SAS/Review Flashcards
A patient receives a 10/10 HLA matched kidney from a relative. After 8 months the kidney function starts to decline and biopsy demonstrates chronic inflammation and arteriosclerosis (thickening/hardening of the vessels). Which cells mediate this process?
CD4+ helper T-cells, macrophages
This is chronic rejection; it takes months to years, and is associated wtih hardening and thickening of vessels and arteriosclerosis
Central CD4+ T-cell tolerance occurs in which of the following tissues?
E - the thymus
Central tolerance occurs in thymus through negative selection; T-cells with high affinity for self peptides presented by MHC undergo apoptosis or become TRegs
26-year-old woman returns from a safari vacation in Tanzania with fever and body aches. She received no vaccines prior to her trip and did not take malaria prophylaxis. Her blood smear is shown. What infection does she have?
A. Plasmodium falciparum
B. Plasmodium vivax
C. Trypanosoma cruzi
D. Leishmania donovani
A. Plasmodium falciparum
Infects many RBCs, causes clumping of RBCs
- P. vivax* does not cause clumping, infects <2% of RBCs (reticulocytes only)
- Trypanosoma* would be in its wiggly form (trypomastigote) in the blood
- Leishmania* don’t live in the blood
Which complement protein is good at opsonizing bacteria?
C3b
You are treating a 35 year old patient with shingles.
What illness did this patient likely have as a child?
What is unusual or concerning about this presentation?
The patient likely had chicken pox (Varicella zoster virus) as a child; shingles is a reactivation of VZV
The presentation of shingles in this patient is concerning because they are young; VZV usually re-activates when the patient’s T-cell function is less than optimal, which happens naturally with age.
Because the patient is young, we might suspect a pathology that is suppressing the function of T-cells
What does it mean if an organism is oxidase positive?
Which organisms are oxidase positive?
Oxidase positive = has cytochrome C in cell membrane = all are aerobic (either strict or facultative)
- Pasteurella
- Pseudomonas Aeruginosa
- Campylobacter
- Vibrio
- Helicobacter
- Neisseria
List some of the relevant encapsulated organisms
SCHENK-PB
- Streptococcus pneumoniae
- Cryptococcus neoformans
- Haemophilus influenzae
- E. coli (some)
- Neisseria meningitidis
- Klebsiella pneumoniae
- Pseudomonas aeruginosa
- Bacillus antrhacis
Which cytokines induce Th2 T cells?
What are the major cytokines produced by Th2 T cells?
What does this trigger?
What is the result?
Th2 cells are induced by IL-4
Th2 cells produce IL-4, IL-5, IL-13
This triggers stimulation of IgE, production/activation of mast cells and eosinophils
-> Host defense against helminthic parasites
~but may cause~
-> Allergies; allergic rhinitis, anaphylaxis, asthma (mediates class switching to IgE)
Which immune component mediates chronic organ rejection?
What is the time scale?
Which antigens are causing problems?
CD4+ helper T cells, macrophages
Months/years
MHC minor proteins
(Characterized by hardening/thickening of vessels, arteriosclerosis)
Which cells express CTLA-4?
What does CTLA-4 do in the body?
TRegs express CTLA-4
B7 on APCs binds CTLA-4
- This blocks costimulation by blocking CD-28 on T-cells from binding to B7
- This dampens the Th2 CD4+ T cell response, thus inhibiting IL-2 secretion
Which component of the immune system is particularly important in fighting fungal infections?
- Th17 CD4+ helper T cells
- Secrete IL-17 -> Promote neutrophilic inflammation
- Respond to extracellular pathogens (like fungus)
- IgA
- Can dimerize and cross epithelium of the gut; fight the organism before it even enters the cells of the body
Which fungus is most likely to cause meningitis?
Cryptococcus
A patient has a history of recurrent infections, many of which are pyogenic and/or granulomatous
Notable organisms include serratia marcescens and staph. aureus
Defects in which immune cells are suspected?
Neutrophils;
This pattern is indicative of a failure to kill organisms that have been phagocytosed;
- A defect in NAPDH oxidase would result in persistent, abscess forming infections, especially from catalase (+) organisms
- Catalase breaks down hydrogen peroxide, preventing the formation of hypochlorite ion; an oxidative burst is needed to kill them
Which antibodies, prescribed in cancer treatment, would enhance T-cell activation?
What are the possible consequences?
Anti-PD-1, anti-CTLA-4 antibodies enhance T-cell activation
Potential problem = loss of peripheral tolerance -> autoimmune response
List the relevant obligate intracellular pathogens
- Viruses
Bacteria: Really, Check your Cox My People (it’s an obligation)
- Chlamydia
- Rickettsia
- Coxiella
- Mycobacterium leprae
- Plasmodium
Parasites - Toxic Toilet Paper = LeManiacsCrying
(they can’t stop, they have to cry)
- Toxoplasma
- Trypanosoma
- Pneumocystis
- Cryptosporidium
- Leishmania
What does IFN-gamma do?
Stimulates phagocytosis by macrophages
Increases expression of MHC I and MHC II
Promotes Th1 response
Inhibits Th2 response
What are the symptoms of antibody deficiency?
Infection with pyogenic bacteria (Staphylococcus aureus, streptococcus pneumoniae)
Which fungi are associated with pneumonia?
