Day 3- Lecture 1- Chronic Inflammation Flashcards
What is chronic inflammation?
Chronic response to injury with associated fibrosis (longer, more variable, overlap with host immunity)
With regards to the 4 clinical signs on acute inflammation which 2 resolve and which 2 persist?
- Redness and heat resolve
- Swelling and pain persist
When does acute inflammation occur?
Seconds to minutes after injury - instant reaction to any type of injury
What is the purpose of acute inflammation?
To phagocytose bacteria, with or without the help of plasma proteins, before they can establish a secured position
How long does it take for modulated chronic inflammation to replace acute inflammation?
It takes over in a few hours if the injurious agent is not quickly removed
What is the dominant cell type of modulated (chronic) inflammation?
Macrophages
Give some examples of the possible persisting injurious agents in chronic inflammation?
- Micro-organism e.g. Bacteria
- A sterile but irritating substance such as necrotic tissue
- A foreign body
- A crystalline substances
- An antigen (e.g. In autoimmune disease)
How does chronic inflammation arise?
1- When it takes over from acute inflammation (most common) - if damage is too severe to be resolved within a few days
2- When it begins without any proceeding acute inflammation (de-novo)
3- When it develops alongside an superimposed on acute inflammation (repeated attacks of acute inflammation can lead to it developing alongside it)
Give some examples of when chronic inflammation may arise without any proceeding acute inflammation?
- Some chronic infections e.g. TB
- Some autoimmune conditions e.g. Rheumatoid arthritis
- Prolonged exposure to toxic agents e.g. Silica
What does chronic inflammation look like under a microscope?
Much more varied than acute inflammation- look for presence of cell types (look at my notes)
Give an example of when chronic inflammation develops alongside acute inflammation?
In an on-going bacterial infection
What does chronic inflammation look like under a microscope?
- Mononuclear cells- macrophages and lymphocytes- are the predominant cell type
- A new type of tissue called granulation tissue begins to form-> part of the healing process
Tip: the shift from neutrophils to macrophages and lymphocytes indicates that they have different functions- macrophages and lymphocytes are always seen in chronic inflammation but the numbers seen and mix present varies considerably
What cells are principally involved in chronic inflammation, and what are they general role?
Macrophages- phagocytosis, presentation of antigens to immune system, synthesis of important proteins and enzymes, control of other cells
Lymphocytes- B type (plasma cells) produce antibodies, T type involved in control and cytotoxic functions
Eosinophils- allergic reactions, parasite infections
Fibroblasts/myofibroblasts- make collagen
What are macrophages called before they enter the tissue?
Monocytes
What is another name for macrophages (in tissue spaces)?
Histiocytes
Where are monocytes made?
Bone marrow
How long do monocytes circulate in the blood for and what happens after this time period?
About 6 days - they then enter the tissues and become dormant until activated by a local challenge
How long do macrophages last for?
Many months- and they can replicate (unlike neutrophils)
Where do macrophages go and what do they initially do?
The arrive at the site of inflammation after the neutrophils and take over from them
List and explain the 6 functions of macrophages?
- Phagocytosis and destruction of debris (e.g. Dead tissue and collagen) and bacteria- not always as effective as neutrophils, however better at destroying some difficult to kill bacteria e.g. Mycobacterium tuberculosis
- Secretion of numerous substance that summon and activate other cells (e.g. Cytokines, complement components, blood clotting factors, proteases)
- Present antigens to the immune system and initiate an immune response
- Stimulates angiogenesis (the formation of new blood vessels) which is important in wound healing
- Induces fibrosis
- Induces fever, acute phase reaction and chachexia
What are the predominant cells of the immune system?
Lymphocytes
What are plasma cells?
Differentiate antibody-producing B lymphocytes (produce, synthesise and secrete antibodies). Usually implies considerable chronicity. As differentiated, takes time, so if present, tells you inflammation has been going on for a while.
Lymphocytes are normally absent in the tissues, if they are present what does it indicate?
That some antigenic material is or has been there
What do lymphocytes do?
- Process antigens
- Secrete antibodies (this is done by B lymphocytes that have undergone differentiation to become plasma cells which secrete antibodies)
- T lymphocytes: Secreting cytokines that influence other inflammatory cells
- T lymphocytes: Killing cells (this is done by natural killer cells which attack virus-infected cells and sometimes tumour cells)
B lymphocytes- produced and mature in bone marrow
T lymphocytes- produced in bone marrow and mature in thymus
Where are eosinophils normally present?
Scattered through the tissues of the body- seen in large numbers in certain circumstances
What do eosinophils do?
- Attack large parasites such as worms
- Present in high numbers in some immune responses e.g. In the bronchi of asthma, and in some tumours e.g. Hodgkin’s lymphoma
What do fibroblasts respond to?
Like leucocytes they respond to a chemotactic stimuli and move to sites where they are needed (recruited by macrophages)
What do fibroblasts do?
Produce connective tissue substances e.g. Collagen, elastin and glucosaminoglycans
What are myofibroblasts?
Differentiated fibroblasts which can contract
When do giant cells form and what are they?
