Pathology summary session Flashcards
Meaning of ‘patho’
suffering
Meaning of ‘logos’
study of
Immunology definition
study of the immune system
Pathology definition
study of the causes/effects of diseases
Why is it important to understand immunology and pathology?
to make the correct diagnosis, to provide correct treatment, referrals, advice and education for patients
Aetiology definition
the cause of a disease or condition (pathology)
What are the 2 natures of aetiology?
genetic and/or environmental
Example: what are the possible aetiologies of a type I hypersensitivity reaction?
genetic - mutations
environmental - hygiene hypothesis or pollution
Pathogenesis definition
progressive changes as disease develops which includes morphological cellular changes
What is the aim of an inflammatory reaction?
eliminating the inciting cause
What are the possible inciting causes of inflammation?
invading microorganisms, particulate materials (allergens/prostheses), altered self cells (growth disorders/cell injury), transformed malignant cells (neoplasia)
What is the aetiology/inciting cause of acute inflammation?
infection or tissue damage
What is the onset of acute inflammation like?
rapid onset (but short-term and localised)
Which part of the immune system is involved in acute inflammation?
only the innate immune system (e.g. neutrophils)
Is there complete resolution in acute inflammation?
yes - complete restoration of function and appearance of tissues
Examples of acute oral diseases
glossitis, stomatitis, cheilitis, gingivitis
What are the possible aetiologies of acute oral diseases?
microorganisms, particulate materials, physical trauma
What is glossitis?
inflammation of the tongue
What is stomatitis?
inflammation of larger parts of the oral mucosa (buccal)
What is cheilitis?
inflammation of the lips
What is gingivitis?
inflammation of the gums
What may result if acute inflammation is persistent?
chronic inflammation
What is the inciting cause of gingivitis?
a build up of dental plaque results in biofilm dysbiosis
Which cells are involved in gingivitis?
epithelial cells and innate immune cells
How do epithelial cells respond to gingivitis?
produce soluble mediators (e.g. AMPs) as part of saliva / gingival crevicular fluid
How do innate immune cells respond to gingivitis?
phagocytosis, degranulation (NETosis), antigen presentation, mediator release
Sequalae for gingivitis
removal of biofilm via scale and polish and OHI
How long can chronic inflammatory diseases last?
up to years (long-term)
Which parts of the immune system are involved in chronic inflammation?
innate and adaptive immune system
Is there restoration of tissues following chronic inflammation?
no restoration - tissue damage (e.g. fibrosis) has occurred
What diseases do chronic inflammatory diseases tend to arise from?
acute inflammatory diseases
Examples of chronic oral diseases
periodontitis, lichen planus, orofacial granulomatosis (also type IV hypersensitivity reaction), candidiasis, abscesses
What is periodontitis?
chronic gum inflammation with destruction of alveolar bone
What is lichen planus?
chronic inflammatory condition affecting skin / mucous membranes similar to orofacial granulomatosis
What is orofacial granulomatosis (OFG)?
A type IV hypersensitivity reaction that is also a chronic inflammatory disease (M1 macrophages). Leads to granulomas in oral mucosa)
What is candidiasis?
fungal infection of the tongue
What is an abscess?
a collection of pus formed by immune cells attempting to fight microorganisms. Can be acute or chronic
What is the inciting cause of periodontitis?
further growth of biofilm into the periodontal pocket and biofilm becomes more dysbiotic
What is the name of the keystone pathogen of periodontitis?
Porphyromonas gingivalis
What is the role of the adaptive immune system in periodontitis?
T cells and B cells are activated, excess soft and hard tissue regeneration occurs
How is alveolar bone destroyed in periodontitis?
imbalance between osteoclastogenesis and osteoblastogenesis. there is increased osteoclast activity (osteoclastogenesis)
Why is there increased osteoclast activity in periodontitis?
Porphyromonas gingivalis PAMPs (e.g. LPS) bind to TLRs on osteoblasts triggering RANKL synthesis and secretion. This results in RANKL>OPG imbalance
Immunological tolerance definition
the body’s ability to recognise self-peptides (proteins)
What happens if there is a loss of immunological tolerance?
can result in autoimmune diseases
What are the tolerance mechanisms in place to prevent autoimmune diseases?
Central tolerance and peripheral tolerance
What happens in central tolerance?
T cells and B cells undergo negative selection during education to ensure no self-reactive cells enter circulation
Function of peripheral tolerance
prevents the activation of self-reactive T and B cells that may escape central tolerance and enter the periphery
What are the 3 signals required for CD4+ T cell activation?
- MHCII-TCR interact as antigen is presented by APC
- Interaction of costimulatory molecules
- APC releases cytokines that trigger CD4+ T cell differentiation
How do self-reactive T cells become anergic in peripheral tolerance?
APCs that take up self-antigens do not upregulate co-stimulatory molecule production. Therefore signal 2 and 3 do not occur so self-reactive T cells are not activated
What happens to anergic T cells?
removed by apoptosis
How does peripheral tolerance prevent the activation of self-reactive B cells?
Anergic T cells are removed by apoptosis therefore self-reactive B cells cannot be activated by thymus-dependent activation
Why can self-reactive B cells not be activated by thymus-independent activation?
microbial components (e.g. LPS) are required as well as the antigen
How does the peripheral tolerance mechanism fail in autoimmunity?
anergic T cells that escape central tolerance are not removed by apoptosis. This can lead to thymus-dependent activation of self-reactive B cells which can produce antibodies against self-antigen
Examples of autoimmune diseases
rheumatoid arthritis and Sjogren’s syndrome
What happens in Sjogren’s syndrome?
self-reactive T and B cells attack the cells of the salivary and lacrimal glands leading to dry mouth and eyes
What causes rheumatoid arthritis?
loss of tolerance to (excess) citrullinated proteins which leads to production of anti-citrullinated protein antibodies (ACPAs)
How is citrulline produced?
citrullination of proteins (such as arginine) by PAD enzymes - normal physiological process
Where does citrullination occur?
in joints (joint proteins are prone to citrullination by PAD enzymes)
Examples of joint enzymes that can undergo citrullination
vimentin, filaggrin, collagen
When may citrulline trigger inflammation?
excess citrulline can be recognised as a threat
What is the aetiology of rheumatoid arthritis?
environmental and/or genetic factors, other diseases (e.g. periodontitis)
What is the pathogenesis of rheumatoid arthritis?
joint inflammation, increased osteoclast activity, circulating ACPA
What is the sequalae of rheumatoid arthritis?
NSAIDs, steroids, treatment of other diseases
Examples of systemic diseases linked to periodontitis
diabetes, rheumatoid arthritis, respiratory disease, stroke, Alzheimer’s disease
How can periodontitis trigger rheumatoid arthritis?
Porphyromonas gingivalis (periodontopathogen) produces PAD enzymes which drives excess citrullination
