Hypersensitivities Flashcards
IgE mediated degranulation of mast cells is a key effector mechanism of which of the following inflammatory events?
Type I Hypersensitivity
What are 4 features of type I hypersensitivity?
Increased vascular permeability
Oedema
Acute inflammation
Infiltrate of eosinophils
What do type one hypersensitivies require first?
Prior sensitiziation -> TH2 switches on B cells via ILs
B cell produces IgE antibodies that bind to mast cell (now are armed and will degranulate next time)
Can type I hypersensitivites be triggered by opioids or drugs?
Yes - things we have never been exposed to before can cause this
What are preformed mediators in mast cells?
Histamine, heparin and tryptase
Serine proteases activate complement (anaphylotoxins)
What are rapidly synthesised mediators in type I reactions?
Prostaglandins + leukotrienes - bronchospasm + vasodilation
What happens in late phase type I?
Cellular infiltrate - onset 4-8h lasts 24h
Mast cells release chemokines -> TFN-a, IL1,3,4,5,6
Epithelial cells release eotaxin, IL6 and IL8
What are some examples of type I?
Allergic rhinitis, acute bronchial asthma, food hypersensitivity, flea bite HS
What is a milk allergy?
Milking delayed - a-casein into blood treated as foregin causing systemic anapyhylaxis and multifocal cutaneous oedema
What is canine and feline atopy?
Allergic dermatitis - from ingested or inhaled antigen
Genetic predisposition (increased IL4) to develop Ag-specigic IgE and IgG against environmental antigens and antibodies attach to cutaneous mast cells
Re-exposure to antigens by any route provokes cutaneous type I hypersensitivity
How does desensitisation work?
High dose of antigen stimulates TH1 response = IgG production
Activates macrophages to produce IL12 and present antigens to CD4
How is type II described?
IgG and IgM mediated - IgG binds to self or foreign agntigens coated onto cells stimulating phagocytosis
NKC, copmlement mediated lysis of cell = tissue damage against own cells
What is antibody dependent cytotoxicity?
Involved in type II
IgG binds with complement -> MAC -> opsonins + chemotaxis for neutrophils + eosinophils damaging accidentally targeted cells
What is drug induced immune mediated haemolytic anaemia?
Type II reaction
What is haemolytic anaemia?
Type II - maternal IgG attack fetus erythrocytes (by colostrum)
What are myasthenia gravis and pemphigus vulagaris part of?
Type II hypersensitivity
Myasthenia - response against nicotinic acetylcholine receptor
Pemphigus - keratinocyte antigens
What are two types of immune mediated haemolysis?
Extravascular - rbc agglutination and rbc phagocytosis by splenic macrophage = jaundice + anaemia
Intravascular - complement binding + activation rbc lysis and red urine
what is type III response?
Lots of antigen -> excess antigen and IgG and IgM complexes form in blood that precipitate in tissues (glomeruli, vessel walls)
Activates complement
Usually chronic disease
Neutrophils attracted to complex causing inflammation
What can stimulate type III?
Large doses of antigen Pyometra Persistent infectious agents Repeatedly inhaled things Persistently available self antigen (lupis)
Examples of Immune complex diseases (Type III)
EIA Adrican swine fever Liver fluke in cattle Pyometra Infectious canine hepatitis
What is immune complex glomerulonephritis?
Circulating Ab:Ag complex deposits in glomerulus
Antibodies leave circulation and complex with glomerular self antigens or endo/exogenous antigens in glomerulus
African swine fever
Membranoproliferative glomerulonephritis
Subendothelial immune complex deposited
Reactive prolferation of mesangial cells
Thickened glomerular capillary BM and amyloid deposits
What is type IV?
cell mediated/delayed type
No antibody involvement
depends on Ag specific sensitised T cells to be present to react (infiltration of tissue by monocytes + lymphocytes)
Intensity delayed until 48-72h
Cell mediated vs delayed type
Protective CMI beneficial
Normal immune respone to poorly digestible antigen
Immunopathological DTH deleterious + causing chronic lymphocyte + granulomatous inflammation
What is tuberculin reaction?
