Disorders of Immune System Flashcards
What is hypersensitivity and how many types are there?
Exaggerated/ inappropriate immune response which leads to tissue damage
Types 1-4
What type of things cause type 1 hypersensitivity?
- Food
- Insect bites
- Pollen
- House dust mite
- Animal hair
- Moulds
- Medicine - penicillin
- Latex
What happens to someone with type 1 hypersensitivity when they are first exposed to pollen?
Sensitisation phase:
- B lymphocytes recognise + internalise pollen Ag and present it to Th2 cells
- Th2 cells secrete IL4 (induce B cells to switch class and become 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?
- Pollen enters and binds to IgE, sometimes CROSS LINKING them
- Pollen binding to antibodies (IgE) on Mast cells releases HISTAMINE
- Mast cells generate other CYTOKINES which stimulate Th cells to produce cytokines too (Late-phase reaction)
- Allergic reaction is prolonged.
Describe type 2 and 3 hypersensitivity and give examples of each
Type 2 + 3 initiated by antigen and antibody interaction IgM and IgG mediated
Examples of type II:
- Myasthenia gravis
- Rhesus isoimmunisastion
- Haemolytic disease of the new born
- Grave’s disease (autoimmune thyroid disease)
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, which block Ach receptors at the postsynaptic neuromuscular junction. Muscle contraction diminished
Describe Rhesus isoimmunisation in pregnancy
RhD antigen carried on RBCs - mother RhD negative, father RhD positive
First pregnancy - mother sensitised and makes antibodies to RhD - usually at birth of first infant
Second pregnancy - foetus Rh positive
- Small amounts of erythrocytes passing across placenta stimulate memory cells
- More anti-RhD antibodies produced and crosses placenta
- Haemolytic disease of newborn
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
- Patients make autoantibody which attacks DNA and nuclear ribonucleoproteins
- Immune complexes form –> 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?
1) B cells are more sensitive to cytokines, leading to excessive activation and abnormal antibody production.
2) Also an unusual problem; B cells undergo polyclonal activation–> diverse Abs which target the body’s own tissues
3) There is an increase in pro-inflammatory cytokines
4) Th1 response reduced
5) Tanto immunocomplex production means phagocytes have difficulties clearing immune complexes
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 T cytotoxic cells = 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
Which 2 GI diseases are 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
Describe AI disease and 6 contributing factors
1) AGE and GENDER: autoantibodies more common in older ppl.
SLE and Grave’s more common in women
2) GENETICS: HLA genes linked w certain AI diseases
3) INFECTIONS: link between EBV and SLE
4) SPECIFIC AUTOANTIGENS: highly conserved proteins usually targets for autoimmune responses (e.g. Heat Shock Proteins can cross-react with similar self-proteins)
5) DRUGS: eg procainamide for arrythmia can cause SLE. Stopping treatment resolves the problem.
6) IMMUNODEFICIENCY: persistent infections or inflammation can cause AI
Describe B cell deficiencies
- Severe combined immunodeficiency syndrome: lack of development of stem cells into B cells and T cells
- Hyper IgM syndrome: increased IgM but little/no IgG
- Common variable immunodeficiency: IgG/IgA deficiency - B cells unable to mature into plasma cells
Describe T cell deficiency
- Lack of thymus is an example
- DiGeorge syndrome – incomplete development of the thymus
