Tissue Responses to Infection Flashcards
T/F:The response an individual shows to an organism is soley dependent upon the qualities of that organism.
False; depends on features of the host and the organism
List the 6 WBCs
- neutrophil
- basophil
- eosinophil
- B lymphocyte
- T lymphocyte
- Monocyte/macrophage
White blood cells can be grouped into granulocytes and mononuclear cells. Divide the WBCs into these categories.
- Granulocytes: neutrophil (hypersegmented), eosinophil(bilobed), basophil
- Mononuclear: macrophage/monocyte (kidneyshaped), lymphocytes/plasma cells
-itis means
-inflammation
T/F: If one sees inflammation, there must be an infection.
False; there are MANY causes of inflammation, and infection is just one of them!
5 categories of microbes
- bacteria
- viruses
- fungi
- parasites: protozoa and helminths
- prions
Where do microbes live: intra or extracellular
- bacteria
- viruses
- parasites
- fungi
- prions
- either
- intracellular
- either
- either
- intracellular
Acute vs. chronic infection
Acute: rapid onset, short duration, “days”
Chronic: slower onset, longer duration, weeks, months,years
subacute is in between
What are the 6 categories of tissue response to infection?
- acute inflammation
- chronic inflammation
- Granulomatous inflammation (subtype of chronic)
- Eosinophilia
- Cytopathic/cytoproliferative changes
- Tissue necrosis
What are the characteristics of inflammation
- rubor (red)
- calor (hot)
- Tumor (swelling)
- Dolor (pain)
What organisms cause acute inflammation?
- extracellular/pyogenic bacteria: GPC and GNR
- some extracellular fungi
________________________ are the first line of defense against extracellular pathogens.
-neutrophils and macrophages
What is pus?
- viable and dying WBCs
- primarily neutrophils, liquified tissue and cellular debris
Acute tonsilitis is an example of acute inflammation. What causes it?
-GAS
Edema
-excess, protein-rich fluid in the interstitial spaces
If you were to microscopically examine exudate (pus), what would you see?
- neutrophils
- macrophages
- protein-rich edemic fluid
3 potential outcomes of acute inflammation
- normal healing (usual outcome!)
- tissue destruction
- progression to chronic inflammation
2 examples of tissue destruction due to acute infections
- abscess formation
- scarring and fibrosis
What organisms are associated with rapid, extensive tissue destruction and abscess formation?
- Staphylococcus
- Klebsiella
What is an abscess?
- lesion consisting of a central area of tissue necrosis and neutrophils
- where acute inflammatory response has resulted in local destruction and replacement with a collection of neutrophils (pus)
How can you tell if an acute infection and become chronic? What does this signify?
- inflammatory cell infiltrate will change primarily from neutrophils and macrophages to lympocytes, plasma cells, and macrophages
- signifies a switch from innate immunity to adaptive immunity
- acute inflammatory cells may still persist and one may see a mix of inflammation
Abscesses with pus are usually due to __________.
-Staphylococcus aureus
Bacterial abscesses are most common, but ________ are often seen, especially in immunocompromised hosts with decreased neutrophilic activity.
-fungal abscesses
What eventually happens to an abscess that is not resolved?
- becomes surrounded by a rim of blood vessels and fibrous tissue
- fibrosis serves to “wall off” the area of infection and necrosis
- blood vessels in wall serve as ongoing source of neutrophils for abscess
What is seen within a chronic abscess?
-neutrophils, macrophages, necrotic tissue
If you see an abscess, there are 2 types of organisms that may cause is, what are they?
- bacteria
- fungi
Vascular changes associated with acute inflammation
- increased blood flow
- edema
What will be the pathology of acute infections due to intracellular microbes?
- see lymphocytic infiltrate as NK cells are first line of defense for extracellular organisms
- early response by NK cells, followed by cell-mediated immune reactions
- NO PUS bc no neutrophils
A patient presents with acute infection and microscopy shows a dense lymphocytic infiltrate, what can be ruled out?
- extracellular bacteria/fungi
- this is classic sign of intracellular infection
- usually this is an acute viral infection
Chronic inflammation is used to describe the pattern of inflammation seen in tissues in which ___________ predominate.
- mononuclear cells: lymphocytes, macrophages, plasma cells
* note the lymphocyte overlap with acute viral infections
What are the potential infection organisms of chronic inflammation?
- viruses (intracellular)
- intracellular bacteria
- intracellular parasites
- spirochetes
- any persistent infection due to any organism
On top of the mononuclear and lymphocytic cells involved in chronic inflammation, what else is a mediating factor?
