DR SUN Flashcards
What is fungal structure like?
Similar to Eukaryotes
• Cell membrane with ergosterol
• Rigid cell wall w/mannan, beta-glucans (Endotoxin-like substances that stimulate immune system), chitin
How does fungus stimulate our immune system?
Fungi bind to TLR2, TLR4, & Lectin-like receptors on phagocytes
How are infections with fungus controlled by our immune system?
infections with distinct fungal pathogens are controlled by innate and/or adaptive immune mechanisms
What are two commensal fungi found on our epithelial surface? Where are they found?
1) Candia albicans a common commensal of mucosal surfaces
2) Malassezia furfur a common commensal of the skin
What are the three key fungal infections?
Mold, Yeast, dimorphic Fungi
What is the fungi genus name that causes mold? is it opportunistic or pathogenic?
Aspergillus, opportunistic, environmental
What does Aspergillus lead to?
Allergic aspergillosis and/or severe invasive pulmonary disease in neutropenic (low WBC) patients - hemorrhagic necrosis in the lung
What are the two species of fungi which cause yeast infections?
Candida and Cryptococcus
What are some clinical manifestations of candida?
• Oral thrush: IC host
• Perleche/Angular cheilitis: Corners of mouth
• Esophagitis: AIDS-defining illness in HIV-infected individuals
• Endocarditis: IV drug abusers
• Yeast vaginitis
Dentures!
What are some clinical manifestations of Cryptococcus?
Brain!
• When inhaled, can cause disseminated disease with predilection to the brain
• Patients with CD4 T cell defects are
at high risk to develop severe
meningo-encephalitis
What are the three genus names of dimorphic fungi that cause systemic health issues issues? How does is happen?
HBC:
Histoplasma, Blastomyces & Coccidioides
Through inhalation
What are the symptoms of Histoplasma? Whats the tx?
This is a dimorphic fungi infection
• Fungus Flu (self-resolve)
What are the symptoms of Blastomyces?
Acute & chronic pulmonary disease
What are the symptoms of Coccidioides?
- Valley Fever (self-resolve) – SW US
- Desert Bumps
- Systemic infections in AIDS & immunocompromised patients
- Disseminate in 3rd trimester
- Oral lesions
What does parasite Entamoeba lead to?
Dysentery
What does parasite Giardia, Cryptosporidium lead to?
Traveler’s diarrhea
What does parasite Trichomonas lead to?
STD: vaginitis, urethritis
What does parasite Plasmodium lead to?
Malaria
What does parasite Trypanosomes lead to?
– Infect blood; Chagas disease, African sleeping sickness
What does parasite Leishmania lead to?
– Infect bone marrow, liver, spleen
What does parasite Toxoplasma lead to?
CNS infection, encephalitis
What does parasite Pneumocystis lead to?
Pneumonia (in AIDS patients)
How do B/T cell receptors recognize antibodies?
Each antibody is unique bc it has a unique antigen recognition region which is variable, called Fab region.
B and T cell receptors are complex molecules and recognize specific antigen differently. How do they recognize them?
B cells recognize various macromolecules: P, polysaccharides. nucleic acids
T cells need molecules MHC1 or MHC2 AG presentation to T cells → T cell receptors only recognize peptide fragments of P AGs
How can AB can recognize so many different AGs?
VDJ (somatic) recombination on AB
What does FC portion of the class of AB defines?
class of AB
What makes the immune responses more specific?
Each epitope (antigenic determinant on Ag) interacts with a different B cell Ag receptor, expanding immune responses
What is the structure of IgM? Function?
Pentameric (soluble) or monomeric (membrane-bound)
First antibody class to be secreted; Peaks in 7-10 d
Activating complement, Agglutinating pathogens
What is the structure of IgG? Function? Peaks?
-monomeric, most common
Highest concentration in blood; Peaks in 2.5 – 3 wks
Complement activation, AB dependent cellular cytotoxicity
What is the structure of IgE? Function? Mechanism?