* = Fungi that can infect healthy people (others typically infect immunocompromised)
- Histoplasma*
- Blastomyces*
- Coccidioides*
- Aspergillus
- Pneumocystis
- agents of mucormycosis
Increased susceptibility to Neisseria is asosciated with deficiencies in which components of the immune system?
Complement proteins from C5-C9; deficiencies of these complement proteins prevent the formation of the membrane-attack complex (MAC) (via the classic pathway) that is required to kill neisseria
Deficiencies in Factor D and properdin, required for the alternate complement pathway, also result in increased risk of Neisserial infections
Infections are likely to be recurrent and invasive
What are the major risk factors for Clostridium botulium infection?
Home-canned foods (everyone; spores germinate in the can)
Honey (babies; the spores can germinate in the baby)
Causes flaccid paralysis
What does TNF-alpha do?
Proinflammatory cytokine
Many effects!
What is the clinical presentation of a neutrophil defect?
Abscesses of skin, soft tissue lymph nodes, bone, and liver
(S. aureus, Klebsiella spp)
Which agent is used to treat pneumocystis?
Trimethoprim-sulfamethoxazole
Although pneumocystis is a fungus, it must be treated wtih trimethoprim-sulfamethoxazole; other anti-fungal agents won’t work
A patient presents with 3 days of painful rash (shown below) that is isolated on his right buttock and thigh
He is not taking any medications and reports no allergies
What is the most likely cause of this rash?
Varicella Zoster Virus
- Isolated; does not cross midline
- Painful
What kind of hemolysis is this?
Which organisms exhibit this pattern?
Beta hemolysis (complete lysis of RBCs)
Group A strep = S. pyogenes
Group B strep = S. agalactiae
List the waterborne parasites
GEN-CS (General Seas… even though some are from freshwater)
- Giardia
- Entamoeba histolytica
- Naegleria fowleri
- Cryptosporidium
- Schistosomiasis
Which cells express CD19?
All B cells
What does TGF-beta do?
Anti-inflammatory cytokine
Turns off imune response
What does IL-1 do?
Pyrogenic
Pro-inflammatory
(Similar to IL-6)
What is the vector of yersinia pestis transmission?
Oriental rat flea
(yersinia pestis causes the plague)
Which T-cell subset is most important in driving the increased production of IgG and IgA antibodies in response to a pertussis infection?
CD4+ Th2 Helper T-cells
A virus is translated immediately upon entry into the host cell.
What can you deduce about its nucleic acid?
It is ss(+) RNA
What does IL-2 do?
Promotes T-cell growth and activation
Can act in an autocrine fashion
What is the clinical presentation of a defect in T cells?
- Persistent thrush
- Sinopulmonary infections
- Skin or soft tissue infections
- Chronic diarrhea
(Candida albicans, S. aureus, Pneumocystis, Herpes simplex viruses)
Which cells express CD40?
B cells, other APCs
(Bind CD40L on CD4+ helper T-cell to induce cytokine production, form germinal center)
How can retroviruses be distinguished from other RNA viruses?
They are transcribed by a RNA-dependent DNA polymerase
The carry their own viral integrase to insert the DNA into the human genome
Which rashe is typically only found in patients with advanced HIV/AIDS?
HHV-8 (Kaposi sarcoma)
52 year old Hatian immigrant presents with fever, profuse sweating, labile hypertension, tachycardia, and facial spasms. Loud noises cause him to contrort his body in muscle spasms.
What is the likely causative agent of his symptoms?
Clostridium tetani
He has tetanus
A new patient in your clinic presents with the following rash. He is a 43 year old male who reports unprotected sexual contact with other men since he became sexually active 20 years ago. He has not seen a doctor in the last 15 years.
What is the most concerning diagnosis for this rash?
How would you confirm your diagnosis?
How would you evaluate progression of the diagnosis?
Kaposi Sarcoma (HHV-8); this is concerning because it typically only appears in patients with advanced HIV/AIDS
Confirm diagnosis with HIV antibody/antigen ELISA
Evaluate progression with T-cell count using flow cytometry
Which complement proteins are involved in the MAC?
C5b - C9
Any deficiencies in the above will result in problems with formation of the MAC -> increased suseptibility to encapsulated bactera (like nesseria meningitidis), and other gram negative bacteria
What is the major risk factor for contracting Vibrio?
Contaminated water, raw shellfish
Vibrio cholerae -> Cholera
(Watery diarrhea, rice-water stools)
Which cytokines induce Th1 T cells?
What are the major cytokines produced by Th1 T cells?
What does this trigger?
What is the result?
Th1 cells are induced by IFN-gamma and IL-12
Th1 cells produce IFN-gamma
This triggers macrophage activation, stimulation of IgG, and antibody production
-> Host defense against intracellular microbes
~but may cause~
-> Autoimmune and other chronic inflammatory diseases (IBD, psoriasis, granulomatous inflammation)
What is the main cell type involved in Type IV hypersensitivity?
What are the major antibodies?
CD4+ Th1 helper T-cells, macrophages
No antibodies!
(Type IV = delayed-type hypersensitivity)
Which disease can be acquired from Triatoma aka Reduviid aka the kissing bug?
