Core Immunology Flashcards
Features of the Innate Immune System? (inflammation in target tissue)
Pattern recognition against broad classes of antigen No memory No amplification Fast response Short duration
Features of the Adaptive Immune System? (learned responses in immune organs)
Highly specific (T & B cell receptors) Strong memory & amplification component Many regulatory mechanisms Slow response, long duration
Examples of Innate vs Adaptive immune cells?
Innate= Macrophages, Dendritic cells, Mast cells, Neutrophils, Complement Adaptive= T & B cells
Give 4 examples of cross-talk between the 2 immune system components?
- Chemokines: attract other immune cells to sites of inflammation
- Cytokines: signal between different immune cells (T cell cytokines activate innate cells to cause inflammation)
- Macrophages: also produce chemokines to attract other immune cells
- Dendritic cells: also present antigen to adaptive immune system
What does the complement component of the Innate immune system do?
Directly attacks pathogens via alternative and lectin pathways.
May be activated by adaptive immune system via antibodies.
What are 2 specific mutations that may lead to an autoimmune disease?
1) Mutation of FOXP3 = failure to develop regulatory T cells, so severe autoimmunity from birth (immune dysregulation, polyendocrinopathy, X-linked syndrome)
2) Mutations in PTPN22 = T cells activated more easily so stronger immune response in general (type 1 diabetes, Rheumatoid Arthritis)
When may infections cause autoimmunity as well as a normal immune response?
Molecular Mimicry (eg in Rheumatoid fever, antibodies against M protein of Streptococcus also react against the glycoproteins of the heart)
3 examples of when a change in the nature or amount of autoantigens may cause autoimmunity?
- Citrillination of proteins make them more immunogenic (–> rheumatoid arthritis)
- Tissue transglutamase alters gluten to help it bind to HLA-DQ (–> coeliac disease)
- Failure to clear apoptotic debris increases availability of sequestered antigens inside cell (–> SLE)
What is the definition of autoimmunity?
The ADAPTIVE immune system recognised & targets the body’s own molecules, cells & tissues.
Main characteristics= T cells that recognise self antigens. B cells & plasma cells that make autoantibodies. Inflammation is then secondary to this action.
What is the definition of autoinflammation?
INNATE immune system. Main cellular involvement are neutrophils & macrophages. Few or no autoantibodies.
No demonstrable source of infection as precipitating cause.
What are some examples of autoimmune and autinflammatory diseases?
Autoimmune= Rheumatoid arthritis, coeliac disease, Addison disease, Myasthenia gravis, Type 1 diabetes, SLE Autoinflammatory= Crohn's, UC, osteoarthritis, gout, giant cell arteritis, sarcoidosis.
(Autoimmune thyroid disease…)
a) Hashimotos Thyroiditis?
b) Grave’s disease?
a) (leads to hypothyroidism)… destruction of thyroid follicles by autoimmune response. Associated with autoantibodies to thyroglobulin & to thyroid peroxidase.
b) (leads to hyperthyroidism)… inappropriate stimulation of thyroid gland by anti-TSH-autoantibody
What is the brief pathology behind myasthenia gravis?
Autoantibodies block the Ach receptor in the post-synaptic membrane.
What is the pathology behind Systemic Lupus Erythematosus? (a connective tissue disease)
Antibodies against antigens in the nucleus combine with their targets to form IMMUNE COMPLEXES in the circulation. Immune complexes deposit in any organ- activate complement & cause inflammation.
Define… Sensitivity?
Specificity?
Sensitivity= measure of how good is the test in identifying people with the disease Specificity= measure of how good is the test at correctly defining people without the disease
What are some non-specific diagnostic tests of Autoimmune diseases?
Inflammatory markers: ESR, CRP, Ferritin, Fibrinogen, Albumin, Complement
(Specific Autoantibodies and clinical disease associations…)
- Anti-dsDNA?
- Anti-extractable nuclear agents (Anti-Sm, Anti-RNP)
- Anti-SSA / Anti-SSB
- Anti-dsDNA (antigenic determinant= dsDNA)… high specificity for SLE.
- (antigenic determinant= Smith, proteins containing U1-RNA)… SLE, RA, scleroderma, Sjogren syndrome
- (antigenic determinant= RNPs)… Sjogren syndrome, SLE, neonatal lupus/SLE
What are 2 markers for Rheumatoid Arthritis?
a) Rheumatoid Factor (RF)… Antibody (IgM, IgG or IgA) directed against the Fc portion of IgG. (Not diagnostic of the disease as seen in other chronic infections)
b) Anti-CCP (ACPA)… more specific for RA than RF, but similar sensitivity. ACPA positive patients have more severe disease.
