Immunity Flashcards
First line of immune defence
Cell wall
Cuticle
Skin
Mucus
How do bacteria defend themselves against viruses?
Using restriction endonucleases (which cut alien DNA sequences)
Features of innate immunity
In the germline Constitutional Rapid Non-specific Does not improve upon repeated contact with the same pathogen
Features of adaptive / acquired immunity
Specific
Slow
Acquired responses no encoded in the germline
Result from genetic rearrangements of genes involved in recognition
A specific receptor for each invading organism is selected from a randomly-created repertoire of receptors
What are the two arms of innate immunity in invertebrates?
Humoral
Cell-mediated
Features of humoral immunity in invertebrates
Use of anti-microbial peptides (AMPs)
What are AMPs?
Small proteins
Secretion of AMPs is induced by parasite recognition
AMPs have a wide range of responses to parasites
Examples of AMPs
Cecropins (lyse bacterial cell membranes) Attacins Defensins Drosomycin Diptericin
Three types of cells involved in cellular immunity in invertebrates
- Hemocytes - circulate in hemolymph (analogous to the blood of mammals, surrounds tissues of arthropods)
- Phagocytic cells - engulf small organisms
- Secretory cells - release effector molecules such as AMPs
What is melanisation?
The deposition of melanin onto invading organisms, which can confine the infection and kill the pathogen
What is melanisation controlled by?
A cascade of serine proteases which activate the enzyme prophenol oxidase, which catalyses the synthesis of melanin from tyrosine
How are pathogens recognised?
By characteristic compounds on their surfaces e.g. lipopolysaccharides and peptidoglycans of bacterial cell walls
These are called pathogen-associated molecular patterns (PAMPs)
What do PAMPs interact with?
Pattern-recognition receptors (PRRs)
The PAMP-PRR interaction triggers the various effector mechanisms that lead to elimination of the pathogen
How does innate immunity in vertebrates occur?
Both humoral and cell-mediated responses
Circulatory system with blood allows for quick immune response
Molecules and cells diffuse out of capillaries into tissue fluid
What are the features of the humoral response in vertebrates?
Anti-microbial peptides (AMPs) Lysozyme Interferons Cytokines Complement
How does lysozyme act?
It is an an enzyme that breaks down peptidoglycan so is very effective against Gram-positive bacteria. Discovered by Alexander Fleming in 1921
What is peptidoglycan?
Made of alternating molecules of two different sugars: N-acetylmuramic acid and N-acetylglucosamine. Lysozyme targets the glycosidic bind between these sugars, rupturing the cell membrane of Gram-positive bacteria
What are interferons?
Cytokines which act directly in viruses by inhibiting viral replication in host cells, but also indirectly by activating antiviral defences in tissue cells and activating several effector cells in the immune system which help destroy pathogens
What are cytokines and what are their 3 characteristics?
They are small, soluble proteins which function as chemical messengers for cells involved in immunity
- Pleiotropic - act on different cell types
- Redundant - more than one cytokines does the same job
- Multi-functional - do several jobs
What is complement?
Discovered by Jules Border in 1895
Complement are a series of proteins in serum and body fluid which circulate in inactive form. Activation of one triggers a complex cascade where each component activates another component. Activation of complement leads to inflammation and chemo-attraction of phagocytes
What does the binding of complement components to bacteria lead to?
It leads to the formation of a pore in the cell wall and lysis of the cell, or opsonisation so bacteria can be more easily phagocytosed
What is opsonisation?
Targeting of a particular cell
What is inflammation?
Capillaries dilate and become permeable to immune effector cells
What are the cell-mediated responses in vertebrates?
Phagocytic cells such as neutrophils and macrophages
Secretory cells such as natural killer cells
What do natural killer cells do?
Induce apoptosis or lysis of other cells by releasing perforin and granzyme
What are the steps in phagocytic action?
- Move towards pathogen
- Make contact - complement or antibody opsonisation
- Engulf - phagosome
- Fusion with lysosome to form a phago-lysosome
- Killing - toxic cells
- Digest remains
What are the key features of adaptive immunity in vertebrates?
