of all bacteria
• Blocks the release of acetylcholine, which is essential for the transmission of nerve impulses across a synapse
• Results in flaccid paralysis, difficulty breathing and swallowing
• Exposure:
• Food-borne: consumption of toxin in contaminated food
• Infant and wound: endospore contamination
• Epidemiology
• About 60 cases of foodborne and wound botulism reported a year
• Of particular concern is infant botulism
• Most associated with honey, which can contain C. bostulinum endospores; infants under 1 should not consume honey
• Botox involves localized injections of the toxin
• Eliminates wrinkles, stops armpit sweating
* Prevention
* Proper canning (toxin not formed in acidic foods)
* Nitrites prevent endospore germination in sausages, lunch meats, hot dogs, etc.
* Four approaches to treatment
* Maintain open and functional airways
* Wash intestinal tract to remove Clostridium
* Administer botulism immune globulin intravenously (BIG-IV)
* Treat with antimicrobial drugs (wound and infant botulism)
* Resistant to many due to endospores
* Chloramphenicol or penicillin
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Tetanus
Caused by clostridium tetani
• Common in soil, dust, intestine of humans/animals
• Anaerobic endospore-forming, gram positive rod
• Produces extremely potent neurotoxin tetanospasmin
• which blocks relaxation of muscles
• Can cause lockjaw and other muscle spasms (e.g., back muscles, respiratory muscles)
• Can be deadly when unrelenting contraction of diaphragm makes breathing impossible
• Enters body through break in skin
• Must grow deep in wounds (anaerobic)
• e.g., those caused by a rusty, dirty nail
• Toxin released by cells; travels to nervous system
• Distance of infection of CNS determines incubation time
• Prevention by vaccination with tetanus toxoid (DTP) and booster (dT) every 10 years.
• Many people do not obtain booster and thus have ineffective immunity
• Treatment with tetanus immunoglobulin (antibody) provides temporary immunity
• Wash all wounds out immediately; keep updated on tetanus shot!
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Polio
* Caused by poliovirus
* Humans ONLY reservoir
* Primarily transmitted thru ingestion of water contaminated with feces containing the virus
* Exposure was once frequent; epidemics among children common
* Infants exposed while protected by maternal antibodies, and thus built up a lifelong immunity
* Adolescent exposure, however, led to disease
* Signs and symptoms
* Initial symptoms: Sore throat and nausea (viruses multiplies in throat and small intestine)
* Viremia may occur; if persistent, virus can enter the CNS; destruction of motor cells and paralysis occurs in <1% of cases.
* If fatal, usually due to paralysis of respiratory muscles
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Rabies
• Caused by Rhabdovirus
o ssRNA virus; high mutation rates (thus making vaccination difficult)
• Zoonotic
o Transmitted by animal bite
o Primary reservoirs bats, but also dogs, raccons, fox, cats, other mammals
• Virus infects skeletal muscles, travels along PNS to CNS
o Initial symptoms may include periods of agitation and calmness; muscle spasms of the mouth and pharynx; hydrophobia; disoriented
o Once symptoms appear, very little chance of survival
• Furious rabies:
o Animals are restless then highly excitable; biting behavior; saliva flow from mouth as paralysis sets in
• Paralytic rabies:
o Animals seem quiet and unaware of surroundings.
• Diagnosis, treatment, and prevention
o Diagnosis by unique neurological symptoms
o Postmortem detection of Negri bodies in the brain
• Long incubation time (30-50 days) allows post-exposure immunization
o Treated by injecting human rabies immunoglobulin (antibodies) followed by a series of injections of the rabies vaccine3
• Pre-exposure treatment of high-risk individuals (lab workers, veterinarians)
• Human cases are rare in the United States
74
Arboviral encephalitis
—Arboviruses are arthropod borne that belong to several families.
• Zoonotic
o Affects birds, horses, rodents, and rarely humans
• Transmitted via blood-sucking arthopods
o Aka: mosquites
• Signs/Symptoms
o Chills, headache, and fever
o Can progress to mental confusion and coma
• Prevention is by controlling mosquitoes.
• Veterinarians can administer effective vaccines against EEE, WEE, VEE, and WNV to horses, but the U.S. Food and Drug Administration (FDA) has not approved human vaccines.
o Scientists have developed an effective human vaccine against West Nile virus; safety trials are ongoing
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Cryptococcal meningitis
—cryptococcus neoformans is causative agent
o Two variants of the yeast found worldwide
• Inhalation of spores from bird droppings, get into soil
• Signs and symptoms
o Similar to those of bacterial meningitis
o Loss of vision and coma may occur in later stages
• Pathogen and virulence factors
o Resists phagocytosis by defensive cells
• Infections often fatal in HIV and transplant recipients taking immunosuppression drugs
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African sleeping sickness
—Causative agent: Trpanosoma brucie
• Vector: tsetse fly
• Occurs regularly in sub-Saharan Africa
• 3 stages:
• (1) the bite wound becomes necrotic;
• (2) fever, swollen lymph nodes, and headache;
• (3) meningoencephalitis and extreme drowsiness, coma, and death
• cycles of parasitemia every 7–10 days
• Parasite randomly changes surface glycoproteins when it replicates, leaving host’s immune system unable to clear infection
• No vaccine available
• Treated with antimicrobials
• Use of insecticide can reduce occurrence
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Primary amebic meningoencephathy
• Caused by 2 amoebae
• Acanthamoeba and Naegleria
• Rare but almost always fatal
• Signs and symptoms
• Same as those of meningitis and encephalitis caused by other microbes
• Symptoms worsen over 3-7 days until patient dies
• Only 3 people in US have ever survived
• Found in warm bodies of freshwater and moist soil
• Enter host through abrasions on the skin or the eyelid, njose, or by inhalation of contaminated water
• Then migrate to brain via cranial nerves
78
What is meant by conjunctivitis? What are the common causes?
