Principles of immune responses Flashcards
Explain the importance of immunology for human health; Summarise the two basic strategies used by the immune system to recognise danger and initiate a response; Innate vs Adaptive immunity; Clonal section; Soluble mediators; Toll-like receptors; Secreted effectors
What is the role of the immune system?
Identify and eliminate harmful microorganisms/substances by distringuishing them from non-self and abnormal-self
Identify danger signals
Minimise collateral damage
Provide memory in case of future infection
Involved in homeostasis
How is the immune system organised?
Complex cellular and protein network
Evolved to protect host from pathogenic molecules
What are the two basic strategies for recognising danger and initiating a response?
Germ-line encoded
Random recombination of gene segments
How does the germ-line encoded strategy recognise danger?
Genes code for many specific, non-changing receptor proteins for molecular patterns
Many cells have same receptors so has a very rapid and effective response
Limited diversity so some pathogens not recognised
How does the random recombination strategy recognise danger?
Millions of receptors recognise specific structures using random recombination of gene segments
Massive diversity allows for recognition of all structures
Few cells express each receptor so they must replicate for an effective response
Why must the immune response be rapid and flexible?
Pathogens replicate much faster than the host
What can immunodeficiency lead to?
SCID can lead to increased infection/cancer susceptibility
Abnormal regulation/function can lead to autoimmune disease
What are pattern recognition receptors?
Germline encoded host sensors
What are PAMPs and what are they used for?
Used to recognise Pathogen Associated Molecular Patterns by manipulating differences in human and pathogenic cells
What are DAMPs and what are they used for?
Used to recognise Damage Associated Molecular Patterns through ECM fragments from damage or proteins released after necrosis
How are antigen-specific receptors created?
Recombination of gene segments during lymphocyte development creates specific, unique receptors on lymphocytes
What is adaptive immunity?
Accquired immunity
Recombination of gene segments
Adaptation to exposure depends on clonal selection
Slower but highly specific to foreign antigens
What is innate immunity?
From birth
Germline encoded
Uses pattern recognition receptors ∴ independent to antigen exposure
Promotes appropriate immune response
Gives time for adaptive immunity to begin
Limited specificity
What does innate immunity dependent on?
Rapidly synthesised/pre-formed components
What does innate immunity do?
Destroy invading nucleic acids in cytoplasm
Activates inflammatory pathways
Elicits type 1 interferons for antiviral defence
What do B-cells do?
Bind to in tact antigens with surface receptor antibody
What do T-cells do?
Have T-cell receptors with alpha/beta chains that bind to processed antigen fragments (epitopes) that have been presented on cell surfaces
What is clonal selection?
A single B or T cell that recognises an antigen that enters the body is selected and reproduced to generate a clonal cell population to eliminate the antigen
Why is there such large clonal diversity?
Random recombination produces many unique antigen receptors
Define cytokines
Small proteins secreted for local, short lived cell to cell communication
Act as messengers of the immune system
Why must cytokines have a short half life?
They have a biological effect at a very low concentration
Short half life controls this effect
What are the different forms of cytokines?
Interleukins Interferons Chemokines Growth factors Cytotoxic tumour necrosis factors
What is the function of interleukins?
Communication between leukocytes
What is the function of interferons?
Has anti-viral effects (interferes with replication)
What is the function of chemokines?
Chemotaxis
What is the function of growth factors?
Help stem cells differentiate and proliferate
What is the function of cytotoxic tumour necrosis factors?
Induced programmed cell death in target cells
What is the general cytokine pathway?
Stimulus in cytokine producing cell causes production and granule fusion with the membrane
Cytokines bind to specific receptors on other cells
Affects gene expression in the target cell to cause biological effects
What do dendritic cells do?
Produce cytokines
Have PRRs
Capture pathogens before migrating to lymph nodes to present antigens
How is clonal selection involved in the primary immune response?
Antigen binds to naive T/B cell receptor
Causes cell to proliferate into clones to fight pathogen
After infection dealt with B/T cells undergo apoptosis
Select few survive as memory cells
How is clonal selection involved in the secondary immune response?
When antigen re-encountered a response by memory lymphocytes is initiated
Response is greater and more rapid
What is complement?
System of functionally linked glycoproteins that interact to help the body’s defences when antibodies combine with antigens
‘compliments’ activity of specific antibodies in lysing bacteria
What are the properties of the complement response?
Triggered enzyme cascade system
Rapid, highly amplified response
What are the 3 ways that complement can be activated?
Classical - antibody binding to antigen causes conformational change
Alternative - direct activation by pathogen surfaces
Lectin - Antibody-independent activation by lectin (a PRR)
What are the functions of complement?
Lysis by the membrane attack complex
Opsonisation
Activation of inflammatory response
Clearance of immune complexes
What is opsonisation?
Coating of micro-organisms with proteins to facilitate phagocytosis
Antibody binds to pathogen receptor
Complement binds to cell surface of pathogen
Antibody and complement bind to neutrophil and activate it
Neutrophil engulfs pathogen
What are opsonins?
Molecules that can bind to antigens and also phagocytes
