immunity Flashcards
What is inflammation?
The body’s response to an irritant, an infectious pathogen, tissue damage etc.
Part of the innate immune response
Immediate and non-specific
what are the categories of inflammation
Acute inflammation (immediate response lasting a few days)
Chronic inflammation (lasting months or years)
Systemic inflammation (SI) – cytokine induced inflammatory response
Follows chronic inflammation.
Can lead to the development of conditions such as cardiovascular disease.
what are the signs of inflammation?
Localised signs of tissue inflammation:
Redness (Rubor)
Heat (Calor)
Swelling (Tumor)
Pain (Dolor)
Reduction or loss of tissue/organ function (functio laesa)
Whole body signs of inflammation:
Tiredness
General feeling of being unwell
Fever
how do you name a disease that is associated with inflammation
itis
what are the causes of acute inflammation
Infection (bacterial, viral)
Exposure to chemicals or radiation
Cell/tissue injury
Excessive immune reaction
Tissue necrosis due to restricted blood flow
what are the causes of chronic inflammation
A resistant infectious agent
Prolonged exposure to endogenous (necrotic tissue) or exogenous (chemicals) materials
Some diseases, e.g. chronic inflammatory bowel disease
Autoimmune disease
what are monocytes
precursors of macrophages
what are the steps in acute inflammation
Vessel dilation and increased blood flow
Vascular permeability
Leukocyte (neutrophil/monocyte) movement (migration)
what happens during acute inflammation
arterioles initially dilate and the opening of the sphincters leads to increased blood flow in the tissue capillary network.
In acute inflammation increased vascular permeability leads to the escape of fluid including blood cells and protein molecules to the extracellular space
- exudation.
what happens during actue inflammation to the capillary hydrostatic pressure
it increases
what do histamines do during vasodilation
Histamine is released from granules in mast cells in response to tissue injury, heat, cold or antibody binding. It binds on G-protein coupled receptors on endothelial cells. It is also released by basophils and platelets. Fast and short-lived response.
what do bradykinin and leukotrienes do during vasodilation
Bradykinin (circulating in the blood plasma) and leukotrienes (produced by leukocytes and mast cells) also increase vascular permeability.
what are leukotrienes mode of action
act on the vascular smooth muscle tissue
what do kinins do
act on the vascular smooth muscle tissue causing contraction and vasodilation
what is the role of neutrophils in inflammation
Neutrophils accumulate near the endothelium (vascular wall).
Adhesion molecules (selectins) produced by the endothelial cells are detected by neutrophil receptors.
Integrin ligands bind strongly on neutrophil integrins, rolling stops and transmigration through the endothelium begins.
how are leukocytes activated in inflammation
via ligand-receptor binding
what does phagocytosis rely on
Phagocytosis relies on reactive oxygen species (ROS) and lysosomal enzymes.
where are ROS formed
ROS are formed in the membrane of the phagosomes in a phagocyte activated following pathogen recognition.
what is inside a phagosome
Inside a phagosome ROS and NO kill pathogens.
what are the steps to phagocytsosis
- microbes bind to phagocyte receptors
- phagocyte membrane zips up around the microbe
- phagosome forms with ingested microbe
- fusion of phagosome with lysosome
- degadation of microbes by lysosomal enzymes in phagolyosome
what is the source histamines
mast cells
basophils
platelets
what is the action of histamine
vasodilation
increased vascular permiability
what is the source of prostaglandins
mast cells
leukocytes
what is the action of prostaglandins
vasodilation
pain
fever
what is the source of cytokines
macrophages
endothelial cells
mast cells
what is the action of cytokines
endothelial activation
fever
hypertension
what is the source of chemokines
leukocytes
activated macrophages
what is the action of chemokines
chemotaxis
leukocyte activation
what is the source of complement factors
leukocyte chemotaxis and inflammation
pathogen killing
vasodilation
what is the most abundant complement factor
C3 which is cleaved to C3a and C3b
what does c3b do
C3b participates in the cleavage of C5 to C5a and C5b → signal amplification involving other complement factors.
it also stimulated phagocytosis
what do complement factors do
Complement factors circulate in the plasma in their inactive form.
