Lesson 3

Question 1

How does chronic inflammation arise?

Answer 1

1. May ‘take over’ from acute inflammation if damage is too severe to be resolved within a few days
2. May arise de novo
   – Some autoimmune conditions (e.g. RA)
   – Some chronic infections (e.g. Hepatitis B, C, Tuberculosis, Leprosy)
3. May develop along with acute inflammation in severe persistent or repeated irritation

Question 2

What does chronic inflammation look like?

Answer 2

Characterised by the microscopic appearances -> more variable than acute inflammation.
Most important characteristic - type of cell present.

Granulation tissue.

Question 3

What are some typical features of chronic inflammation?

Answer 3

• macrophages
• lymphocytes
• plasma cells
• absence of polymorphs
• Angiogenesis
• proliferation of fibroblasts with collagen production leading to fibrosis

Question 4

Provide a summary on macrophages?

Answer 4

• Derived from blood monocytes
• Important in acute and chronic inflammation
• "Masterminds” of chronic inflammation
• Functions:
	– Phagocytosis
	– immune system
	– Synthesis of cytokines.- IL, TNF
	– Control of other cells by releasing: EGF, FGF, PDGF
	– (fibrosis and angiogenesis)

Question 5

What are some typical features of chronic inflammation?

Answer 5

Typical features of chronic inflammation include
• macrophages
• lymphocytes
• plasma cells
• absence of polymorphs
• Angiogenesis
• proliferation of fibroblasts with collagen production leading to fibrosis

Question 6

Provide a summary on B-lymphocytes

Answer 6

B-lymphocytes “shuffle” the DNA encoding their immunoglobulins -> create antibodies -> recognise antigens
B-cell presented to foreign antigen that it “recognises” -> proliferate (under the control of T- helper cells) -> form a population of plasma cells producing antibodies specific for that antigen
Memory B-lymphocytes expand again following re-exposure to the antigen

Question 7

Provide a summary on T-lymphocytes

Answer 7

T-lymphocytes oundergo rearrangement of their T-cell receptor genes in thymus.
CD4+ (T-helper) -> induce proliferation/differentiation of T&B cells, activate macrophages.
CD8+ (T-cytotoxic) -> induce apoptosis in cells that present foreign antigens in the correct MHC context -> punching holes in plasma membrane/ injecting granzyme.

Question 8

Provide a summary on natural killer cells

Answer 8

NK cells -> rapid response to viral infection, important component of innate immunity.
NK cells also recognise “stressed” cells - tumour cells.
Mechanism of killing similar to cytotoxic T-cells -> without requirement for MHC presentation.

Question 9

What other cells are involved in the chronic inflammatory response and what are their purpose?

Answer 9

• Plasma cells:
– Differentiated antibody-producing B lymphocytes - implies considerable chronicity.
• Eosinophils:
– Allergic reactions, parasite infestations, some tumours.
• Fibroblasts / Myofibroblasts:
– Recruited by macrophages; make collagen

Question 10

What are giant cells?

Answer 10

• Multinucleate cells made by fusion of macrophages
• Frustrated phagocytosis 
• Several types recognised
	– Langhans giant cell -> tuberculosis
	– Foreign Body Type
	– Touton type giant cell

Question 11

Give some examples of disease and the more common cells that are present upon infection?

Answer 11

– Rheumatoid arthritis: Mainly plasma cells.
– Chronic gastritis: Mainly lymphocytes and plasma cells.
– Leishmaniasis (a protozoal infection): Mainly macrophages.

– Giant cell type may be a help to diagnosis.

Question 12

Effects of chronic inflammation?

