1. An Overview of Immunology Flashcards
What is an antigen?
Anything the immune system responds to
Usually protein
Not necessarily ‘bad’
What does an antigen receptor do?
It recognises the antigen
This is the fundamental basis of immunity
The basis of division into innate and adaptive immunity
What divides the immune system into innate and adaptive?
Antigen receptors
Germline-encoded pattern-recognition receptors in innate
Antigen-specific T and B cell receptors in adaptive
What does the binding of an antigen to antigen binding receptor do?
It leads to an effector mechanism which is an action to respond to the antigen
What is the main role of the immune system?
To protect from infection
Cells of myeloid lineage
Neutrophils Eosinophils Monocytes/macrophages Dendritic cells Basophils (mast cells in tissue)
Neutrophils
Myeloid lineage
Large cell with granular cytoplasm and lots of nuclei
Function: phagocytosis
Eosinophils
Myeloid lineage
Cloudy reddish pink cell
Function: ?helminth infections
Monocytes/macrophages
Myeloid lineage
Monocytes circulating, macrophages in tissue
big weirdly shaped granular cell
Function: phagocytosis and antigen presentation
Dendritic cell
Myeloid lineage
Lots of dendritic processes
Function: antigen presentation
Basophil
Basophil in blood, mast cell in tissue
Myeloid lineage
Granular (tomato wearing sunglasses)
Function: ?helminth infections?
Lymphoid lineage
Similar size to RBC
Little cytoplasm with few granules
B cells: make antibody, antigen presentation
T cells
CD4: help other components of immunity
CD8: kill infected cells
T cells and B cells=ADAPTIVE IMMUNITY
NK cells: actually INNATE lymphocytes
Direct lysis of infected cells and antibody-dependent cellular cytotoxicity
NK cells
Lymphoid lineage
actually INNATE lymphocytes
Direct lysis of infected cells and antibody-dependent cellular cytotoxicity
Intercellular communication
Communication between cells via soluble mediators
Endocrine - via blood
Paracrine - messengers act on an adjacent cell
Autocrine - acting on itself
Juxtacrine - membrane-bound signalling molecule
Will often get more than one happening together in order to get a response
Communication: cytokines & chemokines
Cytokines are small proteins released by cells that have an effect on another cell
-important for communication between cells of the immune system and between immune system cells and other cells and tissues
Chemokines are similarly defined, but different structure, receptors and nomenclature
-main role is temporal and spatial organisation of cells and tissues
Main role of cytokines
communication between cells of the immune system and between immune system cells and other cells and tissues
Main role of chemokines
temporal and spatial organisation of cells and tissues
Antigen receptors
The receptor that cells use to recognise antigen is a key concept in immunology, and forms the basis of separating two immunological arms: innate and adaptive
Key features of innate antigen receptors
Do not recognise antigen specifically Pattern recognition receptors’ (PRRs) Recognise ‘pathogen associated molecular patterns’ (PAMPS) Genome-encoded Not clonally distributed
Mannose binding ligand
MBL binds with high affinity to mannose and fucose residues with correct spacing
Mannose and fucose residues that have different spacing are not bound by mannose binding ligand
Essentially evolved to recognise foreign things e.g. fungi, but not specifically fungi
Classical features of innate immune receptors/defences
Work quickly – first line of defence
Adaptive immunity takes more time to be activated
Unable to ‘learn’, as germline encoded and therefore cannot change – therefore no memory
Key features of adaptive antigen receptors
Recognise antigen specifically
T cell receptor, B cell receptor (antibody)
Produced by random somatic recombination events between gene segments
Huge receptor diversity
Clonally distributed
Permit specificity and memory in immunity
B cells
B cell receptor (antibody) may be surface-bound or secreted
Recognises intact antigen
The T cell receptor
T cell receptor is very similar to the B cell receptor
Only a surface receptor on CD4 and CD8 T cells
Recognises processed antigen in the form of linear peptides
Generation of adaptive immune receptor by somatic recombination events
T and B cell receptors are produced by random recombination events between V, (D) and J gene segments, producing a huge receptor diversity despite a small number of genes. The most useful receptors are selected after birth upon exposure to pathogens
How do T cells recognise antigens?
T cell receptors recognise peptides - short linear sequences of amino acids 12-18aa long, but only recognise this antigen when presented to them on a major histocompatibility complex (MHC)
Antigen processing pathways
Class I - CD8 - recognise virally infected cells, which will have foreign protein in cytoplasm, some of which goes through proteasome to be degraded into peptides to be presented on class I MHC proteins
CD4 pathway uses MHC II, takes up antigen and presents it on surface on MHC-II. uses phagolysosome not proteasome
What is clonal selection?
Cell gets selected out of many different cells depending on its ability to bind an antigen
What happens after primary infection?
After primary infection, most clonally-expanded T and B lymphocytes die off; a few remain as long-lived memory cells
Some examples of effector mechanisms
Barriers (skin, acid pH in gut etc etc) Cytokines Complement Phagocytosis (enhanced by opsonisation) Cytotoxicity (CD8 T cell, NK cell) Antibody-dependent cellular cytotoxicity Mast cell and eosinophil degranulation
Effector mechanisms are shared between innate and adaptive immunity. Adaptive immunity is defined by its receptors not by its effector mechanisms
CD8 T Cells
virus infects cell, viral protein synthesised in cytosol then this is bound by MHC class I viral proteins in ER, then transported to cell surface to be presented
Acute inflammation
Inflamito – setting alight
Cardinal features: hot, painful, red, swollen
Describes a process, but tells you nothing of the cause
Blood vessel changes underlie the process
Vasodilatation
Adhesion molecules
Increased permeability
The clinical features are therefore defined by an interaction between the pathogen and host immunity