Following cleavage they become active and function in histamine release, chemotaxis (recruitment of leucocytes) pathogen opsonisation (recognition of a pathogen by a phagocyte).
what does c3a do
stimulated inflammation
what do lipotoxins do
inhibit neutrophil recruitment (chemotaxis and adhesion to the vascular endothelium).
what type of molecules are produced in parallel with pro-inflammatory molecules
antiinflammitory molecules
when are mediator molecules expressed
in response to a stimulus
what are features of mediator molecules
short half-lives
quick decay
what happens when the inflammatory response is prolonged
Leukocytes can damage tissue when the inflammatory response is prolonged or when the leukocytes attack host tissues (autoimmune disease). Unchecked release of enzyme rich leukocyte granules can also cause tissue damage.
what are the local benefits of inflammation
- increased vascular permeability- assists transport of blood circulating antibodies and drugs to site of infection
- exudation and fluid release dilutes conc. of toxins
- vascular exudate includes fibrinogen wich coagulates blood
what happens at the end of an acute inflammatory response
complete resolution
healing by tissue replacement
progression to chronic inflammation
how does chronic inflammation form
repeated events of acute inflammaiton
what is chronic inflammation characterised by
increased numbers of lymphocytes plasma cells and macrophages
what are some features of chronic inflammation
Necrotic tissue can be present.
Inflammatory cells cause tissue damage.
Tissue repair mechanisms and angiogenesis are initiated.
What are the sources of TNF
Macrophages
Mast cells
T lymphocytes
What is the action of TNF in acute inflammation
Acute inflammation
Stimulates endothelial adhesion molecules
Secretion of other cytokines
What are the sources of IL-1
Macrophages
Ednothelial cells
Epithelial cells
What are the actions of IL-1 in acute inflammation
Stimulated endothelial adhesion molecules
Secretion of other cytokines
Acute inflammation
What are the sources of IL-6
Macrophages
What are the actions of IL-6 in acute inflammation
Systemic effects
What are the sources of chemokines
Macrophages
Endothelial cells
T lymphocytes
Mast cells
What is the action of chemokines in acute inflammation
Recruitment of leukocytes
Migration of cells in normal tissues
What are the source of IL-17
T lymphocytes
What is the action of IL-17 in acute inflammation
Recruitment of neutrophils and monocytes
What is the sources of IL-12
Dendritic cells
Macrophages
What is the action of IL-12 in chronic inflammation
Increased production of IFN-y
What is the source of IFN-y
T lymphocytes
NK cells
What is the action ofIFN-y in chronic inflammation
Activation of macrophage
What is the action of IL-17 in chronic inflammation
Recruitment of neutrophils and monocytes
Which diseases cause granulomatous inflammation
Tuberculosis
Leprosy
Syphilis
Crohn disease
What are systemic effects of acute inflammation caused by
Cytokine production in response to pathogen infection
What contributes to systemic effects on inflammation
TNF
IL-1
IL-6
Type 1 interferons
what cytokines and chemokines are used in endothelial cell local inflammation
TNF, IL-1-cytokines
IL-1 chemokines
what chemokines and cytokines are used in leucocyte activation
TNF, IL-1 cytokines
IL-1,IL-6 chemokines
what cytokines and chemokines are used within T-cell differentiation.
IL-1,IL6 cytokines
IL-17 chemokines
which cytokines cause fever within the brain
TNF IL-1 IL-6
which cytokines cause acute-phase proteins to exit the liver
Il-1 IL-6
which cytokines cause leukocyte production within the bone marrow
TNF IL-1 IL-6
Which cytokines cause low output of blood from the heart
TNF
which cytokines cause endothelial cells and blood vessels to have increased permeability
TNF
what induces fever
pyrogens
what stimulated the production of prostaglandins
TNF, IL-1 Il-6
what do prostaglandins do?
are molecules that act in the hypothalamus to release neurotransmitters that set the body temperature higher.
what is fever
Increase in body temperature between 1℃ to 4℃.
what is resolution
the restoration of tissue back to normal
what conditions must be satisfied for resolution to proceed
Minimal cell death and tissue damage during the inflammatory phase.