Specificity
Memory
Tolerance to self and harmless antigens
What produces the antibodies involved in the humoral immune response or adaptive immunity?
B lymphocytes
What mediates the cellular immune response of adaptive immunity?
T lymphocytes
Features of B lymphocytes
Short for bursa-derived lymphocytes (although in mammals B lymphocytes are produced in the bone marrow)
B cells make immunoglobulins (Ig). Antibodies are immunoglobulins that bind to specific molecular targets or antigens
What happens to pathogens once they are tagged by a specific antibody?
They are recognised for disposal by complement or macrophages
What is the structure of an antibody?
Dimeric molecule composed of two heavy chains and two identical light chains. The 3D structure is held together by disulphide bondsp
How is antibody diversity generated?
Different combinations of heavy and light chains are used, and gene segments are rearranged to give thousands of different variations of heavy and light chains. There is also junctional diversity
What is junctional diversity?
Arises when the fusion of V, D and J segments is not exact
What transcribes immunoglobulins?
B cells - the rearrangement of VDJ segments takes place early in the development of the B cell
Each mature B cell can make how many different immunoglobulins?
One single immunoglobulin, which it presents on its surface
What happens when this immunoglobulin binds to its specific antigen?
The B cell is triggered to proliferate. During proliferation, somatic mutations occur, leading to further diversity in the specificity of antibodies produced
What stimulates B cells to develop into plasma cells?
Their interaction with T helper cells
What do plasma cells do?
Produce large quantities of the specific antibody
What is the name for the process of B cell proliferation and development into plasma cells?
Clonal expansion
What do some of the B cells also differentiate into?
Memory B cells - they remain in circulation and can quickly proliferate next time the antigen is encountered
What is immunological tolerance?
The ability of the adaptive immune system to ensure there is no response to harmless or ‘self’ antigens - they must be tolerated
During B cell maturation, what happens to B cells that recognise ‘self’ antigens?
They are destroyed - clonal deletion
What are the 5 classes of immunoglobulin possessed by mammals?
- IgD - in B cell surface, unknown function
- IgG - the main Ig in serum and able to cross placenta
- IgM - a pentameric immunoglobulin produces during the immune response
- IgA - secreted at mucosal surfaces and acts as primary defence
- IgE - combats parasite infections but also responsible for allergies
How are the 5 classes of immunoglobulins encoded?
They have the same heavy chain locus, and class switching is achieved by using different C regions
What are monoclonal antibodies?
Produced by a single cloned B cell in vitro, widely used in research, diagnostics and clinical treatments
What is immunocytochemistry?
Cell imaging using labelled antibodies to detect antigens
What is immunohistochemistry?
Similar technique using tissue sections
What is Western blotting?
Separated proteins by gel electrophoresis and used labelled antibodies to detect specific proteins. Useful in diagnosis
Features of T lymphocytes
Short for thymus-derived lymphocyte
T cells originate in bone marrow but migrate to and mature in thymus
What are 2 important T cells?
Helper T cells - activate B cells or macrophages
Cytotoxic T cells - kill virus-infected cells
What do T cells have to aid them in recognition?
T cell receptors
They are also immunoglobulins, and diversity is generated the same way as for immunoglobulins in B cells
What does a T cell receptor recognise?
A peptide fragment held on the surface of another cell. The peptide fragment derived from digestion of either an exogenous or endogenous protein
Where is the peptide fragment held on the cell surface?
In the groove of the MHC (major histocompatability complex)
What is MHC class I?
It is on every nucleated cell. It allows recognition of abnormal cells and self-recognition
How do cytotoxic T cells respond to MHC I?
Via CD8 - they can therefore recognise virus-infected cells and destroy them by secreting perforins and causing apoptosis of the cell
What is MHC class II?
It is on specialised antigen-presenting cell’s (APCs), such as B lymphocytes and macrophages. Helper T cells respond to MHC class II via CD4, thus they can specifically help B cells and macrophages
What happens to T cells after they have responded to an antigen?
They remain in circulation
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What happens to T cell receptors that recognise ‘self’ peptides?
They are destroyed in the thymus
