Immunology Flashcards
What consists of the innate natural immunity
Natural/physical barriers
Soluble factors (cytokines, acute phase proteins, inflammatory mediators, complement proteins)
Immune cells (macrophages, mast cells, natural killer cells, neutrophils)
What consists of the acquired adaptive immunity
Soluble factors (cytokines, antibodies)
Immune cells (B cells, T cells)
What are the routes of entry and attack on the body?
E: Digestive, reso, urogenital, skin
A: Circulatory, lymphatic
What are the barriers to infection?
Physical: skin and mucous membrane lining digestive, urinary, Resp and repro systems
Trap: mucous, cilia (in nose and trachea), hair (body, nose and ears, earwax
Elimination: coughing, sneezing, urination, diarrhoea
Unfavourable pH: stomach acid, sweat saliva, urine
Lysozyme enzyme: in tears, sweat, digests bacterial cell walls
Commensal bacteria
T or F: Both the innate and acquired immune system distinguish self from non-self
True
How does the tissue-resident innate immune cells recognise pathogens as ‘non-self’ and dangerous
Pathogens express ‘signature’ molecules not found on/in human cells:
Pathogen associated molecular patterns (PAMPS)
Innate immune cells express partner receptors for these PAMPS: Pattern-recognition receptors (PRRs)
How do macrophages kill bacteria?
Phagocytosis
Examples of opsonins
C3b
C-reactive protein (CRP)
IgG / IgM
Infection by extracellular bacteria and fungi is mediated by..
Macrophages
Infection by large parasites are mediated by..
Mast cells
How do mast cells work?
Parasite binds to mast cells via PAMPs to PRRs
Degranulation: Release of pre-formed pro-inflammatory substances (e.g. histamine)
Gene expression: Production of new pro-inflammatory substances (e.g. leukotrienes, prostaglandins)
What is released in an early innate immune response?
Nitric oxide
Prostaglandins/leukotrienes
Histamine
Pro inflammatory cytokines (TNFa)
What causes rubor and calor in acute inflammation?
Dilation of small blood vessels
Increased blood flow
Cell accumulation
Increased cell metabolism
What causes swelling in acute inflammation?
Increased permeability of post-capillary venules
Fluid accumulates in extravascular spaces
What causes pain in acute inflammation?
Stimulation of nerve endings
What causes loss of function in acute inflammation?
Swelling/pain
Explain transendothelial migration
Integrins - expressed on leucocytes to facilitate tight adhesion to the endothelium
Selectins - expressed on the endothelial surface to facilitate rolling of leucocytes
ICAM proteins - expressed on the endothelial surface to facilitate tight adhesion of leucocytes
Migration of Neutrophils across the endothelium is done via the process of..
Diapedesis
Movement of Neutrophils within the tissue is via..
Chemotaxis
What activated neutrophils?
PAMPS and TNFa
What are the different killing mechanisms of neutrophils?
Phagocytosis
Degranulation
NETs
How do neutrophils phagocytose?
Pathogens release chemical signals that attract neutrophils
Recognises PAMPS
Kill internalised pathogens via two mechanisms: Phagolysosomal killing or ROS dependant killing
Describe phagolysosomal killing
Bacterium is phagocytose d
Fuses with azurophilic and specific granules
pH of phagosome rises - bacterium is killed
pH then decreases - fusion with lysosomes allowed hydrolyses to degrade the bacterium completely
Describe ROS dependant killing
Neutrophil activation
Assembly of NADPH oxidase complex
Production and release of ROS into phagolysosome
T or F: Degranulation of neutrophils is extracellular. It often results in tissue damage and systemic inflammation
True
Out of neutrophils, macrophages and dendritic cells: Which has the best TNFa production?
Neutrophils
Out of neutrophils, macrophages and dendritic cells: Which has the best killing and degradation?
Neutrophils
Out of neutrophils, macrophages and dendritic cells: Which has the best antigen and presentation?
Dendritic
Out of neutrophils, macrophages and dendritic cells: Which has the best wound healing and anti-inflammatory?
Equal amongst all three
Which cell is responsible for intracellular pathogens eg virus?
NK cells
Define acute phase response. What mediates it?
Changes in the plasma concentrations of specific proteins in response to inflammation
It is driven by pro-inflammatory mediators released by activated macrophages and mediated by liver hepatocytes which produce a variety of Acute Phase Proteins
How does the body response to viruses?
Virally-infected cells produce and release cytokines called interferons (IFNα/β). This is going to signal neighbouring unaffected cells to destroy RNA and reduce protein synthesis/undergo apoptosis and activated NK cells
What stops NK cells from attacking healthy cells?
Presence of MHC class I self-peptides
Examples of cytokines
Interleukins, interferons
Examples of pro-inflammatory mediators
TNF
T or F: Low levels of inactive Complement System proteins are normally found in plasma and extracellular fluids
True
What does activation of complement system cause?