Tissue or organ has regenerative capacity.
Quick destruction of infectious pathogens (macrophage/neutrophil phagocytosis).
Quick removal of cell debris (macrophage phagocytosis) and fluids (good vascular drainage).
End of vascular dilation.
what do monocytes do
circulate the blood and migrate to tissues where they differentiate to mature macrophages
what is the activity of macrophages
Chemotaxis: migration towards a damaged or infected area.
Phagocytosis: ingest cell debris.
Pinocytosis: ingest fluids.
how is debris removed via phagocytosis
recognition
binding
signalling
phagocytosis
label an antibody
what are the 5 antibody istotypes
Describe the lineage of CD4 and CD8 T cells
what is immunity
the ability of an organisms to defend itself against: infectious agents, foreign cells, catastrophic cell destruction
what is immunodeficiency
is the outcome of failed immunity caused either genetically or acquired through life
what is allergy and hypersensitivity
result when the immune system responds inappropriately to antigens
what is tolerance
state of immunological non-reactivity to an antigen
what does red bone marrow produce
Site of production for all blood cells including b and T lymphocytes
what do lymph nodes contain
resident lymphocytes and macrophages which neutralise pathogens and clear.
what do spleens contain
act as an emergency blood store
what does the thymus contain
site of maturation of t lymphocytes
what is a leucocyte
white blood cell
what are barrier systems for immunity
- skin is impermeable to most infectious pathogens
- Lysozymes in tear ducts nasal ducts and saliva breakdown black acidic bonds and assists the destruction of the bacterial cell wall
- Mucus with in the Tokyo traps pathogens that are expelled by epithelial cell cilia
- Lower stomach pH and digestive enzymes within the stomach make the environment uninhabitable for pathogens
- Intestinal flora in the gut in vagina antagonise infection from external pathogens
what is a macrophage
phagocytic, highly migratory, professional antigen presentation
what is a neurtophil
highly abundant and migratory, coordinates inflammatory response
what is an eosinophil
involved in host defence against nematodes and other parasites
what is a basophil
involved in host defences against multicellular parasites
what is a dendritic cell
the most adept of the family of antigen presenting cells (APC)
what is B cell
adaptive, produce antibodies that bind to antigens on pathogens, exhibit immunological memory
what is a t cell
adaptive, involved in killing virus infected cell, involved in coordinating immune responses, orchestrated of activation/termination
what are pattern recognition receptors (PRR)
PRR in innate immunity detect antigens non-specifically using receptors for PAMPS
what are PAMPs Pathogen Associated Molecular Patterns
- PAMPS a molecular structures that occur in lower organisms
- Signalling pathways are initiated when the signal binds its receptor
Explain key immunological events that underlie inflammation and its resolution.
- if you damage causes release of vasoactive and chemotactic factors that trigger local increase of blood flow and capillary permeability
- Permeable capillaries allow an influx of fluid in cells
- Phagocytes migrate to the site of inflammation (chemotaxis)
- Phagocytes and antibacterial exudate destroy bacteria
what to PRRR’s bind to
a limited array of PAMPS
what do PRRs respond to
PAMPs that may be protein, carbohydrate or lipid based
what are the PRR’s molecular memory
exhibits no molecular memory or ability to imrpove/adapt during an immune response
what are the features of PRR genes
genes entirely germ-line encoded
what to adaptive response receptors bind to
bind to a potentially infinite array of pathogen-associated peptides
what are the antigens for ARRs
antigens are always protein peptides for t cells and occasionally carbohydrates or lipids for B cells
what is the molecular memory like for ARR- adaptive response receptor
induces molecular memory and exhibits and ability to improve/adapt during the immune response
what are the genes like for ARRs
gene editing results in a modification to the genome in somatic immune cells
what is a complement in innate immunity
- A family of plasma proteins that activate each other – the complement cascade
- Capable of destabilising the membranes of invading bacteria
- Coat invading bacteria, marking them for destruction by antibodies
- Attracts phagocytes to the site of infection
what are the soluble mediators in innate immunity
complements
lysozymes
cytokines
how to leucocytes communicate
- leucocytes communicate using cytokines and chemokines
- They bind to receptors on the target cell to sugar signalling transduction cascades that ultimately lead to changes in gene expression and therefore cell function
what are antibodies
glycoproteins which bind to a specific antigens.
