14_Pathology of Infections Flashcards
1
Q
what are the attributes of infectious agents?
A
- can replicate either in the environment or in a host (obligate needs a host)
- usually provoke a host response
- may be ACELLULAR, UNICELLULAR, or MULTICELLULAR
2
Q
vwhat are the 2 acellular infectious agents?
how are they different?
A
Prions and Viruses
- PRIONS
- proteinaceous particles resist inactivation by procedures that modify RNA/DNA
- causes spongiform encephalopathies in humans
- mech: formation of insoluble aggregates of intracellular protein w/ modified tertiary structure
- VIRUSES
- infectious agents that attach to and invade host cells;
- contain RNA or DNA
- contain few or no synthetic enzymes or other biochem agents required for replication
3
Q
prions:
define, and diseases
A
- infectious proteins that do NOT contain RNA or DNA (resilient in environment)
- prion protein is a normal protein in brains; but in JC disease – the protein becomes protease-resistant
- diseases –> resulting in dementia
- kuru
- Jakob-Creutzfeld disease
- bovine spongiform encephalopathy (BSE)
4
Q
prion protein (PrP):
define
A
protein changes from alpha-helical –> BETA-PLEATED SHEET, which is protease resistant
(prion protein is normal UNTIL interacting w/ infectious prion –> induces the ^conformational change)
(helical - happy
beta-pleated sheet - BAD)
5
Q
viruses:
define
A
- contain RNA or DNA; infectious agents that attach to and invade host cells to replicate
- (*NOT considered prokaryotes NOR eukaryotes)
6
Q
prokaryotes (bacteria):
define, structure
A
- def: unicellular organism that lacks a membrane-bound nucleys, mitochondria, or other organelles
- bacteria are PROKARYOTES
7
Q
different categories of bacteria, and examples of each
A
- obligate intracellular bacteria lacking ATP synthesis_:_ CHLAMYDIA, RICKETTSIA
- lack cell call, bind to resp mucosa by P1 adhesion; (smallest free living organisms): MYCOPLASMA
- replicate in cytoplasm of endothelial cells (hemorrhagic vasculitis): RICKETTSIA
- possess lipid coats –> protects against inactivation/clearance by host: mycobacteria
8
Q
layman’s terms for mycoplasma respiratory disease?
A
walking pneumonia;
tends to cluster in families
9
Q
which bacteria cause tuberculosis?
A
mycoBACTERIA
10
Q
eukaryotes:
define, and examples
A
- def: organisms w/ cells containing well-defined membrane-bound nucleus and organelles
-
ex:
- humans
- fungi
- protozoa
- algae
11
Q
best stain to identify fungi?
A
GMS or PAS
- Grocott’s methenamine silver stain (GMS) is also good for picking up bacteria as well;
- Periodic acid–Schiff (PAS)
12
Q
helminths:
define, disease mech, transmission
A
- define: multicellular pathogens; parasitic worms
- mech: disease is often from response to pathogen and proportionate to # of organisms
- tx:
- arthropods: ectoparasites; incl: lice, bedbugs, fleas, stinging insects, mosquitoes, which may be disease vectors
13
Q
best way to prevent transmission of malaria?
A
mosquito nets; to protect when sleeping
14
Q
four diff’t types of host-parasite relationships
A
- parasitism: interactions that exploit the living environment
- colonization: proliferation of parasite in host w/o causing disease
- subclinical infection: host undergoes injury, but remains free of symptoms
- clinical infection: disease; damage to host
15
Q
3 key mechanisms of disease by infectious agents?
A
- directly: contact cell –> causing direct cell death
-
toxic infectious agent component (LPS) - indirectly killing cells at a distance, or releasing enzymes that digest tissue components or damage BVs –> causing ischemic damage
- either toxic or releases exotoxins
- induce host immune reponse –> cuase tissue damage (HBV, HCV, or TB)
16
Q
what are various transmission of infectious agents?
A
- contact
- resp droplets
- fecal-oral (vibrio cholerae)
- sexual transmission
- insect/animal vector
- vertical transmission (from mother to baby)
17
Q
routes by which host defenses are breached?
A
- SKIN: wound or burn; low pH, fatty acids
- RESP TRACT: mucociliary clearance, IgA, alveolar macrophages
- GI TRACT: gastric acidity, bile IgA, gut flora
- GU TRACT: flushing, acid from vaginal flora
18
Q
mechanism of toxin elaboration (by vibrio cholerae)
A
- V. cholerae elaborates a toxin in the intestine –> causes diarrhea (but does not actually invade the tissue)
- toxin consists of subunit A (enzymatic) and subunit B (binding)
- subunit A manipulates the host –> affects adenylate cyclase so NaCl goes into the gut lumen –> clears out the sodium –> causing electrolyte imbalance
19
Q
vibrio cholerae:
sxs, transmission, tx, outbreaks
A
- sxs: often fatal, diarrheal disease –> dehydration and electrolyte imbalace
- transm: fecal-oral
- tx: electrolyte replacement therapy
- outbreaks:
- often erupts following large scale tragedies e.g. earthquake in Haiti 2010
20
Q
prior to discovering the true mechanism of Vibrio cholerae, what was thought to be the cause (historically)?
