Module 2 Flashcards
is the innate specific or not
not
what is the innate immunity
first line of defense against foreign invaders
- early phases of an immune response
innate immunity: immune barriers
made of physical, soluble, and cellular barriers that are scattered throughout the body
innate immunity: inflammation
responds immediately to an invading pathogen
- is a breach of the physical barrier by a pathogen is called inflammatory response
innate immunity: pattern-recognition
- recognizes general patterns not specific for any one antigen
how does pattern recognition work
by pattern-recognition receptors (PRR) expressed on innate immune cells
innate immunity: phagocytosis
phagocytic properties (engulfing) are called phagocytes
what are the immune barriers of the innate immune system
physical barrier
cellular barrier
soluble barrier
physical barrier
made of every structure located at the interface between the inside and the outside of the body
- physical and chemical components
examples of physical barrier
skin, cilia, bodily secretions
cellular barrier
made of various cells which play a role in the innate immune response
examples of cellular barriers
- neutrophils
- macrophages
- dendritic cells
- natural killer cells
soluble barrier
made of macromolecules which contribute to the mediation of an innate immune response
examples of soluble barrier
complement and cytokines
physical components (physical barrier)
skin
- barrier that pathogens cannot cross unless it is breached
mucous membrane
- cover body cavities
- contain cilia and produce mucous
chemical component (physical barrier)
tears and saliva
- contain active antimircobial substance such as lysozyme, gastric acid
lysozyme
catalyzes the destruction of the cell walls of certain bacteria
cellular barrier: neutrophils
- most common leukocyte in blood
- phagocytes (engulf and destroy)
- in blood for 12h before entering tissue by diapedesis
- recruited to site of infection by macrophages
- 1-3 days of life in tissue
cellular barrier: macrophages
- phagocyte that patrols the body to engulf pathogens
- be in specific tissue or move freely/patrol large areas tissues
- contributes to tissue repair and present antigens to other immune cells like T-Cell
when does macrophages become activated
after phagocytosing pathogens or in response to cytokine signalling
diapedesis
process by which blood cells such as neutrophils move from blood to tissues by passing through intact vessel walls
cellular barrier: dendritic cells
- phagocyte often in contact with the external environment
- present antigens on their cell surface through peptide: MHC complexes, which can be rexognized by helper T-cells
what is a big function of dendritic cells
major link between the innate and adaptive immune system
cellular barrier: natural killer cells
- recognize abnormal cells lacking antigen-specific receptors
- destroy abnormal cells
(tumors, virus) - bind to cell surface of target cells and release chemicals causing them to die
soluble barrier: complement system
what is it?
- made up of over 30 soluble proteins
soluble barrier: complement system
where is it?
circulate in the blood, normally in an inactive form
soluble barrier: complement system
when is it activated
directly activated in the presence of extracellular pathogens or indirectly by pathogen-bound antibody
soluble barrier: complement system
how is it activated
cascade of reaction between various complement proteins, leading to formation of a membrane attach complex (MAC) and in parallel, enhances or complements the efficiency of other immune function, such as inflammation and phagocytosis
soluble barrier: complement system functions/what are the three activating pathways
classical, alternative, and lectin pathways
soluble barrier: complement system functions
inflammation, phagocytosis, membrane attack complex
soluble barrier: complement system-inflammation
includes the attraction of various immune cells to the site of infection through the release of chemotactic molecules, such as histamine and cytokines
- activated complement proteins bind to complement receptors on immune cells, such as mast cells and basophils, and release of these substances which enhance the inflammatory response
chemotactic molecules
including the movement of cells toward the site where the substance are originally released
- histamine
- cytokines
soluble barrier: complement system- phagocytosis
activated complement proteins, predominately C3b, opsonize pathogens thereby targeting them for destruction by phagocytes
opsonize
making a foreign particle more susceptible to phagocytosis by binding to the antigen and marking for ingestion
soluble barrier: complement system- membrane attack complex
destroy extracellular foreign invaders through the formation of membrane attack complexes
- creates holes in the pathogen which leads to its lysis and death
what would be the result of a complement deficiency?
there would be reduced lysis of microbes and less inflammation.
- resulting in reduced bacterial clearance and therefore longer periods of infection
soluble barrier: cytokines
- small proteins secreted by various immune cells in response to a number of different stimuli.