what is a epitope
The part of an antigen where the antibody binds to
what determines the isotypes of an antibody
The variable (V) regions near the tip of the antibody can differ from molecule to molecule in countless ways, allowing it to specifically target an antigen
what is antigenic specifity
the ability of the host cells to recognize an antigen specifically as a unique molecular entity and distinguish it from another with exquisite precision
what is immunological memory
the ability of the immune system to respond more rapidly and effectively to pathogens that have been encountered previously
what is somatic recombination
type of gene rearrangement by which cells of the adaptive immune system physically cut out small regions of DNA and then paste the remaining pieces of DNA back together in an error-prone way
what is affinity maturation?
additional changes in the structure of the antibody can occur if it encounters an antigen to which the antibody can bind
what is primary and secondary immune response
A primary (1°) immune response is the response that occurs following the first exposure to a foreign antigen. A secondary (2°)/anamnestic immune response occurs following subsequent exposures.
how is diversity of an antibody created
The diversity of antibodies is created by the combination of variable regions of H chains and L chains.
what is the primary and secondary response of a responding b cell
naive b cell
memory b cell
what is the primary and secondary response of lag period following antigen administration
generally 4-7 days
generally 1-3 days
what is the primary and secondary response of time of peak response
7-10 days
3-5 days
what is the primary and secondary response of magnitude of peak antibody response
varies depending on the antigen
generally 100-1000 times higher than the primary response
what is the primary and secondary response of isotype produced
IgM predominates early in response
igG predominates
what is the primary and secondary response of antigens
thymus dependent and thymus independent
thymus dependent
what is the primary and secondary response of antibody affinity
lower
higher
what happens at first antigen exposure
lag period of 1-2 days before the first response begins with
the production of IgD and then IgM antibodies
pentameric structure of IgM leads to a high functional affinity
changes to the structure of the antibody constant region (class switching) and affinity maturation, IgG is produced.
- Once the antigen has been sufficiently neutralized, the levels of IgM and IgG deplete over time.
what happens at second antigen exposure
the speed of the response is faster.
the bulk of the antibody synthesized is of the IgG isotype.
- The speed of the response depends on the memory B cells,
- When the antigen has been removed, the amount of antigen-specific IgG in blood circulation may or may not decrease,
what are cytotoxic t cells
Search for and destroy target cells that bear non-self antigens presented in MHC class I context.
what are t helper cells
Secrete cytokines that bind to receptors on B cells and T cells to stimulate their activity.
what are t supressor cells
Secrete signaling molecules that bind to receptors on other immune cells to terminate their activity, thus suppressing immune responses that are no longer needed.
what are t memory cells
Persist for life in a semi-dormant state, but rapidly re-activated on a second exposure to the antigen (pathogen) they are specific for. Bypass the need for the primary immune response on second infection.
what does CD stand for
cluster of differentiation
what do CD4+ mean
A cell that is CD4+ expresses CD4 and is therefore likely to be a T helper cell.
what does CD8+ mean
A cell that is CD8+ expresses CD8 and is therefore likely to be a cytotoxic T cell.
what does MHC do
to bind peptide fragments derived from pathogens and display them on the cell surface for recognition by the appropriate T cells.
Explain how CD8 T cells recognise antigens
- Once the peptide is loaded into the MHC class I complex it engages with cytotoxic CD8+ T cell.
The CD8 molecule simultaneously “double checks” that the peptide is presented correctly
The cytotoxic T cell will only kill the target cell once these engagements are complete.
