Week 0 Flashcards
What are the 2 categories of innate immunity?
Soluble factors and cellular factors
What are the types of soluble factors?
antibacterial factors and complement system
What are the cellular factors of innate immunity?
scavenger phagocytes
What are the main types of antibacterial factors?
lysozyme and lactoferrin
Describe lysozyme
enzymes at mucosal surfaces
Active in breaking down the gram positive cell wall
Describe lactoferin
Protein found at mucosal surfaces
Chelates iron and therefore reduces soluble iron in the GI / respiratory ttract
Inhibits the growth of bacteria
What are the 3 types of complement pathways?
Classical
MB-lectin
Alternative
Describe the classical pathway
antigen:antibody complexes
Describe the MB-lectin pathway
lectin binding to pathogen surfaces
Describe the alternate pathway
pathogen surfaces
What does the activation of complement lead to?
Recruitment of inflammatory cells
Opsonisation of pathogens
Killing of pathogens
What is c3a involved in?
Inflammation
What is c3b involved in?
opsonisation and phagocytosis
What is c5a involved in?
Late inflammation
What are the major functions of macrophages?
Phagocytosis
Antigen presentation
Cytokine production
What are macrophages differentiated from?
Monocytes
Describe pattern recognition receptors
recognise molecules found commonly in micro-organisms.
Able to recognise extracellular and intracellular threats
Respond to bacteria, fungi and yeast
What are the main actions of neutrophils?
Chemotaxis
Phagocytic
Degranulate
Die locally
Describe neutrophils
The foot solider of the immune system
50-70% of WBCs
provide a rapid response to infection
Describe eosinophils
Classically respond to parasites
pathological role in allergy
What are the main roles of eosinophils?
chemotaxis
degranulation
cytokine production
Describe Basophils /mast cells
mast cells are the border guard of the immune system, guarding mucosal sites
important role in allergy
What are the main roles of basophils / mast cells?
degranulation
cytokine release
Describe dendritic cells
derived from the same precursor as macrophages
Prototype antigen presenting cell
What are the main roles of dendritic cells?
phagocytosis
migration
antigen presentation
What are the two types of adaptive immunity?
humoral and cellular
Describe the humoral response
B cells
antibodies
extracellular pathogens
Describe the cellular adaptive response
CD4 T cells and CD8 T cells
What are the actions of antibodies?
opsonise for phagocytose
activate complement for lysis
neutralise toxins and pathogen binding sites
Where do antibodies differ?
In Fc regions
Describe IgM
Main antibody of primary immune response
low affinity
activates complement
Describe IgG
Main antibody of secondary immune response
Higher affinity as part of secondary response
Activates complement, Binds Fcy receptors of phagocytes, crosses placenta
Describe IgA
Antiseptic paint
present in secretions and lines epithelial surfaces.
neutralises by blocking binding of pathogens
Describe IgE
High affinity binding to mast cells
Role in allergy
Describe the primary antibody response
usually 5-10 days
Smaller
Usually more IgM>IgG
lower average affinity, more variable
Describe the secondary antibody response
usually 1-3 days
larger
Relative increase in IgG and under certain situations, in IgA or IgE (heavy chain isotope switching)
Higher average affinity
How do T cells help B cells?
Clonal expansion of specific B cells Progression to antibody secreting cells progression to memory B cells Isotope switching to IgG, IgA and IgE affinity maturation
Describe T cell receptors
on the surface of T cells and only recognises antigen when it is presented in a MHC molecule
Recognises short peptide lengths
How do B cells develop to prevent autoimmunity?
develop in bone marrow
if receptor binds strongly to self antigen in bone marrow it dies by apoptosis
How do T cells develop to prevent autoimmunity?
originate in bone marrow and migrate to thymus
if binds strongly to self antigen in thymus it dies by apoptosis
What is meant by the second signal, involved in preventing autoimmunity?
activation of lymphocytes requires presence of danger signals to activate. if antibody/TCR engaged in absence of “second signal” then cell likely to become anergic
Describe class 1 MHC
presents to CD8 T cells
found on all nucleated cells
Presents intra-cellular antigen
Describe class II MHC
presents to CD4T cells
Presents extra-cellular derived antigen
Found on APCs, macrophages and B cells
Describe Th1 cells
IFN gamma secretion
host defence against intracellular microbes, inflammation
Describe Th2 cells
IL-4, IL5, IL13 secretion
host defence against helminths; allergic reactions
Describe Th17 cells
IL17 secretion; host defence against some bacteria; inflammatory disorders
Describe T regulatory cells
Act to regulate function of other immune cells
What are the primary organs of the adaptive immune system?
