Lecture 1: Introduction to the Immune System Flashcards
What year was smallpox eradicated?
1979
How many years were no cases of smallpox recorded?
3 years
What is the immune system made up of?
- Tissues
- Cells
- Molecules
What is innate immunity?
- the early phase of the host response
- Present in all individuals at all times
- Does not increase with repeated exposure
- Discriminates between groups of pathogens
- Predates separation of animal and plant lineages
What is adaptive immunity?
- is generated by specific lymphocytes
- Discriminates between individual pathogens
- Is associated with “memory”
- Appears abruptly in evolution in the cartilaginous fishes
Where do all the cellular elements of the blood, including the cells of the immune system, arise from?
Pluripotent hematopoietic stem cells in the bone marrow
What are the effector cells?
- Plasma cell
- Activated T cell
- Activated NK cell
- Activated ILC
What are the anatomic barriers against protection against pathogens?
- Skin
- Oral mucosa
- Respiratory epithelium
- Intestine
What are the innate immune cells?
- Macrophages
- Granulocytes
- Natural killer cells
What are the complement/ antimicrobial proteins?
- C3
- Defensins
- RegIIIy
What are part of adaptive immunity?
- B cells/ antibodies
- T cells
What are the steps in innate immunity?
- Inflammatory inducers
- Sensory cells
- Mediators
- Target tissues
What are the inflammatory inducers?
- Bacterial loppolysaccharides
- ATP
- Urate crystals
What are the sensor cells in innate immunity?
- Macrophages
- Neutrophils
- Dendritic cells
What are the mediators in innate immunity?
- Cytokines
- Cytotoxicity
What are the target tissues in innate immunity?
- Production of antimicrobial proteins
- Induction of intracellular antiviral proteins
- Killing of infected cells
What are the three phases in the response to an initial infection?
- Innate phase
- Early induced innate response
- Adaptive immune response
What do the first two phases of the response to an initial infection rely on?
Rely on the recognition of pathogens by germline-encoded receptors of the innate immune system
What does adaptive immunity of the response to an initial infection rely on?
Uses variable antigen-specific receptors that are produced as a result of gene segment rearrangements.
Why does adaptive immunity occur late?
Because the rare B cells and T cells specific for the invading pathogen must first undergo clonal expansion before they differentiate into effector cells that migrate to the site of infection and clear the infection.
What is the function of a macrophage?
Phagocytosis and activation of bactericidal mechanisms
What do myeloid cells participate in?
- Innate immunity
- Adaptive immunity
What is the function of a dendritic cell?
- Antigen uptake in peripheral sites
What is the function of a neutrophil?
Phagocytosis and activation of bactericidal mechanisms
What is the function of a eosinophil?
Killing of antibody coated parasites
What is the function of a basophil?
Promotion of allergic response and augmentation of anti-parasitic immunity
What is the function of a mast cell?
- Release of granules containing histamine and active agents
What is the function of a mast cell?
- Release of granules containing histamine and active agents
What receptors does the innate immune system use?
Germline encoded receptors
What receptors does the adaptive immune system use?
Antigen receptors of unique specificity assembled from incomplete gene segments during lymphocyte development.
How are antigen receptors of the adaptive immune system distributed?
Clonally distributed on individual lymphocytes and their progeny
How are receptors of the innate immune system expressed?
Non-clonally - they are expressed on all the cells of a given cell type.
How are NK cells expressed?
Express various combinations of NK receptors from several families, making individual NK cells different from one another. A particular NK receptor may not be expressed on all NK cells.
What are the receptor characteristics of innate immunity?
- Specificity is inherited in the genome
- Triggers immediate response
- Recognizes broad classed of pathogens
- Interacts with a range of molecular structures of a given type
- Able to discriminate between even closely related molecular structures
What are the receptor characteristics of adaptive immunity?
- Encoded in multiple gene segments
- Require gene rearrangemnet
- Clonal distrubution
- Able to discriminate between even closely related molecular structure
Why do macrophages express a number of receptors?
To allow them to recognise different pathogens
What receptors do macrophages express?
- Mannose receptor
- Nucleotide oligomerization domain (NOD)
- Glucan receptor
- Scavenger receptor
- TLR 4
- TLR 1: TLR 2 dimer
What is toll required for?
Antifungal responses in Drosophila melanogaster
What is shown in a Toll deficient fly?
Increased susceptibility to Aspergillus fumigatus
What are toll like receptors?
Transmembrane proteins whose extracellular region contains 18–25 copies of the leucine-rich repeat (LRR),
Where are toll like receptors located?