```
• Conjunctivitis: inflammation of the conjuctiva (mucous membrane around the eye)
o Pink eye
• Most commonly caused
o By an allergic reaction or virus
o Some bacterial
• Haemophilus influenzae
• Neisseria gonorrhoeae
```
79
Describe the following diseases of the eyes (causative agent, type of microbe, etc.):
—Trachoma
o Greatest single cause of blindness
o 500 million cases; 7 million blinded victims
o Caused by Chlamydia trachomati bacteria
o Inflammation leads to trichiasis (in-turning of the eyelashes)
80
Describe the basic structure and function of both the Cardiovascular and Lymphatic system. Describe some defense mechanisms of each.
Cardiovascular System
• Heart, blood, and blood vessels
• Circulate blood throughout body
• Delivering nutrients and oxygen
• Removing wastes and carbon dioxide
Lymphatic system
• Lymph, lymph nodes, lymph vessels, and lymph organs (tonsils, appendix, spleen, thymus)
• Picks up excess interstitial fluid and returns it to blood
• Defense mechanisms
o Many of the body’s innate and adaptive defenses are found in the lymph
• White blood cells and antibodies in blood
• Fixed macrophages and lymphocytes in lymph nodes
o Lymph capillaries very permeable and readily pick up microbes and their products
• Deliver them to lymph nodes where macrophages, B-cells, and T-cells go to work
81
```
Define the following:
o Septicemia (sepsis)
o Bacteremia
o Toxemia
o Lymphangitis
```
o Septicemia (sepsis)—Any microbial infection of the blood that produces illness
o Bacteremia—Bacterial septicemia
o Toxemia— Release of bacterial toxins into the blood
o Lymphangitis—Infection and inflammation of the lymphatic vessels
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Gram negative sepsis
* Severe sepsis (leading to septic shock) most often caused by gram-negative bacteria
* Staphylococcus cause blood pressure decrease
* Sever sepsis of the blood (disseminated intravascular coagulation (DIC)
* Up to 300,000 cases occurring each year in the United States alone
* Early symptoms are non-specific; later symptoms are difficult to reverse
* Antibiotics can worsen condition by killing bacteria (releasing endotoxin)
83
Gram positive sepsis
caused by Staphylococcus aureus and Streptococcus pyogenes usually
o Toxins result in toxic shock syndrome (or toxic shock-like syndrome)
• Nosocomial infections
o esp. Enterococcus faecium and E. faecalis
• Neonatal sepsis (peuperal fever)
o Group-B Streptococcus
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Endocarditis (subacute and acute)
— inflammation of the inner layer of the heart (endocardium)
• Subacute: develops slowly
o Likely arises from a focus of infection elsewhere in the body
• e.g., tooth extractions and tonsillectomies release microbes that enter the blood stream
• e.g., body piercings
• Often caused by alpha-hemolytic streptococci that live in the throat and mouth
• e.g., Streptococcus mutans
o Signs/Symptoms
• Fever, general weakness, difficulty breathing, tachychardia, and murmurs (if heart valve infected)
• Can usually be treated by antibiotics if caught early
• Acute endocarditis: progresses rapidly
o Usually caused by virulent Staph aureus
o Proliferation in valves leads to a rapid deterioration of heart valves
o Fatal within a few days/weeks if not caught and treated
• With both types (sub-acute and acute)
o Bacteria become lodged in heart valves
• Usually targets defective heart valves; but not always
o Multiplication leads to a formation of a vegetation
o Bacteria continue to multiply within the vegetation and it enlarges
o Pieces become dislodge; can block vessels
o Deteriorates the function of heart valves
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Rheumatic fever
—Inflammatory disease that may develop after a Strepto progenies infection
o e.g., strep throat
• Type II autoimmune rxn: antibodies that were produced to attack M proteins of S. pyogenes start attacking the myocardium (of heart), joints, skin, or CNS
o In 50% of cases, damages heart valves
• Most common in young (4-18 years old)
o Today, not common in the U.S.
o A leading cause of heart disease in children in developing nations
• Signs/Symptoms
o Vary…depending on where it shows itself
o Arthritis, Heart palpitations, Chest pain, Subcutaneous nodules, Skin rash
o Sydenham's chorea
• Involuntary movements; Only 10% of cases; Outbursts of unusual behavior
86
Tularemia
Caused by Francisella tularensis
o Gram negative, rod
• zoonotic
o Diverse host range includes mammals, birds, fish, ticks, and insects
o Transmitted via bite of infected tick or contact with infected animal
o Small size of bacteria allows entry through seemingly unbroken skin
• Signs and symptoms:
o typical of many viral infections (though its bacterial)
o include fever, chills, headache, fatigue, shortness of breath, joint stiffness, and myalgia.
