1G Foundations 7 - Inflammation Flashcards
What are the characteristics of a cell undergoing apoptosis?
- Cellular shrinkage
- Nuclear shrinkage (pyknosis)
- Karyolysis (fading of the nucleus)
- Apoptotic bodies
- Membrane blebbing
What are some of the substances that can trigger apoptosis?
- Deprivation of cell signals (growth factors)
- Cell stress
- DNA repair process fails –> triggers apoptosis
- Cytokines (TNF)
- Cytotoxic T cells can insert Granzyme B into cells
What neural crest derivatives are found in this adult structure? PNS
- ANS
- Dorsal root ganglia
- CNs
- Schwann cells
What neural crest derivatives are found in this adult structure? Ear
Bones of the middle ear
What neural crest derivatives are found in this adult structure? Eye
Structures of the anterior chamber
What neural crest derivatives are found in this adult structure? Adrenal gland
Chromaffin cells in medulla
What neural crest derivatives are found in this adult structure? Mouth
Odontoblasts
What neural crest derivatives are found in this adult structure? Heart
Aorticopulmonary septum (spiral septum)
What neural crest derivatives are found in this adult structure? Digestive system
- Enteric nervous system
- Celiac ganglion
- Enterochromaffin cells
What neural crest derivatives are found in this adult structure? Thyroid
Parafollicular cells (C cells)
What neural crest derivatives are found in this adult structure? Skin
Melanocytes
Inflammation is characterized by?
- Rubor
- Dolor
- Calor
- Tumor
- Functio laesa
Acute inflammation: Release of which inflammatory mediators?
- IL-1
- IL-6
- TNF-alpha
Acute inflammation: Vasodilation and increased vascular permeability fluid exudation is mediated by?
- Histamine
- Serotonin
- Bradykinin
Acute inflammation: Fibrosis. Fibroblasts lay down BLANK and requires BLANK
Collagen, vitamin C
Acute inflammation: Tissue remodelling by BLANK which contain BLANK
Metalloproteinases, Zinc
Intermediary stage in wound healing. Occurs 3-5 days into the healing process?
Granulation tissue
Fibrotic shell that seals inflammatory process off. (body considers this as a success outcome)
Abcess
Acute inflammation is mainly mediated by which cell type?
Neutrophils
Chronic inflammation is mainly mediated by whuich cell type?
Mononuclear cells (like macrophages and lymphocytes)
Multi nucleated giant cells are what?
Several macrophages that have connected their plasma membranes and cytoplasms to create one cell
What is a granuloma
Nodule of macrophages found in chronically inflamed tissue
Chronically inflamed tissue is characterized by which two processes?
Ongoing cycles of tissue damage and tissue repair
Meaning of the word extravasation
something is leaving the circulation to enter a tissue
What cells can be involved in leukocyte extravasation?
- Neutrophils
- Polymorphonuclear cells (PMNs)
- Granulocytes
- Monocytes
- Certain types of T-cells
Steps in leukocyte extravasation. What’s the role of E- and P-selectin?
They are expressed on endothelial cells lining the inside of vasculature and adhere to leukocytes
Outcomes of chronic inflammation?
Scarring and Amyloidosis
Steps in leukocyte extravasation. Where can you find L-selectin?
On leukocytes
Steps in leukocyte extravasation. How is expression of selectins triggered in the endothelium?
By acute-phase cytokines
- IL-1
- IL-6
- TNF-alpha
Steps in leukocyte extravasation. Tight binding. Surface receptor involved?
ICAM-1
Steps in leukocyte extravasation. Tight binding. Leukocyte protein involved?
LFA-1 (an integrin)
Steps in leukocyte extravasation. Diapedesis, what is it?
Leukocyte travels between endothelial cells and exits blood vessel
Steps in leukocyte extravasation. Diapedesis. Protein involved?
PECAM-1 (on the intercellular junctions between endothelial cells)
-Also found on Neutrophils, Monocytes, platelets)
Steps in leukocyte extravasation. Migration-inducing signals?
- Chemotactic signals
- Neutrophil chemotactic factors: C5a, IL-8, LTB4, Kallikrein
Binding, diapedesis and migration is enhanced by?
Platelet activating factor
Leukocyte adhesion deficiency syndrome is characterised by?
- Abnormal integrin molecules
- Delayed separation of the umbilicus
- Recurrent bacterial infections
Describe transudate
- Mostly water
- Decreased cells
- Decreased protein
- Low specific gravity due to:
- Increased hydrostatic pressure
- Decreased oncotic pressure
Describe exudate
- Rich in proteins and cells
- Inflammatory cells due to:
- Lymphatic obstruction
- Inflammation
List the three basic forms of inflammation
- Serous
- Fibrinous
- Suppurative
Feature of serous inflammation
Transudate
Feature of fibrinous inflammation
Exudate
Feature of suppurative (purulent) inflammation
Pus
Granuloma?
-Collection of macrophages that make TNF-alpha – > maintains granuloma
What does Infliximab block?
TNF-alpha
What does blocking of TNF-alpha lead to (in a granuloma context)?
Breakdown of granuloma
Why do you have to be careful before giving anti-TNF-alpha drugs?
It might breakdown latent granulomatous abcesses (i.e. TB) leading to disseminated disease
Name granulomatous diseases
- Mycobacterium Tuberculosis (caseating)
- Fungal infections (blastomycosis, histoplasmosis, coccidiomycosis)
- Sarcoidosis
- Granulomatosis with polyangiitis (Wegener’s)
- Berylliosis (people who work in Beryllium mines get this)
- Treponema Pallidum (syphilis)
- M. leprae (leprosy)
- Bartonella henselae (cat scratch disease)
- Crohn’s disease
- Churg-Strauss syndrome
- Silicosis
- Listeria
- Chronic granulomatous disease
- Foreign bodies
Is ESR high or low in inflammation?
- Higher (products of inflammation e.g. fibrinogen coat RBC’s –> aggregation –> They fall faster)
- It’s very non-specific
Potential causes of elevated ESR (“sed rate”)
- Polymyalgia rheumatica
- Temporal arteritis
- Disease activity in RA and SLE
- Infection, inflammation (e.g. osteomyelitis)
- Malignancy
- Pregnancy
How can we classify C-Reactive Protein?
- Acute phase protein synthesised in the liver
- Part of the innate immune system
- An opsonin as it binds to microbial surfaces (opsonizes and activates complement)
Acute phase proteins?
activated during acute inflammation
- ESR
- CRP
- Fibrinogen
- Ferritin
In active inflammation you can see?
(Factors mediated by cytokines, non-specific)
- Elevated ESR
- Elevated CRP
- Fever
- Leukocytosis
- Elevated HR and BP
Information about CRP
- Can be secreted from cells within atherosclerotic plaques to activate local endothelial cells to induce a prothrombotic state and increase the adhesiveness of the endothelium to leukocytes
- Elevations are a strong predictor of MI, stroke, PAD, and sudden cardiac death
- Can be lowered by smoking cessation, exercise, weight loss, and statins
Reasons for decreased ESR?
- Sickle cell (altered shape)
- Polycythemia (too many)
- CHF (unknown)
Steps in Leukocyte extravasation and what the steps are mediated by
- Rolling: selectins
- Tight binding: Integrins
- Diapedesis: PECAM-1
- Migration: IL-8, LTB4, C5a, Kallikrein
What cytokine is particularly important in the formation of granulomas?
TNF-alpha
What cell type plays a role in inflammation by generating both fibrinogen and C-reactive protein?
Hepatocyte