Thymus and bone marrow
What are the secondary organs of the adaptive immune system?
lymph nodes
spleen
Mucosal associated lymphoid tissue of GI tract and bronchial tracts
Give an overview of the adaptive immune system
provides specific antibodies to the innate immune system to enhance pathogen clearance
Provides cytokines to the innate immune system to upregulate activity
Finishes off the job of clearing pathogens
Develops a memory to prevent future infection
Describe the secondary response
Memory B cells and memory T cells already present at a high frequency
Memory lymphocytes have lower threshold for activation and actively patrol the sites of previous pathogen entry
Preformed antigen specific IgA prevents pathogen binding
Preformed high affinity IgG rapidly opsonises pathogen for phagocytosis
How many types of hypersensitivity are there?
4/5
Describe type I hypersensitivity
immediate, atopic
IgE mediated
Describe type II hypersensitivity
cytoxic, antibody dependent
IgM or IgG bound to cell / matrix Ag
Describe type III hypersensitivity
Immune complex
IgM or IgG bound to soluble Ag
Describe type IV hypersensitivity
T cells (CD4+ and CD8+)
Describe type V hypersensitivity
Receptor mediated
IgM or IgG bound to receptor (i.e Grave’s disease)
What are the specific characteristics of type I hypersensitivity?
Response to challenge occurs immediately
Tends to increase in severity with repeated challenge
Predominantly mediated by IgE bound to mast cells
Give examples of type I hypersensitivity
Asthma
Eczema
Hay fever
Describe the steps involved in allergy
Sensitisation
Mast cells primed with IgE
Re-exposure to antigen
Antigen binds to IgE assoiciated mast cells
Mast cells degranulate releasing; toxins, tryptase, cytokines. chemokines, prostaglandins, leukotrienes
Pro-inflammatory process stimulates and amplifies future responses
Describe the early tissue effects in allergy
occurs within minutes of exposure to antigen exposure
Occurs largely as a result of histamine and prostaglandins - smooth muscle contraction and increased vascular permeability
Describe the late phase tissue effects in allergy
hours to days after exposure
Principally mediated through recruitment of t Cells and other immune cells to site
Results in; sustained smooth muscle contraction/hypertrophy, tissue remodelling
Describe anaphylaxis
Severe, systemic type I hypersensitivity
Widespread mast cell degranulation caused by systemic exposure to antigen (e.g. penicillin)
Vascular permeability is principle immediate danger; soft tissue swelling threatening airway. loss of circulatory volume causing shock
What is meant by type II hypersensitivity
caused by binding of antibodies directed against human cells
IgG usual cause
Uncommon cause of allergy (drug associated haemolysis)
Common cause of autoimmune disease
Give an example of an illness caused by type II hypersensitivity
Bullous pemphigoid
Describe the steps involved in type II (V) hypersensitivty
sensitisation
Opsonisation of cells
Cytotoxicity - complement activation, inflammation, tissue destruction
Describe the specific step involved in type V hypersenstivity
direct biological activation with antigen (i.e receptor activation, impaired enzyme action)
Graves disease
Give a description of type III hypersensitivity
Mediated by immune complexes bound to soluble antigen
Cause of autoimmune disease and drug allergy
Aggregates in small blood vessels _ direct occlusion, complement activation, perivascular inflammation
Give a description of type IV hypersenstivity
also known as delayed type hypersensitivity
presents several days after exposure
mediated by the action of lymphocytes infiltrating area
What is autoimmune disease?
harmful inflammatory response directed against “self” tissue by the adaptive immune response - organ specific or systemic
Describe myasthenia Gravis
syndrome of fatiguable muscle weakness - limbs, respiratory, head and neck
Caused by IgG against acetylcholine receptor
Antibody blocks receptor and prevents signal transduction
Give examples of systemic autoimmune diseases
Rheumatoid arthritis
systemic lupus erythematosus
inflammatory bowel disease
systemic vasculitis
What are the systemic effects of RA?
pulmonary nodules and fibrosis Percarditis and valvular inflammation small vessel vasculitis soft tissue nodules skin inflammation weight loss anaemia
Describe rheumatoid factor
IgM and IgA directed against IgG Fc region
Forms large immune complexes; high concentration within synovial fluid
Also found in other tissues
Describe the general pathophysiology of RA
inflammation leads to release of PAS from inflammatory cells
Alters variety of proteins by converting alanine to citrulline
In RA, anti-citrullinated protein/peptide antibodies are common
Describe the pathophysiology of RA in the joints
Amplification of inflammatory cascade
Further chemoattraction of inflammoty cells into synovial; macrophages, neutrophils, lymphocytes
Osteoclast activation and joint destruction
Fibroblast activation and synovial hyperplasia
Systemic inflammation
Describe the pathogenesis of autoimmune disease
genetic predisposition
environmental factors
Recognition of self antigens by the immune system as foreign
Persistence of inflammatory response to develop chronic of disease
What are the environmental factors associated with autoimmune disease?
infection
geographical factos
modifiable personal risk factors
