Immunology - Hypersensitivity Flashcards
Th1 vs Th2
Th1 - T helper cells responsible for promoting cell-mediated immunity & killing infected cells. CD4+ T cells secrete IL-2 (T cell growth factors) and interferon gamma (inhibits viral replication)
Th2 - T helper cells responsible for humoral immunity –activates B cells to differentiate into plasma cells for allergic response.
Basic immunology:
1) Innate immunity: how are pathogens recognised?
2) What are PMNs?
2.5) Describe action of neutrophils
3) What’s complement system
4) List the Inflammatory cytokines and anti-inflammatory cytokines.
5) Types of Ig
1) Pathogens are recognised by the body via PRRs (pattern recognition receptors) found on surface of cells (epithelial, endothelial cells, phagocytes, DCs, lymphocytes incl NK cells) which detect PAMPs (pathogen-associated molecular patterns)
2) PMNs –polymorphonucleate cells - granulocytes eg eosinophils, basophils and neutrophils – which are the most abundant. Unselectively biocidal–
2.5) NETosis: after neutrophils phagocytose pathogen, releases neutrophil enolase which hydrolyses its histones, decondensing chromatin –> extrudes –> NET
3) Complement system: a system of complement proteins produced by cells (via classic, lectin and alternate pathways) which direct immune system response by controlling T,B cells – (MEMBRANE ATTACK COMPLEXES), promote phagocytosis & trigger inflammation ;
4) Pro-inflammatory cytokines:
IL-1 & TNF-a: Increase blood vessel permeability
IL-2: T cell growth factor
IL-6: C-reactive protein from liver –> activate complement system
IL-8: recruit PMNs
IL-12: increase NK cell activity
Anti-inflammatory cytokines:
IL-10: inhibits pro-inflammatory cytokines
IL-37: broadly suppresses inflammation
TGF-b (transforming GF): cleaves extracellular domain of cytokine receptors for inflammatory mediators
5) IgG - default secretion by plasma cells, can cross placenta to foetus
IgA - found on mucosal surfaces, in secretions like mucus, saliva, breast milk
IgE - allergic reactions
IgM - early immunity, aggs of 5, can be att to B cells or secreted in blood
IgD - attached to B cells, activates basophils and mast cells
Tolerance
- What are the 3 principles of tolerance
- Name and describe the difference types of tolerance
3 principles:
1) Immune system must react to a wide variety of microbes/pathogens
2) Must not attack self
3) Must not attack commensal microbiome/harmless antigens
1) Central tolerance
- Both positive and negative selection for T cells:
* Negative selection of self-reactive B and T lymphocytes during dvpt in bone marrow/thymus by macrophages and dendritic cells or apoptosis, or receptor editing for B cells
* Positive selection of T cells for ability to bind to MHC and peptide; to form MHC:peptide complexes & Positive selection for Treg cells by specialised epithelial cells
* Positive selection of B cells with pre-B cell receptor with binding affnity to its designated antigen ligand.
2) Peripheral tolerance
- Destruction of self-reactive T,B cells that have escaped from bone marrow/thymus
- By maturation and anergy (inactivation of self-reactive lymphocytes) - suppression by Treg cells
- Deletion/apoptosis - by absence of costimulation, expression of deletor receptors or production of pro-apoptotic protein
2.5) Immunological homeostasis
- Type of peripheral tolerance where immune tolerance generated via env exposure - in peripheral tissues & lymph nodes
- At birth we have strong Th2 response and acquire balance with Th1 with exposure to microbes
Types of hypersensitivity
Give egs
Type I - Immediate
- Primary exposure - sensitisation by IgE produced by B cells which bind to mast cells. Secondary exposure - allergic response: allergen binds to adj IgE molecs, cross-linking mast cells –> degranulation releases histamine, inflammatory cytokines/chemokines –> inflamm
Eg latex allergy, asthma, peanut allergy, anaphylaxis
Tx: antihistamines
Type II - Antibody mediated
- Cytotoxic reaction w IgG/IgM Abs, complement system
Eg: RHD, penicillin allergy, mistmatched blood transfusion
Type III - Immune complex mediated
- Immune complexes (Ab-antigen complex)
Eg: Systemic lupus erythematosus, vasculitis
Type IV - Delayed
- Cell-mediated (activated by Th1 helper cells) - mediated by macrophages, DCs, NK cells, increase in non-humoral lymphocytes; Reaction to chemical molecs
Eg: Contact dermatitis, graft tissue/organ transplant, delayed latex allergy
Name 4 examples of autoimmune diseases and describe them
Rheumatoid arthritis (Type II)
Systemic inflammatory disorder affecting mainly joints, cartilage but also other organs
B cells differentiate into plasma cells producing rheumatoid factor (an auto-antibody), which bind to antigens on cells → increased inflammation → joint damage
Cause issues with periodontium - bone loss, TMJ, salivary gland function (SS)
Tx: Anti-rheumatic drugs, NSAIDs (non steroidal anti-inflammatory drugs) for pain relief
OHI: electric toothbrush
Sjorgen’s syndrome (Type II)
Syndrome of dry mouth/eyes occurring in 50% of RA cases
Auto-antibodies IgG, IgM → overexpression of inflammatory cytokines → CD4+ T cells & B cells → neural degeneration and destruction of salivary duct acinar cells
Dental Tx: good OH, regular dental visits, higher F toothpaste for caries risk (?)