Explain how CD4 t cells recognise antigens
Once a peptide is loaded into the MHC class II complex and presented on a professional antigen-presenting cell (APC) surface, it engages with the T cell receptor on a passing CD4+ helper T cell. The helper T cell “double checks” the identity of the presenting cell before it becomes activated to secrete molecular messengers (cytokines) that further promote immune responses.
How to CD4+ recognise antigens
recognise antigen presented in MHC class II context by professional APCs
How do CD8+ recognise antigens?
recognise antigen presented in MHC class I context on infected body cells
how are CD4+ activated
on activation secrete a variety of chemical messengers that stimulate immune responses
how do CD8+ activated
on activation engange with and attack target cells by triggering apoptosis and damaging the cell membrane
how does CD4+ receptors respond
t cell receptor typically responds to antigens derived from exogenous pathway
how do CD8+ receptors respond
t cell receptor responds to antigens derived from the endogenous pathway
how are CD4+ cells stimulated
requires stimulation from APC
how are CD8+ cells stimulated
requires stimulation by an infected target cell and a CD4+ helper T cell
where are MHC class I found
all nucleated cells
where are MHC class II found
only on antigen-presentic cells
what does MHC class I present antigens to
directly to CD8+ cytotoxic T cells
what does MHC class II present antigens to
to CD4+ helper T cells
what does MHC class I present peptide fragments derived from
derived from intracellular antigens
what does MHC class II present peptide fragments derived from
extracellular antigens
where is the peptide fragment of the MHC class I loaded in to
rough ER
where is the peptide fragment of the MHC class II loaded in to
ENDOSOMAL VESICLES
what is the endogenous pathway
deals with intracellular infections
most peptides presented in class I context are self-derived and will not trigger an immune response.
what is the exogenous pathway
The exogenous pathway evolved to deal with extracellular infections. Only a select group of immune cells are capable of class II MHC presentation, including dendritic cells, macrophages, B cells
where do B cells develop
develop and partially mature in the bone marrow then fully mature in the spleen
where to T cells develop
originate in the bone marrow and develop in the thymus
what do b cells recognise
intact protein antigen-soluble or pathogen associated
what do t cells recognise
peptides derived from processed antigen and presented to them by another cell
what are b cells subset
no major differences
what are t cells subsets
CD4 and CD8
what happens to b cell receptors during affinity maturation
mutate their receptor
what happens to t cell receptors during affinity maturation
no affinity maturation takes place
what is the response time for innate immunity
minutes/hours
what is the response time for addaptive immunity
days
what is the specificity of innate immunity
specific for molecules and molecular patterns associated with pathogens
what is the specificity of adaptive immunity
highly specific
discriminates even minor differences in molecular structure
details of microbial or non-microbial structure recognised with high specificity
what is the diversity of innate immunity
a limited number of germ line-encoded receptors
what is the diversity of adaptive immunity
highly diverse
a very large number of receptors arising from genetic recombination of receptor genes
what is the memory response of innate immunity
none
what is the memory response of adaptive immunity
persistent memory with faster response of greater magnitude on subsequent infection
what is the self/nonself discrimination of innate immunity
perfect
no microbe-specific patterns in host
what is the self/nonself discrimination of adaptive immunity
very good
occasional failures of self/nonself discrimination result in autoimmune disease
what are the soluble components of blood or tissue fluids of innate immunity
many antimicrobial peptides and proteins
what are the soluble components of blood or tissue fluids of adaptive immunity
antibodies
what are the major cell types of innate immunity
phagocytes
natural killer
dendtritic
what are the major cell types of adaptive immunity
t cells
b cell
APCs
how are t cells b cells and dendritic cells made
hematopoietic stem cells
lymphoid porgenitor
how are most cells except b and t and nk cells made
hematopoietic stem cells
myeloid porgenitor
what soluble molecules are in the innate immune response
lysozyme complement factors
cytokines
chemokines
what soluble molecules are in the adaptive immune response
antibodies
cytokines
