Pathology summary session

Question 1

Meaning of ‘patho’

Answer 1

suffering

Question 2

Meaning of ‘logos’

Answer 2

study of

Question 3

Immunology definition

Answer 3

study of the immune system

Question 4

Pathology definition

Answer 4

study of the causes/effects of diseases

Question 5

Why is it important to understand immunology and pathology?

Answer 5

to make the correct diagnosis, to provide correct treatment, referrals, advice and education for patients

Question 6

Aetiology definition

Answer 6

the cause of a disease or condition (pathology)

Question 7

What are the 2 natures of aetiology?

Answer 7

genetic and/or environmental

Question 8

Example: what are the possible aetiologies of a type I hypersensitivity reaction?

Answer 8

genetic - mutations
environmental - hygiene hypothesis or pollution

Question 9

Pathogenesis definition

Answer 9

progressive changes as disease develops which includes morphological cellular changes

Question 10

What is the aim of an inflammatory reaction?

Answer 10

eliminating the inciting cause

Question 11

What are the possible inciting causes of inflammation?

Answer 11

invading microorganisms, particulate materials (allergens/prostheses), altered self cells (growth disorders/cell injury), transformed malignant cells (neoplasia)

Question 12

What is the aetiology/inciting cause of acute inflammation?

Answer 12

infection or tissue damage

Question 13

What is the onset of acute inflammation like?

Answer 13

rapid onset (but short-term and localised)

Question 14

Which part of the immune system is involved in acute inflammation?

Answer 14

only the innate immune system (e.g. neutrophils)

Question 15

Is there complete resolution in acute inflammation?

Answer 15

yes - complete restoration of function and appearance of tissues

Question 16

Examples of acute oral diseases

Answer 16

glossitis, stomatitis, cheilitis, gingivitis

Question 17

What are the possible aetiologies of acute oral diseases?

Answer 17

microorganisms, particulate materials, physical trauma

Question 18

What is glossitis?

Answer 18

inflammation of the tongue

Question 19

What is stomatitis?

Answer 19

inflammation of larger parts of the oral mucosa (buccal)

Question 20

What is cheilitis?

Answer 20

inflammation of the lips

Question 21

What is gingivitis?

Answer 21

inflammation of the gums

Question 22

What may result if acute inflammation is persistent?

Answer 22

chronic inflammation

Question 23

What is the inciting cause of gingivitis?

Answer 23

a build up of dental plaque results in biofilm dysbiosis

Question 24

Which cells are involved in gingivitis?

Answer 24

epithelial cells and innate immune cells

Question 25

How do epithelial cells respond to gingivitis?

Answer 25

produce soluble mediators (e.g. AMPs) as part of saliva / gingival crevicular fluid

Question 26

How do innate immune cells respond to gingivitis?

Answer 26

phagocytosis, degranulation (NETosis), antigen presentation, mediator release

Question 27

Sequalae for gingivitis

Answer 27

removal of biofilm via scale and polish and OHI

Question 28

How long can chronic inflammatory diseases last?

Answer 28

up to years (long-term)

Question 29

Which parts of the immune system are involved in chronic inflammation?

Answer 29

innate and adaptive immune system

Question 30

Is there restoration of tissues following chronic inflammation?

Answer 30

no restoration - tissue damage (e.g. fibrosis) has occurred

Question 31

What diseases do chronic inflammatory diseases tend to arise from?

Answer 31

acute inflammatory diseases

Question 32

Examples of chronic oral diseases

Answer 32

periodontitis, lichen planus, orofacial granulomatosis (also type IV hypersensitivity reaction), candidiasis, abscesses

Question 33

What is periodontitis?

Answer 33

chronic gum inflammation with destruction of alveolar bone

Question 34

What is lichen planus?

Answer 34

chronic inflammatory condition affecting skin / mucous membranes similar to orofacial granulomatosis

Question 35

What is orofacial granulomatosis (OFG)?

Answer 35

A type IV hypersensitivity reaction that is also a chronic inflammatory disease (M1 macrophages). Leads to granulomas in oral mucosa)

Question 36

What is candidiasis?

Answer 36

fungal infection of the tongue

Question 37

What is an abscess?