o Lymph nodes may be swollen, and lymphangitis usually is present
• Treatment
o Antibiotics
• Produces B-lactamase so resistant to penicillin
o Vaccine available to high risk people
o Plague (differentiate bubonic and pneumonic)—
• Known as the Black Death
o After the dark blue areas of skin that form
• Causative agent: Yersinia pestis
o Gram-negative, rod-shaped, capsuled
o Bacteria able to survive and proliferate within phagocytes (in blood and lymph nodes)
• Zoonotic
o Vector: rat flea
• Flea bite introduces bacteria into blood
o Or acquired from infected animals (rats and wild rodents)
• Treatment
o Antibiotics (streptomycin) immediately
o Untreated fatal within a week
• Prevention: rodent and flea control; good hygiene
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Bubonic plague
o Bacteria proliferating in lymph nodes
o Enlarged lymph nodes (in groin and armpit) called buboes
o 50-75% mortality if not treated
o Can enter blood and be carried to lungs
88
Pneumonic plague
```
o Bacteria infect lungs
o 100% mortality
• In the 14th and 15th century
o Pandemic killed more than 25% of the population (estimated 75 million people)
o Particularly Europe
• In the 19th century
o Pandemic struck primarily Asian countries
o Estimated 12 million people died
```
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Lyme disease
o Causative agent: borrelia burgdorferi
o Spirochete
o Avoids immune systems by rearranging its outer membrane proteins
o Vector: deer tick (Ixodes)
o Most common tick-borne disease in the U.S.
o Show seasonal pattern
o 3 stages: larval, nymph, and adult
o Each takes in 1 blood meal (except adult male)
o Adult feeds and mates on deer (and other warm blooded animals)
o Nymph stage most likely to infect human
o Adults are easily detected and removed
o Tick attaches to humans (dogs, etc.)
o Usually from perch on grass
o Heat sensitive
o It takes 2-3 days before tick transmits bacteria and infection occurs
• Only 1% of tick bites result in Lyme disease
o Signs/Symptoms
o bull’s eye rash
o Flu-like symptoms: headache, dizziness, fever, chills, stiff neck, mucle and joint paint
o In the absence of treatment (antibiotics), a second phase of the disease develops
• Irregular heartbeat, cardiac inflammation, meningitis, encephalitis, facial paralysis, arthritis
o Treatment:
o Antibiotics (amoxicillin) for 3-4 weeks
o Prevented with tick repellents and protective clothing
o No vaccine
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Infectious mononucleosis
—Caused by the Epstein Barr virus/ Herpesvirus
o Typically harmless
o Establishes life-long infection in most people
o Causative agent of several other diseases
• Burkitt’s lymphoma, chronic fatigue symdrome, B cell lymphoma, oral hairy leukoplakia
o Infectious mononucleosis
o Severe sore throat and fever, enlarged lymph nodes, enlarged spleen, extreme fatigue, nausea, skin rash
o Infects B lymphocytes
• Virus suppresses apoptosis of infected B-cells
o Transmitted through saliva
o 15-25 years old; college
o Diagnosed by presence of large, lobed B lymphocytes and neutropenia
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Viral hemorrhagic Fever
• Yellow Fever—transmitted by mosquito; Flavivirus, Dengue: transmitted by mosquito; Flavivirus
92
Ebola
```
Ebolavirus, Marburg: Marburgvirus
o Occurs primarily in Africa
o Zoonotic
o Infects humans an non-human primates
o Transmitted via contact with bodily fluids of infected individual
o Reservoir: likely bats
o HIGHLY contagious
o Initial infection from animal to host
o Then person to person
o 90% fatal
o Signs and symptoms
o Fever and fatigue
o Minor petechiae progress to severe internal hemorrhaging (leaking from body orifices…mouth, eyes, ears)
o Death from shock, seizures, kidney failure
o Treatment:
o Quarantine infected/exposed individuals
o Supportive care
```
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Toxplasmosis
Causative agent: Toxoplasma gondii
o Cats are essential in the life cycle of T. gondii
o Sexual phase of life cycle in intestine tract
o Shed oocyts in feces
o Up to one third of the world's population is estimated to carry a Toxoplasma infection
o Majority of cases are asymptomatic
o Major disease of immunocompromised (AIDS patients) and unborn children
o Fever, malaise, inflammation of lungs, liver, heart, vision damage, encephalitis, death
o Transplacental transfer from mother to fetus can cause a variety of birth defects (epilepsy, mental retardation, blindness, etc.) or fetal demise
o Infection occurs by eating undercooked, infected meat, contact with cat feces that has itself recently been infected, or by transmission from mother to fetus
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Malaria
o plasmodium parasite
o At least 4 different species
o Disease severity depends on the species
• P. falciparum causes the most severe malaria
o mosquito vector: Anopheles
o Worldwide, effects 300-500 million people
o 2-3 million deaths a year
o Effective mosquito control has greatly reduced the number of cases in the U.S.
o In recent years, numbers have increased
o Increased travel to malarial areas
o Increased immigration from malarial areas
o Resistance to medications
o Signs and symptoms
o Fever, chills, vomiting, headaches, jaundice
o Malignant malaria is associated with high rates of anemia; red blood cells stick to capillary walls and clog vessels; cannot reach spleen; tissue death…
o If people survive acute phase, then immunity gradually develops
• Periodic episodes; less severe
o Diagnosis, treatment, and prevention
o Diagnosis made by identifying Plasmodium in blood
o Treated with various antimalarial drugs
• Some Plasmodium strains are resistant to antimalarial drugs
o Prevention requires control of mosquitoes
• Use of mosquito nets is important way to reduce contact
o Malaria Infection
o Mosquito bite introduces Plasmodium sporophytes into the blood
o Proliferate in liver into merozoite, which are released back into the blood
o Merozoites infect RBCs and reproduce
• RBCs release merozoites and toxins
• Which cause the fever and chills
• Some merozoites infect new RBCs
• Others mature into male and female gametocytes
o Taken up by mosquito and transmitted!