American trypanosomiasis (T. cruzi)
Which cells are most critical in controlling the growth of M. tuberculosis?
CD4+ Th1 Helper T-cells
(Combat intracellular pathogens; in the case of MTB, they mediate the granulomatous response)
What tissue is this?
Lymph node
How do capsules contriubute to the virulence of some bacteria?
Block phagocytosis
Prevent against dessication
Which cell subsets are typically inhibited in the treatment of Crohn’s disease?
Why?
Th1 and Th17 CD4+ helper T-cells
- These cells are involved in IBD and psoriasis
- Downregulating these cells helps to control these conditions
What is the major risk factor for contracting a Treponema infection?
Close contact with an infected person
(Syphillis)
Which gram-negative bacilli can tolerate oxygen, but cannot ferment glucose or lactose?
Pseudomonas aeruginosa (Oxidase +)
Acinetobacter (Oxidase -)
Which components of the immune system mediate Type II allergic reactions?
Cells: CD8+ T cells, NK cells, neutrophils
Antibodies: preformed IgG, IgM (attached to cells or ECM)
Which cells express CD56?
NK cells
What is Cell C?
A neutrophil
A patient presents with blurry vision, trouble swallowing and speaking, and labored breathing.
Which of the following toxins might be causing her symptoms?
A. Staphylococcal enterotoxin
B. Botulinum toxin
C. Tetanus toxin
D. Diphtheria toxin
B. Botulinum toxin
Symptoms are associated with flaccid paralysis
(Would be an even stronger connection if people who had eaten the same poorly canned food all presented together)
What is the major risk factor for contracting MRSA?
Close contact with an infected person
For which clinical diseases would you prescribe CTLA-4?
Why?
Rheumatoid arthritis (or other diseases in which you want to suppress the Th2 CD4+ T cell response)
CTLA-4 binds B7 (CD80/CD86); this prevents the T-cell’s CD28 from binding to B7, blocking the costimulatory signal
This decreases the Th2 T-cell response
What tissue is this?
Colon
(The cirles are Peyer’s patches?)
Rheumatoid arthritis may have a hereditary basis due to the inheritance of MHC class II alleles.
The involvement of MHC class II suggests that ___________ cells are involved in the pathogenesis of rheumatoid arthritis
The involvement of MHC class II suggests that CD4+ helper T-cells cells are involved in the pathogenesis of rheumatoid arthritis
CD4+ helper T-cells recognize antigen on MHC II
Describe the structure and action of diphtheria toxin
A/B toxin
Blocks protein synthesis, induces cell lysis
-> Thick pseudomembrane that covers the back of the throat
What type of hypersensitivity reaction involves the fomation of immune complexes?
Type III
What tissue is this?
Spleen
Which antibiotics inhibit protein synthesis?
- Macrolides (50S)
- Lincosamides (50S)
- Oxazolidinones (23S RNA of 50S Ribosome)
- Tetracyclines (30S)
- Aminoglycosides (30S)
Which cells in the body does botulinum toxin bind to?
What is the effect?
Botulinum toxin binds to presynaptic motor end plates, preventing ACh release
The result is flaccid paralysis (Blurry vision, impaired swallowing/speaking, may lead to difficulty breathing)
Your body has lots of IgA floating around in it right now
Compare the affinity of IgA for B. pertussis produced by a plasma cell after infection with the affinity of IgM on a naive B-cell before infection
Explain.
The IgA produced by the plasma cells after a B. pertussis infection is most likely has a higher affinity than the original IgM produced by a naive B cell
The original IgM has some affinity for B. pertussis.
Upon infection, Th2 CD4+ helper T-cells are activated by APCs (Bind antigen on MHC II, CD40:CD40L interaction) to form a germinal center and release cytokines
- This promotes both class switching from IgM -> IgA and somatic hypermutation
- Somatic hypermutation and selection by folicular dendritic cells will select for the IgA antibodies with the highest affinity for B. pertussis antigen
Which enzyme catalyzies the formation of the hypochlorite ion?
Myeloperoxidase
Which test tube represents the growth of Neisseria meningitidis?
Test tube 1
Neisseria meningitidis is an obligate aerobe; will need oxygen, which is located near the surface of the liquid
What kind of animal causes this characteristic bulls-eye?
What disese is it associated with?
Ticks
Lyme disease (specifically Ixodes, the black-legged tick)
Peripheral CD4+ T-cell tolerance occurs in which of the following tissues?
A - Colon
B - Lymph node
C - Tonsil
D - Spleen
Peripheral tolerance occurs in secondary lymphoid tissues; T-cells that react with antigen in the absence of co-stimulation (ex: self antigen) in the peripheral immune tissues become anergic to that specific antigen
What is the major risk factor for contracting Leptospirosis?
Leptosporisis is caused by Leptospira interrogans
Transmitted in urine from infected animals (rats and mice)
Causes fever, jaundice, vomiting, general sickness. May cause meningitis
What is the major risk factor for contracting Borrelia?
Tick bite -> Lyme disease
Louse bite -> Relapsing fever
Intracellular Trypanosoma cruzi parasites in myocardium are called…
Amastigotes
- Trophomastigotes are in human blood
- Epimastigotes and promastigotes are in the reduviid bug (kissing bug)
Ixodes, the black legged tick, is the vector for which diseases?
