Immunology Flashcards
What is an appropriate immune response?
Occurs to foreign harmful agents such as viruses, bacteria, fungi and parasites - Required to eliminate pathogens - Maybe concomitant tissue damage as a side effect, but as long as pathogen is eliminated quickly it will be minimal and repaired easily Involves antigen recognition by cells of the immune system and antibody production
What is appropriate immune tolerance?
Occurs to self, and to foreign harmless proteins: - Food, pollens, other plant proteins, animal proteins, commensal bacteria Involves antigen recognition and generation of regulatory T cells and regulatory (blocking) antibody (IgG4) production - Antigen recognition in context of “danger” signals leads to immune reactivity, absence of “danger” to tolerance
What is a hypersensitivity reaction?
Occur when immune responses are mounted against: - Harmless foreign antigens (allergy, contact hypersensitivity) - Autoantigens (autoimmune diseases) - Alloantigens (serum sickness, transfusion reactions, graft rejection)
What are the different types of hypersensitivity reaction?
Type I: Immediate hypersensitivity Type II: Antibody-dependent cytotoxicity Type III: Immune complex mediated Type IV: Delayed cell mediated (Delayed-type hypersensitivity) Types I, II and III depend upon the interaction of antigen with antibody Type IV involves T cell recognition
Give examples of type I hypersensitivity
Immediate: - Anaphylaxis - Asthma - Rhinitis - Seasonal - Perennial - Food allergy
How does antigen exposure contribute to type I hypersensitivity?
1° antigen exposure - Sensitisation not tolerance - IgE antibody production - IgE binds to mast cells and basophils 2° antigen exposure - More IgE antibody production - Antigen cross-links IgE on mast cells/basophils - Degranulation
What is the clinical presentation of type II antibody-dependent hypersensitivity?
Depends on target tissue 1. Organ-specific autoimmune diseases - Myasthenia gravis (Anti-acetylcholine R Ab) - Glomerulonephritis (Anti-glomerular basement membrane Ab) - Pemphigus vulgaris (Anti-epithelial cell cement protein Ab) - Pernicious anaemia (Intrinsic factor blocking Ab) 2. Autoimmune cytopenias (Ab mediated blood cell destruction) - Haemolytic anaemia - Thrombocytopenia - Neutropenia
What tests can you do for specific autoantibodies in type II hypersensitivity?
- Immunofluorescence - ELISA e.g. anti-CCP (Cyclic Citrullinated Peptide Abs for rheumatoid arthritis)
What is type III immune complex mediated hypersensitivity?
- Formation of antigen-antibody complexes in blood - Deposition of complexes in a tissue - Complement and cell recruitment/activation - Activation of other cascades e.g. clotting - Tissue damage (vasculitis) • Systemic lupus erythematosus (SLE) • Vasculitides (Poly Arteritis Nodosum, many different types
Where do the immune complexes deposit and cause vasculitis in type III hypersensitivity?
- Renal (glomerulonephritis) - Skin - Joints - Lung
Give examples of conditions associated with type IV hypersensitivity.
- Chronic graft rejection - CVHD - Coeliac disease - Contact hypersensitivity
What are the varieties and mechanisms of type IV hypersensitivity?
Three main varieties: - Th1 - Cytotoxic - Th2 Mechanisms - Transient - T cell activation of macrophages, CTLs - Much of tissue damage dependent upon TNF
What is the common cause of type IV contact hypersensitivities?
Nickel
What is the immune reactant in hypersensitivity reactions?
Type I: IgE Type II: IgG Type III: IgG Type IV: Th1, Th2 and CTL
What is the effector mechanism in hypersensitivity reactions?
Type I: Mast-cell activation Type II: Complement, FcR cells (phagocytes, NK cells); antibody alters signalling Type III: Complement phagocytes Type IV: Macrophage activation; eosinophil activation; cytotoxicity
What are the features of inflammation?
- Vasodilation, increased blood flow - Increased vascular permeability - Inflammatory mediators and cytokines - Inflammatory cells and tissue damage
What are the signs of inflammation?
- Redness - Heat - Swelling - Pain - Loss of function
What causes increased vascular permeability in inflammation?
- C3a - C5a - Histamine - Leukotreines
What cytokines are involved in inflammation?
- IL-1 - IL-6 - IL-2 - TNF - IFN-γ
What chemokines are involved in inflammation?
- IL-8 / CXCL8 - IP-10 / CXCL10
What is the prevalence of atopy in young adults in the UK?
50%
What are the different severities of atopy?
- Mild occasional symptoms - Severe chronic asthma - Life threatening anaphylaxis
What are the risk factors for atopy?
Genetic - ~80% - Polygenic • 50-100 genes linked to asthma/atopy • Genes of IL-4 gene cluster (chromosome 5) linked to raised IgE, asthma, atopy • Genes on chromosome 11q (IgE receptor) linked to atopy and asthma • Genes linked to structural cells linked to eczema (filaggrin) and asthma (IL-33, ORMDL3) Environmental - Age (increases from infancy, peaks in teens, reduces in adulthood) - Gender (more common in males in childhood, females in adulthood) - Family size (More common in small families) - Infections (Early exposures protect) - Diet (breast-feeding, anti-oxidants and fatty acids protect)
What are the types of inflammation in allergy?
Anaphylaxis, urticaria, angioedema - Type I hypersensitivity (IgE mediated) Idiopathic/chronic urticaria - Type II hypersensitivity (IgG mediated) Asthma, rhinitis, eczema: - Mixed inflammation •Type I hypersensitivity (IgE mediated) Type IV hypersensitivity (chronic inflammation)