W05 - IMM.: Hypersens; AuImm.; 1º Immunodeficiency Flashcards
Contrast the mechanisms of Types I, II, III and IV hypersensitivity.
I - immediate,
II - cell-bound ag.,
III - immune complex,
IV - delayed,
V
Define the roles of allergen, IgE, mast cells, inflammatory cells, mediators and cytokines in Type I hypersensitivity.
IgE = trigger immediate hypersensitivity, which manifests as allergy symptoms such as asthma or rhinitis
* instant onset if IgE preformed
* adaptive immune response mediator
Mast cells and eosinophils act as innate immune system mediators => degranulate
= allergy, hypersens.
Explain the pathophysiology of early and late phase allergic reactions.
B cells produce IgE when co-stimulated with IL-4 (secreted by TH2 cells)
=> IgE
=> MC degran across tissues, eosinophils localise
- prostaglandins and leukotrienes (mucus & smc conrtraction) via cyclooxygenase and lipoxygenase
+ histamine in skin
=> vasodilation = permeability
Define atopy.
Immediate hypersensitivity reaction to environmental antigens mediated by IgE.
Illustrate the clinical effects of Type I Hypersensitivity.
Rhinitis, Asthma, Anaphylaxis, Dermatitis
- angioedema
- eczema
- acute urticaria
Define the roles of antibody, complement, Fc receptor bearing cells and ADCC in Type II hypersensitivity.
Ab-mediated. IgG or IgM reacting with Ag present on surface of cells.
=> complement or FcR on macrophages
=> opsonisation of targt cells
*IgM associated with antigens
Illustrate the clinical effects of Type II hypersensitivity.
=> immune mediated haemolysis
=> drug-induced haemolysis
Define the pathophysiology of immune complex formation in localised and systemic Type III hypersensitivity.
Immune-complex, IgG also responsible
=> dmg caused by ag-ab complex whcih circulate
=> innate immun activation = mast cell, thrombi, capillary permeability
*usually will be cleared by complement = phagocytosis
Explain the factors involved in formation of abnormal immune complexes.
polvalent antigens, and creation of large complexes that circulate and initiate innate immunity
- drugs eg. vaccines
*
Illustrate the clinical effects of Type III hypersensitivity.
glomerulonephritis, SLE, arthus reaction, farmer’s lung
Define the roles of haptens, carrier proteins, Th1 cells, Th17 cells, antigen presenting cells and monocytes/macrophages in Type IV hypersensitivity.
Slowest, delayed response mediated by T cells
*dendritic cells present antigens in LN presenting to Tc.
* Proliferaation of specific Tc which migrate to site of inflammation
* TNF secreted by macrophages and Tc stimulate draamage
Th1 and Th17 infiltrate synovium (RhArth.) or produce inflammatory lesions in NS (MS)
> avoid antigen triggers
anti-inflamm: NSAIDs, steroids, TNF-blockers, IL-6 blocker, Ab against B cells
imm. suppr.
Illustrate the clinical effects of Type IV hypersensitivity.
rheumatoid arth.,
- joints, tendons
- citrullinated proteins = ag drive.
= anti-CCP antibodies
+osteoclast activation
+ persistent IL-6 = acute phase reponse
+ smoker associated, porphyromonas infection (gum infection)
MS.
- inflamm. lesions = relapse-remitting nature
= myelin loss/time
T cells in plaques react to protein
Antibody associated with different hypersensitive conditons
IgE, it may subsequently trigger immediate hypersensitivity, which manifests as allergy symptoms such as asthma or rhinitis.
dust stimulates IgG antibodies, it may trigger a different kind of hypersensitivity, such as farmer’s lung.
Define hapten
Haptens are small molecule irritants that bind to proteins and elicit an immune response.
Mechanism of corticosteroids in the therapy of atopic disease
inhibit the synth of MC mediators.
+similarly, epinephrine, and SABA inhibt the effects of MC mediators also.
Alloimmune haemolysis
IgG = rhesus antigen
=> incompatibility illicited from prior exposure, and hemolysis occurring at the second pregnancy.
Autoimmune mediated hemolysis
AuImm:
- induced by infection, drugs
- SLE
- autoantibodies produced by malgnant b cells
Type II AuImm Solid Tissue:
- goodpasture syndrome IgG = basement membrane of lung and glomeruli.
anti-basement membrane elicits complement = immune response
Graves Disease
hyperthyroidism = young women, fh dt stimulation of THS receptor
Define the mechanisms by which immunological tolerance arises.
*same ag may induce imm response or tolerance depending on environmental conditions and other stimuli
TOLEROGENS = ag inducing tolerance
- self-tolerance arises from elimination of self-reaactive T and B cells
* central and peripheral toleran e
AUIMM arises from failure of self-tolerance
Define Autoimmune Disease.
adaptive immune response to self-ag, facilitated by autoantibodies
*autoractive T cells or AuAb facilitate tissue damage via type II, III, IV sensitivity
Illustrate the factors involved in the aetiology of autoimmune disease.
genetic predisposition: poor HLA binding for self-ag, poor expression of self-ag in thymus
- polymorphism clusters in families implicated in breakdown of tolerance
infective:
- molecular mimicry
environmental factors: free radicals, radiation = alter self-peptide
- UV radiation - skin inflamm.
Describe the pathogenetic mechanisms involved in autoimmune disease.
breakdown at diffent points of maintenance
- disrupted self-ag presentation at thymus
- less autoreactive t cells deleted = more escape to periphery
- leaked dna not cleared by complement: SLE has DNA-IgG complexes
- physical barriers around cells defective
- infection may trigger molecular mimicry
Contrast organ-specific and non-organ specific autoimmune disease.
NON-ORGAN-SPECIFIC => affect multiple organs dt wide distirbution of responses against self-molecules
- SLE
- RhArth.
- Dematomyositis
ORGAN-SPEC => restricted to one organ, endocrine glands (T1DM)
- MS
- Hashimotos & other thyroid etc.
- MGravis
- Pernicious anemeia
- Addisons
- Pancreeas
Define the role of HLA molecules in autoimmune disease.
The human leukocyte antigen (HLA) system, which corresponds to the major histocompatibility complex (MHC) in humans, plays a pivotal role in the antigen presentation of intracellular and extracellular peptides and the regulation of innate and adaptive immune responses
he development of protease inhibitors designed to alter the antigen presenting properties of HLA molecules, by blocking the presentation of potentially auto-antigenic peptides, could direct the immune system away from a particular antigenic motif and in turn the autoimmune disease process
