Immunology - CLS Flashcards
Material recognised and damaged in Immunity
Both foreign
Material recognised in allergy/hypersensitivity
Foreign recognised, self damaged
Material recognised/damaged in Autoimmunity
Both Self
Type 1 Hypersensitivty
- Atopic allergy/immediate hypersensitivity
- Involves allergens, mast cells and IgE
- Produce high levels IgE, binds to mast cells
- Recognise antigens of allergen
- IgE produced against allergen
- Mast cell degranulates
- Instant: Histamine, Heparin, tryptase
- Produces: arachadonic acid-> prostaglandins, leukotrines, cytokines
Role of Th2 cells in IgE and eosinophil development
- Alleregen taken up by APC
- Peptide loaded to HLA II
- Interacts with CD4 of TH2
- TH2 produces cytokines
- IL-4 causes calss switching to IgE specific to allergen
- IL-5 stimulates eosinophils; degranulate, tissue damage, hypersensitivity
- IL-10 co-stimulates mast-cell growth; more deranulation etc
Different routes of allergen entry and their response
Outline Skin prick test
Inject 0.02ml of an extract of particular antigen
- immediate reaction: 20 min, IgE activated
- immediate+late: IgE +/- Tcells activated
- delayed: TH1 cells
Outline type II hypersensitivity
antibodies produced by immune system bind to own antigen on own cells
e.g. haemolytic disease of newborn
Blood transfusions
Goodpasture’s
Outline type III hypersensitivity
- Immune complexes too large
- Not enough complement/RBS to clear antigen
- Immune complexes deposited in tissues
- Antibodies bind to neutrophils; tissue damage
e.g. Extrinsic allergic alveolitis (allergy)
- ABs to fungal spores; repeated exposure cause increased size of complexes
- Complexes deposit in lungs
- Fc interaction with neutrophils; relase mediators; tissue damage i.ie farmers lung
Autoimmune e.g.g SLE, rheumatoid arthritis
(An immune complex, sometimes called an antigen-antibody complex, is a molecule formed from the integral binding of an antibody to a soluble antigen.[1] The bound antigen and antibody act as a unitary object, effectively an antigen of its own with a specific epitope. After an antigen-antibody reaction, the immune complexes can be subject to any of a number of responses, including complement deposition, opsonization,[2] phagocytosis, or processing by proteases. Red blood cells carrying CR1-receptors on their surface may bind C3b-coated immune complexes and transport them to phagocytes, mostly in liver and spleen, and return to the general circulation.)
Outline type IV hypersensitivity
- Not anti-body mediated, cell-mediated (T cell)
- Chronic overstimualtion of macrophages by excessive cytokine release
- Macrophages form multinucleated giant granulomas; tissue damge
- e.g. Contact dermatitis (allergy), pulmonary TB, LEprosy
- e.g. Autoimmune Thyroiditis, addisons, gastritis, T1DM
Immunological basis of tissue transplant rejection
Recipient and donor not genetically identical, different range of HLA alleles
Leads to type IV Hypersensitivity
- APC donor cells in allograft present foreign antigens to recipient TH(due to need for protein binding for stability)
- Recognised as being different to recipeint’s HLA
- Trigger TC and macrophages
- Donor cells destroyed
Treat by lifelong immunosupressants
Antigen recognised in SLE
Double stranded native DNA
Antigen recognised in rheumatoid arthtritis
Synovial IgG
/Rheumatoid factor
Outline Autoimmune aspect of Grave’s disease
TSHR stimulating antibodies
- Stimulates thyroid hormone production
- Not regulated anymore by feedback;overproduction = hyperthyroidsism
Anti-TSHR can pass to foetus; neotal graves
Features of graves:
- Diffuse goitre, weight loss, irratable
- Graves Ophtalmopathy
- Inflammation of extra-occular tissues
- Pushes eyes forwards
- Pretibial myxodeama
Outline immuno basis of atrophic thyroiditis
Hypothyroidism (type IV)
Caused by TSHR _blocking(_not stim) antibodies
- Block TSH bidnning; destruction and fibrosis of thyroid tissue
- Atrophy; hypothyroidism
Weight gain, depression, primary myxodeama
Outline Immuno of Hashimoto’s thyroidits
Antibodies to thyroid peroxidase & thyroglobulin
- Leads to destruction of thyroid tissue
- Hypothyrodisism
- Goitre(due to infiltration of lymphocytes rather than proliferating thyroid celles in graves)
Autoimmune basis of pernicious anaemia
TYPE IV
- Autoimmune destruction of gastric parietal cells
- reduces IF production: less B12 absorbed
- Production of AB to intrisic factor; bind; block or decrease IF/B12 interaction.