-cytokines
Compare acute to chronic inflammation microscopic pathology
Acute: neutrophils, macrophages, edema
Chronic: lymphocytes, plasma cells, macrophages, but primarily lymphocytes
Compare microorganism causes of acute and chronic inflammation
- acute: extracellular organisms (bacteria and fungi)
- Chronic: intracellular organisms (viruses, some bacteria and fungi)
If a patient presents with a microscopically “chronic”-looking illness, what are the potential causes?
- chronic persistent infection with intracellular organisms or any hard to eradicate organisms
- acute infection with intracellular organisms
- *can be acute or chronic**
Acute and chronic inflammation may co-exist when?
-in chronic, hard to eradicate infections of any cause
What is the hallmark of a granuloma?
-a collection of activate macrophages (epithelioid cells or epithelioid histiocyte” which are large cells with abundant pink cytoplasm
Epithelioid cells often fuse to form _______.
-giant cells
What may or may not accompany granulomas in a granulomatous inflammation?
- with or without a rim of lymphocytes, fibroblasts
- with or without central necrosis (caseous necrosis)
What 2 things are involved in granuloma formation?
- CD4+ T cells
- cell mediated immunity
Steps of granuloma formation
- APC present intracellular organism to CD4+ TH1 cell
- T cell is activate and produces cytokines which recruit monocytes/macrophages from circulation to the tissue where they are needed
- macrophages are also activated by these cytokines to increase their phagocytic activity
- on going interactions between T cells and macrophages maintain the granuloma
When you identify a granuloma, it indicates what? Main examples?
-that there has been a cell mediated response against a poorly degradable intracellular microbe
What organisms elicit granulomatous inflammation?
- intra cellular
- poorly digestible, poorly soluble
- resistant to eradication
- Mycobacterium: TB!!!!!
- Some fungi (Histoplama)
- Some worms (Schistosoma)
If you see granulomatous inflammation in the lungs, what should you be thinking?
-TB!!!
__________ is a characteristic of TB
-caseous necrosis that accompanies granulomatous inflammation
Pathology of granulomatous inflammation
- epithelioid histiocytes (activated macrophages)
- giant cells
- lymphocytes
- plasma cells
Clinical presentation of granulomatous inflammation
-chronic infections due to a limited number of organisms (TB!!!!!, some fungi and worms)
How to tell an abscess and caseating necrosis apart?
- Microscopically: abscess have neutrophils and pus in it, while caseating necrosis doesnt have cells despite them both have necrosis tissue
- Cultures
Eosinophils defend against __________. How?
- helminthic (worm) infections
- IgE abs bind to helminthic parasites and the Fc regions recognized by eosinophils which activates release of granules
Why do eosinophils rely moreso on granule release that phagocytosis?
- worms are extracellular organisms and are too large to be ingested
- they are also resistant to most of the phagocytic enzymes and antimicrobial products
Eosinophilic granules contain _________. What is good and bad about this compound?
- Major basic protein
- it is toxic to helminths, but also causes extensive host tissue damage
When we see eosinophils in the inflammatory infiltrate, we look for _______ as a potential cause.
-worms
Granulomas often form in response to foreign materials, and as such may else be present with _______ infections due to eggs.
- worm
* *remember granulomas can also signify hard to digest tissues, like foreign objects and eggs or parasites
Cytopathic changes are ______ induced. What are some common features?
- virus induced
- nuclear inclusions, cytoplasmic inclusions (both due to viral aggregates) and multinucleated cells due to cell fusion, cell enlargement
- amount of inflammation is variable
Viruses can cause observable changes in the morphology of the cells. These changes are called ___________.
-cytopathic effects
Cytomegalovirus cytopathic effects
-intranuclear and cytoplasmic inclusions
Cytopathic changes see with herpes simplex virus
-multinucleated cells (cell fusion)
HPV cytopathic changes
- enlarged nucleus
- binucleated
- perinuclear halo
Adenovirus cytopathic changes
-intranuclear inclusion
T/F: Not all viruses cause cytopathic changes.
-True; but when they do, they give us insight into their identification
Cytoproliferative changes are _____ mediated. What are they a mechanism for?
- virus-mediated
- mechanism to transform cells into benign or malignant cells
HPV as an example of benign and malignant cytoproliferative changes
- Benign proliferative=warts; viral proteins free in cytoplasm, NOT DNA
- Cervical cancer: viral proteins integrated into host DNA
T/F: HPV infection alone is sufficient for the development of cancer.
-false; many other co-factors must be involved as well
Characteristics of tissue necrosis
- tissue damage due to toxins
- little inflammation
- widespread necrosis
What can cause tissue necrosis?
- toxin mediated via bacteria, parasites
- viruses