Answer 37

a collection of pus formed by immune cells attempting to fight microorganisms. Can be acute or chronic

Question 38

What is the inciting cause of periodontitis?

Answer 38

further growth of biofilm into the periodontal pocket and biofilm becomes more dysbiotic

Question 39

What is the name of the keystone pathogen of periodontitis?

Answer 39

Porphyromonas gingivalis

Question 40

What is the role of the adaptive immune system in periodontitis?

Answer 40

T cells and B cells are activated, excess soft and hard tissue regeneration occurs

Question 41

How is alveolar bone destroyed in periodontitis?

Answer 41

imbalance between osteoclastogenesis and osteoblastogenesis. there is increased osteoclast activity (osteoclastogenesis)

Question 42

Why is there increased osteoclast activity in periodontitis?

Answer 42

Porphyromonas gingivalis PAMPs (e.g. LPS) bind to TLRs on osteoblasts triggering RANKL synthesis and secretion. This results in RANKL>OPG imbalance

Question 43

Immunological tolerance definition

Answer 43

the body's ability to recognise self-peptides (proteins)

Question 44

What happens if there is a loss of immunological tolerance?

Answer 44

can result in autoimmune diseases

Question 45

What are the tolerance mechanisms in place to prevent autoimmune diseases?

Answer 45

Central tolerance and peripheral tolerance

Question 46

What happens in central tolerance?

Answer 46

T cells and B cells undergo negative selection during education to ensure no self-reactive cells enter circulation

Question 47

Function of peripheral tolerance

Answer 47

prevents the activation of self-reactive T and B cells that may escape central tolerance and enter the periphery

Question 48

What are the 3 signals required for CD4+ T cell activation?

Answer 48

1. MHCII-TCR interact as antigen is presented by APC 2. Interaction of costimulatory molecules 3. APC releases cytokines that trigger CD4+ T cell differentiation

Question 49

How do self-reactive T cells become anergic in peripheral tolerance?

Answer 49

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

Question 50

What happens to anergic T cells?

Answer 50

removed by apoptosis

Question 51

How does peripheral tolerance prevent the activation of self-reactive B cells?

Answer 51

Anergic T cells are removed by apoptosis therefore self-reactive B cells cannot be activated by thymus-dependent activation

Question 52

Why can self-reactive B cells not be activated by thymus-independent activation?

Answer 52

microbial components (e.g. LPS) are required as well as the antigen

Question 53

How does the peripheral tolerance mechanism fail in autoimmunity?

Answer 53

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

Question 54

Examples of autoimmune diseases

Answer 54

rheumatoid arthritis and Sjogren's syndrome

Question 55

What happens in Sjogren's syndrome?

Answer 55

self-reactive T and B cells attack the cells of the salivary and lacrimal glands leading to dry mouth and eyes

Question 56

What causes rheumatoid arthritis?

Answer 56

loss of tolerance to (excess) citrullinated proteins which leads to production of anti-citrullinated protein antibodies (ACPAs)

Question 57

How is citrulline produced?

Answer 57

citrullination of proteins (such as arginine) by PAD enzymes - normal physiological process

Question 58

Where does citrullination occur?

Answer 58

in joints (joint proteins are prone to citrullination by PAD enzymes)

Question 59

Examples of joint enzymes that can undergo citrullination

Answer 59

vimentin, filaggrin, collagen

Question 60

When may citrulline trigger inflammation?

Answer 60

excess citrulline can be recognised as a threat

Question 61

What is the aetiology of rheumatoid arthritis?

Answer 61

environmental and/or genetic factors, other diseases (e.g. periodontitis)

Question 62

What is the pathogenesis of rheumatoid arthritis?

Answer 62

joint inflammation, increased osteoclast activity, circulating ACPA

Question 63

What is the sequalae of rheumatoid arthritis?

Answer 63

NSAIDs, steroids, treatment of other diseases

Question 64

Examples of systemic diseases linked to periodontitis

Answer 64

diabetes, rheumatoid arthritis, respiratory disease, stroke, Alzheimer's disease

Question 65

How can periodontitis trigger rheumatoid arthritis?

Answer 65

Porphyromonas gingivalis (periodontopathogen) produces PAD enzymes which drives excess citrullination