o Virulence factors
o Reproductive cycle hides parasite from immune surveillance
o Malaria secretome injects toxins into host cells
o Adhesins allow infected red blood cells to adhere to certain tissues
o Merozoites form within vesicles and avoid detection
o Changes in body chemistry attract other mosquitoes
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Schistosomiasis
—helminth infection
Schistosomiasis
o Parasitic blood fluke
o Genus Schistosoma
o One of the most common parasitic infections of the world.
o Humans become infected by contact with contaminated water.
o Snails are the intermediate host in water contaminated with human excrement
o Humans only definitive host
o The larvae migrate through the body system and mature into worms that mate to produce eggs.
o The eggs can lodge in the intestines, bladder
o Later, even lungs, brain, and other organs, causing organ failure and sometimes death.
o Manifests initially as a transient dermatitis called swimmer’s itch where infective larvae burrow into the skin.
o Later fever, chills, muscle aches
o Three geographically limited species cause schistosomiasis
o Not found in the United States
o Vaccine is clinical trials
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what are the components of the upper respiratory tract? Lower respiratory tract?
Upper respiratory tract
o Includes nose, nasal cavities, pharynx (throat)
o Associated structures include ears, tonsils, and sinuses
o Defense structures include
• Coarse hairs of nose (filter)
• Ciliated mucous membranes of the nose and throat
• Lymphoid tissue (tonsils)
• Normal Flora (microbial antagonism)
lower respiratory tract
o Includes larynx (voicebox), trachea, bronchi, bronchioles, lungs (alveoli)
o Pleurae: membrane that surrounds lungs
o Diaphragm: below lungs; major muscle used for breathing
o Defense structures include
• Ciliary escalator
• Alveolar macrophages
• IgA in mucous membranes
97
What are some of the defenses of both the upper and lower respiratory tracts
```
Upper Defense structures
• Coarse hairs of nose (filter)
• Ciliated mucous membranes of the nose and throat
• Lymphoid tissue (tonsils)
• Normal Flora (microbial antagonism)
Lower Defense structures
• Ciliary escalator
• Alveolar macrophages
• IgA in mucous membranes
```
98
Describe some of the members of the normal flora of the respiratory tract.
The upper respiratory tract is inhabited by many types of microbes
o Diptheroids
o Stapylococcus
o Streptococcus
• alpha-hemolytic Strep. pneumoniae
o Some healthy carriers of Haemophilus and Neisseria
o Normal flora may be opportunistic pathogens
• In contrast, the lower respiratory tract is sterile (microbe free)
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Pharyngitis
infection in the throat (sore throat)
100
Laryngitis
infection in the larynx
101
Tonsillitis
tonsil infection
102
Rhinosinusitis
sinus infection
—sinuses: cavities in cranial bones; lined with mucous membranes, most cases are viral; 10% bacterial
• Typicially caused by normal flora of pharynx that spread to nose, sinuses, middle ear
o Streptococcus pneumonia (about 35% of cases), Staph. aureus, Haemophilus influenza, Strep. pyogenes
• Signs/Symptoms include:
o Heavy nasal discharge
o Blocked sinuses lead to localized pain (sinus headache) depending on which sinuses are infected
o Cheeks, teeth, between and behind eyes
o Often considered secondary infection
• Preceded by an upper respiratory infection such as the common cold
o Chronic sinusitis usually caused by allergens
• Treatment
o IF bacterial…amoxicillin-clavulanic combo
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Epiglottitis
--infection of the epiglottis
o Flap that covers the larynx when swallowing
• Considered a medical emergency
• Develops rapidly; can be deadly within a few hours
• Caused by primarily by Haemophilus influenzae
o A gram-negative, coccobacillus bacteria
o Also Strep. pneumoniae and pyogenes
o Hib vaccine
• Directed at meningitis, but targets same bacteria that causes epiglottitis
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Strep Throat
—streptococcus pyogenes
o M proteins help escape phagocytosis, Hyaluranidase (spreading factor), Streptokinase (dissolve blood clots), Streptolysins (lyse red blood cells), etc….
• Signs/Symptoms
o red and inflamed pharynx; sore throat; pus-fill patches over tonsils, ; swollen lymph nodes in back of neck; fever; malaise; bad breath; headache
• Complications (although rare)
o Endocarditis, scarlet fever, TSLS, pneumonia, and rheumatic fever
• Pathogenesis
o Occurs when normal microbiota are depleted, large inoculum is introduced, or adaptive immunity is impaired
• Epidemiology
o Spread via respiratory droplets
o Occurs most often in winter and spring, especially among day-care, elementary kids
• Diagnosis, treatment, and prevention
o Often confused with viral pharyngitis
o Most sore throats are viral!!!