Type IV
What is canine allergic contact dermatitis?
Type IV - intitiated by transdermal absorbed haptens (formaldehyde)
IFN-g from CD8+ and CD4+ cells attracts monocytes + lymphocytes
Self tolerance
Central clonal deletion of self-reactive T cells and B cells in fetal thymus and bone marrow - t cell receptors on trial in thymus (self react = deleted)
What are anatomically sequestered antigens?
Exposed by tissue damage - milk allergy, post traumatic sympathetic uveitis, sperm granulomas
What is molecularly sequesered antigen?
exposure of epitopes normally hidden in globular proteins
What is bacterial superantigens?
+++ immunostimulatory proteins = bind to MHC and T cell receptor domains, activating large % of bodies APCs and T lymphocytes
Which of the following protects spermatozoa from immune attack?
a. High background levels of IL-1a, Il-6 and TGF-b and Activin-A in the testis.
b. Immune tolerance generated by Hassall’s corpuscles during thymus development.
c. Low expression of MHC-I by spermatogonia.
d. Down-regulation of IL-17 by spermatogonia and spermatocytes.
a. High background levels of IL-1a, IL6 and TGF-b and activin-A in the testis
What is canine phemigus?
Bullous vesicular disease - lesions appear at mucocutaneous junctions
What are two examples of inherited immunodeficiency?
Chediak-higashi syndrome
Severe combined immune deficiency of arabs
- Chédiak-Higashi Syndrome results in:
a. Normal CD8+ cytotoxicity & NK functions but impaired B-cells.
b. Failure of phagolysosome formation in neutrophils and macrophages.
c. Failure of phagocytosis by neutrophils.
d. Normal circulating neutrophil numbers but abnormal neutrophil granules.
e. A defective adaptive immune system due to a defective immunoglobin gene.
d. Normal circulating neutrophil numbers but abnormal neutrophil granules.
Chediak-higashi syndrome
Neutropaenia and partial albinism
Neutrophils, macrophages, lymphocytes and melanocytes have defective giant intracellular granules due to microtubule effect
Neutrophils and macrophages can phagocytose but phagolysosome fusion is delayed
Cd8+ cytotocivity and NK impaired - B cells are fine
- Severe Combined Immune Deficiency (SCID) in Arabian foals has which of the following features?
a. There is partial failure of adaptive immune responses.
b. Antibody response is retained.
c. Defective Ig gene results in loss of B and T cell receptors.
d. They can be diagnosed at age 1 week by measuring plasma IgG.
e. Haematology at 1 week of age reveals an absence of circulating lymphocytes (absolute lymphocytopaenia).
c. Defective Ig gene results in loss of B and T cell receptors.
SIDS
Complete failure of adaptive response - coat linked autosomal recessive
Defective B and T cell receptors
Normal at birth, fine until 1-3 months surviving on colostrum - rely only on neutrophils
Dead by 5 months
Acquired immunodeficiency examples
Retrovirus/lentivirus
AIDS like - decreased T cell function (FIV, SIV)
T-2 toxin, corticosteroids
- In older animals which of the following is a recognised feature of immunosenescence?
a. There is a random deletion of CD4 lymphocytes
b. Phagocytes increase in number to counteract a decline in lymphocytes.
c. Response to vaccination is usually still strong.
d. There is an increase in CD4:CD8 lymphocyte ratio
e. There is diminished self-renewal capacity of haematopoietic stem cells.
e. There is diminished self-renewal capacity of haematopoietic stem cells.
Immunosenescence
Gradual deterioration of immune system with aging
Decreased self-renewal of haematopoietic stem cells
Less phagocytes
NK cells less cytotoxocity function
Decline in humoral immunity
Reduction in CD4:CD8 ratio