(autoimmune liver diseases)
a) Primary biliary sclerosis marker?
b) Autoimmune hepatitis?
a) Anti-mitochondrial Ab
b) Anti-smooth muscle and anti-liver/kidney/microsomal Abs
What are the 4 types of Hypersensitivity reaction?
Type-I anaphylactic
Type-II cytotoxic
Type-III immune complex
Type-IV delayed type
What are the antibodies and antigens associated with each?
Type-I–> antibody= IgE antigen= exogenous
Type-II–> antibody= IgG, IgM antigen= cell surface
Type-III–> antibody= IgG, IgM antigen= soluble
Type-IV–> antibody= none (transferred with T cells) antigen= tissues and organs
What innocuous antigen in of each type of hypersensitivity reactiion?
Type-I anaphylactic= pollen/ hayfever
Type-II cytotoxic= penicillin
Type-III immune complex= mouldy hay, farmer’s lung
Type-IV delayed type= tuberculin test, poison ivy, metals (nickel)
What is the immune response to a Parasitic Infection?
- Increased levels of IgE
- Tissue inflammation with Epsinophilia & mastocytosis, Basophil infiltration
- Presence of CD4+ T cells secreting IL4, IL5 & IL13
Genetic Influences on the ‘allergic’ immune response- what are the 4 characteristic groups of gene function?
1- Sensing the environment
2- Barrier function
3- Regulation of (atopic) inflammation
4- Tissue response genes
What are some examples of Group 2 genes that create susceptibility for allergic disease by modifying barrier function?
FLG: directly affect dermal barrier function, associated with increased risk of atopic dermatitis.
ORMDL3/GSDML, PCDH1: help regulate epithelial barrier function.
What are some examples of Group 3 genes that create susceptibility for allergic disease by regulating atopic inflammation?
IL13, IL4RA, STAT6: genes that regulate TH1/TH2 differentiation & effector function
IRAKM, PHF11: regulate atopic sensitization and inflammation.
What are allergens?
Antigens that initiate an IgE-mediated response
First encounter results in innate and IgM response
What is the role of IgE in Allergic response?
Immunopathogenesis: IgE Ab mediated mast cell and basophil degranulation- release of preformed and de novo inflammatory mediators.
Clinical features= fast onset, wheal and flare.
What is the roll of the Th2 T cell?
Multiple cytokine release for INNATE inflammatory response, and also drive for immunoglobulin production.
What is the Atopic Triad?
Rhinitis + Asthma + Eczema (atopic dermatitis)
What is anaphylaxis?
An acute, potentially life-threatening, IgE mediated systemic hypersensitivity reaction.
Tests for diagnosis= skin prick test, oral challenge test (gold standard), Basophil activation test.
Immunodeficiency with defects in both T-cells and B-cells?
Severe Combined Immunodeficiency
Immunosuppressive drugs with side effects that includes diabetes, hyperlipidaemia, poor wound healing and osteoporosis?
Corticosteroids
Anti-mitochondrial Antibody is a specific test for?
Primary biliary sclerosis
Nitroblue tetrazolium test is a diagnostic test for?
Chronic Granulomatous Disease
A cytotoxic drug that commonly causes cystitis? (cross links DNA)
Cyclophosphamide
A commonly used cytotoxic drug that is a folate antagonist? (and side effect is pneumonitis)
Methotrexate
Inflammatory cell that is commonly elevated in response to parasitic disease?
Eosinophil
Locus of genes that encode for proteins on the surface of cells that are responsible for regulating the human immune system?
Human Leukocyte Antigen
Basics of MHC?
- Found in all higher vertebrates
- Present ‘self’ and ‘non-self’ antigens for inspection by T cell antigen receptors
- Highly polymorphic
- Mendelian inheritance. Codominant expression.
Human infection by this parasite is commonly due to contact with cat faeces?
Toxoplasma gondii (opportunist pathogen in T cell deficiencies)
Prophylaxis after splenectomy?
Haemophilus influenzae type B vaccine
Penicillin
X-linked condition associated with a lack of antibodies in the bloodstream?
Agammaglobulinaemia
can be acquired through multiple myeloma
What is Rituximab used for?
- Lymphomas/ leukaemias
- Transplant rejection
- Autoimmune disorders