Opsonisation of pathogens
Direct pathogen killing
Acute inflammation
Leukocyte recruitment
Explain the alternative pathway
Low level cleavage of C3 to C3b and C3a. C3b is a very unstable protein and rapidly degraded unless it is bound to a carbohydrate or protein ligands on the surface of the cell. When a pathogen is present, the C3B can attach and bind to the ligands and become stabilised. It can now activate downstream complement system events. C3B can also feedback to or activate the Alternative pathway, which can generate an enzyme complex called C3 convertase, which can convert more C3 from its inactive single components into more active C3B and C3A. This is called an amplification loop
Why is the complement system inactive in a sterile environment, when our host cells contain carbohydrate/protein ligands that C3B can bind into?
Human cells express on their surface special inhibitory proteins that prevent the C3b from activating downstream complementary pathways. This ensures that this pathway is only activated in the presence of a pathogen.
Describe mannose lectin binding pathway
Mannose binding lectin once bound to its target molecule mannose, will activate a downstream series of events that will lead to the formation of C3 convertase enzyme - that can cleave inactive C3 to its active components C3B and C3A.
The C3b is stabilized on the surface of pathogens, it can then interact with other inactive components of the complement system. These can then generate an enzyme complex that can cleave inactive C5 into two active components: C5B which remains attached on the surface of the pathogen and soluble C5A. C5B also interacts with a large number of other complement cascade proteins. These together generate complex that forms a pore within the membrane of the pathogen. This channel penetrates the pathogen membrane and cell wall. This complex is called the Membrane Attack Complex (MAC). Extracellular salts and water can enter the pathogen by osmotic pressure, causing the pathogen to swell and burst.
T or F: The main difference between classical and alternative pathway is that the initiation of alternative pathways is not dependent on the presence of immune complexes
True
Which complement protein acts in a positive feedback loop of acute inflammation?
C5A and C3A can directly affect mast cells which will degranulate and release more histamines + pro inflammatory mediators
Which complement protein activates MAC?
C5B
Which complement protein acts as an opsonin?
C3B
What do macrophages and mast cells cause?
Local vascular changes
Neutrophil migration
Fever
Acute phase response
T or F: Mast cell response to both pathogens and injured tissue cells. Macrophages only response to pathogens
True
Differentiate between B cells and T cells
B: Humoral immune responses (deals with antigens from pathogens that are freely circulating, or outside the infected cells)
Defense against extracellular pathogens
T: Cellular immune responses (occurs inside infected cells and is mediated)
Defense against intracellular pathogens
What do B and T cells need to detect invading pathogens?
Antigens and antigen receptors
What antigens do B cells and T cells respond to?
B: Membrane associated or soluble antigens
T: Single antigen receptor
Differentiate between BCR and TCR
BCR: Complex of four polypeptide chains
2× Light chain + 2× Heavy chain
Each antibody has unique variable region that binds to one specific antigen
TCR: Membrane bound protein heterodimer. A hypervariable region formed by the tips of the α/β TCR chains
What is another name for MHC class molecules?
Human Leucocyte Antigens
Differentiate between MHC class I and II
I: Expressed on all nucleated cells. Present peptide antigens to CD8+T cells
II: Expressed only on professional Antigen Presenting Cells (APC) such as dendritic cells, macrophages and B cells. Present peptide antigen to CD4+ T cells
Where do B cells and T cells develop?
Primary lymphoid tissues: Bone marrow and thymus
T or F: Mature T cell and B cells constantly re-circulate between different the blood, primary lymphoid tissues and lymphatic vessels
False
Secondary lymphoid tissue
How do naive B cells and T cells enter secondary lymphoid tissue?
High endothelial venules are lined with endothelial cells that express specialized adhesion molecules, which allow T-cells and B-cells to arrest on those endothelial cells and undergo migration, exit and enter into the lymph nodes – similar to how neutrophils enter into infected an tissue. Difference is that migration of B cells and t-cells occurs even in the absence of infection or inflammation
How do B cells find antigen?
Coincidentally meet in the secondary lymphoid tissue
How do T cells find antigen?
Dendritic cells phagocytose pathogen-derived particles and antigens
Pro-Inflammatory TNFα stimulates immature tissue-resident Dendritic cells to increase expression of co-stimulatory molecules
Dendritic Cells digest ingested proteins and display small peptides derived from these on their cell surface in complex with
What are the first abs released from short lived plasma cells?
IgM
Why do some B cells mutate to secrete ‘better’ antibodies?
Switch from low to high affinity antibody
production (IgG) to allow delivery of the pathogen to phagocytes
What differentiates between different abs?
Different antibody classes have the same basic structure and same antigen-specificity but different heavy chains
What do B cells differentiate into and what do they secrete?
