Inflammatory Arthritis: Chronic inflammation, regeneration and repair - pathology Flashcards
1
Q
What is Chronic Inflammation?
A
- Prolonged inflammation due to persistent stimulus
- Characterised by macrophages, lymphocytes (adaptive/specifc immune reaction), plasma cells
- Delayed response but more specific
2
Q
What is an absess?
A
neutrophils persistent reaction ie fluid build up
3
Q
Causes of Chronic Inflammation?
A
- Persistent infection - most commonly
- Autoimmune condition
- Foreign materials
- Carcinomas
4
Q
How do Macrophages link to chronic inflammtion?
A
- Dominant in most chronic inflammation and 2-3 days post-acute inflammation
- Named differently depending on the site e.g Kupffer cells in liver, sinus histiocytes in lymph nodes, microglia in CNS, alveolar macrophages (get rid of debris) in lungs
- Lifespan - months or years
5
Q
What are the macrophage subtypes?
A
M1 & M2
6
Q
What do M1 macrophage subtypes do?
A
- Activated by bacteria or interferon gamma from T cells
- present antigens - Stimulates inflammation
7
Q
What do M2 macrophage subtypes do?
A
- Activated by IL-4 or IL-13 from T cells
- Stimulates repair
8
Q
What do Lymphocytes do in chronic inflammtion?
A
- All produced in bone marrow but T cells mature in thymus
- Ischemia isa condition in which blood flow (and thus oxygen) is restricted or reduced in a part of the body
- In thymus - progenitor cells differentiate to CD4+ helper T cells or CD8+ cytotoxic T cells
- T cells use TCR complex (combination of CD3 (common antigen present on an T cells) and T Cell Receptor, TCR) for surveillance
- Recognises antigen bound to MHC, needs 2ᴺᴰ signal to activate
9
Q
what is CD4+ Helper T Cell Activation in chronic inflammation?
A
- Two types of T helper cells…
- Th1 - secretes interferon gamma to recruit macrophages
- Th2 - involved in allergy, recruits eosinophils, cause B cells to produce IgE
- Activated by…
- TCR complex bound to MHC class II on APC
- CD28 bound to B7 on APC
10
Q
what is CD8+ Cytotoxic T Cell Activation in chronic inflammtion?
A
- Activated by….
- Antigen bound to MHC class I binds to TCR + CD8 Co-receptor
- IL-2 produced by CD4+ helper T cell, activating cytotoxic T cell
- Killing occurs in two ways…
- Perforin secreted and creates pores, allowing granenzyme to enter cell and destroy target cell
- Binding of FAS ligand with FAS on target cell
- Target cell dies via apoptosis or programmed cell death
11
Q
How are B cells activated in chronic inflammation?
A
- Occurs by antigen binding to IgM or IgD, causing maturation to IgM-secreting plasma cells or IgD-secreted plasma cells
- CD40 on B cells binds to CD40 ligand on helper T-cell
- Causes release of cytokines (IL10 for plasma cells), causing plasma cell to proliferate
12
Q
what is Granulomatous Inflammation?
A
- Granuloma - collection of activated macrophages, aka epithelioid histiocytes
- Can be either non-caseating (formed by foreign bodies, vasculitis inflammatory conditions e.g Crohns) or caseating (formed by infections e.g M. tuberculosis), meaning cheese in latin
13
Q
describe the Pathogenesis of Granulomas
A
- Macrophages present antigen MHC 2 to CD4+ helper T-cells
- Secretes IL-12 causing helper T-cells → Th1 subtype
- Th1 secretes interferon 𝛾, converts macrophages → epithelioid histiocytes + giant cells
14
Q
describe Wound Healing
A
- Initiates when inflammation occurs - platelets, macrophages and neutrophills
- Occurs through regeneration and repair
- fibroblasts secrets collagen
15
Q
How Wounds Heal?
A
- Tissue divided into three types based on regenerative capacity
- Labile - have stem cells, e.g skin, bowel lining, bone marrow
- Stable - normally inactive, regenerates if needed, e.g liver → undergo hyperplasia
- Permanent - lack of significant regenerative potential, e.g myocardium, skeletal muscle, neurons
- Occurs if stem cells lost or in permanent tissues
- Layers - fibrin + neutrophils > granulation tissue > fibroblasts + collagen (scar tissue)
- Granulation forms initially
