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94. Microbiology p206-217

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Sexually transmitted diseases
What are the three clinical stages of syphilis
1st degree, 2nd degree, and thrid degree
Lymphogranuloma venereum is caused by what organism?
Chlamydia trachomatis
A painless chancre is a sign of what disease?
1st degree syphilis
What organism causes chlamydia?
Chlamydia trachomatis
What are the clinical features of Gonorrhea?
Urethritis, cervicitis, PID, prostatitis, epididymitis, arthritis
What serotypes of Chlamydia trachomatis cause chlamydia?
D-K
What are the features of AIDS?
Opportunistic infections, Kaposi's sarcoma, lymphoma
The clinical feature of Trichomoniasis is what?
Vaginitis
Chancroid is caused by what organism?
Haemophilus ducreyi
Gummas, tables dorsalis, general paresis, aortitis, Argyll Robertson pupil are clinical features of what STD?
3rd degree syphilis
HSV-2 causes what disease with what features?
Genital herpes with painful penile,vulvar, or cervical ulcers
Ulcers, lymphadenopathy, and rectal strictures are signs of what disease?
Lymphogranuloma venereum
Which organisms cause Condylomata acuminata?
HPV 6 and 11
Hepatitis B causes what clinical feature?
Jaundice
What are the clinical features of 2nd degree syphilis?
Fever, lymphadenopathy, skin rashes, condylomata lata
Chancroid has what clinical feature?
Painful genital ulcers
What serotypes of Chlamydia trachomatis cause Lymphogranuloma venereum?
L1-L3
Trichomonas vaginalis causes what disease?
Trichomoniasis
Urethritis, cervicitis, conjunctivities, Reiter's syndrome, and PID are features of what diesease?
Chlamydia
Koilocytes are characteristic of what diease?
Condylomata acuminata
What organism causes 1st, 2nd, and 3rd degree syphilis?
Treponema pallidum
Pelvic inflammatory disease
What are the top bugs that cause PID?
Chlamydia trachomatis (subacute, often undiagnosed), Neisseria gonorrheae (acute, high fever)
What is a risk factor for ectopic pregnancy, infertility, chronic pelvic pain, and adhesions?
Salpingitis
What is the most common STD in the US?
Chlamydia trachomatis (3-4 million cases per year)
What type of abscesses can occur in PID?
Tubo-ovarian abscesses
What does the chandelier sign test for?
Cervical motion tenderness
What are some of the manifestations of PID?
Purulent cervical discharge, salpingitis, endometriosis, and hydrosalpinx
What STDs other than C. trachomatis and N, gonorrhea cause PID?
Gardnerella (clue cells) and Trichomonas (motile on wet prep)
Nosocomial infections
p. 207
What are 2 of the most common causes of nosocomial infections?
E. Coli (UTI) and S. aureus (wound infection)
When in a renal dialysis unit which pathogen should you be concerned about?
HBV (blood products)
What is the most likely pathogen when a water source (water aerosols) is involved?
Legionella
What pathogen is often found on respiratory therapy equiptment?
Pseudomonas aeruginosa (AIRuginosa when AIR or burns are involved?
What are the two pathogens most commonly associated with urinary catheterization?
E. coli and Proteus mirabilis
Being in a newborn nursery is a risk factor for what pathogens?
CMV and RSV
Which pathogen would most associated with hyperalimentation (total parenteral nutrition)
Candida albicans
Infections dangerous in pregnancy
What are the organisms that can cross the blood-placenta barrier and be dangerous in pregnancy?
ToRCHcS=Toxoplasma, Rubella, CMV, HSV/HIV, Syphilis
Bug hints (if all else fails)
Name the associated bug
Branching rods in oral infection
Actinomyces israelii
Surgical wound
S. aureus
Pus, empyema, abscess
S. aureus
Pediatric Infection
Haemophilus influenzae (including epiglottis)
Sepsis/meningitis in newborn
Group B strep
Dog or cat bite
Pasteurella multocida
Pneumonia in cystic fibrosis, burn infection
Pseudomonas aeruginosa
Currant jelly sputum
Klebsiella
Traumatic open wound
Clostridium perfringens
Antibody structure and function
p. 208
Which part of the light and heavy chain recognizes the antigen?
Variable part
The interchain and intrachain bonds in the antibody are of what type?