Answer 12

• Fibrosis e.g. gall bladder (chronic cholecystitis), chronic peptic ulcers, cirrhosis
• Impaired function e.g. chronic inflammatory bowel disease
– Rarely increased function e.g. Thyrotoxicosis, mucus secretion.
• Atrophy
– Autoimmune gastritis.
• Stimulation of immune response (inappropriate)

Question 13

Describe chronic cholecystitis (fibrosis)

Answer 13

• Very common disease
• Can affect both sexes any age
• “Typically” female, fair, fat, fertile, forty
• Cause - Gall stones
• Obstruction - inflammation

Question 14

Describe chronic peptic ulcer (gastric ulcer - fibrosis)

Answer 14

• Ulceration -> imbalance of acid/pepsin attack and mucosal defence.
• Sites- antrum, first part of duodenum
• Causes- Helicobacter pylori (HP gastritis),
hyperacidity
• Drugs-NSAID, genetic , alcohol, cigarettes, steroids
• Fibrosis- narrowing or pyloric stenosis.
• Common a few decades ago

Question 15

Describe liver cirrhosis

Answer 15

Inflammation with destruction of hepatocytes, fibrosis and nodular regeneration- cirrhosis

Question 16

What are common causes of cirrhosis?

Answer 16

• Alcohol
• Fatty liver disease
• Infection with HBV, HCV
• Immunological- PBC

Question 17

What are some complications as a result of liver cirrhosis?

Answer 17

Portal hypertension, liver failure, HCC

Question 18

Describe inflammatory bowel disease?

Answer 18

• Idiopathic inflammatory disease affecting large and small bowel.
• Present with diarrhoea, rectal bleeding and other symptoms.
• Ulcerative colitis and Crohn’s disease.

Question 19

Explain Crohn’s disease

Answer 19

small bowel and large bowel but 50% rectum spared
skip lesions
Granulomas
transmural inflammation
fibrosis (can cause shortening)
obstruction/strictures
fistula formation
anal lesions in 75%

Question 20

Explain ulcerative colitis (UC)

Answer 20

large bowel (90% rectum)
continuous mucosal inflammation
no granulomas
malignant change

Question 21

Explain increased function of thyrotoxicosis (Graves’ disease)

Answer 21

• Autoimmune disease
• Exophthalmos, thyrotoxic signs (palpitation, tremor etc.), enlarged thyroid
• Auto Ab - LATS (TSI – thyroid stimulating immunoglobulin)
• Ab acts on TSH surface receptor on thyroid epithelium -> mimics TSH
• Increased T4 and T3 and reduced TSH

Question 22

Explain rheumatoid arthritis

Answer 22

• Autoimmune disease- Rheumatoid factor.
• 3 female : 1 male
• Common, systemic disease, invariably affects joints.
• Localised chronic inflammation leads to joint destruction - small joints
• Systemic immune response – rheumatoid nodule, splenomegaly, amyloid.

Question 23

What is a granuloma?

Answer 23

Organised collection of epithelioid cells (modified macrophages)

Question 24

Describe foreign body granulomas

Answer 24

Deal with particles which are poorly soluble (foreign bodies) or organisms which are difficult to eliminate (mycobacterium tuberculosis or mycobacterium leprae).

Question 25

What are main causes of granulomatous inflmmation

Answer 25

• Mildly irritant ‘foreign’ material: Suture material
• Infections
Mycobacteria: Tuberculosis, leprosy
Other infections e.g. some fungi
• Unknown causes
– Sarcoidosis
– Granulomatosis with polyangiitis GPA– Crohn’s disease

Question 26

Explain Tuberculosis?

Answer 26

• Caused by Mycobacteria
– especially M. tuberculosis. Difficult & slow to culture.
• Nature of organism: see microbiology
– n.b. wall lipids (Mycosides).
• Produces no toxins or lytic enzymes.
• Causes disease by persistence/induction of cell-mediated immunity

Question 27

What is the impact of tuberculosis on the body?

Answer 27

1) Arrest (stop progression), fibrosis, scarring.
2) Erosion into bronchus
Tuberculous bronchopneumonia
T.B. in gastro-intestinal tract
3) Tuberculous empyema
4) Erosion into blood stream

Question 28

What is the specific name of tuberculosis when there are many bug presents?

Answer 28

Miliary tuberculosis

Question 29

What is the specific name of TB when there are a few bugs present?

Answer 29

Single organ TB

Question 30

What are some examples of Granulomas infections?

Answer 30

• Leprosy
• Syphilis
• Chronic fungal infections
• ‘Cat-scratch’ disease

Question 31

Explain Sacridosis
(How it manifests, who it is common in, common places of infection)

Answer 31

Variable clinical manifestations
More common in young adult women
Involves lymph nodes, lungs…
Non-caseating granulomas, giant cells.