A
MIASMA THEORY: diseases—such as cholera, chlamydia, or the Black Death—were caused by a miasma, a noxious form of “bad air”, also known as night air. The theory held that the origin of epidemics was due to a miasma, emanating from rotting organic matter
21
Q
how does a nucleid acid w/in a capsid –> enter the cell?
A
- adhere to cell membrane
- engulfed by cell membrane
- w/in the cell in a vesicle
- intracellular release to escape vesicle
22
Q
how does an enveloped helical nucleocapsid enter the cell?
A
- adhere to cell membrane
- fusion of envelope w/ cell membrane
- intracellular release of nucleocapsid into cell
23
Q
diff’t mechanisms of immune evasion by infective agents?
A
- antigenic variation (flu)
- inactivation of host antibodies/complement
- resist phagocytosis –> produces a capsule (tuberculosis)
-
suppress immune response
- e.g. inhibiting MHC expression and Ag presentation (antigen presentation)
24
Q
what are the diff’t ways by which host develops RESISTANCE TO INFECTIONS?
(host-parasite relationships)
A
- neutralize/inactivate toxins by antibodies
- cytotoxic/cytolytic rxns directed against infectious organisms
- delayed hypersensitivity –> results in mobilization of phagocytes to the infection site
- granulomas localize toxic material and organisms
25
which types of organisms are known for causing **granulomas** to localize toxic materal and organisms (in host-parasite resistance to infections)?
MYCOBACTERIA (tuberculosis)
and fungal infections
26
list the factors that affect **resistance?**
* \*\***immune system deficiencies:**
* *immune globulin deficiency, defect in lysosome fxn, thymic aplasia, leukocyte adhesion deficiency, neutrophil oxidative burst deficiency*
* **hormonal factors (steroids)**
* **aging**
* **nutritional status**
27
key immune defense mechanisms for:
## Footnote
**bacterial infections**
* antibody (B-lymphocyte, immune complex)
* lysis by complement
* inflammatory response
28
key immune defense mechanisms for:
## Footnote
**viral infections**
* antibody (immune complex)
* T-lymphocytes
29
key immune defense mechanisms for:
## Footnote
**mycobacterium**
* **T lymphocytes (DTH)**
* **granulomatous**
30
key immune defense mechanisms for:
## Footnote
**protozoa**
**helminths**
**fungi**
* **protozoa:** \*antibody; *T-lymphocytes*
* **helminths: \***antibody; _granulomatous_
* **fungi**: *T-lymphocytes*; _granulomatous_
31
what are the key **hematologic effects of infection?**
* "**shift to the left" --\>** leukocytosis (inc. in neutrophils and bands)
* **anemia;** *assoc. w/ chronic disease*
* **\*\*erythrocyte sedimentation rate**
* spec gravity of RBC: 1.09
* spec grav of plasma: 1.03
* **inc. rouleaux formation**
* **\*\*C reactive protein (CRP)** --\> elevated and indicates infxn
* **coagulation** (fibrinogen can be acute phase protein)
32
**acute phase** response to infxn INCREASES WHICH MARKERS?
* increase in:
* **cytokines**
* **complement (C3)**
* **C-reactive protein; opsonins**
* **Fibrinogen**
* **ceruloplasmin (elaborated by liver)**
33
EFFECTS OF INFECTION
| (symptoms)
* **fever**, caused by pyrogens
* cardiovascular
* inc. in HR
* dec in BP; (hypotension)
* \*\*SHOCK *(if severe)*
* renal
* inc excretion of protein and glucose in urine
* retenion of BUN/creatinine (**azotemia)**
* low urine output(**oligouria)**
* **hepatic**
* inc. protein synthesis (hypergammaglobulinemia)
34
what are the **6 major patterns of host response** to infectious agents?
how is this helpful?
