DR SUN Flashcards
1
Q
What is fungal structure like?
A
Similar to Eukaryotes
• Cell membrane with ergosterol
• Rigid cell wall w/mannan, beta-glucans (Endotoxin-like substances that stimulate immune system), chitin
2
Q
How does fungus stimulate our immune system?
A
Fungi bind to TLR2, TLR4, & Lectin-like receptors on phagocytes
3
Q
How are infections with fungus controlled by our immune system?
A
infections with distinct fungal pathogens are controlled by innate and/or adaptive immune mechanisms
4
Q
What are two commensal fungi found on our epithelial surface? Where are they found?
A
1) Candia albicans a common commensal of mucosal surfaces
2) Malassezia furfur a common commensal of the skin
5
Q
What are the three key fungal infections?
A
Mold, Yeast, dimorphic Fungi
6
Q
What is the fungi genus name that causes mold? is it opportunistic or pathogenic?
A
Aspergillus, opportunistic, environmental
7
Q
What does Aspergillus lead to?
A
Allergic aspergillosis and/or severe invasive pulmonary disease in neutropenic (low WBC) patients - hemorrhagic necrosis in the lung
8
Q
What are the two species of fungi which cause yeast infections?
A
Candida and Cryptococcus
9
Q
What are some clinical manifestations of candida?
A
• 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!
10
Q
What are some clinical manifestations of Cryptococcus?
A
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
11
Q
What are the three genus names of dimorphic fungi that cause systemic health issues issues? How does is happen?
A
HBC:
Histoplasma, Blastomyces & Coccidioides
Through inhalation
12
Q
What are the symptoms of Histoplasma? Whats the tx?
A
This is a dimorphic fungi infection
• Fungus Flu (self-resolve)
13
Q
What are the symptoms of Blastomyces?
A
Acute & chronic pulmonary disease
14
Q
What are the symptoms of Coccidioides?
A
- Valley Fever (self-resolve) – SW US
- Desert Bumps
- Systemic infections in AIDS & immunocompromised patients
- Disseminate in 3rd trimester
- Oral lesions
15
Q
What does parasite Entamoeba lead to?
A
Dysentery
16
Q
What does parasite Giardia, Cryptosporidium lead to?
A
Traveler’s diarrhea
17
Q
What does parasite Trichomonas lead to?
A
STD: vaginitis, urethritis
18
Q
What does parasite Plasmodium lead to?
A
Malaria
19
Q
What does parasite Trypanosomes lead to?
A
– Infect blood; Chagas disease, African sleeping sickness
20
Q
What does parasite Leishmania lead to?
A
– Infect bone marrow, liver, spleen
21
Q
What does parasite Toxoplasma lead to?
A
CNS infection, encephalitis
22
Q
What does parasite Pneumocystis lead to?
A
Pneumonia (in AIDS patients)
23
Q
How do B/T cell receptors recognize antibodies?
A
Each antibody is unique bc it has a unique antigen recognition region which is variable, called Fab region.
24
Q
B and T cell receptors are complex molecules and recognize specific antigen differently. How do they recognize them?
A
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
25
How can AB can recognize so many different AGs?
VDJ (somatic) recombination on AB
26
What does FC portion of the class of AB defines?
class of AB
27
What makes the immune responses more specific?
Each epitope (antigenic determinant on Ag) interacts with a different B cell Ag receptor, expanding immune responses
28
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
29
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
30
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
31
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
32
4 Major Functions of Antibodies?
1. Act as central component of B cell receptors (BCR)
2. Neutralization (or blocking) of pathogens and toxins
3. Mediate responses to antigen by Fc Receptor-expressing effector cells
4. Activation of the complement cascade
33
How does Ab acts as a central component of B cell receptors (BCR) ?
see the steps
34
How does AB helps with Neutralization (or blocking) of pathogens and toxins?
see
35
How does AB Mediate responses to antigen by Fc Receptor-expressing effector cells?
Opsonization: Fc-Dependent Phagocytosis (through Fc receptors stimulates phagocytosis)
1. Ab binds to AG and neutralizes virus, etc
2. Antibody then binds to **Fc receptors (handle region) on phagocytes** via its constant Fc region
3. • 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 )
1. Ab vinds AG on surface of target cells
2. NK cell Fc receptors recognize cell bound AB
3. degranulation and apoptosis
36
Hoe does AB Activate the complement cascade?
Classical pathway
37
How does TCR get activated? What is the TCR structure like?
TRC binds to peptides presented on
MHC1→ activates CD8 →perforin, granzyme or Fas/Fasl
MHC2 → CD4 helper
• TCR can only recognize Ags presented on MHCs
TRC structure: Variable and constant domain: TCR chain has 3 CDRs, thus highly diverse, allowing T cells to recognize millions of different peptides
38
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
39
What are the 3 different T cells? What are the functions?
1. CD4 T helper: activate cytotoxic T cells and B cells
2. CD8 cytotoxic kill pathogen and infected cells
3. 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
40
What drives the differentiation of the T cell response into an appropriate effector T cell for that infecting pathogen?
PAMPs ligate PRRs which cause the DC to secrete cytokines
• **These cytokines drive the differentiation of the T cell response into an appropriate effector T cell for that infecting pathogen**
41
Why does graft rejection happen?
BC foreign MHC
Large numbers of recipient T cells react strongly to foreign MHCs on donor tissues (Alloimmune response)
42
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
43
What happens if a bacterial or viral P binds outside of binding region on T cell receptor?
