Immunology 1: Hypersensitivity + allergy Flashcards
What occurs in appropriate immune reactions?
- required to eliminate pathogens
- -> Involves antigen recognition by cells of the immune system and antibody production
What occurs in appropriate immune tolerance ?
- occurs to self / foreign harmless proteins
–> Involves antigen recognition and generation of regulatory T cells and regulatory antibody (IgG4) production
e.g food, pollen
Hypersensitivity Reactions occur when immune responses are mounted against:
- Harmless foreign antigens (allergy, contact hypersensitivity)
- Autoantigens (autoimmune diseases)
- Alloantigens (serum sickness, transfusion reactions, graft rejection)
hypersensitivity reactions are classified by: Type I : Type II : Type III : Type IV :
Type I : Immediate Hypersensitivity
Type II : Antibody-dependent Cytotoxicity
Type III : Immune Complex Mediated
Type IV : Delayed Cell Mediated
give examples of allergic responses of type 1: immediate hypersensitivity
- Anaphylaxis
- Asthma
- Rhinitis (Seasonal, Perennial)
- Food Allergy
Describe the onset of Type 1 immediate hypersensitivity .
a) primary antigen exposure
b) secondary antigen exposure
a) primary Antigen exposure
- develop Sensitisation (not tolerance)
- involved IgE antibody production
- IgE binds to Mast Cells & Basophils
b) secondary Antigen Exposure
- More IgE Ab produced
- Antigen cross-links IgE on Mast Cells/Basophils
- -> causes Degranulation + release of inflammatory mediators
Clinical presentation of Type II Antibody-Dependent Hypersensitivity depends on:
target tissue
e.g organ specific autoimmune disease
(myasthenia gravis)
e.g autoimmune cytopenias
(hemolytic anaemia, thrombocytopenia)
in Type II Antibody-Dependent Hypersensitivity, what are some tests you could perform for specific autoantibodies?
- Immunofluorescence
- ELISA
- -> e.g anti-CCP (Cyclic Citrullinated Peptide Antibodies for Rheumatoid Arthritis)
What happens in Type III Immune Complex Mediated Hypersensitivity ?
- Formation of Antigen-Antibody complexes in blood
- Complex deposition in blood vessels/tissue
- leads to Complement + Cell activation
- Activation of other cascades eg clotting
- Tissue damage (vasculitis)
- -> Systemic lupus erythematosus (SLE)
- -> Vasculitides (Poly Arteritis Nodosum, many different types)
What are some types of type IV Delayed Hypersensitivity Responses ?
- Chronic graft rejection
- GVHD
- Coeliac disease
- Contact hypersensitivity
- Many autoimmune diseases….
- -> MOSTLY Th1 mediated
describe the mechanisms involved in type IV Delayed Hypersensitivity Responses.
- Transient/Persistent Ag
- T cell activation of macrophages, CTLs
- Much of tissue damage dependent upon TNF & CTLs
what common features might you seen in an inflammation?
what clinical symptoms might this cause ?
- increased recruitment of immune cells
- increased activation of immune cell
- inflammatory mediators released
- Vasodilatation –> redness
- Increased vascular permeability –> swelling
- Inflammatory mediators &cytokines –> selling + pain + heat
- Inflammatory cells & tissue damage
- -> redness
- -> heat
- -> heat
- -> pain
note: Increased vascular permeability Caused by:- C3a, C5a, histamine, leukotrienes Cytokines IL-1, IL-6, IL-2, TNF, IFN-γ Chemokines IL-8/CXCL8, IP-10/CXCL10 Inflammatory cell infiltrate Cell trafficking – chemotaxis Neutrophils, macrophages, lymphocytes, mast cells Cell activation
-
What are common allergens?
allergies = type 2 hypersensitivity
- cat fur
- dust
What are risk factors of allergy?
genetic factors
- -> polygenic risk
- -> 80% of atopics have family history
- -> genes on chr 11q linked to atopy + asthma
- IL4-gene cluster linked to raise IgE, allergy
environmental factors
- -> age
- -> gender (more common in male children, more common in female adults)
- -> family size
- -> infections (early life infection protects from allergy)
- -> animal
- -> diet (breast feeding,fatt acids = protective)
What are the different types of inflammation in allergy?
- Anaphylaxis, urticaria, angioedema
- -> type I hypersensitivity (IgE mediated) - Idiopathic/chronic urticaria
- -> type II hypersensitivity (IgG mediated) - Asthma, rhinitis, eczema:
- -> mixed inflammation
- type I hypersensitivity (IgE mediated)
- type IV hypersensitivity (chronic inflammation)
Expression of disease requires what 2 aspects?
a) Development of sensitisation to allergens instead of tolerance (primary response - usually in early life)
b) Further exposure to produce –> disease manifestation (memory response - any time after sensitisation)
Sensitisation in Atopic Airway Disease
START HERE
Subsequent exposure
???
Note: Eosinophils
Recruited during allergic inflammation
Generated from bone marrow
Nucleus - two lobes
Contain large granules
toxic proteins
Lead to tissue damage
-
Crosslinking of IgE’s on mast cell surface can lead to =
- Mediator release
–> Pre-formed
histamine + cytokines + toxic proteins - Newly synthesized
- -> leukotrienes + prostaglandins
Note: Neutrophils
- Polymorphonuclear cells (PMNs)
- -> nucleus contains several lobes
- Granules contain
- -> digestive enzymes
- Also synthesize
- -> oxidant radicals
- -> cytokines
- -> leukotrienes
-
Describe the immunopathogenesis of asthma.
also, what happens in chronic inflammation of the airways
- causes Acute inflammation of the airways
- mast cell activation & degranulation
- Pre stored mediators
(histamine) - Newly synthesised mediators
(prostaglandins+leukotrienes) - acute airway narrowing
QUESTION: Chronic inflammation of the airways - Cellular infiltrate (Th2 lymphocytes, eosinophils) - Smooth muscle hypertrophy - Mucus plugging - Epithelial shedding - Sub epithelial fibrosis
Two-phase response to single allergen challenge
???