Long-lived Plasma cells, which will mass produce antigen-specific antibodies against the same opsonised antigen that started the process in the first place, and long-lived memory B cells
Give examples of non-protein antigens
BCR + Antigen
PPR + PAMP
Give examples of protein antigens
BCR + Antigen
Help from T-cells
Disadvantages of of non-protein antigens
Low-affinity antibodies only
Short-lived plasma cells only
No Memory B cells
What’s a germinal centre reaction?
Rapid proliferation and a clonal divison of an expansion of the B-cell population
What do TFH cells do?
Stimulate the B cell to proliferate and differentiate into long-lived plasma cells and memory B cells
What are the two functions of abs?
Recognition function
Effector function - clearance mechanisms mediated interaction of the Heavy chain constant region (Fc region) with effector molecules complement and fc receptors
What are the two forms of IgM
Membrane-bound monomeric form: IgM serves as the B cell antigen receptor
Secreted, pentameric form IgM is the first Ig type produced during a humoral immune response
Functions of Secreted, pentameric form IgM
Agglutination (immune complex formation)
Complement system activation
What mediates agglutination?
Specific antigen binding to IgM and IgG antibodies
What activates the classical system pathway?
Fc region of IgM and IgG antibodies when they are bound to specific antigens
What conformational changes does and doesn’t fix complement?
Does not: Planar or starfish
Does: Stable or crab
Why does stable/crab conformation fix complement?
Cause a conformational binding of C1 to pentameric region antigen bound IgM, allows the C1 complex to then engage with and activate downstream components of the complement system pathway to eventually lead to cleavage of C3
Most abundant antibody in normal human serum and extracellular tissue fluids
IgG
Dominant Ig type produced during a secondary (memory) immune response
IgG
Second most abundant antibody in normal human serum and extracellular tissue fluids
IgA
Most commonly produced antibody
IgA
Which antibody is found on mucosal membranes? (Resp, go, urogenital)
IgA
Functions of IgG
Agglutination Complement system activation Foetal immune protection (VIA PLACENTA!) Neutralisation Opsonisation Natural Killer cell activation
What happens in the 3-6 month window of age in children?
Transient hypoglycemic gamma globulin anaemia (at birth there’s no more source of maternal IgG until 6 months of age)
What is neutralisation? What abs mediate it?
Neutralises viruses and bacterial
toxins by either preventing uncaring of viral genomes or causes agglutination of
viruses in the extracellular
environment
Mediated by IgG and IgA
What do phagocytes such as neutrophils express on their surface?
Fcy receptors
What state does IgG exist in?
Monomeric
Function of membrane-bound monomeric form IgD
Mediates B cell activation
Function of the secreted form of IgD
Not well understood but found at extremely low concentrations in blood
What is the form of IgA in serum?
Monomeric
What is the form of IgA in fluids?
Dimeric
Functions of IgA
Neonatal defence (via breast milk) Neutralisation
What do T cells need in order to differentiate?
Engagement of the TCR by peptide MHC
Costimulatory molecules that were induced on the dendritic cell back when it was in the peripheral tissues due to the presence of pro-inflammatory mediators such as TNF-alpha
The copies on T cell antigen receptor on their surface that is specific for the same..
Peptide MHC complex that the original parent cell was.
Naïve CD4+ T cell proliferate to.. then differentiate to…
CD4+ TH0 cell
CD4+ Effector TH cells (TH1, TH2, TFH, THreg)
What secrets IL-2?
CD4+ T cells
CD4+ TH1 cell
CD8+ T cells
What do Th1 cells do?
Help macrophages kill internalised pathogens
What pathogens escape phagolysosomal killing?
Listeria, Shigella, Mycobacteria, Legionella
What are the proteins in lytic granules of Cyt. toxic T cells and what are their functions?
Perforin - Polymerises to form a pore in the target membrane
Granzymes - Serine proteases, which activates apoptosis once in the cytoplasm of target T cell
Granulysin - Induces apoptosis
What happens after an inflammatory response?
Lots of immune cells will eventually die off at the end of an immune response (eg; neutrophils have a short half life)
Leaving behind a pool of memory T/B cells so higher level of antigen specific T cells or B cells after an immune response
Macrophages switch from pro-inflammatory to anti-inflammatory to initiate tissue repair processes and wound healing. They will also phagocytose an apoptotic cells that had been killed by cytotoxic t cells and natural killer cells. This mops up all the debris, switches off inflammation, immunity. Body might return to a steady-state
Lymph fluid transport is aided by..
Breathing Muscle contractions Pulsation in the arteries External compression including: Manual lymphatic drainage Short stretch bandages Gradient compression garments
What do monocytes give rise to?
Dendritic Cells (DC) and Macrophages (Φ)
What do lymphoid progenitors give rise?
T cells, B cells and Natural Killer (NK) cells
Where are complement system proteins produced?
Liver
Examples of cytokines and their functions
Interferons: Anti-viral activity
TNFa: Pro-inflammatory
Chemokines: Control and direct cell migration
Interleukines: Various functions
