Immunology
EXAM: 1 ESSAY, 2 SAQ’S
08/10/2019
Interferons interfere with replication of viruses
Extracellular infection – complement, macrophages, neutrophils (interstitial spaces like
blood and lymph), antimicrobial peptides (epithelial surfaces)
Intracellular infection – NK cells (cytoplasmic), activated macrophages (vascular)
Persistence of the pathogen e.g. HIV is weak outside human body, anthrax has tough heat-
resistant spores
Complement – soluble and membrane bound proteins, made in an inactive form requiring
activation, activation leads to cascade of enzymatic reaction. 30 proteins in complement
system (C3 most important)
C3b tags bacterium for destruction (C3b coats the pathogen’s surface) , C3a recruits’
inflammatory cells
Phagocytes have receptors for C3, so protective mechanisms stop the lysis of our cells:
Properdin maintains C3 convertase. Factor H and Factor I (plasma proteins), Factor H binds
to C3b on the pathogen surface, and calls in Factor I. DAF and MCP (membrane proteins),
DAF binds C3b for inactivation and MCP makes factor I more susceptible – this stops C3
convertase tagging our own cells for destruction.
Opsonisation – tagging a pathogen for destruction.
CR1 on macrophages can sense C3b on bacterium, leading to phagocytosis, a membrane
bound vesicle in phagosome containing bacterium is formed.
C5 convertase begins the MAC, C9 at the end can carry on the convertase chain for this.
Protectin (CD59) – Binds to C5678 and stops C9 forming so it protects our cells from MAC
MAC perforates (makes holes in) the bacterium cell membrane
C3, CD, etc. means they’re membrane bound proteins. Properdin is not membrane bound.
Complement activation induces inflammatory response , increasing vascular permeability.
This means they’re less tightly bound and can induce fluid leakage, helping complement
proteins and phagocytes arrive at the site of infection.
Receptors recognising microbial carbohydrates – lectins; mannose R, Scavenger R, Glucan R.
LPS receptors are PRRs (pattern recognition receptors), recognising microbial surfaces.
TLRs – signalling receptors, tailored by immune responses so like WHAT and WHERE is the
infection? So, it informs T cells, B cells, and other cells so adaptive immune responses can
take place. Can switch on cytokine production.
TNF alpha and IL-1 attract neutrophils
Stem cell niche – in trabecular bone, containing blood vessels that are large in size, and
neutrophils are stored in there along with stem cells and differentiating cells (huge reserve
of mature neutrophils here). They go through the sinusoids and into the circulation to the
site of infection (leakage in blood vessels).
Pus can be formed after neutrophils die – will die hours after entering infected tissue.
Neutrophils can work without oxygen as an adaptation.
PRR (pattern recognition receptors) CR (complement receptors) can recognise both
unopsonized and opsonized pathogens.
, Once neutrophils have engulphed enough bacterium, they go through apoptosis and send
signals to macrophages to ingest them. Macrophages will also send the same signals to other
macrophages if they die. The PH inside the neutrophil increases as the antimicrobial
response increases, and the PH is decreased once fusion with lysosomes allows acid
hydrolases to degrade the bacterium.
Different techniques are there for oxygen dependent and oxygen independent pathogens.
IL-1, IL-6 and TNF-a released by macrophages in response to bacteria, reducing bacterial
growth, enhancing adaptive immunity, and stimulate production of acute phase proteins (2 nd
response of innate immunity); C-reactive proteins (CRP) and mannose-binding lectin (MBL),
referring to the complement system.
Liver cells are stimulated by IL-6 to form C-reactive proteins, fibrinogen, and MBL.
Activation pathways differ in time – C3 fixation happens at beginning of infection.
Interferon response – IFN-a and IFN-b induce resistance viral replication, increase expression
of ligands for receptors or NK cells, and activate NK cells to kill virus infected cells.
NK cell increases 10-200x on exposure to interferons, providing early response to viruses
until Tc cells are ready.
NK cells use receptors to distinguish healthy and infected cells. Infected cells express MIC
ligands for the NK receptor NKG2D
Cytokines bring in second acute phase responses
IFN production for viruses induces NK activity
15/20/2019
Damage-associated molecular patterns (DAMPs)
Pathogen-associated molecular patterns (PAMPs)
^ both recognised by pathogen recognition receptors.
B cells are made and matured in the bone marrow, make 1 billion B cells every day
B cells express surface antibodies (immunoglobulins) like receptors
Differentiated B cells turn to plasma cells and secrete soluble antibiotics that can travel to
the microorganism without the B cell body.
Plasma cells appear bigger under the microscope with more ER
Antibodies – 2 identical heavy chains and 2 identical light chains, constant regions (legs),
variable regions (tips of arms), hinge region (arms, below the variable regions).
Hinge regions allow antibody flexibility so variable regions can attach to bacterium
receptors.
Variable regions contain hypervariable regions and are flanked by framework regions. There
are 3 hypervariable regions (or CDR; complementary determining regions) in each of the 4
variable regions. This makes 12 CDRs per antibody.
Antibodies bind to epitopes of carbohydrates and proteins on the pathogenic cell, as they’re
exposed on the surface, but the epitopes need to be accessible to the antibody. The antigen
epitope must be complementary to the antibody, it’s usually a 3D structure so there are lots
of variables.
There are 100 billion different antigens that an antibody could possibly recognise, so once an
antibody is found that matches the specific C, D, V, J sequences to the antigen, it goes
through clonal selection to fight off the antigen in bigger numbers.