Lyme disease
Anaplasmosis
What is thWhat is the human intracellular life cycle form of Malaria?
Trophozoite and Schiznot
What is the major risk factor for contracting Clostridium tetani?
Soil-contaminated wound
(Tetanus: stiff/rigid paralysis)
What is the main cell type involved in Type I hypersensitivity?
What are the major antibodies?
Mast cells
IgE
(Type I = immediate/anaphylactic reaction)
What is the intracellular life cycle form of Trypanosoma?
Amastigote
Imbalance in which immune cells leads to allergies and asthma?
Skew towards Th2 CD4+ helper T-cells
(and away from TRegs)
List the waterborne bacterial pathogens
SEALS are Very Cute Mammal Leopards
(Seals live in water and leopard seals are a thing)
- Shigella
- E. coli
- Aeromonas
- Legionella
-
Salmonella
- Vibrio
- Campylobacter
- Mycobacterium marinum
- Leptospirosis
What is the major risk factor for Tularemia?
Rabbit exposure or tick bite -> transmission of Francisella tularensis
Causes skin ulcer (granuloma) at site of bite; swollen lymph nodes, fever, headache, fatigue
Which components of the immune system mediate anaphylaxis?
Mast cells and pre-formed IgE
Which patients should not recieve vaccines for MMR, smallpox, and chickenpox?
Patients who are immunosuppressed;
These vaccines are all live, attenuated virus vaccines; they are likely to cause illness in anyone who is immunosuppressed
Which bacteria causes a painless, blackened eschar surrounded by edema?
Which agent secreted by this bacteria causes eschar formation?
Bacillus anthracis causes anthrax, which presents with a painless blackened eschar surrounded by edema
Toxin: anthrax toxin, a 3-part toxin: Edema factor (EF), Lethal Factor (LF), Protective antigen (PA)
-
EF has adenylate cyclase activity wich increases intracellular cAMP, leading to edema
- Inhibits neutrophil phagocytosis
-
LF is a protease that cleaves host-cell MAP-Kinase
- Causes tissue necrosis and eschar formation
-
PA is the “protective subunit”
- Basically functions as the B subunit of an A-B toxin
- EF and LF function as A subunits
Which test tube represents the growth of E. coli**?
Test tube 3
E. coli is an facultative aerobe; it can grow near the top of the liquid near the oxygen, but it can also survive without it and grow everywhere
What is the major risk factor for contracting Rickettsia?
Tick bite
Rocky Mountain Spotted Fever, African tick bite fever, louse bite (typhus), chigger bite (scrub typhus)
Which antibody is the best opsonizer?
IgG
An otherwise healthy 52-year-old man presents with a RML pneumonia unresponsive to broad-spectrum antibacterial therapy. Lung biopsy is shown. Which fungus is most likely the cause of his pneumonia?
Coccidioides immitis
(Could also be histoplasma casulatum, but more likely coccidioides becasue of size)
Coccidioides immitis, histoplasma casulatum, and blastomyces dermatitidis are the fungi most likey to affect healthy people. Look for broad-based budding yeast in blastomyces.
Describe the immunity that is established by a polysaccharide conjugate vaccine
T-cell and B-cell involvement; congjucation to a peptide allows for activation of a T-cell response
- Good long-term memory
- Isotype switching (T-cell dependent B-cell response)
- IgG, IgE, IgA involved
What does IL-13 do?
Activates eosinophils
What does IL-6 do?
Pyrogenic
Pro-inflammatory
(Similar to IL-1)
Which antibiotic binds to the D-Ala-D-Ala terminal of the peptide chain inhibiting cell wall synthesis?
Vancomycin
Which of the following parasitic infections is transmitted via penetration of intact skin by cercariae?
Shistosoma
(S. mansoni, S. japonicum, S. haematobium)
If an infant has a pertussis infection, what laboratory findings would you expect to find 4 weeks after the start of symptoms
IgM: (positive or negative)
IgG: (positive or negative)
4 weeks after the start of symptoms…
IgM = positive
IgG = positive
IgM is present at the beginning of a new infection. 4 weeks is long enough for class switching to have occured to produce IgG as well
Describe the mechanism of action of diphtheria toxin.
What is the effect on patients?
Diphtheria toxin ADP-ribosylates EF-2, inhibiting protein synthesis
This leads to cell necrosis and pseudomembrane formation in the oropharynx, palate, nasopharynx, nose, and larynx; patients will present with sore throat, fever, difficulty swallowing, hoarseness, and rhinorrhea
Most often seen in children or immigrants who were not vaccinated
Which cells expresss CD28?
T cells
CD28 on T cells binds CD80/86 (B7) on antigen presenting cells = 2nd signal
Bacteria X has a very short incubation period.
Assuming serology and PCR can both detect the presence of Bacteria X, which test will provide results soonest after the onset of symptoms?
PCR (from sputum or pus sample)
Serology studies examine antibody production, so the immune response must be fully functional for results to be accurate
Your 82 year old patient receives a shingles vaccine (live attenuated viral vaccine). Which of the following statements explains how he can generate a memory CD8+ T cell and memory B cell response against the viral antigens?