- The cell surface of dendritic cells, macrophages, and other cells, where they are able to detect extracellular pathogen molecules
- Intracellularly - in the walls of endosomes
How do toll like receptors act?
As dimers - heterodimers or homodimers
What do TLR located intracellularly do?
Recognize microbial components, such as DNA, that are accessible only after the microbe has been broken down
What is recognized by the heterodimeric receptors TLR-6:TLR-2?
Diacyl lipopeptides
What is recognized by the heterodimeric receptors TLR-1:TLR-2?
Triacyl lipopeptides
Where are diacyl and triacyl lipopeptides derived from?
The lipoteichoic acid of Gram-positive bacterial cell walls and the lipoproteins of Gram-negative bacterial surfaces.
What do infections trigger?
An inflammatory response
What does bacteria trigger macrophages to relaese?
Cytokines and chemokines
What do cytokines do?
Increase the permeability of blood vessels and chemokines, which direct the migration of neutrophils to the site of infection.
What are the principal inflammatory cells?
Neutrophils and macrophages
What causes pain during a infection?
Inflammatory cells migrate into tissue, releasing inflammatory mediators that cause pain
What causes redness, heat and swelling during an infection?
- Vasodilation
- Increased vascular permeability
What are the two regions of an antibody molecule?
- Variable region (antigen binding site)
- Constant region (effector function)
What chains do antibodys have?
- Heavy chain
- Light chain
What chains do T cell receptors have?
- Alpha chain
- Beta chain
What are antigens?
Molecules recognised by the immune response
What are epitopes?
Sites within antigens to which antibodies bind
What is a paratope?
The variable part of the antibody, which binds to the epitope
What do T cells bind?
- Complex of an antigen fragment
- Self molecule
What can T cells recognize?
Epitopes buried within antigens
How do Biologically active lymphocytes arise
Via clonal selection
What is clonal selection?
process that occurs during the immune response when a specific immune cell, such as a B cell or T cell, is selected to proliferate and differentiate into a population of identical cells, known as clones.
How do Dendritic cells initiate adaptive immune responses?
by up-taking antigen in the tissues, migrating to regional lymph nodes and stimulating naïve T lymphocyte activation, proliferation and differentiation.
What forms a bridge between innate and adaptive immune responses?
Dendritic cells
How are dendritic cells particularly important in promoting adaptive immunity
they are specialised to ingest a wide range of pathogens and to then express co-stimulatory molecules that support T cell proliferation and differentiation.
What classes of pathogens does the immune system protect against?
- Viruses
- Intracellular bacteria, protozoa, parasites
- Extracellular bacteria, parasites, fungi
- Parasitic worms
Name types of antigens
- Infectious agent
- Innocuous agent
- Grafted organ
- Self organ
- Tumour
What is the normal response to infectious agents?
Protective immunity
What is the normal response to innocous subsatnces?
Allergy
What is an innocuous substance?
substance or organism that does not cause harm or disease to an organism, even though it may be recognized as an antigen by the immune system.
What is the normal response to a grafted organ?
Rejection
What is the normal response to self organs?
Autoimmunity
What is the normal response to a tumor?
Tumor immunity
What is the deficient response to an infectious agent?
Recurrent infection
What is the deficient response to an innocuous subsatnce?
No response
What is the deficient response to a grafted organ?
Acceptance
What is the deficent response to a tumor?
Cancer
What are common stumili for systemic anaphylaxis?
- Drugs
- Venoms
- Food eg peanuts
What are the responses to systemic anaphylaxis reactions?
- Edema
- Increased vascular permeability
- Laryngeal edema
- Circulatory collapse
- Death
What are common stimuli for acute urticaria?
- Post viral
- Animal hair
- Bee stings
- Allergy testing
What are common stimuli for seasonal rhinoconjunctivitus?
- Pollens
- Dust mite fecer
What are common stimuli for food allergy?
- Peanuts
- Tree nuts
- Shellfish
- Fish
- Milk
- Eggs
- Soy
- Wheat
What are the responses to acute urticaria?
- Local increase in blood flow and vascular permeability
- Edema
What are the responses to seasonal rhinoconjunctivitis?
- Edema of conjunctiva and nasal mucosa
- Sneezing
What are the responses to asthma?
- Bronchial constriction
- Increased mucus production
- Airway inflammation
- Bronchial hyperactivity
What are the responses to food allergy?
- Vomitting
- Diarrhea
- Pruritus (itching)
- Urticaria (hives)
- Anaphylaxis (rare)