Disulfide bonds
What is the term called when the antibody prevents bacterial adherence?
Neutralization
The amino terminal is part of which fragment of the antibody?
Fab fragment
The fab fragment of the antibody is composed of which chain(s)?
Light and heavy chains
Describe the Fc fraction of the B cell receptor.
Constant, Carboxy terminal, Complement-binding (IgG + IgM only), Carbohydrate side chains
What is the purpose of opsonization?
The antibody promotes phagocytosis
The hypervarible region is a compontent of which fragment of the antibody?
Fab fragment
Only the heavy chain contributes to which fraction of the antibody?
Fc
Why does an antibody activate complement?
To enhance opsonization and lysis
The constant part of the heavy chain of IgM and IgG does what?
Fixes complement
Immunogloblulin isotypes
p. 209
Which isotype has an unclear function?
IgD
What is the main anitbody in a second response to an antigen?
IgG
When is IgM produced?
Primary response to an antigen
Which isotype induces the release of mediators from mast cells and basophils when exposed to an antigen?
IgE
Where is IgD found?
On the surface of many B cells and in serum
Which isotype fixes complement, crosses the placenta, opsonizes bacteria, and neutralizes bacterial toxins and viruses ?
IgG
Which isotype that guards the mucous membranes from attachement of bacteria and viruses?
IgA
IgE stimulates which type of hypersensitivity reaction?
Type I
IgE mediates immunity to what?
Worms
Which isotype fixes complement but does not cross the placenta?
IgM
Which isotype has the lowest concentration in the serum?
IgE
Which isotype found in secretions?
IgA
Which isotype crosses the placenta?
IgG
Ig epitopes
Which Ig epitope is common to a single class of Ig (5 classes, determined by the heavy chain)?
Isotype (IgG, IgA, IgM, IgE, IgD) Isotype=iso (same). Common to same class.
Which Ig epitope is determined by antigen-binding site?
Idiotype (specific for a given antigen) Idiotype=idio (unique). Hypervariable region is unique.
Which Ig epitope differs among members of the same species and can be on the light or heavy chain?
Allotype (polymorphism)
MHC I and II
Antigen presenting cells have which type(s) of MHC protein?
MHC I and MHC II
Which class MHC proteins is the main determinants of organ rejection?
MHC II
How many class I genes does the MHC consist of?
3 (A, B, C)
What class of MHC antigen loading occurs in acidified endosomes?
MHC II
All nucleated cells have which type of MHC protein(s)?
MHC I
Which class MHC protein has 1 polypeptide with beta 2 microglobin?
MHC I
Where does MHC I antigen loading occur in the cell?
RER (viral antigens)
What are the 3 MHC II genes?
DP, DQ, DR
Which class MHC protein has 2 polypeptides and and alpha and beta chain?
MHC II
Differentiation of B and T cells
p. 210
Which helper T cell is involved in antibody-mediated immunity?
Th2 cell
In an environment with a lot of IL-12, naïve helper T cells will mature to which helper T cell?
Th1 cell
Why do Th2 cells produce IL-4 and IL-5?
To help B cells make antibody (B=2nd letter of alphabet)
Gamma interferon is secreted by what cell to activate macrophages?
Th1 cell
Which growth factor induces the maturation from naïve helper T cell to Th2 cell?
IL-4
Th1 secretes what growth factor to activate CD8 cells?
IL-2
IL-4 and IL-5 are released from Th2 to activate what type of cell?
B cell
Why do Th1 cells produce IL-2 and gamma-interferon?
To activate macrophages (increase killing efficiency of intracellular bacteria) and CD8 cells
Which helper T cell is involved in cell-mediated immunity?Th1 cell
Major function of B cells and T cells
Choose either B (antibody-mediated immunity) or T cell (cell-mediated immunity)
Allergy (hay fever)
B cell
Regulation of antibody response (help and suppression)
T cell
Autoimmunity
B cell
Allergy (poison oak)
T cell
Host defense against infection (opsonize bacteria, neutralize toxins and viruses)
B cell
Host defense against infection (especially Mycobacterium uberculosis, viruses, and fungi)
T cell
Graft and tumor rejection
T cell
Adjuvant definition
What is the short definition of an adjuvant?
That which aids another
Human vaccines contain aluminum hydroxide or what?