Monomeric
Response to parasites, Allergic reactions
Binds to receptors on mast cells and activates cells to cause histamine release when antigen binds
1-What is the structure of IgA? 2-Function? 3-Whats special? 4- Where can we see it?
1-Dimeric
2-agglutinating pathogens
3- Can cross epithelium; Passive immunity (to infants)
4-Main antibody secreted onto mucosal surfaces - Tears, saliva, mucus, colostrum
4 Major Functions of Antibodies?
- Act as central component of B cell receptors (BCR)
- Neutralization (or blocking) of pathogens and toxins
- Mediate responses to antigen by Fc Receptor-expressing effector cells
- Activation of the complement cascade
How does Ab acts as a central component of B cell receptors (BCR) ?
see the steps
How does AB helps with Neutralization (or blocking) of pathogens and toxins?
see
How does AB Mediate responses to antigen by Fc Receptor-expressing effector cells?
Opsonization: Fc-Dependent Phagocytosis (through Fc receptors stimulates phagocytosis)
- Ab binds to AG and neutralizes virus, etc
- Antibody then binds to Fc receptors (handle region) on phagocytes via its constant Fc region
- • Binding causes the phagocytes to become activated, make oxidative burst, etc.
Also AB dependent cytotoxicity (Macrophages, neutrophils, & eosinophils can also mediate ADCC, perforin and granzyme mediated )
- Ab vinds AG on surface of target cells
- NK cell Fc receptors recognize cell bound AB
- degranulation and apoptosis
Hoe does AB Activate the complement cascade?
Classical pathway
What lets TRC recognize millions of different peptides?
TCR chain has 3 CDRs, thus highly diverse, allowing T cells to recognize millions of different peptides
What are the 3 different T cells? What are the functions?
- CD4 T helper: activate cytotoxic T cells and B cells
- CD8 cytotoxic kill pathogen and infected cells
- T regulatory: both CD4 and CD8 ca mature into it, but Mostly CD4 t cells. T reg Help distinguish between self & non-self, prevent autoimmune diseases
Why does graft rejection happen?
BC foreign MHC
Large numbers of recipient T cells react strongly to foreign MHCs on donor tissues (Alloimmune response)
Explain Graft vs host disease? How to prevent?
If a transplant contains donor T cells, many of them will react strongly to “foreign” MHCs on recipient tissues
Human leukocyte Antigen matching
What happens if a bacterial or viral P binds outside of binding region on T cell receptor?
Non-specific T cell activation → cytokine storm:
What pathogens (viruses, bacteria, protazoa) cause watery diarrhea?
Viruses: Rotavirus, novovirus, Adenovirus
Bacteria: Vibrio Cholera, Enterotoxigenic E. coli
Protazoa: Giardia, Cryptosporidium
What are the clinical features of watery diarrhea?
large volume of watery stools w/o inflammatory cells or blood,
can lead to dehydration
can be with nausea, vomiting, abdominal pain and bloating
What is pathogenesis of watery diarrhea?
- called travellers diarrhea
- Non-invasive (Fimbriae-mediated colonization of intestine)
- Several toxins are mediated (enterotoxin (LT & ST) w/o tissue damage)
- Toxin-mediated fluid and electrolyte loss
- Low or no fever
- Absence of neutrophils in stool
- secretory vs malabsortive
What pathogens (viruses, bacteria, protazoa) cause inflammatory/bloody diarrhea?
Viruses: none!
Bacteria: Shigella, Shiga-toxigenic E coli (varient of E.coli, very low infectious dose!!), (EHEC, StEC) EIEC, Campylobacter jejuni, non-Typhi-Salmonella, Yersinia
Protazoa: Entamoeba histolytica
What are the clinical features of bloody/ inflammatory diarrhea? How do you get infected?
-small volume stools
streaks from blood, mucosy from pus
pain on defecation (tenesmus)
fever
Ileocolitis, colitis
→ From contaminated food, unpasteurized milk, water that has not been disinfected • C. jejuni also from poultry
What is pathogenesis of bloody/ inflammatory diarrhea?