- chemical mediators that play a key role in cell-to-cell communication
what do cytokines have a strong affinity for
specific type of cytokine receptor
- they are expressed on the cell surface of various immune cells depending on their needs/functions
what is the function of cytokine signaling?
is to regulate immune process, such as immune responses, inflammation and hematopoiesis
soluble barrier: autocrine Vs endocrine
autocrine- the sending and receiving cell is the same
paracrine- the sending and receiving cells are near to each other
endocrine- the sending and receiving are distant from each other
what do majority of cytokine do
act locally, having autocrine or paracrine effects
soluble barrier: specificity and affinity
cytokines bind to specific receptors on the membrane of their target cells
- cytokines and their receptors exhibit very high affinity for one another
soluble barrier: alter gene expression
- cytokine binding to its receptor initiates a series of reactions that ultimately alter gene expression, which may affect cell growth and maturation, and have roles in the hosts response to infection and disease
soluble barrier: pro-inflammatory cytokines
- made by most immune cells
- when secreted will induce an inflammatory response within the body
soluble barrier: anti-inflammatory
- made by several immune cells and work to limit the inflammatory response within the body
- do so by inhibiting pro-inflammatory cytokine production and activating immune cells that promote healing
what happens if there is a shift in the balance towards one side or the other of anti- and pro inflammatory cytokines
if pro are not properly controlled, they lead to complications such as tissue damage due to an excessive inflammatory
- if anti are not controlled, a lack of an immune response to a pathogen may occur which can result in spreading of the pathogen
what happens when a pathogen evades the physical barriers of the innate immune system
the surrounding cells work to induce an inflammatory response
where does inflammation occur
as a localized tissue response to injury or invasion and has both local and systemic effects within the body
how can inflammation be characterized?
redness
heat
pain
swelling
what happens during inflammation? steps;
- alteration of blood flow to the injured area
- influx of phagocytic and other immune cells
- removal of foreign antigens
- healing of damaged tissue
loss of function
what is the main purpose of inflammation?
the bodies attempt at self-protection by removing harmful stimuli, including damaged cells, irritants or pathogens
- localize and eliminate the invading pathogen, in an effort to stop it from spreading and to remove damaged tissue
major events of inflammation: 1.
Breach
- pathogen needs to find a breach in skin to enter body
- a cut and pathogen can enter
major events of inflammation: 2.
vasodilation
- increase in diameter of blood vessels and permeabilization of the capillaries near the affected area
- changes are induced by vasoactive and chemotactic factors secreted by damaged tissues and activated immune cells, like macrophages and mast cells
major events of inflammation: 3.
permeabilization
- vasodilation results in the increase in capillary permeability facilitating the entrance of fluids in tissues
- with vasoconstriction from carry blood area from cut allow accumulation of excess fluid at the site of infection called exudate
exudate fluid
Exudate fluid contains proteins that help with inflammation. These include:
Pro-inflammatory cytokines (like chemokines) and complement proteins.
These proteins attract immune cells to the infection site to help fight pathogens.
the swelling characteristic of inflammation is a consequence of accumulation of fluids at the infection site is called what??
edema
major events of inflammation: 4.
extravasation
- the chemotactic factors released by cell during the vasodilatation and permeabilization steps induce the recruitment of more immune cells to the site of infection
- when neutrophils that are circulating in the blood arrive to an infection site, they adhere to the endothelial cell walls via process called margination and migrate between the capillary-endothelial cells into the infected tissue by extravasation or diapedesis
what are the first type of cells to arrive by chemotaxis
neutrophils
major events of inflammation: 5.
phagocytosis:
- at infection site, neutrophils, phagocytes, macrophages, dendritic cells engulf the pathogens
- is one of the major processes used by innate cells to destroy extracellular pathogen
why is heat and swelling beneficial during an inflammatory response
heat increases the metabolic rates of cells allowing them to repair themselves faster
- swelling leaks proteins which help clot blood and form scabs, and recruits local phagocytes and lymphocytes to help destroy pathogens and clean up dead cells
how is the innate immune system able to recognize structure as being self or non self
pattern recognition receptors (PRRs)
patter recognition receptor
capable of recognizing repeated molecular patterns of pathogens
example of patter recognition
Toll-like receptors (TLRs)
where do PRRs come from
has to be able distinguish self from non self
- that is unique to the microorganisms and necessary for their survival
are PRRs in innate and adaptive immune cells
they are in both however, they are an integral signaling component of the innate immune system
molecular pattern
- recognized by PRRs are conserved motifs and certain subsets can be found in various groups of pathogens
called pathogen-associated molecular patterns (PAMPs)
PAMPs
are molecular structure either expressed on the surface of or found inside pathogens
examples of PAMPs
lipopolysaccharides (LPS) found on the cell surface of gram-negative bacteria
- double stranded RNA found inside dsRNA
are the molecular patterns found in host cells?
