Immunology Flashcards
What is an immune response against self cells called?
Autoimmunity
What is an immune response against non-harmful cells called?
Hypersensitivity
What is caused by an under-reaction of the immune system?
Cancer and infection
What occurs during Car-T cell therapy?
A persons own T cells are genetically modified to target specific cancer cells and reinserted in to fight off cancer
What are the 2 types of immunity?
Innate immunity - generic and rapid
Acquired immunity - unique and slow
How does the skin act as a physical barrier against pathogens?
It is composed of tightly packed, highly-keratinised cells that are sloughed off and constantly renewed
How does the skin act as a physiological barrier against pathogens?
It is acidic and has a pH of 5.5
What substances are produced by the sebaceous glands to protect against pathogens?
Hydrophobic oils
Lysozymes
Ammonia
Antimicrobial peptides
How does the nose and throat protect against pathogens?
They have ciliated epithelium and produce mucus to trap pathogens and move them out of the body or into the stomach
How does a pathogen stimulate an immune response?
They express Pathogen Associated Molecular Patterns (PAMPs)
How do innate immune cells detect pathogens?
They have Pattern-Recognition Receptors (PRRs) on their cell surface for detection of pathogens
What are the 3 modes of ingestion by macrophages?
Pinocytosis
Receptor-mediated endocytosis
Phagocytosis
What occurs during phagocytosis by macrophages?
Macrophages’ PRRs bind to the pathogens PAMP
The pathogen is ingested into a phagosome in the cytoplasm
Lysosomes fuse with the phagosome and release hydrophilic enzymes and acid to digest the pathogen
What is expressed after phagocytosis by macrophages?
Pathogen derived peptides are expressed on MHC-II molecules on the cell surface membrane
What are released during phagocytosis by macrophages?
Pro-inflammatory mediators e.g. TNFα (Tumour necrosis factor)
What is opsonisation?
The coating of pathogens by soluble factors (opsonins) to enhance phagocytosis
What are some example of opsonins?
C3b
C-reactive protein
IgG/IgM (Immunoglobulin G/M)
What type of immune cells are used to destroy large pathogens such as parasites?
Mast cells
In what 2 ways do mast cells react to pathogens?
Degranulation - release of pre-formed substances from granules e.g. histamines
Gene expression - Production of new inflammatory substances e.g. leukotrienes and prostaglandins
What are the 5 cardinal signs of inflammation?
Rubor - Redness
Calor - Heat of extremities
Tumor - Swelling
Dolor - Pain
Function laesa - Loss of function
What causes redness and heat during inflammation?
Localised vasodilation causes increased blood flow and metabolism, resulting in heat production
What causes swelling?
The endothelium of post capillary venues becomes more permeable, so immune cells and excess fluid moves in
What molecules are present on the endothelial cells to recruit neutrophils?
Platelet-Endothelial Cell Adhesion Molecules (PECAMs)
What name is given to the recruitment and activation of neutrophils?
Transendothelial migration
How does vasodilation allow transendothelial migration to occur?
Vasodilation results in a decrease in blood flow rate, meaning neutrophils are travelling slow enough to move to the edges of the blood vessels (margination), bind to PECAMs and then move into the endothelium (Diapedesis)
What attracts neutrophils into the Tunica intima?
Chemicals released by the bacteria
What is an example of a PECAM?
ICAM-1 (Intercellular Adhesion Molecule) A.K.A CD54 (Cluster of Differentiation 54)
What are the 3 methods of pathogen destruction by neutrophils?
Phagocytosis
Degranulation
Neutrophil Extracellular Traps
What are the 2 methods of phagocytosis by neutrophils?
Phagolysosomal killing
ROS-dependant killing
What occurs during Phagolysosomal killing by neutrophils?
The neutrophil engulfs the pathogen into a phagosome
Specific granules, azurophilic granules and lysosomes bind to the phagosome
What occurs during ROS-dependant killing?
A Reactive Oxygen Species (NADPH oxidase complex) is assembled in the lysosome walls and is then released into the phagolysosome
What occurs in degranulation of neutrophils?