Lipid adjuvants
Adjuvants are ________ stimulators of the immune response but are not immunogenic by themselves.
Nonspecific
What are adjuvants given with to enhance response?
Weak immunogen
T-cell glycoproteins
p. 211
Cytotoxic T cells have which type of co-receptor?
CD8
CD4 cell secretes which 3 cytokines to activate B cells?
IL-2, IL-4, IL-5
What is the CD3 complex?
A cluster of polypeptides associated with a T-cell receptor. It is important in signal transduction
When a cell first gets infected with a virus which three cells respond?
APC, B cell (through IgM BCR), and CD8 (through TCR and MHC I on infected cell)
Name three antigen-presenting cells.
Macrophage, dendritic cell, and B cell
CD4 are on which type of T cells?
Helper T cells
CD4 cell secretes which growth factor to activate the CD8 cells?
IL-2
CD4 on helper T cells bind to what?
MHC II on antigen-presenting cells. Product of CD and MHC=8
CD8 on cytotoxic T cells bind to what?
MHC I on virus-infected cells. Product of CD and MHC=8
T cell activation
What recognizes the foreign antigen that is presented by MHC II?
TCR on the Th cell
IL-2 from the helper T cell activates which cell to kill virus-infected cells?
Cytotoxic T cell
A foreign body is phagocytosed by what type of cell?
APC
The helper T cell is activated to produce which two cytokines in cell-mediated immunity?
IL-2 and gamma-interferon
What recognizes endogenously synthesized (viral or self) proteins that are presented by MHC I?
TCR on cytotoxic T cell
What is the costimulatory signal needed for a helper T cell to be activated by MHC II on an APC?
B7 (protein on APC) and CD28 (receptor on helper T cell)
Anergy
p. 212
The state when an immune cell matures but does not respond to antigens, this process is calledÂ…..
Anergy
Anergy in both T and B cells is caused byÂ…
Their response to a self-antigen
Where are B cells exposed to self-antigen
bone marrow
Which type of cell is more sensitive to anergic stimulus?
T cells
Important Cytokines
P. 212
What cytokine is an endogenous pyrogen?
IL-1
Which major cytokines are produced by Macrophages?
IL-1, IL-6, and TNF-alpha
What are the effects of the cytokines produced by macrophages?
(1) causes the liver to make more complement, (2) fever, (3) mobilizes neutrophils from bone marrow, (4)helpts T-cells migrate to lymph nodes and mature, therefore, helps acute phase reaction
IL-1 by itself causes what effects?
Fever, stimulates the growth and differentiation of T and B cells, neutrophils, fibroblasts and epithelial cells
What cytokine stimulates the growth of helper T and NK cells
IL-2
What cells secrete IL-2
Helper T cells
What cytokine has the same effect as GM-CSF
IL-3
What cytokines promote the growth and differentiation of B cells
IL-4, IL-5, TNF-alpha
What cytokine stimulates the synthesis of IgE and IgG?
IL-4
What cytokine stimulates eosinophil production?
IL-5
T-helper cells secrete which cytokines?
IL-2, IL-4, IL-5, gamma interferon
What cytokine stimulates the synthesis of IgA?
IL-5
What cytokine acts to attract neutrophils?
IL-8 (major) and TNF-alpha (minor)
What cytokine stimulates macrophages?
gamma-interferon
What is the difference between TNF-alpha and TNF-beta?
TNF-alpha is secreted by macrophages, and TNF-beta is secreted by T lymphocytes. Their functions are similar.
What do TNF-alpha and TNF-beta do?
increase IL-2 output and B-cell proliferation, attracts neutrophils
Cell Surface Proteins
p. 212
What markers identify T cells
TCR and CD3
what cells have receptors for MHC I
NK cells
What does MHC I do?
presents self-antigens, in viral infections the molecules presented by MHC I will change, which is why NK cells respond to viral infections best.
What cells have MHC I on their surface?
all cells except RBCs
what does MHC II do?
Presents non-self antigens
What cells have MHC II?
macrophages, monocytes, dendritic cells (called professional antigen presenting cells)
What markers are specific for B cells?
CD20, CD19, IgM
What marker disappears when B cells become anergic?
IgM is internalized in anergic cells
What is a marker for Macrophages?
