Basics of Immunology Flashcards
Where do specialised cells of the immune system originate?
The bone marrow via the common progenitor cell (haematopoetic stem cell)
What does the common progenitor divide into?
Common myeloid progenitor
Common lymphoid progenitor
What does the common lymphoid progenitor?
NK Cells
Small lymphocyte
- T Lymphocyte
- B lymphocyte
- plasma cell
What does the common myeloid progenitor specialise into?
Megakaryocyte
Erythrocyte
Mast Cell
Myeloblast
What do megakaryocytes specialise into?
Platelets
What do myeloblasts specialise into?
Basophils
Neutrophils
Eosinophils
Monocyte
What do monocytes specialise into?
Macrophage
Dendritic Cells
What is the innate immune system?
A fast but non-specific immune response
Shows no immunological memory
What is the adaptive immune system?
A slow but specific immune response that establishes an immunological memory
Where are MHC I’s found on human cells?
On the surface of all nucleated cells
What do HLA genes code for?
Cell surface proteins that present antigens to T Cells
What does class I of HLA present to?
the APC for presentation of antigen to Tc
What does class II of HLA present to?
the APC for presentation of antiben to TH cells
What kind of APC’s present with both MHC class I and class II ?
Dendritic cells and macrophages
What do naive CD8+ Tcells need to become Tc Cells?
professional APC such as dendritic cells and macrophages
What are examples of innate immunity?
Barriers
Cells (phagocytes, eosinophils, basophils, mast cells, NK cells)
Actions of the complement system
Soluble mediators (acite phase reactants, cytokines, chemokines, matrix metallo-proteinases, defensins)
What does TH1 do?
Secrete interferon Y, IL-2, TNF, fights against intracellular pathogens, has a disease role in autoimmunity and chronic inflammation
What does TH2 do?
Secrete IL4, IL5, IL13. Defends against helminths and plays a disease role in allergy
What does TH17 do?
Secrete IL-17, IL-22 important in host defence against extracellular bacteria and fungi. Plays a diseaserole in autoimmunity and inflammation
What is the role of T Reg cells ?
Exert a controlling and regulatory influence on immune responses
What do Tc Cells do?
Secrete IFNY, kill cells infected by intracellular microbes
What is the role of B Cells?
They detect antigens via antibodies
What are the subclasses of antibodies?
IgG, IgA, IgM, IgD, IgE
What is the structure of antibodies?
2 heavy and 2 light chains
What are the functions of antibodies?
To bind and neutralise toxins, to form the immune complex, opsonisation, complement activation, cellular cytotoxicity
Give examples of primary lymphoid tissues?
Thymus and bone marrow
What occurs and the thymus?
T cells mature
What occurs at the bone marrow?
B cells mature
What are secondary lymphocytes?
Places where lymphocyte responses to foreign antigens are initiated
- lymph nodes, spleen, tonsils, adenoids, intestines
What is the naive state of an antigen?
immunoglobulin
What happens to immature B cells that recognise self antigen in the bone marrow?
They are negatively selected and die through apoptosis
When are developing T cells in the thymus not selected?
If they do not recognise self MHC
When are developing T Cells negatively selected?
When they recognise self-peptide plus self-MHC with high affinity
= apoptosis
What are the most important mechanisms of peripheral tolerance?
Anergy and T regulatory cells
What is the principle of Anergy?
where the T cell regognises the antigen presented on an MHC molecule but does not respond as there is no costimulation. Cell becomes anergic
What is the function of T-regulatory cells ?
Inhibit neighbouring T-Cells
What is hypersensitivity?
An exaggerated or inappropriate fashion to environmental antigens which do not normally cause tissue damage
What is bystander damage?
The tissue damage is done by the exaggerated response rather than the antigen itself
What are hypersensitivities Types I, II and III mediated by?
Antibodies
What mediates hypersensitivity type IV reactions?
Inappropriate actions of TH1 and TH17 cells
What is involved in a type I hypersensitivity reaction?
Allergen, IgE, mast cell, TH2 cells, eosinophils and genes
Give examples of an airbourne allergen?
pollens, house dust mite, animal products
Give examples of an ingested allergen?
Milk, eggs, fish/shellfish, cereals, nuts
Give an examples of occupational allergens?
Latex, drugs (hospital)
Industrial
What is the definition of an atopic reaction?
Where you have a genetic potential to produce allergic reactions but will not suffer from any kind of clinical problem
What is atopy?
a genetic tendency to produce IgE to normally innocuous environmental allergens
What is allergy?
