Lesson 3 Flashcards
(31 cards)
How does chronic inflammation arise?
- May ‘take over’ from acute inflammation if damage is too severe to be resolved within a few days
- May arise de novo
– Some autoimmune conditions (e.g. RA)
– Some chronic infections (e.g. Hepatitis B, C, Tuberculosis, Leprosy) - May develop along with acute inflammation in severe persistent or repeated irritation
What does chronic inflammation look like?
Characterised by the microscopic appearances -> more variable than acute inflammation.
Most important characteristic - type of cell present.
Granulation tissue.
What are some typical features of chronic inflammation?
- macrophages
- lymphocytes
- plasma cells
- absence of polymorphs
- Angiogenesis
- proliferation of fibroblasts with collagen production leading to fibrosis
Provide a summary on macrophages?
• 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)
What are some typical features of chronic inflammation?
Typical features of chronic inflammation include
• macrophages
• lymphocytes
• plasma cells
• absence of polymorphs
• Angiogenesis
• proliferation of fibroblasts with collagen production leading to fibrosis
Provide a summary on B-lymphocytes
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
Provide a summary on T-lymphocytes
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.
Provide a summary on natural killer cells
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.
What other cells are involved in the chronic inflammatory response and what are their purpose?
• Plasma cells:
– Differentiated antibody-producing B lymphocytes - implies considerable chronicity.
• Eosinophils:
– Allergic reactions, parasite infestations, some tumours.
• Fibroblasts / Myofibroblasts:
– Recruited by macrophages; make collagen
What are giant cells?
• Multinucleate cells made by fusion of macrophages • Frustrated phagocytosis • Several types recognised – Langhans giant cell -> tuberculosis – Foreign Body Type – Touton type giant cell
Give some examples of disease and the more common cells that are present upon infection?
– 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.
Effects of chronic inflammation?
• 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)
Describe chronic cholecystitis (fibrosis)
- Very common disease
- Can affect both sexes any age
- “Typically” female, fair, fat, fertile, forty
- Cause - Gall stones
- Obstruction - inflammation
Describe chronic peptic ulcer (gastric ulcer - fibrosis)
• 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
Describe liver cirrhosis
Inflammation with destruction of hepatocytes, fibrosis and nodular regeneration- cirrhosis
What are common causes of cirrhosis?
- Alcohol
- Fatty liver disease
- Infection with HBV, HCV
- Immunological- PBC
What are some complications as a result of liver cirrhosis?
Portal hypertension, liver failure, HCC
Describe inflammatory bowel disease?
- Idiopathic inflammatory disease affecting large and small bowel.
- Present with diarrhoea, rectal bleeding and other symptoms.
- Ulcerative colitis and Crohn’s disease.
Explain Crohn’s disease
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%
Explain ulcerative colitis (UC)
large bowel (90% rectum)
continuous mucosal inflammation
no granulomas
malignant change
Explain increased function of thyrotoxicosis (Graves’ disease)
- 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
Explain rheumatoid arthritis
- 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.
What is a granuloma?
Organised collection of epithelioid cells (modified macrophages)
Describe foreign body granulomas
Deal with particles which are poorly soluble (foreign bodies) or organisms which are difficult to eliminate (mycobacterium tuberculosis or mycobacterium leprae).