A. The viral peptides are present in both the ER and endosome/phagosome/lysosome compartments of the cell.
B. The viral peptides are produced only in the cytosol.
C. The viral peptides do not enter the cytosol.
D. The MHC class II proteins can be loaded with viral peptide in both the ER and the endosome/phagosome/lysosome compartment.
E.The MHC class II proteins can be loaded at the cell surface with viral peptides that are deposited there.
A. The viral peptides are present in both the ER and endosome/phagosome/lysosome compartments of the cell.
The vaccine in the bloodstream is uptaken by monocytes and other APCs into an endosome/phagosome/lysosome compartment
- If the peptides escape the compartment -> Cytosol -> end up in the ER -> load onto MHC I
- Activate CD8+ cytotoxic T-cells
- If he peptides to not escape the compartment, they are loaded onto MHC II
- Activate CD4+ helper T-cells
Which assay would be most useful to evaluate for the presence of HIV antigens and antibodies
Combination ELISA (aka immunoassay); can test for both antigens andtibodies at the same time
Nephelometry can do both, but not at the same time
Which test would be most useful to determine a patient’s CD4+ T-cell count?
Flow cytometry
What pathogens are implicated in chronic granulomatous disease?
Which immune cells might be defective?
Bacteria (LESS BurgerKiNg)
- Listeria
- E. coli
- Staphylococcus aureus
- Serratia marcescens
- Burkholderia cepacia
- Klebsiella
- Nocardia
Fungi (AC)
- Aspergillus fumigatus
- Candida
Which life cycle form of Schistosoma is found in the human blood circulation?
Schistosomulae
Which bacteria secrete Shiga-like toxin?
What is the effect of the toxin?
EHEC - Patients present with bloody diarrhea
Shiga-like toxin binds to globotriaosyceramide (BG3) in kidney and CNS
It inhibits the 60S unit of the bacterial ribosome to inhibit protein synthesis and cause cell death
Which components of the immune system mediate immune-complex mediated allergies?
Cells: Neutrophils
Antibodies: IgG (soluble/floating in the plasma)
Which cells in the body does tetanus toxin bind to?
What is the effect?
Tetanus toxin binds to presynaptic inhibitory motor nerve endings (Renshaw cells) to block the release of GABA and glycine (inhibitory neurotransmitters)
The result is constant muscle contraction; lockjaw, muscle spasm
Infection with which of the following is NOT associated with exposure to contaminated water?
A. Schistosoma mansoni
B. Legionella pneumophila
C. Ancylostoma duodenale
D. Vibrio parahemolyticus
E. Hepatitis E virus
C. Ancylostoma duodenale (a hook worm)
Which complement proteins activate mast cells?
C3a, C5a
Which cell is a lymphocyte?
A - could be a B-cell or a T-cell
What are the main differences in presentation of
T cell defects vs. B cell defects?
T cell defects
- Life-threatening
- Infection with intracellular organisms
- Viruses
- Opportunistic parasites (cryptosporidium)
- Mycobacteria
- Fungi (candida, pneumocystis)
- Bactera - gram negative enteric
B cell defects
- Upper and lower respiratory infections
- Diarrhea
- Cellulitis
- Meningitis
- Sepsis
- Low antibodies -> Staph. aureus, Strep. pneumoniae
Which cells express CD40L?
CD4+ T cells after activation
Binds CD40 on B cells and APCs -> Cytokine production, germinal center formation
Which gram-negative bacilli can tolerate oxygen and ferment glucose?
Which can also ferment lactose?
Oxidase positive (OP = AP)
- Aeromonas
- Pasteurella
Oxidase negative
- Can also ferment lactose = SEEK
- Serratia
- E. coli
- Enterobacter
- Klebsiella
- Cannot ferment lactose = PiSSY
- Proteus
- Salmonella
- Shigella
- Yersinia
Describe the respiratory burst.
Which cells are most important?
Oxygen-dependent killing
NADPH oxidays forms the superoxide radical (O2-)
Superoxide dismutase forms hydrogen peroxide (H2O2)
Myeloperoxidase forms the hypchlorite ion (CLO-)
Hypochlorite is the most effective killer of bacteria
List 4 antiparasitic drugs and their uses
- Albendazole
- Cysticercosis, Echinococcosis, Enterobiasis, Ascariasis, Trichuriasis, Hookworm
- Ivermectin
- Strongyloidiasis, Onchocerciasis
- Praziquantel
- Schistosomiasis, Taeniasis, Diphyllobothriasis
- Metronidazole (or Tinidazole)
- Amebiasis, Giardiasis, Trichomoniasis
What is the major function of C9?
Participates in the MAC
Which cells express CD20?
B cells
Target for anti-rheumatoid arthritis drugs
What diseases can be acquired from the Aedes mosquito?
Dengue
Zika
Chikungunya
Yellow fever
Which antibody is most effective at activating complement?
IgM
Which test for tuberculosis will most rapidly confirm a diagnosis of an active TB infection?
a) Tuberculin skin test
b) Interferon-gamma release assay
c) Nucleic acid amplification
d) Solid media
e) Liquid broth
- a) Tuberculin skin test
- 48-72 hours
- Will tell you if exposed not necessarily if infection is active
- b) Interferon-gamma release assay
- 24-48h
- Indicates immune response, but not necessarily active infection
- **c) Nucleic acid amplification
- Results in 1-2 hours**
- d) Solid media
- Weeks
- e) Liquid broth
- Weeks
Which components of the immune system mediate delayed-type hypersensitivity reactions?