o Oral penicillin is an effective treatment
o Cephalosporins for those allergic to penicillin
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Scarlet Fever
—streptococcus pyogenes
• produces pyrogenic toxin (erythrogenic toxin)
• Begins as strep throat
o Release of toxins triggers a dangerously high fever and a red rash
o Strawberry tongue (enlarged and spotted)
o After about a week, rash disappears and skin sloughing occurs
• Not all streptococci bacteria make this toxin and not all kids are sensitive to it (it is basically a hypersensitivity
o Occurs when it has been lysogenized by a bacteriophage
• Considered a pandemic in the mid 1800s
o Today, however, considered relatively minor and rare due to treatment of strep throat with antibiotics
106
Diphtheria
—corynebacterium diphtheriase
o Gram-positive bacteria
o Virulent strains contain a phage that produces powerful diphtheria exotoxin killing cells it infects
• Signs/symptoms
o Sore throat; fever;
o pseudomembrane: Tough, grayish membrane forms in the throat
• “leather tonguee”
• Composed of dead tissue cells, fibrin, and bacterial cells
• can block passage of air to lungs
• Pathogenesis and epidemiology
o Spread via respiratory droplets or skin contact
o Symptomatic in immunocompromised or nonimmune individuals
o Leading cause of death among unimmunized children
• DPT (DpaT) vaccination (diphtheria, pertussis, and tetanus)
o Humans only known host, so vaccination most effective prevention
o Fewer than 5 cases reported annually in the U.S.
o Evidence suggested that less than 20% of adults have effective immunity
o Boosters recommended (Tdap or Td vaccine)
107
Otitis media
—Middle ear infection (ear ache)
o Often a secondary infection
o Usually preceded by the common cold
• Caused by several bacteria species
o Same that cause rhinosinusitis
• Inflammation/build-up of pus puts pressure against ear drum
o Rupture of tympanic membrane releases pressure
• Most frequent during childhood
o Eustachian tube connecting tube to throat is small and easily blocked
• About 8 million cases a year in the U.S.
o ¼ of all antibiotic prescriptions
o Usually broad spectrum penicillins: amoxicillin
o Chronic ear infections often require a tube inserted into middle ear drum to drain fluid
108
The common cold (name the most common causative agent of sickness)
Caused by many different viruses
o About 200+ different causative agents
o 50% caused by the rhinovirus
• Also Coronavirus and adenovirus
• Reproduce most effectively at 33 C,
o Temperature of nasal cavity
• VERY contagious
o When symptoms are most severe, there may be over 100,000 virions/ml of nasal mucus
o A single rhinovirus is sufficient to cause a cold in 50% of infected individuals
o More common in winter….why????
• Signs:
o Sneezing, Nasal secretions, Cough and congestion
• We accumulate immunities against cold viruses throughout our lives
o IgA antibodies are produced to specific serovars
o Thus fewer colds are we age
o A young child may get 6-12 colds a year
• Prevention
o Handwashing—prevents spread
• Treatments
o Antibiotics worthless (why?)
o Most treatments treat the symptoms, and NOT the causative agent
o Throat lozenges
o Cough suppressants
o antihistamines
109
Bacterial Pneumonia
—inflammation/infection of the lungs, alveoli and bronchioles become fluid filled
o Pneomococcal
• Common bacterial causes
o pneumococcal (streptococcus pneumoniae)
• About 85% of cases
• Forms capsules; preventing phagocytosis
• Blood enters lungs leading to rust colored sputum
• Treated with penicillin (growing resistance)
• Pneumococal vaccine available
o Atypical Pneumonia—mycoplasma pneumonia, walking pneumonia
• Flu-like symptoms; persistant cough (lasting weeks)
• Treatment: erythromycin; no vaccine
o Other causes:
• Klebsiella pnuemoniae (often nosocomial infection)
• Many members of normal flora
• Haemophilus influenzae and Staphylococcus aureus
• Yersinia pestis: pneumonic plague
110
Legionaires’ Disease
—legionella pneumophila
o Becomes intracellular parasite of macrophages
o Named after outbreak in 1976 at American Legion convention in which 29 people died
• Survives in domestic water sources
o Such as air conditioner units, showers, whirlpools, etc.
o The elderly, smokers, and immunocompromised individuals are at increased risk for infection
• Signs and symptoms
o Typical pneumonia symptoms
o In untreated: inflammation of lungs can cause pulmonary function to rapidly decrease
111
Pertussis
—whooping cough
• Causative agent: bordetella pertussis
o Gram-negative coccobacillus; forms capsules
• Produces several toxins, including
o tracheal cytotoxin
• Destroys ciliated cells in trachea
o Pertussis toxin
• Excess mucous production
• Signs/symptoms
o Hacking cough following by “whooping” breath intakes
o Can be so severe that it causes vomiting, diarrhea, ruptured blood vessels in eyes, suffocation, and even death
• Highly contagious (Spread through airborne droplets)
• DPT (DPaT) vaccine
o Although research indicates waning effectiveness after 10-12 years; Tdap booster
112
Tuberculosis
—mycaobacterium tuberculosis
o Rod-like (bacillus); Cell wall rich in lipids (mycolic acid)
o resistant to dessication and antimicrobials
• Inhalation of just a single bacterium can cause a new infection
o Grows very slowly
• Primary and secondary Tuberculosis
o If bacteria reach lungs, they are ingested by macrophages and should be destroyed
• However…some survive and start multiplying within macrophages
• Releases cytokines that attract new macrophages to area
o Primary TB: Formation of tubercle
• Walled off lesion that surrounds and isolates tuberculosis pathogens; multiplication of bacteria continues (slowly)
• In a healthy response, should become dormant (Can remain dormant for decades
o Secondary TB
• If Tubercle ruptures and infection re-established
• Releasing bacteria throughout the lungs,
• Can enter circulatory system, spread to bone marrow, spleen, kidneys, spintal cord, brain
• Epidemiology
o Leading disease killer in the world
o One-third of the world’s population is infected
• Most deaths occur in Asia and Africa
• Not everyone infected develops secondary TB
• Host resistance varies greatly
• Weakened immune system (co-infection with HIV), malnutrition, etc.