not found in host cells, which gives the ability to innate cells to distinguish non-self from self
what are two major categories of molecular patterns that can be recognize by PRRs
- pathogen-associated molecular patterns (PAMPs)
- danger-associated molecular patterns (DAMPs)
- play a key role in the ability of innate immune cells to recognize invaders
pathogen-associated molecular pattern (PAMP)
- molecules associated with groups of pathogen that are recognized by immune cells:
- functional structures of a pathogen
- repeated sequences of protein, glycoprotein, lipoprotein, amino acids
examples of PAMP
- lipopolysaccharide
- peptidoglycan
- flagellin
- viral nucleic acids
damage-associated molecular pattern (DAMP)
- molecules released by stressed cell undergoing necrosis
- are host biomolecules
- indicate damage to the body
- initiate an inflammatory response
examples of DAMP
- abnormal location of a cell structures
eg. DNA found outside of mitochondria or the nucleus - cell-stress indicator molecule
eg. heat-shock proteins
toll-like receptors (TLRs)
- are a class of PRRs whose signalling play an essential role in the innate immune response
where are TLRs expressed?
on the plasma membrane or endosomal/lysosmal membranes of mammalian cells depends on the type of PAMP or DAMP it recognizes
before activation what to toll-like receptors initiate the transcription of gene encoding for;
- inflammatory cytokines
- chemokines
- costimulatory molecules
what are the two major roles or toll-like receptor
- recognize PAMPs and/or DAMPS
- induce expression of signaling to activate T-cell
TLR signaling process 1.
sense the presence of an infection through recognition of PAMPs and/or DAMPs
- the bacterium will be engulfed through phagocytosis by the phagocytic cell, (ex. dendritic cell)
TLR signaling process 2.
after engulfing the bacterium, the immune cell, (antigen presenting cell) will present pieces of the pathogen on its cell surface through peptide :MHC complex
TLR signaling process 3.
the antigen presenting cell will also increase its production of costimulatory molecules, which are involved in the strength and the stability of the antigen presenting process
TLR signaling process 4.
an immunocompetent naive T cell specific for the antigen presented by the dendritic cell will bind to the peptide: MHC complex through its TCR
- activating the T-cell and make adaptive immune happen
phagocytosis
is an example of the next line of defense against the invading pathogen within innate immunity
what is phagocytosis
- type of endocytosis
- cell takes up particulate material from its environment by invaginating’s its membrane to form a vacuoles
how can phagocytosis be induced
the recognition of a PAMP by phagocyte through its PRR is one way
- pathogen opsonization
neutrophil
- first cell to arrive from blood to the site of infection
- early phagocytosis, quickly
- initiate an inflammatory response
macrophages
- monocytes migrate from blood to tissue to become macrophages
- most efficient at phagocytosis
- release cytokines that stimulate inflammation and recut other immune cells
dendritic cells
- recognize microbes and initiate phagocytosis
- most efficient antigen presenting cells
- play a major role in initiations of adaptive immune response
steps of phagocytosis 1.
attachment
- the pathogen becomes attached to the membrane evaginations called pseudopodia
evaginations
a protruding structure produced by turning a membrane outward
steps of phagocytosis 2.
ingestion
- the pathogen gets ingested
- forms a vacuole (phagosome) within the cell
phagosome
a vesicle composed of cell membrane of a phagocyte, containing the phagocytosed material
steps of phagocytosis 3.
fusion
- phagosome fuses with a lysosome, releasing lysosomal enzymes that degrade macromolecules and other materials such as bacteria
steps of phagocytosis 4.
digestion
- the pathogen is destroyed and digested by the lysosomal enzymes
steps of phagocytosis 5.
release
- digestion products are released from the cell via exocytosis
- the vacuole membrane fuses with the cell membrane
what are the 4 major components of the cellular barrier
- neutrophils
- macrophages
- dendritic cells
- natural killer cells
true or false
toll-like receptor family contains membrane-bound receptors which contribute to the activation of innate immune cells by recognizing pathogen-associated molecular patterns of invaders
True
what is the main functions of the complement system made of?