Cells: Th1 CD4+ T cells, macrophages
Antibodies: none
Which immune component mediates acute organ rejection?
What is the time scale?
Which antigens are causing problems?
CD8+ Cytotoxic T-cells
Weeks (usually starts after ~7 days)
Problematic antigens = MHC major and minor proteins
What is the human bloodstream life cycle form of Malaria?
Merozoite
Which of the following protozoa is
non-pathogenic in humans?
A. Entamoeba coli
B. Toxoplasma gondii
C. Trypanosoma cruzi
D. Plasmodium knowlesi
E. Giardia lamblia
A. Entamoeba coli
What is the major risk factor for contracting a Neisseria infection?
Close contact with an infected person
(Meningitis or gonorrhea)
Which disease is carried by the tsetse fly (Glossina)?
African sleeping sickness (T. brucei)
What is the major risk factor for Brucella infection?
Unpasteurized dairy products
What does the MAC do?
Kills microbes directly
Especially gram negative bacteria
What kind of hemolysis is this?
Which organisms exhibit this hemolysis pattern?
Alpha-hemolysis (greenish color, partial lysis of RBCs)
Streptococcus pneumoniae
Viridans stretococci (S. mitis, S. mutans)
List the waterborne viruses
- Hepatitis A
- Hepatitis E
- Norovirus
- Adenovirus
A patient taking corticosteroids develops these white patches in her mouth
What organism is causing these patches?
Candida albicans (aka thrush)
Patients with T-cell suppression (due to steriod treatment or HIV) are more susceptible to mucosal candida
Patients with neutrophil defects (chemotherapy, inherited) are more susceptibel to invasive candida
Which pharmacokinetic parameter governs concentration-dependent antibiotics?
Cmax/MIC
Aminoglycosides, Fluoroquinolones
A patient who immigrated from the Democratic Republic of the Congo last year presents with a tetanus infection.
Which treatment should be given immediately?
Injection of tetanus immunoglobulin to confer passive immunity to the patient
- Works rapidly (faster than Tdap vaccine)
(Tdap vaccine should be given to prevent subsequent infection)
Which pharmacokinetic parameter governs time-dependent antibiotics?
Which antibiotics are time-dependent?
T > MIC (AUC/MIC if T > MIC is not a choice)
All beta lactams
Linezolid
What does IL-8 do?
Recruits neutrophils
What is the major risk factor for Coxiella infection?
Exposure to pregnant/birthing sheep
Tick bite
(Causes Q fever: Fever, headache, no rash)
What kind of hemolysis is this?
Which organism exhibits this pattern?
Gamma hemolysis = no hemolysis
Enterococcus faecalis
What is the most important consideratio when interpreting a positive IgM for pertussis?
(Ex: What could cause an inaccurate test result?)
If the patient was recently immunized with acellular pertussis vaccine, they may have a positive IgM test result without actually having the illness
What does IL-17 do?
Promotes neutrophilic inflamation
(Produced by Th17 T cells)
Which cells express CD38/CD138?
Plasma cells
What is the clinical presentation of a defect in humoral immunity?
Recurrent sepsis, sinopulmonary disease
(S. pneumoniae, S. aureus)
Which of the following infections is not transmitted by insect bite?
A. Coxiella burnetii
B. Zika virus
C. Chikungunya virus
D. Ebola virus
E. Wuchereria bancrofti
What is the vector for transmission of Rocky Mountain Spotted Fever?
Dog tick (Dermacentor) carries Rickettsia ricketsii, the causative agent of RMSF
What is Cell B?
A mast cell or a basophil
(Both are granulated; basophils leave the bone marrow already mature, mast cells mature when they reach their tissue home)
How can environmental stimuli drive loss of peripheral T-cell tolereance?
Environmental stimuli may induce co-stimulatory molecules on APCs when the APC is presenting a self-antigen
This will cause the T-cells to become active against a self-antigen, thus compromising peripheral tolerance
A patient with an invasive candida infection likley has defects in which immune cells?
Neutrophils
(Defects in T-cells predispose the patient to mucosal candida)
What is the only fungus that should be treated with trimethoprim-sulfamethoxazole?
Pneumocystis
What does IL-12 do?
T-cell growth factor
Stimulates Th1 subset of CD4+ T cells
What is the major risk factor for contracting a Listeria infection?
Unpasteurized dairy, improperly processed deli meats
(Fever and diarrhea, worst for pregnant women)
Which antibiotics inhibit folate synthesis?
- Sulfonamides (Trimethoprim-sulfamethoxazole)
Which statement is true regarding immune tolerance?
A. T regulatory cells mediate antigen-specific tolerance
B. T cells can become self-reactive during somatic hypermutation in the germinal center
C. T cells undergo receptor editing in the thymus
D. B cells are positively selected in the bone marrow
A. T regulatory cells mediate antigen-specific tolerance
(T cells do not undergo somatic hypermutation or receptor editing; B cells only undergo negative selection)
What does IL-4 do?