• Diagnosis, treatment, and prevention
o Tuberculin skin test identifies exposure to tuberculosis
• Does not identify clinical disease
o Chest X-ray images can identify tubercles in the lungs
o Treatment requires combination of drugs for a minimum of 6 months
• Typically rifampin and isoniazid
113
Inhalation Anthrax
—Bacillus anthracis
• Gram-positive rods; forms endospores; long lived
• Found in specific soil types
• Often ingested by grazing animals (e.g., cows and sheep)
• Thus, cattle are routinely vaccinated.
• Transmitted by inhalation of endospores in dust, animal hides, etc.
• 3 forms:
• Cutaneous (already discussed; skin chapter)
• Gastrointestinal (rare)
• Inhalation (most dangerous; 100% mortality)
114
RSV—Respiratory Syncytial Virus
o Enveloped ss RNA virus
• Most common childhood respiratory disease
• Fever, runny nose, coughing
• Common cause of bronchiolitis (croup) and pneumonia in infants
• Causes synctyia—Giant, multinucleated cell formed from the fusion of virally infected cells to neighboring cells
o Cell-mediated response (Tc Cells) can cause further damage to lungs
• The flu (influenza)—influenzavirus is an enveloped RNA virus, found in birds
o 2 species of virus: types A and B
o RNA is in 8 segments
o Envelope contains hemagglutinin (H) spikes and neuraminidase (N) spikes
Signs/Symptoms
o Chills, fever, headache, pharyngitis, cough, muscle aches
o Most people recover in 1-2 weeks
• HPS (Hantavirus Pulmonary Syndrome)—Hantavirus Pulmonary Syndrome (HPS)
o Enveloped, ssRNA virus
o Infects mice (esp deer mice)
• Transmitted by inhalation of virus in dried mouse urine or feces
o Person-to-person contact does not occur
• Signs and symptoms
o Fever, fatigue, muscle aches in trunk/legs
o Symptoms progress to cough and labored breathing as lung fill with fluid;
o Travels in blood, becoming systemic
• blood pressure drops resulting in shock
o 50% mortality rate
• Drowning in own fluids
115
Fungal diseases (just list 4 types found in North America)
—Increased globally over the last few decades
o Opportunistic pathogens to immunocompromised
o Largely due to AIDS patients being susceptible to fungal infections
• Fungi produce spores small enough to invade the lower respiratory system
o Most found in soils
o Become yeast-form in longs (vegetative/reproductive)
• Fungal infections seen in North America include
o coccidioidomycosis
• Caused by Coccidioides immitis
• Southweast U.S.
o Blastomycosis
• Caused by Blastomyces dermatitidis
• often seen in AIDS patients
116
What does the DPT vaccine target?
DPT (DpaT) vaccination targets (diphtheria, pertussis, and tetanus) viruses
117
Why do we get fewer colds as we age? Why are colds more common in Fall/Winter?
—we accumulate immunities against cold viruses throughout our lives, so we get less colds when we are older
—The most common cold-causing viruses survive better when humidity is low-the colder months of the year. Cold weather also may make the inside lining of your nose drier and more vulnerable to viral infection
118
Describe how tuberculosis infection progress (make sure to describe the immune system cell that harbors the bacteria)?
Primary and secondary Tuberculosis
o If bacteria reach lungs, they are ingested by macrophages and should be destroyed
• However…some survive and start multiplying within macrophages
• Releases cytokines that attract new macrophages to area
o Primary TB: Formation of tubercle
• Walled off lesion that surrounds and isolates tuberculosis pathogens; multiplication of bacteria continues (slowly)
• In a healthy response, should become dormant (Can remain dormant for decades
o Secondary TB
• If Tubercle ruptures and infection re-established
• Releasing bacteria throughout the lungs,
• Can enter circulatory system, spread to bone marrow, spleen, kidneys, spintal cord, brain
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Does does MDR and XDR stand for regarding tuberculosis infections?
—Drug-resistant strains of M. tuberculosis:
• MDR: multiple drug resistant TB
• XDR: extensively drug resistant TB
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How are the different strains of influenza identified? What type(s) appears to be the most virulent?
—2 species of virus: types A and B, identified by varying in their H and N antigens
— type A strain, H5N1 (swine flu) is most virulent
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Describe why the flu immunization must be altered annually. What is “in” a flu shot?
—Tamiflu: oseltamivir; prevents virus from spreading to new cells
—Flu shot changes each year due to high mutation rate of virus
122
Briefly describe the structure and function of the urinary system. Describe some differences between males and females in regards to the urinary system.
—2 kidneys, 2 ureters connected to bladder
—prone to infections
—females: 2 ovaries, 2 uterine tubes, uterus, cervix, vagina, external genitalia
—males: 2 testes, system of ducts, penis, accessory glands
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Briefly describe the structure and function of the urinary-reproductive system.
function: filter blood, remove wastes, excrete urine
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Describe the normal flora of the urinary tract and reproductive system.
—urethra: avirulent lactobacillus and staph
—vagina: lactobacilli inhabit a few weeks after birth, also corynebacterium, candida
—male system: many bacteria in foreskin
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What organism is most often associated with UTIs? Why?
—e coli from enteric/intestinal bacteria due to catheterization
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Why are UTI’s more common is females?