Anti-bacterial proteins are released from the granules of the neutrophils, into the extracellular milieu
What is a Neutrophil Extracellular Trap?
At the end of their life, neutrophils will release their chromatin and DNA to form a sticky trap to catch bacteria
What is the acute phase response?
A hepatocyte mediated response in which concentrations of specific proteins are changed. It is driven by pro-inflammatory mediators released by the activated macrophages
What is the function of C reactive protein?
It primes certain bacteria for destruction and plays a role in determining severity and duration of inflammation
What do virally infected cells produce and release in response to infection?
α and ß Interferon
What are the 3 functions of Interferon?
They signal neighbouring cells to destroy RNA and reduce protein synthesis to prevent viral replication
They signal neighbouring cells to undergo apoptosis
They activate immune cells such as natural killer cells
What is the function of a MHC-I (Major HistoCompatibility class I) receptor?
They survey proteins produced by the cell and present fragments of peptides produced by the cell
How does a virus affect the presentation of MHC-I receptors?
They prevent the formation or presentation of MHC-I receptors so that they won’t present non-self proteins
What 2 signals are required for the activation of B cells?
Antigens
Helping signals
Where in the lymph nodes does B cell activation occur?
In the germinal centre
What is the first type of antibody to be produced by short-lived B plasma cells?
IgM antibodies
How can some B cells mutate to improve the immune reaction?
They can switch from low to high affinity antibody production
They can switch the class of antibody that they produce, such as from IgM to IgG
They can differentiate into long-lived plasma cells or long-lived memory B cells
What 2 processes occur in the germinal centre reaction?
Proliferation (reproduction)
Differentiation
What occurs in a somatic hypermutation response?
The mutation of antibodies to allow for a tighter fit to protein antigens
What are the 2 signals required for most activation by non-protein antigens?
Non-protein antigen
Pathogen Associated Molecular Pattern (PAMP)
What are repetitive antigenic epitomes?
A large number of the same B cell receptor to the same antigen
What is required to activate a B cell containing repetitive antigenic epitomes?
Many copies of the antigen without the need for the PAMP
What are the characteristics of a non-protein antigenic response?
Only low-affinity antibodies produced
Only short-lived plasma cells produced
No B memory cells
What 2 stimuli are required to activate a B cell, when a protein antigen is present?
The protein antigen
T-h cell (CD4+ T cell) stimulation
What types of MHCs do B cells express?
Both class I and class II as they can phagocytose a pathogen and splay its antigens
How do T - Follicular Helper cells activate B cells?
T-fh cells have a receptor complementary to the MHC-II and protein antigen complex
This causes the T-fh cell to release co-stimulatory molecules that re-activate B cells
What happens to a B cell after it has been activated by a T-fh cell?
It proliferates and more T-fh activate the further copies of the B cells
They then differentiate to form long-lived B plasma cells
What is the complement system?
A system of low level, inactive proteins that circulate in the blood. When activated, they trigger a chain reaction that amplifies to produce a large response to a pathogen
What does the complement system promote?
Opsonisation
Direct killing
Acute inflammation
Leukocyte recruitment
What are the 3 pathways of C3 breakdown?
Classical pathway
Mannose-binding lectin pathway
Alternative pathway
What enzyme converts C3 into C3b and C3a?
C3 convertase enzyme
What occurs in the Mannose-binding lectin pathway?
MBL binds to mannose of the surface of a bacterium
This causes the activation of the MBL which in turn activates the C3 convertase enzyme
What occurs in the alternative pathway?
C3b binds to the surface of a pathogen
This stabilises the C3b and triggers the activation of C3 convertase enzyme
What occurs in the classical pathway?
Planar IgM or IgG bind to the surface of a pathogen by their antigens
IgM converts to a staple form and both IgG and IgM act as a platform for C1 to bind
C1 can then activate C3 convertase enzyme
What are the functions of C3b in the complement system?
C3b can act as an opsonin
C3b can also activate the enzyme C5 convertase enzyme
What is the function of the C5 convertase enzyme?