A clinical expression of the atopic tendency
Give examples of preformed mast cell mediators?
Histamine, heparin, tryptase, chymase, ECF, NCF
What mast cell mediators are newly synthesised as and when needed?
Prostaglandins, leukotrienes
What is the pathogenesis of an allergic reaction?
Allergen exposure –> ,mast cell + IgE production –> degranulation –> synthesis –> mucosal oedema/ capillary leakage/ secretios/ smooth muscle contractions/ vasodilation
What is the early phase response of an allergic reaction?
preformed mast cell mediators are released
What is the late phase response of an allergic reaction?
Newly synthesised mast cell mediators, Th2 cytokines and eosinophil mediators are released
What are type II hypersensitivity reactions?
Reactions mediated against antigens found on the surface of cells or fixed within certain tissues
How does antigen damage occur in a type II hypersensitivity reaction/.
Complement activation
Fc binding and stimulation of phagocytes
ADCC
Inhibition of function of target cell function or stimulation of target cell function
Name some clinical type II hypersensitivity disorders?
Haemolytic reactions
Haemolytic disease of the newborn
Hyperacute graft rejection
Graves disease, myaesthenia gravis, goodpasture’s syndrome, pemphigus
What is a type III hypersensitivity reactions?
occurs when there is accumulation of immune complexes that have not been adequately cleared by innate immune cells, giving rise to an inflammatory response and attraction of leukocytes
Give examples of clinical presentations of type III hypersensitivity disorders?
Farmers lung, post-strep glomerulonephritis, tumours, SLE
What is an autoimmune disease?
Response to self-antigen, loss of tolerance
What are the functions of complement cells?
Chemotaxis of phagocytes to sites of inflammation
Opsonisation
Lysis of micro-organisms
Maintenance of solubility of Ag/Ab
What do C1,4,2,3 deficiencies lead to?
Immune complex disease
Infection
What is MBP function?
Activates a classical complement pathway
An opsonin in that it can bind to the cell surface of micro-organisms whose cell walls contain mannan
What do deficiencies of MBP result in?
A susceptibility to recurrent bacterial infections
What is SCID?
Severe Combined Immune Deficiency
- Heterogeneous group of conditions with variable underlying genetic defects but generally produce severe dysfunction in T and B cell development
Why does SCID occur?
defects in pluripotent stem cells, lymphoid stem cells or T & B celsl
How does SCID present?
Infant usually well for the first 3 months then:
- persistent superficial candida
- diarrhoea and failure to thrive
- chronic bronchiolitis
- interstitial pneumonitis
- overwhelming bacterial sepsis
What treatment is available for SCID?
Intensive supportive therapy, nutritional support, prophylactic and therapeutic antibiotics, anti-fungals, anti-virals, Ig replacement therapy, bone marrow transplant
What is an autograft?
Transfer of tissue between different sites within the same organism e.g skin graft
What is an isograft?
Transfer between genetically identical individuals
What is an allograft?
Transfer between genetically non-identical members of the same species
What is a Xenograft?
Transfer between species
What major antigens must donor and recipient share?
ABO blood group antigens
HLA-A, HLA-B and HLA-HR
When is blood or tissue match not required?
In tissue where little blood or lymphatic supply is present
What are the complications of transplantation?
Graft rejection Graft vs Host disease infection neoplasia drug side effects recurrence of original disease Ethical, surfical problems
What causes graft rejection?
HLA mismatch
What causes hyperacute rejection?
Pre-formed antibodies
What causes accelerated rejection?
TCell presence
What causes acute rejection?
Newly sensitised TCells
What causes chronic rejection?
Multifactorial
How can graft rejection be prevented?
ABO matching and detection of pre-sensitisation to donor organs
Close tissue matching
Prophylactic immunosuppressive therapy
How do corticosteroids work?
Affect T and B cell function which affects cytokine networks, inflammation, TCell and monocyte function and transit or immunologically active cells
How does azathioprine work?
Purine analogue which inhibits DNA synthesis. Inhibits T and NK cell function
How does cyclophosphamide work?
Alkylating agent which interferes with DNA synthesis which suppresses B cells and Ab production
What does cyclosporin and tacrolimus do?
Suppresses T cells and NK cells
What does sirolimus cell do?
Decreases IL-2 production by TH cellsq
What does mycophenolic acid do?
Inhibits purine and prevents T cell proliferation, antibody production and leukocyte migration