Promotes B cell growth and class switching to IgE and IgG
Promotes differentiation of Th2 Cd4+ T cells
Inhibits differentiation of Th1 CD4+ T cells
Patients without a functional spleen are most susceptible to which infections?
Infection by encapuslated bacteria
- Streptococcus pneumoniae
- Haemophilus influenza
- Niesseria meningitidis
What is the main cell type involved in Type III hypersensitivity?
What are the major antibodies?
Neutrophils
IgG (soluble antigen)
(Type III = immune complex-mediated)
Which cytokines induce Th17 T cells?
What are the major cytokines produced by Th17 T cells?
What does this trigger?
What is the result?
Th17 cells are induced by TGF-beta, IL-6, IL-23
Th2 cells produce IL-17, IL-22
This triggers recruitment of neutrophils and monocytes
-> Host defense against extracellular bacteria, fungi
~but may cause~
-> Autoimmune and other chronic inflammaotry diseases (IBD, psloriasis, MS)
Describe the structure and action of pertussis toxin
A/B toxin
Blocks inhibition of adenylate cyclases -> Increase in cAMP -> interferes with intracellular signaling
Pertussis = whooping couch
22 yo presents with sudden onset of bloody diarrhea and abdominal cramps. He treats himself with some ciprofloxacin he has left over from a trip to Mexico. The diarrhea improves but he becomes more ill with cramping in his lower back, bloody urine and severe fatigue. On presentation to the ED, he is found to have anemia, thrombocytopenia and renal failure. What is the cause of his illness?
Shiga-like toxin, produced by enterohemorrhagic E. coli (EHEC)
- Associated with travel to Mexico
What is the vector of disease for malaria infection?
Anopheles (mosquito)
Describe the immunity that is established by a polysaccharide vaccine
T-cell independent B-cell memory
- Limited memory
- Limited isotype switching
- Mostly IgM response (Activates complement)
*
(peptides are required to activate T-cells)
What are the symptoms of C3b deficiency?
Infection with pyogenic bacteria (Staphylococcus aureus, streptococcus pneumoniae)
List the relevant faculative intracellular pathogens
Your Best Best Friend for Life moved to Salt Lake City, Not NewHampshire, to chaseMormonMen
(But they chose to move there and can move back any time, hence facultative)
- Yersinia
- Bartonella
- Brucella
- Francisella
- Listeria
- Salmonella
- Legionella
- Cryptococcus
- Nocardia
- Neisseria
- Histoplasma
- Mycobacterium
- Mycoplasm
What is the rationalle for recommending combination anti-retroviral therapy?
The RNA-directed DNA-polymerase that copies the HIV genome from RNA->DNA is error prone
Mutations arise that demand broader, more comprehensive coverage to kill the different strains of HIV that may arise in a single patient; this prevents resistance to antiretroviral therapy
You treat a patient with cancer with anti-CTLA-4 antibody. You are concerned this could potentially increase autoimmune disease because anti-CTLA-4 antibody could
A. Block normal peripheral tolerance mechanisms
B. Induce production of natural self-reactive antibodies
C. Drive a TH2 T cell response as opposed to a TH1 T cell response
D. Inhibit the second signal of T cell activation through CD28
A. Block normal peripheral tolerance mechanisms
CTLA-4 typically binds to B7 (CD80/CD86) on antigen preventing cells to prevent costimulation and dampen Th2 T-cell response
anti-CTLA-4 prevents this dampening; Th2 T-cells will become more active, and ideally fight the tumor cells; however, this may cause an increase inself-reactivity as well
What life cycle form of the malaria parasite is transmitted to humans?
Sporozoite
What is the mechanism of resistance to semi-synthetic penicillins in MRSA?
MRSA has PBP-2A, an alternative penicillin-binding protein
Penicllins cannot bind to PBP-2A; beta-lactamse inhibitors will not help to overcome this resistance
Which antibiotics inhibit DNA gyrase?
- Fluroquinolones (-floxacin)
Compare the locations of primary and reactivation tuberculosis
Primary typically takes hold in the mid/lower lobe
Reactivation TB typically occurs in the apex of the lung
What is the human bloodstream life cycle form of Leishmania?
Promastigote
What is the difference in the microscopic appearance of c**andida and blastomyces?
- Candida* = narrow budding yeast
- Blastomyces* = broad-based budding yeast
What are the risk factors for toxoplama lymphadenititis?
Eating undercooked meat (especially lamb)
Contact with cat litter
What signal would promote the differntiation of Th2 T cells rather than Th1 T cells?
IL-4
Which complement protein recruits neutrophils?
C5a
A patient who does not have an active infection are concerned about possible exposure to M. tuberculosis.
Which test is recommended? When?
- Interferon gamma release assay two months after last suspected contact
- Testing sooner may give a false negative
- Tuberculin skin test
- False positive is more likely (test has low specificity)
What does IL-10 do?
Anti-inflammatory
(Turns off immune response)
Which organisms form pink colonies on MacConkey agar?
Why?
Escherichia, Klebsiella, Serratia and some Enterobacter
They can ferment lactose
All of the above are also oxidase negative
Which life cycle form of Schistosoma infects snails?
Miracida = newly hatched, penerate snail
Inside of snail, sporocysts replicate
Cercariae are released into fresh water
Which diseases can be acquired from the culex mosquito?