CD14
What is a marker for NK cells?
receptors for MHC I, CD 16
Acute Phase Response
p. 213
What cytokines are responsible for the Acute Phase Response?
IL-1, IL-6, TNF-alpha
How does the acute Phase Reaction cause a fever?
IL-1 acts on the hypothalamus to increase body temp, fat is mobilized to increase energy, and muscle mass is used to create heat
The Acute Phase Reaction involves the mobilization of which cells?
B cells, T cells, Neutrophils
Why is fever useful in an infection?
Viruses and bacteria divide less in higher temperatures, it increases antigen production, and increases parts of the immunes response
What does the liver do in the Acute Phase Reaction?
Creates acute phase proteins (ex: C-reactive) which then activate complement and help in opsinization
What does bone marrow do in the Acute Phase Reaction?
Releases CSF which causes leukocytosis
What do Dendritic cells do in the Acute Phase Reaction?
the Professional antibody presenting cells migrate to the lymph nodes to initiate the adaptive response.
Complement
P. 214
What kind of bacteria does complement act against?
Gram negative
Why does complement act preferentially against gram - bacteria?
Complement initiators like to behind to carbohydrates, so gram- bacteria or noticed more than others.
The classic pathway is initiated byÂ….?
IgM or IgG (remember, GM makes Classic cars) antibody-antigen complexes
The alternate pathway is initiated byÂ….?
basically, everything else - endotoxins, microbial surfaces, IgA, etc.
C1, C2, C3, C4 do what?
Viral neutralization
C3b does what?
think B for Binding - anything that ends in b acts to opsinize bacteria
What does C3a do?
Think A for Inflame - anything that ends in a acts to increase the inflammatory response. C3a leads to anaphylaxis, along with C5a
What is MC5b6,7,8,9?
This is the name for the membrane attack complex that punches holes in membranes and actually kills the bacteria.
What does a lack of C1 esterase cause and why?
causes angioedema - which is basically overactive complement. This is because C1 is the initial step in the classic pathway, and if it cannot be limited, you over-react.
What does a lack of C3 cause?
sever and recurrent pyrogenic infections of the sinuses and UR tract, because C3 is the first common step in both pathways, and without it both pathways are crippled.
Lack of C6, C7, and C8 cause what?
Nisseria bacteremia. I have no idea why.
Lack of decay accelerating factor (DAF) leads to what?
Paroxysmal nocturnal hemaoglobinuria because the complement attacks the RBCs. DAF stops C3.
What is the first step in the complement cascade that combines the two pathways?
C3 activation
What is the first step to bind to the cell membrane?
C5a (after C5 is cleaved by C3 products)
Interferon Mechanism
P. 214
What is the purpose of interferons?
Interferons interfere is viral infection of cells and replication. They also activate NK cells to kill infected cells
What do Alpha and beta interferon do?
degrade viral mRNA, thereby inhibiting viral protein synthesis.
what does gamma interferon do?
upregulates MHC I and II in all cells
Hypersensitivity
P. 215
What is another name for Type I hypersensitivity
anaphylactic or atpoic
What do type I, II, and III have in common?
they all use antibodies
What cells are involved in Type I?
Mast cell and Basophils
What Ig triggers Type one reactions?
IgE
What molecule acts as a mediator of this reaction?
IgE causes the release of histamine. This is a very fast reaction. Think First is Fast.
What are some examples of Type I reactions?
Anaphylactic shock, asthma, hives, local wheal and flare reactions.
What is another name for Type II Hypersensitivity?
Cytotoxic (think Cy-2-toxic)
What happens in this reaction?
antibodies bind to a perceived "enemy" cell and use complement and phagocytosis to kill it.
What antibodies are common in this reaction?
IgM and IgG
What are some examples of Type II reactions?
Goodpasture's, autoimmune hemolytic anemia, graves disease, rheumatic fever, etc.
What do Type II and Type III have in common
They both use complement MAC (Membrane attack complexes) to do some of the work.
What is different between Type II and Type III reactions
Type III reactions involve neutrophils and the release of a large number of cytokines and inflammatory mediators. Type II also happens to specific cells or tissues, while type III is soluble.
What is the mechanism of a Type III Hypersensitivity Reaction?
Soluble antibody-antigen complexes activate complement and attract inflammatory cells
What are some examples of this?