Gene configuration is done in the bone marrow to make the different sequences. Different
gene segments encode different regions, and are all configured in chromosome 2, 22, (light
EXAM: 1 ESSAY, 2 SAQ’S
08/10/2019
Interferons interfere with replication of viruses
Extracellular infection – complement, macrophages, neutrophils (interstitial spaces like
blood and lymph), antimicrobial peptides (epithelial surfaces)
Intracellular infection – NK cells (cytoplasmic), activated macrophages (vascular)
Persistence of the pathogen e.g. HIV is weak outside human body, anthrax has tough heat-
resistant spores
Complement – soluble and membrane bound proteins, made in an inactive form requiring
activation, activation leads to cascade of enzymatic reaction. 30 proteins in complement
system (C3 most important)
C3b tags bacterium for destruction (C3b coats the pathogen’s surface) , C3a recruits’
inflammatory cells
Phagocytes have receptors for C3, so protective mechanisms stop the lysis of our cells:
Properdin maintains C3 convertase. Factor H and Factor I (plasma proteins), Factor H binds
to C3b on the pathogen surface, and calls in Factor I. DAF and MCP (membrane proteins),
DAF binds C3b for inactivation and MCP makes factor I more susceptible – this stops C3
convertase tagging our own cells for destruction.
Opsonisation – tagging a pathogen for destruction.
CR1 on macrophages can sense C3b on bacterium, leading to phagocytosis, a membrane
bound vesicle in phagosome containing bacterium is formed.
C5 convertase begins the MAC, C9 at the end can carry on the convertase chain for this.
Protectin (CD59) – Binds to C5678 and stops C9 forming so it protects our cells from MAC
MAC perforates (makes holes in) the bacterium cell membrane
C3, CD, etc. means they’re membrane bound proteins. Properdin is not membrane bound.
Complement activation induces inflammatory response , increasing vascular permeability.
This means they’re less tightly bound and can induce fluid leakage, helping complement
proteins and phagocytes arrive at the site of infection.
Receptors recognising microbial carbohydrates – lectins; mannose R, Scavenger R, Glucan R.
LPS receptors are PRRs (pattern recognition receptors), recognising microbial surfaces.
TLRs – signalling receptors, tailored by immune responses so like WHAT and WHERE is the
infection? So, it informs T cells, B cells, and other cells so adaptive immune responses can
take place. Can switch on cytokine production.
TNF alpha and IL-1 attract neutrophils
Stem cell niche – in trabecular bone, containing blood vessels that are large in size, and
neutrophils are stored in there along with stem cells and differentiating cells (huge reserve
of mature neutrophils here). They go through the sinusoids and into the circulation to the
site of infection (leakage in blood vessels).
Pus can be formed after neutrophils die – will die hours after entering infected tissue.
Neutrophils can work without oxygen as an adaptation.
PRR (pattern recognition receptors) CR (complement receptors) can recognise both
unopsonized and opsonized pathogens.
, Once neutrophils have engulphed enough bacterium, they go through apoptosis and send
signals to macrophages to ingest them. Macrophages will also send the same signals to other
macrophages if they die. The PH inside the neutrophil increases as the antimicrobial
response increases, and the PH is decreased once fusion with lysosomes allows acid
hydrolases to degrade the bacterium.
Different techniques are there for oxygen dependent and oxygen independent pathogens.
IL-1, IL-6 and TNF-a released by macrophages in response to bacteria, reducing bacterial
growth, enhancing adaptive immunity, and stimulate production of acute phase proteins (2 nd
response of innate immunity); C-reactive proteins (CRP) and mannose-binding lectin (MBL),
referring to the complement system.
Liver cells are stimulated by IL-6 to form C-reactive proteins, fibrinogen, and MBL.
Activation pathways differ in time – C3 fixation happens at beginning of infection.
Interferon response – IFN-a and IFN-b induce resistance viral replication, increase expression
of ligands for receptors or NK cells, and activate NK cells to kill virus infected cells.
NK cell increases 10-200x on exposure to interferons, providing early response to viruses
until Tc cells are ready.
NK cells use receptors to distinguish healthy and infected cells. Infected cells express MIC
ligands for the NK receptor NKG2D
Cytokines bring in second acute phase responses
IFN production for viruses induces NK activity
15/20/2019
Damage-associated molecular patterns (DAMPs)
Pathogen-associated molecular patterns (PAMPs)
^ both recognised by pathogen recognition receptors.
B cells are made and matured in the bone marrow, make 1 billion B cells every day
B cells express surface antibodies (immunoglobulins) like receptors
Differentiated B cells turn to plasma cells and secrete soluble antibiotics that can travel to
the microorganism without the B cell body.
Plasma cells appear bigger under the microscope with more ER
Antibodies – 2 identical heavy chains and 2 identical light chains, constant regions (legs),
variable regions (tips of arms), hinge region (arms, below the variable regions).
Hinge regions allow antibody flexibility so variable regions can attach to bacterium
receptors.
Variable regions contain hypervariable regions and are flanked by framework regions. There
are 3 hypervariable regions (or CDR; complementary determining regions) in each of the 4
variable regions. This makes 12 CDRs per antibody.
Antibodies bind to epitopes of carbohydrates and proteins on the pathogenic cell, as they’re
exposed on the surface, but the epitopes need to be accessible to the antibody. The antigen
epitope must be complementary to the antibody, it’s usually a 3D structure so there are lots
of variables.
There are 100 billion different antigens that an antibody could possibly recognise, so once an
antibody is found that matches the specific C, D, V, J sequences to the antigen, it goes
through clonal selection to fight off the antigen in bigger numbers.
Gene configuration is done in the bone marrow to make the different sequences. Different
gene segments encode different regions, and are all configured in chromosome 2, 22, (light