West Nile Virus
Filariasis
What are the 3 major functions of antibodies?
- Neutralize toxins and viruses
- Opsonize bacteria
- Activate complement
What is the major risk factor for Pasteurella infection?
Cat or dog bite
(Skin + soft tissue infection)
What is the main cell type involved in Type II hypersensitivity?
What are the major antibodies?
CD8+ T cells, NK cells, Neutrophils
IgG, IgM (Cellular or matrix antigen; not free-floating)
(Type II = cytotoxic/antibody-mediated)
What tissue is this?
Thymus
27-year-old woman presents with fever and chills 8 weeks after returning from India. Her blood smear is shown. What infection does she have?
A. Plasmodium falciparum
B. Plasmodium vivax
C. Trypanosoma cruzi
D. Leishmania donovani
B. Plasmodium vivax
- P. falciparum* would infect a higher percentate of RBCs
- Trypanosoma* would be in its wiggly form (trypomastigote) in the blood
- Leishmania* don’t live in the blood
What are the symptoms of neutropenia?
Infection with pyogenic bacteria (Staphylococcus aureus, streptococcus pneumoniae)
Fungal infections
Which antibiotics inhibit cell wall formation?
Beta-lactams
- Penicillins
- Cephalosporins
- Carbapenems
- Monobactams (Aztreonam)
Glycopeptides
- Vancomycin
Lipopeptides
- Daptomycin
What tissue is this?
Tonsil
What is the difference in the microscipic appearance of Aspergillus and Mucor?
- Aspergillus* = septate hyphae, acute angle branching
- Mucor* = Broad, non-septate hyphae, right angle branching
What symptoms would you expect in a newborn with AIRE deficiency?
Increased self-reactive T-cells - autoimmune reactions
AIRE is important for expressing self-antigen in the thymus during T-cell maturation to promote central tolerance during negative selection
What is the clinical presentation of a complement defect?
Infections with encapsulated bacteria
(S. penumoniae, H. influenzae, N. meningitidis)
Which test for tuberculosis will tell you if an individual has a latent infection?
a) Tuberculin skin test
b) Interferon-gamma release assay
c) Nucleic acid amplification
d) Solid media
e) Liquid broth
a) Tuberculin skin test - But may cross react if the patient had any mycoplasm infection or the BCG vaccine
b) Interferon-gamma release assay
c) Nucleic acid amplification
d) Solid media
e) Liquid broth
Both answers in bold are correct
Which life cycle form of Schistosoma is transmitted to humans?
Cercariae swimming in water penetrate human skin
Stimulation of adenylate cyclase or guanylate cyclase in the GI tract is likely to cause what symptom?
Which organisms do this?
Diarrhea
ETEC: Enterotoxigenic E. Coli, resulting in traveller’s diarrhea
LT stimulates cAMP
ST stimulates cGMP
What kind pathogen cause colitis with “owl eye inclusions” in patients who are immunosuppressed?
Human cytomegalovirus (HCMV)
This is a double-stranded DNA virus (like all herpesviruses)
What signal would stimulate Th1 CD4+ T cells?
IL-12
IFN-gamma
A 5 year-old boy presents with a fever, knee pain, and this rash
Which encapsulated, gram-negative diplococcus is the likely cause of this infection?
Neisseria meningitidis
Which cells express CD3?
All T-cells
What is the principle reason to treat B. pertussis with antibiotics?
To limit the risk of secondary spread
Antibiotic treatment does not greatly affect the course of the disease for the infected individual
What is the presentation of decreased neutrophil function?
Chronic granulomatous disease (CGD)
Infection with catalase (+) organisms (Staphylococcus aureus, serratia)
Infection with aspergillus fumigatus
A patient cuts his hand washing dishes and then rubs his nose with his hand. Staphylococcus aureus that were residing in his nose enter the wound. If this is the first exposure to Staphylococcus aureus, what is the first thing that will happen after the bacteria enter the wound?
A. B cells bind to the staphylococci via B cell receptors
B. Mast cells and APCs bind to the staphylococci via TLRs and other pattern recognition receptors (PRRs)
C. T cells bind to the staphylococci via TCRs
D. Neutrophils bind to the staphylococci via TLRs and other pattern recognition receptors (PRRs)
B. Mast cells and APCs bind to the staphylococci via TLRs and other pattern recognition receptors (PRRs)
Innate Immune system is fastest; neutrophils are in the tissues, not the bloodstream
Which immune component mediates hyperacute/antibody organ rejection?
What is the time scale?
Which antigens are causing problems?
Pre-formed antibody
Minutes
Problematic antigens = ABO on endothelium, MHC proteins
What does IL-5 do?
Promotes differentation/activation of eosinophils
Promotes class switching to IgA
A 29-year-old intravenous drug user has suffered from recurrent pneumonias, fungal infections in the axillae, and a recent ear infection. He now presents with a cough and painful swallowing. Physical examination reveals a patchy, white oral lesion. Cells with which of the following markers are most likely to be deficient in this patient?
A. CD56
B. CD8
C. CD20
D. CD40
E. CD4
E. CD4
- A 29 year old with recurrent fungal infections likley has HIV
- HIV destroys CD4+ T-cells
Where in the human body do Schistosoma mature?
The liver
