Disorders of the Immune System Flashcards
Hypersensitivity is an exaggerated or inappropriate immune response which results tissue damage
Hay types I-IV
What type of things cause type 1 hypersensitivity?
Food
Insect bites
Pollen
House dust mite
Animal hair
Moulds
Medicine - penicillin
~15% of population suffer from IgE mediated allergic diseases. Asthma is another example
What happens to someone with type 1 hypersensitivity when they are first exposed to pollen?
Sensitisation phase: B cells recognise pollen Ag
They become pollen APCs to Th2 which secrete IL4
IL4 induces class switch, B cells make IgE
Effector phase: IgE binds to mast cell receptors by its tail end (Fc region)
What happens to someone with type 1 hypersensitivity when they are exposed to pollen for a second time?
2nd pollen exposure: Ya hay mast cells w IgE attached.
Pollen enters and binds to IgE, sometimes cross linking them
Mast cells release histamine + generate cytokines which stimulate Th cells to produce cytokines too
Late-phase reaction also happens
Allergic reaction is prolonged.
Describe type 2 and 3 hypersensitivity
Type II involves Abs binding to Ags on cell surfaces.
Type III involves immune complexes w soluble antigens.
Both types initiated by Ag and Ab interaction, can be IgM and IgG mediated.
Examples of type II: Rheusus isoimmunisation, HDN
Myasthenia gravis, Grave’s disease- (type V in some reports)
Examples of type III: SLE
Describe the pathophysiology of Myasthenia gravis
Normal muscle contraction: impulses trigger Ach release which binds to Ach receptors on muscle cells triggering contraction.
In Myasthenia gravis autoantibodies to Ach receptors are produced. These block Ach receptors at the postsynaptic neuromuscular junction. Muscle contraction diminished.
Describe SLE autoimmune disease (systemic lupus erythematosus)
Which organ can get esp affected?
What kind of B cell activation do SLE patients have?
Aetiology unknown – familial pattern
Pts make autoantibody which attacks DNA and nuclear ribonucleoproteins
These antibodies form immune complexes, which can trigger complement-> tissue injury
Complexes get trapped in kidney–>glomerulonephritis
B cell activation abnormal/higher in patients with SLE
What 5 other problems arise in SLE patients?
- B cells are more sensitive to cytokines, leading to excessive activation and abnormal antibody production.
- Also an unusual problem; B cells undergo polyclonal activation–> diverse Abs which target the body’s own tissues
- There is an increase in pro-inflammatory cytokines
- Th1 response reduced
- Tanto immunocomplex production means phagocytes have difficulties clearing immune complexes
Describe type 4 hypersensitivity. Give an example of a bacterial infection which is type 4 in your explanation
Type IV- Delayed hypersensitivity
Mantoux test/tuberculin skin test= examples
T cell mediated: react to specific Ags e.g. mTB
T cells release cytokines inc TNF-a that activate macrophages etc which cause tissue damage
Characteristic response= granuloma containing epithelioid, giant cells, caseous necrosis
Granulomas may form w other infections e.g. leprosy,
syphilis and schistosomiasis. Necrosis may be absent in these
Describe Type 1 diabetes and Coeliac disease
What type of hypersensitivity are these diseases?
T1DM: Beta cells in islets of Langerhans act as autoantigen
APCs present MHC II, stimulate CD4+ Th cells
Th1 cells release cytokines, activate CTLs, damage Beta cells
Coeliacs: Patients’ HLA type is important
Pts have IgA anti-gliadin, antiendomysium and antireticulin Abs
Ab + T cell = inflammation, causes villous atrophy, malabsorption
Both diseases= type 4 hypersensitivity
Describe GI disease associated w type 4 hypersensitivity
What do these entail, which types of T cells are involved in each?
Crohns and ulcerative colitis. In both these diseases:
High B cell numbers produce auto-antibodies on GI site
Complement components are deposited in the intestinal mucosa
Autoantigens presented on MHC II
Increased interleukin levels
Crohn’s= Th1 involved. Ulcerative colitis= Th2 involved
Auto immune disease is acquired immune reactivity to self antigens, ~3.5% of individuals.
Describe AI disease and its contributing factors
Age: autoantibodies more common in older ppl.
Sex: SLE and Grave’s more common in women
Genetics: HLA genes linked w certain AI diseases
Infections: link between EBV and SLE
Drugs: eg procainamide for arrythmia can cause SLE. Stopping treatment resolves the problem.
Immunodeficiency: persistent infections or inflammation can cause AI
How can specific autoantigens contribute to AI disease?
Specific autoantigens – highly conserved proteins are often targets for autoimmune response.
Eg: Heat Shock Proteins can cross-react with similar self-proteins.
HSPs are stress-response proteins found in both microbes and human cells.
If the immune system generates Abs against microbial HSPs, these Abs may mistakenly recognise and target self-HSPs due to similarities.
This cross-reactivity–> development of autoimmune disease.
Describe B cell deficiencies
Describe T cell deficiency
T- cell deficiency
Lack of thymus is an example
DiGeorge syndrome – incomplete development of the thymus