When foreign bodies or infection with certain bacterial are present, macrophages can fuse with each other to form single cells called giant cells (they are multinucleate cells)
Give 2 characteristics of giant cells
- Can be very large
- Contain dozens to hundreds of nuclei
When is giant cells seen?
In granulomatous inflammation - frustrated phagocytosis where macrophages cannot remove the pathogen
What are the 3 types of giant cell?
1- Langhans giant cells
2- Foreign body giant cells
3- Touton giant cells
1- How are the nuclei arranged in the langhans giant cells?
Nuceli are arranged around the periphery of the giant cell
Notes- image!
1- Where do you see langhans giant cells
Often (but not exclusively) seen in tuberculosis
2- How are the nuclei arranges in foreign body giant cells?
Nuclei are arranges randomly in the cell
Look at notes- image!
2- when are foreign body giant cells seen?
Often (but not exclusively) seen when a hard to digest foreign body is present- if the foreign body is small it is phagocytosed by the giant cell and can be seen within it. If it is large the foreign body giant cell sticks to its surface.
3- How are the nuclei arranges in Touton giant cells?
Nuclei are arranged in a ring towards the centre of the cell
Look at notes- image!
3- When do Touton giant cells form?
They form in lesions where there is a high lipid content - Examples include
- Fat necrosis
- Xanthomas
3- Touton giant cell lesions will also contain foam cells- what are formal cells?
Macrophages whose cytoplasm appears foamy as they have phagocytosed a lot of lipid
What are the possible complications of chronic inflammation?
- Tissue destruction (stimulation of immune response)
- Excessive fibrosis (scarring) e.g. Gall bladder (chronic cholecystitis), chronic peptic ulcers, cirrhosis
- Impaired tissue function e.g. Chronic inflammatory bowel disease
- Atrophy- reduced tissue size e.g. Gastric mucosa, adrenal glands
What is fibrosis?
An excess of fibrous tissue
When does fibrosis occur??
When fibroblasts are stimulated by cytokines to produce excess collagen- typically seen in chronic inflammation
Production of collagen is initially helpful in chronic inflammation as it helps wall of infected areas and the production of a fibrous scar replacing damaged tissue is essential in wound healing- so what causes the problem?
If it is excessive or inappropriate it can replace normal parenchymal tissue and impair the function of an organ
Give an example of when fibrosis can cause impaired function
Interstitial fibrosis of the lung
Give an example and explain how further problems can arise due to myofibroblasts?
-Area of fibrosis containing enough myofibroblasts, it can slowly contract
Example:
Contraction in a cirrhosis liver would impair the flow of portal blood resulting in ascites
Chronic infection can dad to involvement in inappropriate immune responses- explain why and how
- Immune system involves cells and antibodies programmed to attack and bind to specific target
- When these cells and antibodies meet with targets, mediators are released leading to inflammation
- Inflammation causes destruction of targets
HOWEVER
-The immune system can sometimes attack innocuous targets
Give some examples of inappropriate immune responses
- Immune system targeting pollen- leads to hay fever
- Autoimmune diseases like rheumatoid arthritis
Chronic inflammation becomes a disease process!
What is granulomatous inflammation?
A type of chronic inflammation in which granulomas are seen
When do granulomas form?
A granuloma is the body’s way of dealing with particles that are poorly soluble or difficult to eliminate for some reason
Give some examples of particles which would lead to granuloma formation
- Foreign bodies e.g. Thorns and splinters
- ‘Tough bacteria’ e.g. Mycobacterium tuberculosis or myobacterium leprae
What do granulomas do?
A granuloma forms around a particle, which can be free or phagocytised within the centre of the granuloma, and walls it off whilst concentrating mononuclear cells within its centre with which it hopes to destroy the particle
Granuloma often contain epithelioid cells- what are they?
-Macrophages that have become modified to look like epithelial cells
-They are elongated
-Have eosinphilic cytoplasms
-Appear tightly packed together
…as epithelial cells do
What 2 general types do granuloma fall into?
1- foreign body granulomas
2- hypersensitivity or immune type granulomas
What cells do foreign body granuloma contain and what do they develop around?
- Contain macrophages, foreign body giant cells, epithelioid cells and some fibroblasts (at the periphery) but very few, if any, lymphocytes
- Develop around material that is not antigenic e.g. Surgical thread
What cells do hypersensitivity or immune type granulomas contain?
Macrophages, giant cells (may be langhans type), epithelioid cells (usually more prominent than in foreign body granuloma), some fibroblasts (at the periphery) and lymphocytes
What is particularly seen in granuloma assosicated with tuberculosis?
Central necrosis
What do hypersensitivity or immune type granulomas develop around?
Insoluble but antigenic particles that cause cell-mediated immunity
Give some examples of organisms that hypersensitivity or immune type granulomas develop around
Organisms that cause syphilis, tuberculosis, leprosy, cat scratch disease, fungi
Also seen in sarcoidosis- which is a disease with an unknown cause in which granulomas are seen in organs throughout the body
Also seen in wegeners granulomatosis and Crohn’s disease
Why can hypersensitivity or immune type granulomas be harmful?
They occupy parenchymal space within an organ