IIRC Don’t write chewing gum bcs it doesn’t work if salivary glands are nonfunctional; but I think it can help if it’s mild damage?
Systemic lupus erythematosus (Type III)
Chronic autoimmune disease affecting connective tissue
Higher predisposition for oral infection. May take corticosteroids (anti-inflammatory) or immunosuppressants → silent infections (reduced pain & swelling)
Pemphigus vulgaris (Type II)
Autoantibodies directed at skin/oral mucosa desmosomes
Ulceration and slough of buccal mucosa, gingiva
‘Benign’ Mucous membrane pemphigoid (Type II)
Auto-antibodies against hemidesmosomes; aka basement membrane of oral mucosa
Red inflamed gingiva, subepithelial clefting
Rheumatic heart disease
- Describe origin
- Treatment and considerations
Type II - autoimmune disease (Ab-mediated hypersensitivity)
1) Strep infection
Infection by Group A Streptococcus - commonly Strep pyogenes
Can lead to scarlet fever - rash reaction.
2) Host cells can mistake the actual heart cells for bacteria
Molecular mimicry - Strep A bacteria are coated w M proteins which mimic the structural components of heart myosin cells
→ autoimmunity (antibody cross-reactivity) → acute rheumatic fever
3) If ARF untreated, can progress into Rheumatic Heart Disease
ARF leads to scarring of heart tissue and valves → valval incompetency → Need prosthetic valve
Scarring - rough surface, easy for circulating bacteria to bind to → Increased predisposition to infective endocarditis
Antibiotic prophylaxis for pt at high risk of dvping IE and having subsequent adverse outcomes AND undergoing dental procedures w risk of bacteraemia associated with IE.
Amoxicillin/ampicillin 2g oral/IV, 1h prior to procedures
Clindamycin 600mg for severe penicillin allergy (cefazolin if non-severe) 1-2h prior to procedures.
Common oral flora causing endocarditis: Streptococcus viridans, Staphylococcus Aureus, Fusobacterium
Latex hypersensitivity
Latex-protein cross reactivity
Eg of cross-reactive substances: banana, avocado, nuts, kiwi, tomato, potato
More exposure → higher risk among healthcare workers
Management:
Equipment
Hypo-allergenic, powder-free gloves
Plastic LA ampoules - no rubber stopper
Silicone dam instead of RD
Early appoint - lessen exposure to airborne latex
Severe allergic reaction:
Stay with patient, call for help, ambulance 000
Patient’s own medication if prescribed
Administer adrenaline
Administer EpiPen
Immunodeficiency
and its effects on oral health
Things for dental practitioners to note.
Primary immunodeficiency → born with defects in immune system
Secondary immunodeficiency → acquired (from transplant immunosuppressants, diseases affecting immunity, environmental toxins, aging, malnutrition)
Neutrophil defects → severe periodontitis
Due to inefficient PMN migration
Leukocyte adhesion deficiency
Immunocompromised patients: Bacteraemia from dental procedures can be fatal
Additional antibiotic prophylaxis before invasive dental Tx
Atopy
And how to prevent atopic diseases
Atopy = genetic tendency to develop allergy
Atopic diseases are prevented by:
Prenatal exposure (infected mother) - antibiotic used in pregnancy alters gut flora
Birth through birth canal vs C-section
Contact with siblings
Attending childcare with other children
No Antibiotic use in children <1y