* patterns
1. **suppuration (abscess)**
2. **mononuclear and granulomatous inflammation**
3. **cytopathic effect and proliferative rxn (CPE)**
4. **tissue necrosis**
5. **chronic inflammation and scarring**
6. **neoplasia**
* helpful bc **infectious agent** may be **inferred from the pattern**
35
**suppuration**
*define, sxs, examples*
* response to infxn --\> inc in neutrophils
* inc vascular permeability
* leukocytic (neutrophilic infiltration)
* causes tissue destruction
* forms **abscess**: from accumulation of pus (*from accumulation of neutrophils)* in a confined space; usually occurs w/ deep seating of pyogenic bacteria in tissue
* ex:
* staphylococcus
* streptococcus (*rheumatic fever - image)*
36
**mononuclear inflammation:**
*define, cause*
* def: Mononuclear cell infiltrates are characteristic of inflammatory lesions, where white blood cells, mainly macrophages and lymphocytes, collect at the site of injury to help clear away the debris
* results in mixture of host cells: **lymphocytes, plasma cells, macrophages**
* **but proportion of inflammatory cells may depend on the pathogen**
* causes:
* viruses
* intracellular bacteria
* intracellular parasites
* helminths
37
a lot of **plasma cells in** mononuclear inflammation is indicative of what?
treponemes;
## Footnote
**syphilis infection**
38
**granulomatous inflammation:**
*define, mech, cause*
* def: **small nodules comprised of macrophages** of epithelioid appearance, and **giant cells mixed w/ lymphocytes, plasma cells, and PMNs**
* mech: formed by host cells reacting to poorly-digested foreign antigens --\> to isolate the foreign antigens
* causes
* bacteria: *tuberculosis, leprosy, syphilis*
* dusts and metals: *silicosis, berylliosis*
* fungi and parasites: *histoplasmosis and schistosomiasis*
## Footnote
*sarcoidosis in image*
39
**cytopathic effect (CPE):**
*define, mech, cause*
* def: **formation of blisters by viral infxn and damage to epithelial cells**
* mech: *may result in formation of viral aggregates visible as inclusion bodies by light microscopy*
* cause: **viral-mediated cell injury**
40
**neoplasia:**
*define, causes*
* def: **inducing the growth of warts and/or cancer**
* causes:
* viruses such as HPV
41
which are the key HPV variants that cause cancer?
**16, 18,** and **45**
42
**angioinvasion:**
*def, sxs*
* def: **colonization of blood vessels**
* sxs:
* can cause thrombosis;
* or cause infarction of tissue supplied by infected vessel
43
**necrotizing inflammation:**
*def, mech, sxs, cause*
* def: **severe tissue damage**
* mech: **caused by powerful toxins (**characterized by few inflammatory cells)
* sxs: *resembles infarction or ischemic injury*
* causes:
* **\*clostridium perfringens** - a gram positive rod --\> causes gas gangrene w/ extensive necrosis of skeletal muscle, gas production and sparse inflammation
* (or any clostridium)
44
**which type of inflammation is characterized by sparse/or few inflammatory cells?**
necrotizing inflammation
(characterized by few inflammatory cells)
45
why is Clostridium difficult to contain, esp in hospital setting?
* due to SPORE formation and transport
* (bc spores are not killed by alcohol; very difficult to kill)
need to wash hands to prevent spread
46
**pseudomembranous inflammation:**
*def, mech, cause, risk factor*
* def: **yellow and white exudate** (up to 20 mm thick) **distributed on surface of the colon --\> forming pseudomembrane**
* mech: \*\*NOT ACTUALLY INVADING THE TISSUE; psudomembrane (coating) formed from mucin & neutrophils --\> assoc. w/ damage of **crypt epithelial cells**
* cause: **Clostridium difficile (**gram POSITIVE rod; obligate anaerobe) - produces 2 diff't toxins --\> cuase pseudomembranous colitis
* risk factors:
* antiobiotic use
* advanced patient age
47
which infectious diseases cause the most **worldwide deaths every year?**
1. **Tuberculosis -** ~1.2M deaths/yr
2. **HIV/AIDs -** ~1M deaths/yr
3. **Malaria -** ~400,000 deaths/yr
(could also include influenza)
48
**tuberculosis:**
*sxs, frequency*
* sxs: image
* *productive cough*
* *night sweats*
* *fever*
* *weight loss*
* frequency
* **1/3 of world population is affected (90% latent, 10% active)**
* mostly developing countries
* in 2012 - 8.6 M chronic cases; in 2010 - 1.2-1.4M deaths
49
**HIV/AIDS:**
*sxs, frequency*
* sxs: image
* central, eyes, lungs, skin, GI
* frequency:
* second most WW deaths annually
* **global pandemic** (36.7M people had HIV WW, w/ 1.8M new infections per year)
* sl over 1/2 of infected are women, and ~2M are children
* caused 1M deaths in 2016 *(peak in 2005 - 1.9M deaths)*
50
**malaria:**
*sxs, frequency*
* sxs: image
* \*\***fever** is most known manifestation of malaria
* *spread by mosquitoes*
* frequency:
* 3rd most deadly infectious disease;
* WHO estimated 214 M new cases in 2015 --\> 438,000 deaths
* *other estimates are 350-550 M cases of falciparum malaria*