SLE, rheumatoid arthritis, etc
What is serum sickness
When you have a type III reaction to a foreign protein, such as an injected drug. It takes about 5-10 days, and you present with fever, utricara, arthralgia, and proteinuria
What is Arthus Reaction?
A local, subacute reaction to injected antibodies. Happens in the skin.
Examples of the Arthus reaction?
hypersensitivity pnemonitis and thermophilic actinomycetes
What is the mechanism of a Type IV reaction?
This is T-cell mediated and therefore delayed. Think that 4 is last.
What are examples of this type of reaction?
TB skin test, poison ivy, transplant rejection
Immune Deficiencies
P. 216
Lack of B cells lead to what kind of disorders?
Lack of Ig
Give two examples of thisÂ…..
Burton's Agammaglobulinemia, Selective Immunoglobin deficiency
Burton's agammaglobulinemia is caused by what?
X-linked defect that cause low levels in all Igs. Causes all kinds of bacterial infects. Think Boys and Bacteria for Burton's
At what age do the infections start in Burton's?
6 months, because that is when the maternal IgG declines.
What is the defect in Selective immunoglobulin deficiency?
A lack of a certain class of Ig, probably caused by a defect in iostype switching.
What Ig is most likely to be lacking?
IgA, which results in sinus and lung bacterial infections
What are three diseases that involve B and T cells?
Wiscott-Aldrich syndrome, and Ataxia-telangiactasia
What is SCID?
Stem cell defect (can be anything, no one gene), leads to total lack of an immune system.
How do the patients present?
patients present early with viral, bacterial, fungal, and protazoal infections
What is Wiskott-Aldritch Syndrome
an X-linked defect that results in depressed cellular immunity and IgM formation
How does it present?
Triad of Eczema, thrombocytopenia, and pyrogenic infections. There is a specific inability to fight off encapsulated bacteria
What are the Ig titers in a patient like this?
IgA is elevated, IgE is normal, and IgM is depressed
What is ataxia-telangiactasia?
Defect in DNA repair that leads to neurologic problems (ataxia) and spider angiomas (telangiectasia) and IgA deficiency
Name six phagocytotic disorders.
Il-12 receptor deficiency, Hyper IgM syndrome, Job's syndrome, Chediak-Higashi disease, Chronic granulomatous disease, Leukocyte adhesion syndrome. (Use: In Heaven Jesus Can Comtemplate Love, use Job to remember the biblical link)
What does Il-12 receptor deficiency cause?
Myobacterial infections
What does Hyper IgM syndrome cause?
Because the cells can't class switch, you have only IgM, and nothing else, resulting is never pyrogenic infections at 6 months
What will the titers look like in this disease?
High IgM, low IgA, IgE, and IgG
What causes Job's disease?
T-cells fail to make interferon gamma and therefore neutrophils are not attracted to sites of infection
What is the clinical picture in Job's disease?
recurrent "cold" staph abscesses, eczema, and high levels of IgE
What is Chronic Granulomatous Disease?
a group of disorders that result in impaired neutrophils function
How does CGD present?
multiple opportunistic infections with bacteria
What is the test for CGD?
negative nitoblue tertraolium dye reduction test
What is Chediak-Higashi disease?
autosomal recessive disease of microtubule dysfunction, leading to impaired phagocytosis
How does Chediak-Higashi disease present?
Multiple pyrogenic Staph and strep infections
What is Leukocyte Adhesions deficiency syndrome?
deficiency of LFA-1 in phagocytotic cells, presents with pyrogenic infections
Of the phagocytotic disorders, which two do not present with pyrogenic bacterial infections?
Job's disease (no neutrophils action leads to "cold" abcesses) and IL-12 (mycobacterial infections)
Passive vs. Active Immunity
P. 217
What is active immunity?
slow onset, leads to long-lasting memory, happens after you are exposed to an antigen, basis for vaccines
What is passive immunity?
When you receive pre-formed antibodies, limited by the lifespan of the antibodies, rapid onset
What diseases are treated by using passive immunity?
Tetanus, Botulism, HBV, Rabies (To Be Healed Rapidly)
What Igs are used for this treatment?
high-affinity IgA and IgG
What is another scenario in which Igs are transferred from host to patient?
Maternal Igs are transferred to the infant.

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