2.3 Hypersensitivity + Autoimmunity and Microbe Immune Evasion Flashcards
What are the causes of hypersensitivity?
- Autoimmunity / Self-antigens
- Excessive microbial response
- Non-microbial antigens (allergic diseases)
What are the 2 types of non-microbial environmental antigens (allergic diseases)?
IgE mediated (histamine based)
T-cell mediated (cytokine based)
Type 1 hypersensitivity is associated with asthma. What are the different factors involved?
IL-4, IL-5, and IL-13 produced by Th2 cells
These lead to increase in IgE antibodies
IgE tagged Mast cells + eosinophil activation release histamine + inflammatory mediators
Type 2 hypersensitivity leads to inflammation / blocking through antibodies (Ab) + cells. What diseases are associated with this type of IgG / IgM mediated hypersensitivity?
Rheumatoid arthritis
Pemphigus vulgaris
Grave’s disease
Hashimoto’s disease
Type 3 hypersensitivity causes inflammation through Ab-Ag complexes in the vascular bed. What are the key targets of this IgG / IgM mediated hypersensitivity?
Blood born targets
Immune plasma antigen complexes damage vessel walls leading to inflammation, thrombosis, and tissue injury
What are causes of type 3 hypersensitivity?
Vasculitis
Systemic lupus erythematosus (SLE)
Serum sickness
Type 4 hypersensitivity is T-cell mediated (CD-4 or CD-8) and features no antibody involvement. What diseases are associated with this type of hypersensitivity driven by neutrophils and macrophages?
TB, coeliac disease, leprosy, graft vs host disease, chronic transplant rejection, MS, viral hepatitis
What are the key differences between the 4 types of hypersensitivity?
Type 1 = IgE mediated, inflammation via histamine
Type 2 = IgG / IgM mediated, inflammation via Ab + cells
Type 3 = IgG / IgM mediated, inflammation via Ab-Ag complexes in vascular bed
Type 4 = T-cell mediated, driven by neutrophils + macrophages
What are examples of type 1 hypersensitvity diseases?
Asthma, contact allergy, drug response, angioedema, anaphylaxis
Priming is the immune response to a first exposure to an antigen. What is the process behind this in asthma priming?
- Allergen + dendritic cell = response
- Th2 responds by releasing IL-4 + IL-5
- IL-4 = mast cell growth, IL-5 = eosinophil growth/activaiton
- IL-4 + IL-5 both drive B cells to IgE production
- IgE binds to mast cells, arming them
Rechallenge occurs during a re-exposure to an antigen. What is the process behind astham rechallenge?
- Allergen + IgE armed mast cell in epithelium
- Activated IgE mast cell receptor = degranulation of mast cells
- Opens epithelial tight junctions allowing penetration of allergen to mucosal amst cells
- Further degranulation of mast cells + release of imflammatory mediators
What are gingipains?
Cysteine proteinases of Porphyromonas gingivalis with the potential to disrupt T-cell mechanisms
Gingipains are large protein molecules. What is their structure and how does this help attack many host proteins?
Enzymatic head linked to a long body called adhesin domain
Adhesin domain finds + captures target
Proteolytic enzyme head degrades captured target molecule
Tissue inhibitors of almost all proteolytic enzymes are not effective against gingipains (RgpA), negatively affecting immune response against P. gingivalis infection. Why is this?
Gingipains potentially disrupt immune responses
Gingipains efficiently disrupt neutrophil function
Macrophages are the main form of defence against gingipains. Why are they not always so effective?
- Macropphages recognise active gingipains which the absorb and deactivate
- Once deactivated, the gingipain is no longer recognised by macrophage and remains inert in cytoplasm
- High levels of gingipain kill the macrophage
- Limited macrophage recruitment + activation in diseased periodontium, gingipains easily outnumber them