—urethritis: infection in urethra occurs, then bladder infection and kidney infection in women
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What are the following (also what are their causes, signs/symptoms, etc.)
o Urethritis—infection of urethra
o Cystitis—bladder infection
o Pyeloneophritis—kidney infection, results from cystitis
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• Toxic Shock Syndrome (and TSLS)
• Toxic Shock Syndrome (and TSLS)
—caused by staph aureus, produces toxin and causes excessive cytokine production by T cells
—signs/symptoms: sudden-onset fever, chills, vomiting, diarrhea, low BP, confusion, severe rash
—treatment: antibiotics
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Vaginosis
—caused by bacteria, fungi, protozoan—opportunistic pathogen
—bacterial vaginosis infection, but no inflammation, which discharge, fishy odor, itching, clue cells
—yeast infection: caused by candida albicans, opportunistic; thick white discharge, yeast odor, itching
—trichomoniasis: sexually transmitted, green discharge in women, opportunistic
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Gonorrhea
—caused by neisseria gonorrhoeae, considered notifiable disease, attaches to mucous-secreting columnar epithelial via fimbriae, inflammation and pus formation from leukocytes
—symptoms: include painful urinating, pus discharge from urethra
—diagnosed from gram stain
—treated by antibiotics, although there are many resistant strains
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Chlamydia
—caused by chlamydia trachomatis
—most common STD
—asymptomatic in women, but painful and watery discharge in men
—treated with erythromycin or doxycycline
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Pelvic Inflammatory Disease (PID)
—bacterial infection of female pelvic organs
| —salpingitis: infection of uterine tubes, scarring can occur and lead to sterility and ectopic pregnancy
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Syphilis
—caused by treponema pallidum, produces glycocalyx, hyalyronidase
—sexually transmitted or woman to fetus
—can result in mental retardation and malformed organs, abortion
—treatment: penicillin G
—primary (hard sore forms), secondary (rash), tertiary stages (gummas/lesions on skin, weakens aorta, loss of motor control, dementia, blindness
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Genital Herpes
—herpes simplex virus, HSV-1 most common
—blisters on genitals, rectum, groin
—transmitted via fluid filled vesicles
—treatment is drugs that keep it in a latent stage, no cure
135
Genital Warts
—most common STD in US
—papillomavirus
—warts in genital area
—can lead to cervical cancer
136
What is ophthalmia neonatorum? What causes it? How is it prevented?
—form of conjunctivitis and a type of neonatal infection contracted by newborns during delivery. The baby's eyes are contaminated during passage through the birth canal from a mother infected with either Neisseria gonorrhoeae or Chlamydia trachomatis.
—prevention: silver nitrate was used, but drops of medication are placed in the newborn’s eyes
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What are the stages of syphilis? Briefly describe what happens during each stage.
—primary (hard sore forms),
—secondary (rash),
—tertiary stages (gummas/lesions on skin, weakens aorta, loss of motor control, dementia, blindness
138
What causes neonatal herpes? What are some of the effects?
—herpes crosses placenta and affects fetus during delivery, can create spontaneous abortion or fetal damage
—C-section required
139
Describe the components of the digestive system (including accessory structures).
—mouth, pharynx, esophagus, stomach, small/large intestine, also accessory structures (teeth, tongue, liver, gallbladder etc.)
140
What route are most digestive diseases transmitted?
—fecal-oral route
141
Describe some of the normal flora of the digestive system
—oral: viridans streptococcus, found in mouth, millions in every mL of saliva
142
What is dental plaque?
—biofilms created by bacteria living in the mouth, can lead to dental caries/cavities (infections)
143
What is gingivitis? What is its primary cause?
—inflammation of the gums, caused when bacteria are allowed to infect the areas between teeth or between teeth and gums
144
Describe how dental caries form.
—Appear as holes or pits in the teeth, then tooth enamel and dentin are eroded and the pulp is exposed to bacterial infection
145
What is gastroenteritis? In general, what are signs/symptoms? How is it diagnosed? How is it treated?
—Inflammation of the stomach or intestines caused by bacteria
—Usually caused by consumption of contaminated food or water, Manifestations typically include nausea, vomiting, diarrhea, loss of appetite, abdominal pain, and cramps, rarely kidney failure or anemia can occur
146
What is dysentery?