It hydrolyses C5 to form C5b ad C5a
What is the function of C5b?
It attaches to the surface of a pathogen and begins the formation of an MAC (Membrane Attack Complex)
What are the components of an MAC?
C5b, C6, C7, C8 and C9
What is an MAC?
A membrane attack complex is a pore that is formed in the membrane of a pathogen that causes cell death by osmotic lysis
What is the function of C3a and C5a?
They are pro-inflammatory substances so promote acute inflammation
What are the 2 types of T cell?
CD8+ T cells
CD4+ T cells
Where do B cells differentiate?
In the bone marrow
Where do T cells differentiate?
In the Thymus
How do T cells get their name?
T = Thymus
How do B cells get their name?
B = Bursa of Fabricius (The place of B cell formation in birds)
What forms the antigen receptors on B cells?
Antibodies
What are the 2 types of polypeptides that make up an antibody?
2x Light chains
2x Heavy chains
What are the 2 components of a T cell antigen receptor?
An α-chain and a ß-chain
What do T cell antigen receptors bind to?
A complex formed from an antigenic peptide (Not the full protein) and an MHC molecule
What is the other name for an MHC (Major Histocompatability Complex)?
HLA (Human Leukocyte Antigens)
What are the 2 types of MHC molecule?
Class-I
Class-II
What are the 2 types of MHC molecule?
Class-I
Class-II
On which cells are MHC-I expressed?
An all nucleated cells
What T cells bind to MHC-I molecules?
CD8+ T cells
On which cells are MHC-II expressed?
On Antigen Presenting Cells (APCs)
What T cells bind to MHC-II molecules?
CD4+ T cells
What is bound to MHC-I molecules?
Self-produced peptides for surveillance
What is bound to MHC-II molecules?
Antigenic peptides
Where do T and B cells circulate?
Between the blood, secondary lymphoid tissues and lymphatic vessels
What are the 2 zones of the lymph nodes?
T zones and B zones
How do lymphocytes enter the lymph nodes?
Via the afferent lymphatics
Via High Endothelial Venules (HEVs)
How do lymphocytes enter the lymph nodes by HEVs?
The endothelial cells of the HEVs express adhesion molecules that allow T and B cells to move in
How do B cells encounter antigens in the lymph nodes?
Opsonised antigens enter the lymph nodes via circulation and are held there until the correct B cell moves into the lymph node, where they bind
What stimulus dendritic cells in an immune response?
TNFα
What change occurs in dendritic cells when stimulated by TNFα?
Dendritic cells are stimulated to increase expression of co-stimulatory molecules
What occurs when dendritic cells phagocytose antigens and pathogen debris?
They express peptide antigens on MHC-II molecules on their cell surface
Where do activated dendritic cells move to when activated?
They move into the lymph nodes
What do dendritic cells do in the lymph nodes?
They stimulate and activate T cells in the lymph nodes by MHC-II molecules and co-stimulatory molecules
What is agglutination?
The action of an antibody when it cross links many antigens to form clumps
How does agglutination help in immunity?
It increases efficiency of phagocytosis and prevents viruses binding to host cells
What are the 5 types of mammalian antibodies?
IgM
IgG
IgA
IgD
IgE
What are the 2 forms of IgM antibodies?
Membrane-bound monomeric
Secreted, pentameric form
What is the function of membrane bound, monomeric IgM?
It serves as a B cell receptor
What is the function of secreted, pentameric IgM?
It is the 1st antibody produced in the humeral response.
It is used in agglutination and complement system activation
What type of heavy chain does IgM contain?
Mu heavy chain
What is the most abundant antibody in normal human serum?
Monomeric IgG
What are the functions of IgG?
Agglutination
Complement system activation
Foetal immune protection
Neutralisation
Opsonisation
Natural killer activation
How does IgG provide foetal immune protection?
IgG receptors on placental cells allow movement of IgG from the maternal circulation to the foetal circulation
What is the name given to the low IgG levels after birth, before the baby begins to produce its own antibodies?
Hypogammaglobulinemia
What occurs during viral uncoating?