- Damage to enterocytes with local inflammatory resposes
- direct invasion and cytotoxic damage - locally invasive
HUS (hemolytic uremic syndrome-complication): Kidney failure, blood vessels (low blood platellets), hemolytic anemia, thrombocytopenia. Dont use Antbiotics for HUS
Oral Manifestations of Thrombocytopenia?
Hemorrhagic lesions
Petechiae
Gingival hemorrhage
What is pathogenesis of ab associated diarrhea?
- Ab kill normal flora and may affect gut absorptive functions
- C diff produces toxins that damage colonic mucosa and are pro-inflammatory
- Most commonly associated with Fluoroquinolones, Cephalosporins, Penicillin, Clindamycin
- Mild, generally requires no treatment
What pathogens (viruses, bacteria, protazoa) cause intoxication?
Viruses: none, mimicked by norovirus
bacteria: S. Aureus eneterotoxin and Bacillus cereus enterotoxin
Protazoa: none
What is pathogenesis of intoxication? Whats the treatment?
Preformed toxins made by bacteria (Food contaminated with Staph toxin may not smell or look spoiled)
Abx not effective against these toxins – Oral/IV rehydration
What are the clinical features of intoxication?
Food poisoning - nausea, vomiting, followed by diarrhea, rapid onset in hours after ingestion, not contagious
short duration
What pathogens (viruses, bacteria, protazoa) cause Enteric fever?
only bacteria: Salmonella Typhi, para-Typhi, Listeria, Brucella, non-typhi salmonella, Yersinia
What is the pathogenesis of Enteric fever? Where does it hide?
known as Typhoid fever
Spread systemically, Survives in macrophages, may reseed the bowel and transmit through feces. Survives in lymph nodes, liver, spleen, bone marrow, gall bladder
Humans are the only reservoir!
how one gets infected with Typhoid fever.? How to prevent?
- Most people in the US become infected while traveling abroad
- Vaccines only partially effective – Booster needed in high-risk group
- Chronic carriers – Not common but are capable of infecting others
How is Salmonella gastroenteritis divided into for clinical purpose?
Typhoidal (enteric fever) vs non-typhoidal (acute gastroenteritis)
Most common cause of salmonella in the US?
Salmonella enterica
Possible reactions of immunocompromised host with salmonella enterica?
bacteremia, septic arthritis, meningitis
What is Vibrio cholerae reservoir? How infectious is it?
watery diarrhea (enterotoxin)
-aquatic environment reservoir
a large inoculum is needed to cause a disease
Which 2 bacteria causes gastroenteritis in humans from shellfish?
Vibrio vulnificus and V. parahaemolyticus
Whats the most common cause of bacterial diarrhea in the US?
Campylobacter
What is Guillain-Barre syndrome?
a post-infectious sequelae of Campylobacter
- Body’s immune system attacks own nerves
- Exact cause unknown – Associated with COVID-19 & Zika virus infections
What is a transmission method of H.pylori?
Transmitted within families: Gastric-oral, oral-oral, oral-fecal
How does H.pylori survives in the stomach?
enzyme Urease breaks down ammonia which neutralizes gastric acid
Three ways H pylori avoids our immunity?
- LPS modified to avoid triggering TLR-4
- Flagella mutated to avoid TLR-5
- O-antigens coated w/sugar to mimic blood group Ags
What are the two virulence factors of H pylori and how do they work?
-
Cytotoxin-associated gene A •
- Protein secreted into the target epithelial cell
- Triggers reorganization of actin cytoskeleton
- Disrupts cell signaling
-
Vacuolating cytotoxin A
- Causes apoptosis of gastric epithelial cells
- Induces inflammatory cytokines
Some key characteristics of Haemophilus influenzae?
diseases? age group? virulence?
- Normal flora,
- causes meningitis, pneumonia, bronchitis, otitis media
- 6mo-2yr age group
- virulence: polysaccharide capsule