- Less B12 absorbed from gut, affect proliferating cells e.g. reticulocytes
- Tired, washed out. treat by b12 injections
Outline autoimmune basis of T1DM
Caused by autoreactive T cells
Destroys insulin-producing beta-cells
Immunological basis of Mysthenia gravis
Type II
cause: Autoantibodies specific for ACh receptors
- inhibits ACh receptors; block binding
- Induce receptor internalisation and degradation
- Lack of nerve stimulus of muscle contraction
Treat by anticholinesterase; blocks breakdwon of ACh
Autoimmune haemolytic anaemia
TYPE II
cause: Autoantibodies specific for RBC surface antigen
- Opsonisation of RBS, inducing
- Complement activaition; lysis, RBC destruction
- Desctruction by phagocytes
Goodpastures disease
TYPE II
Cause: autoantibodies specific for type IV collagen
- Binds directly to glomerular basement membrane
- Activatin of complement and neutrophils
- Tissue damage, kidney failure
- Also bind to BM of alveoli; lung damage
Pemphigus vulgaris
TYPE II
Cause: Autoantibodies to epidermal cadherin
- Blisters
SLE
Type III/II
cause: Autoantibodies to a range of ubiquitous cellular constituents
- Complexes forms, deposit in various tissues; damages
- Glomeruli, nephritis
- Skin, joints, sCNS
- Buttefly rash
Rheumatoid arthritis
cause: Rheumatoid factors specific for IgG
- Bind and form complexes
- Targets synovial joints
Primary vs Secondary immunodfeiciency
10: Inherited
Mainly autosomal recessive, some X-linked
20: Acquired (manifest in adults)
From enviornment or other disease processes
Characteristics of infections in immunodeficient patient
Serious
Persistent
Unusual
Recurrent
Antibody deficiencies
Commonly have
- bacterial infection (ears, sinus, chest)
- giardi gut infection
- Permanent damage
Other
- Enteroviral infection
Examples of antibody deficiencies
Bruton’s disease: X-linked
- presents early
- encodes tyrosine kinase essential for B cell development from precursors; no ABs in blood
Hyper IgM syndrome:
- Defective Th, don’r activate B cells or cause class shifting
- Unusally high levels of IgM
Primary T cell deficiency
E.g. DiGeorge syndrome
- Thymus (reduced/absent)
- Infections: fungal, viral
AIDS as a secondary T cell deficiency
Caused by HIV infection
- Binds to CD4
- Infects Th
- Tc kill infected Th
- Progressive decline in CD4 cells
- Worsening immune function
Appearance of opportunistic infections: Karposis, Pneumonia, cryptosporidum
Outline SCID
Primary immunodeficiency from inherited stem cell defect; lack of functional lymphocytes
- Increased susceptibility to all infectious agents
Bone marrow transplantation
Neutrophil deficiencies
Reduced numbers
- Primary: Kostmanns, cyclic neutropenia
- Secondary: Leukaemia, chemotherapy, infection
Abnormal function
- adhesion deficiency
- chemotaxis
- killing activity by defects in enzymes; increased bacterial and fungal infections
Complement deficiencies
Particularly associated with bacterial infections
Main categoriesof secondary immunodeficiencies
Latrogenic
- Immunosupressive treatment
Malignancies of immune system
- Leukaemia, Lymphoma, Myeloma
Inections
- HIV, malaria, measles
Malnutrition