Non-specific T cell activation → cytokine storm:
44
What pathogens (viruses, bacteria, protazoa) cause watery diarrhea?
Viruses: Rotavirus, novovirus, Adenovirus
Bacteria: Vibrio Cholera, Enterotoxigenic E. coli
Protazoa: Giardia, Cryptosporidium
45
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
46
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
47
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
48
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
49
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
50
Oral Manifestations of Thrombocytopenia?
Hemorrhagic lesions
Petechiae
Gingival hemorrhage
51
What pathogens (viruses, bacteria, protazoa) cause ab associated diarrhea?
viruses: none
Bacteria: C. difficile in the context of ab damage to normal microbiota
Protazoa: none
52
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
53
What are the complications from ab associated diarrhea?
C diff- pseudomembranous colitis, toxic megacolon, sepsis
54
What pathogens (viruses, bacteria, protazoa) cause intoxication?
Viruses: none, mimicked by norovirus
bacteria: **S. Aureus** eneterotoxin and **Bacillus cereus** enterotoxin
Protazoa: none
55
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
56
What are the clinical features of intoxication?
Food poisoning - nausea, vomiting, followed by diarrhea, rapid onset in hours after ingestion, not contagious
short duration
57
What pathogens (viruses, bacteria, protazoa) cause Enteric fever?
only bacteria: Salmonella Typhi, para-Typhi, Listeria, Brucella, non-typhi salmonella, Yersinia
58
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!
59
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
60
What is the disease that can be caused by turtles?
Salmonella enterica is a part of normal flora in turtles
61
What is the bacteria causing gastroenteritis?
Salmonella enterica
62
How is Salmonella gastroenteritis divided into for clinical purpose?
Typhoidal (enteric fever) vs non-typhoidal (acute gastroenteritis)
63
Most common cause of salmonella in the US?
Salmonella enterica
64
Possible reactions of immunocompromised host with salmonella enterica?
bacteremia, septic arthritis, meningitis
65
What is Vibrio cholerae reservoir? How infectious is it?
watery diarrhea (enterotoxin)
-aquatic environment reservoir
a large inoculum is needed to cause a disease
66
Which 2 bacteria causes gastroenteritis in humans from shellfish?
Vibrio vulnificus and V. parahaemolyticus
67
Whats the most common cause of bacterial diarrhea in the US?
Campylobacter
68
What are the three post infectious sequelae of Campylobacter?
(inflamm. diarrhea)
1. reactive arthritis
2. irritable bowel syndrome
3. Guillain-Barre syndrome
69
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
70
What is a transmission method of H.pylori?
Transmitted within families: Gastric-oral, oral-oral, oral-fecal
71
Is H. pylori associated with cancer?
yes, definitive carcinogen type 1
70-75% of gastric cancer are associated with H. pylori
gastric adenocarcinoma
72
How does H.pylori survives in the stomach?
enzyme Urease breaks down ammonia which neutralizes gastric acid
73
What are the three diagnostic tools for H.pylori?
1. urea breath test- only for active H.pylori
2. Culturing of gastric biopsy speciment
3. Fecal Ag (need high H. pylori number)
74
Three ways H pylori avoids our immunity?
1. LPS modified to avoid triggering TLR-4
2. Flagella mutated to avoid TLR-5
3. O-antigens coated w/sugar to mimic blood group Ags
75
What are the two virulence factors of H pylori and how do they work?
1. **Cytotoxin-associated gene A** •
1. Protein secreted into the target epithelial cell
2. Triggers reorganization of actin cytoskeleton
3. Disrupts cell signaling
2. **Vacuolating cytotoxin A**
1. Causes apoptosis of gastric epithelial cells
2. Induces inflammatory cytokines
76
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
77
Some key characteristics of Bordetella pertussis?
diseases? virulence?
* whooping cough
* toxin- Pertussis toxin
78
Some key characteristics of Legionella pneumophila?
reservoir? diseases? transmission?
* Reservoir: Rivers/streams/amebae; Air-conditioning water-cooling tanks
* Legionnaires disease (Atypical pneumonia); Pontiac fever
* No human-to-human transmission
79
Some key characteristics of Chlamydia pneumoniae?
diseases? age group?
* Atypical pneumonia
* Most common in school-aged children (mild pneumonia or bronchitis)
80
Some key characteristics of Mycoplasma pneumoniae?
diseases? symptoms?
Atypical pneumonia
Mild illness - “Walking pneumonia”
81
How does typical CAP presents?
* Presents with “typical” severe, acute infection
* Infectious agent is culturable/identifiable
82
What is the causative agent for typical CAP? what kind of antibiotics?
Streptococcus pneumoniae; Haemophilus influenzae
Responsive to cell-wall active antibiotics
83
What is the causative agent for atypical CAP?
Mycoplasma pneumoniae (Lacks CW, so not responsive to penicillin); Legionella pneumophila; Chlamydia pneuminiae
84
can you culture causative agent for Atypical CAP?
Causative pathogens are difficult to culture/identify by standard methods, in contrast to typical CAP
85
What are the two vaccines against pneumoniae?
• Vaccine directed against polysaccharide antigens of Streptococcus pneumoniae capsule
1. Pneumococcal polysaccharide vaccine (23-valent) • Adults \> 65 • Patients with chronic medical conditions and increased risk of pneumococcal disease
2. Pneumococcal conjugate vaccine (13-valent) • Children \< 2 YO • Adults \> 65 • Patients unresponsive to polysaccharide antigens