—caused by bacteria: severe and painful type of gastroenteritis is dysentery, stools are loose, frequent, and contain mucus and blood
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Peptic Ulcers
—erosions of the linings of the stomach or duodenum of small intestine, caused by the bacteria Helicobacter pylori, produces enzymes that prevents mucus production,
—signs and symptoms: abdominal pain, nausea, vomiting
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Shigellosis
—caused by Shingella bacteria
—fever, abdominal cramps, diarrhea, and bloody stool
—intracellular pathogens…inserting themselves into host cells of the large intestine, Death of host cells results in abcesses in the mucosa of the large intestine
—Antimicrobial drugs are used in treatment of severe cases, and a vaccine is under development
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Traveler’s diarrhea
—Causative agent: Escherichia coli, produce enterotoxins leading to diarrhea
—Antibiotics cause the bacteria to release more toxin, leading to worsening conditions
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Campylobacter diarrhea
—Campylobacter jejuni
| —Chickens are the primary source of human infections
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Antimicrobial-associated diarrhea
—caused by endospore-forming bacillus Clostridium dificil is a member of the intestinal microbiota
—C. difficile overgrows in the colon when antimicrobial treatment reduces the numbers of other bacteria which normally keep it in check
—treatment includes antibiotics, prevention includes avoiding use of antibiotics
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Salmonellosis
Salmonella enterica, Virulent strains can tolerate the acidity of the stomach and pass into the intestine, Acquired thru the consumption of contaminated food or water or undercooked animal products
153
Typhoid fever
—Salmonella enterica (some strains cause typhoid), Virulent strains can tolerate the acidity of the stomach and pass into the intestine, Acquired thru the consumption of contaminated food or water or undercooked animal products
154
Cholera
—caused by the bacteria Vibrio cholerae, produces toxin
| —Treatment includes administration of a tetracycline, which reduces the production of the toxin
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Food poisoning (intoxication)
—consuming pathogens or their toxins, bacteria either not present or not the immediate cause of illness
• Signs and symptoms: nausea, vomiting, diarrhea, abdominal cramping, loss of appetite, fever
• Most cases are self-limiting…gone within 24 hours
• Staphylococcal food poisoning (intoxication)
• Caused by Staphylococcus aureus
• Certain strains contain enterotoxins, which trigger nausea, simulate smooth muscle contractions of the intestines, and cause vomiting
• Outbreaks usually associated with picnics, school cafeterias, or other large social functions where food stand unrefrigerated
• Includes foods such as processed meats, custard pastries, potato salad, ice cream
• Treatment: hydration and replacement of fluids
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Mumps
—Caused by Rubulavirus
• Viral infection of the large salivary glands on each side of the face
• Enters thru the respiratory tracts
• can get into the blood, and enters various organs
• Causes swelling of the large salivary glands on the side of the face, pain, fever, headache, and sore throat
• Today, nearly non-existent in developed nations due to vaccination (MMR)
• Although epidemics still occur in nations with inadequate immunization programs
• There is no treatment, but recovered individuals have lifelong immunity
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Viral Gastroenteritis
—Caused by noroviruses, astroviruses, and rotaviruse
• About 90% caused by noroviruses
• These viruses infect cells lining the intestinal tract
• The viruses enter the digestive tract in contaminated food or water and infect the cells lining the intestinal tract, where they undergo lytic replication
• Signs and symptoms
• Similar to those of bacterial gastroenteritis but usually less severe
• Dehydration is common complication
• Epidemiology
• More cases occur in winter
• Rotaviruses are important cause of childhood deaths in developing countries (vaccine available)
• Prevention involves proper treatment of water and sewage and good hygiene
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Hepatitis
— inflammation of the liver produced by autoimmune disease, alcohol or drug abuse, genetic disorders, or microbial infection
* Hepatitis A (HAV)—Also called infectious hepatitis
* can survive on countertops and cutting boards for days, and resists commonly used disinfectants
* Transmitted fecal oral route
* Considered relatively mild;
* Hepatitis B (HBV)—replicates in liver cells; moves to blood
* Spread by sexual intercourse (esp. anal sex)
* Also contaminated needles
* Babies can infected by mother during childbirth
* Can result in serious liver damage
* HBV carriers 200x more likely to get liver cancer
* Virus integrates into host cell chromosome
* Hepatitis C (HCV)—Spread by sexual intercourse and contaminate needles
* Many cases spread thru blood transfusions; although testing of blood now makes this rare
* Immune system unable to clear virus due to high mutation rate
* Often called chronic hepatitis
* Causes severe liver damage / patients often require liver transplants /Kills 9000 Americans each year
* Hepatitis delta (HDV)— Requires HBV—uses hepatitis B capsomeres to build its own capsid
* coinfection of HBV with HDV results in more severe complications compared to infection with HBV alone
* Hepatatitis E (HEV)—Can also infect monkeys, apes, swine, and rodents
* ecal-oral transmission route
* Typically self-limiting; low mortality rate
* However, in immunocompromised, can become chronic hepatitis leading to liver failure/transplants
* Treatment/Prevention
* There is no cure
* For HAV, wash hands and avoid undercooked foods
* For HBV and HCV
* Avoid sharing contaminated needs (drugs, tattoos, piercings)
* Interferons help decrease the spread
* Use of condoms
* Vaccines:
* HAV: given in 2 doses
* HBV: given over a 6 month period; lasts at least 15 years (probably longer)
* Protects against HDV as well
* No vaccines for HCV, HEV
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Giardiasis
—Caused by protozoa Giardia intestinalis
• Infection usually results from contaminated drinking water
• Also occurs from swimming in water, eating contaminated foods, contaminated toys from daycare
• Causes severe, frothy, foul-smelling diarhhea (rotten eggs), abdominal pain, vomiting, loss of appetite
• Can last 1-4 weeks
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Tapeworm
—caused by helminth Taenia saginata, the beef tapeworm, and Taenia solium, the pork tapeworm
• Obtained by eating meat with tapeworm cysts, that mature into worms in the human body
• Lack their own digestive system (thus they are parasitic)
• Usually asymptomatic
• Cause no visible signs or symptoms
• People don’t know they have it until they pass it thru their feces
• Prevention: thorough cooking of meat, good sewage treatment
• Infections in the U.S. relatively rare
o Pinworm—caused by nematodes Enterobius vermicularis
• Infections commonly occur in children
• Signs and symptoms
• Perianal itching, irritability, and decreased appetite
• One-third of cases are asymptomatic
• Pathogen and infestation
• Male and female worms mate in the intestinal tract, and the female crawls out of the anus to lay eggs
• Eggs can be dislodged and spread the disease