The virus attaches to the surface of a phagocyte and is endcytosed
It then releases its RNA into the cell so that it can be synthesised by the cell
What occurs during neutralisation?
Antibodies bind to the capsid of the virus and can either prevent its attachment to the cells surface or can prevent RNA release by fusion interference or capsid stabilisation
How do IgG antibodies act as opsonins?
Many phagocytes have Igγ receptors on their surface that can bind to IgG antibodies, bound to a pathogen
How do antibodies activate natural killer cells?
Natural killer cells have antibody-dependent cell-mediated cytotoxicity, in which Igγ receptors on the NK cells can bind to IgG and become activated to cause cell apoptosis and pro-inflammatory cytokines
What is the heavy chain present in IgG antibodies?
Gamma heavy chain
What are the 2 forms of IgD antibodies?
Membrane-bound monomeric form
Secreted form
What is the function of the membrane-bound monomeric form?
They serve as B cell antigens
What is the heavy chain present in IgD antibodies?
Delta heavy chains
What are the 2 forms of IgA antibodies?
Monomeric form in serum
Dimeric form in secretory fluids (secretory IgA)
What binds IgA in its dimeric form and IgG in its pentameric form?
J chains
What is the function of IgA in serum?
Neutralisation
What is the function of secretory IgA?
Neonatal defence and neutralisation sat mucosal sites
How does secretory IgA provide neonatal defence?
sIgA antibodies are transported into the colostrum and breast milk by receptors in breast tissue to protect the GI tract of neonates
What type of heavy chain is present in IgA?
Alpha heavy chain
What type of heavy chain is present in IgE?
Epsilon heavy chain
What is the function of IgE?
They bind to Igε receptors on mast cells and basophils and stimulate degranulation
This can trigger allergic responses such as asthma, allergy and anaphylaxis
What molecule stimulates both CD8+ and CD4+ T cells?
Dendritic cells as they express both MHC-I and MHC-II
What is the inactive form of CD4+ T cells known as?
Naïve CD4+ T cells
What is the undifferentiated form of CD4+ cells known as?
CD4+ Th0 cells
What are 4 MAIN types of differentiated CD4+ effector Th cells?
Th1 cells
Th2 cells
Tfh cells
Regulatory T cells
What is released upon binding of CD4+ T cells that causes activation?
Interleukin-2 (IL-2)
What is the function of a Th1 cell?
They leave the lymph nodes and enter infected tissue
They then bind to infected macrophages and release IFNγ which increases macrophage activity
How can some pathogens infect and propagate macrophages?
Some pathogens can escape the phagosome and enter the cytosol of the macrophage
What are some examples of pathogens that can escape a phagosome?
Listeria
Shigella
Mycobacteria
Legionella species
How can Th1 cells help in the destruction of pathogens that can escape the phagosome?
They switch on the expression of NADPH oxidase genes that produce toxic reactive oxygen species (ROS)
What stimulates the differentiation of CD8+ T cells into Cytotoxic T cells?
Interleukin-2 (IL-2)
How do Cytotoxic T cells destroy cells?
CTL bind to MHC-I molecules containing viral peptides on the surface of infected cells
They release substances that cause DNA fragmentation and apoptosis
They then move to the next target
What is the function of Perforin released by CTLs?
It polymerises to form a pore in the infected cells membrane, inducing cell death by osmotic lysis
What is the function of Granzymes released by CTLs?
They are a family of serine proteases that activate apoptosis
What is the function of granulysin?
It induces apoptosis
How is an immune response ended?
Effector T-cells are short lived and so die
When all pathogens are destroyed, no more cytokines or pro-inflammatory substances are produced
This means macrophages have no pathogenic stimuli, so instead engulf and ingest cell debris from destroyed cells and pathogens
They then release Anti-inflammatory cytokines such as Interleukin-10 (IL-10) and play a part in tissue repair
What are examples of acute phase proteins?
Mannose-binding lectin
C reactive protein
C3
What is the acute phase response?
A response to cytokines by the liver in which complement system proteins are released
What cells are precursors to dendritic cells and erythrocytes?
Myeloid progenitor cells