- opsonization (phagocytosis)
- chemotaxis (inflammation and lysis through membrane attack complexes)
what are the major steps of inflammation
vasodilatation
permeabilization
extravasation
phagocytosis
characteristics applicable to cytokines
- chemical mediator
- specificity
- alter gene expression
- pro-inflammatory
- anti-inflammatory
major steps of phagocytosis
- attachment
- ingestion
- fusion
- digestion
- release
about adaptive immune
is the second line of defense
- longer time to initiate
creates specific response
- memory cells to respond faster and stronger
adaptive immune system: specificity
each cell of the adaptive immune system recognizes one specific epitope of pathogen
what happen each time the adaptive immune system encounters a pathogen
it creates a unique immune reaction to eliminate the infectious agent
epitope
also called antigenic determinant, it is a part of an antigen recognized by adaptive immunity components
what are the major characteristic’s of adaptive immunity
specificity and diversity
adaptive immunity: diversity
because it is specific it is composed of countless numbers of cells to be able to fight any pathogen encountered
what can adaptive be further divided into
humoral immunity
cell-mediated immunity
cells of the humoral immunity
- B-cells
- antibodies
cell-mediated immunity
T-cells
what is humoral immunity characterized by
b-cells which differentiate into specialized subsets following their activation
B-cell characteristics
- key component of humoral response
- mature in the bone marrow
- surface receptor B-cell receptor (BCR)]
- antibody factory
B-cell subsets
plasmocyte
memory b-cell
plasmocyte
- effector cell
- produce large quantities of antibodies
memory b-cell
memory cell
- express BCR on their cell surface
what is cell-mediated immunity characterized by
t-cell
t-cell specificity
key component of the cell-mediated response
- mature in the thymus
- surface receptor: T-cell receptor (TCR)
function of t-cell
cytotoxic activity or help the activation of immune response
t-cell diversity
CD4 helper t-cell
CD8 cytotoxic t-cell
memory t-cell
CD4 helper t-cell
effector cell
- help the activation of the adaptive immune response
CD8 cytotoxic t-cell
- effector cell
- kill infected cell
memory t-cell
memory cells
- express TCR and CD4 or CD8 on their cell surface
activation of adaptive immunity
- antigen presenting cells (APCs), like dendritic cells, that have engulfed pathogens by phagocytosis can present the antigens to naive CD4 helper t-cells
differentiation of adaptive immune system
depending on type of antigen it encounters, t-helper cells differentiate into 2 subsets
what are the 2 subsets during differentiation of adaptive immunity
- induce cell-mediated immunity, activated by t-helper with differentiate into t-helper 1
- induce humoral immunity, activated by t-helper cells with differentiate into t-helper 2
activation steps of humoral immune response
- activated and differentiated t-helper 2 cells activate B-cells and induce their differentiation into plasmacytes
- plasmacytes produce antibodies specific for the invading antigen
steps to activate a cell-mediated immune response
- activated and differentiated t-helper 1 cells activate CD8 cytotoxic t-cells and induce their differentiation into CTL
- CTL recognize and eliminate cells displaying specific antigen presented at their cell surface by M<HC class I complex
what are antibodies?
immunoglobulin or AB
- large y shaped protein
- each antibody is highly specific and recognizes one epitope
where do antibodies come from?
are produced by b-cells and exists in 2 forms
- one b-cell will produce one specific antibody for one specific epitope
what are the 2 forms antibodies exist in
surface antibodies
soluble antibodies
surface antibodies
membrane bound on B-cells, forming part of the b-cell receptor (BCR)
soluble antibodies
secreted by B-cells (plasmocyte) and circulate freely in the blood
b-cell receptor (BCR)
is made of a membrane-bound antibody and signal transduction molecules
what are the antibodies functions
humoral immunity
- eliminate a pathogen
how does an antibody eliminate a pathogen
- neutralization
- opsonization
- complement activation
- effector cell activation
neutralization
neutralize the biological effect of a pathogen or a toxin
opsonization
mark foreign invaders for phagocytosis
complement activation
induce the formation of membrane attack complexes and opsonization
effector cell activation
recognized by immune cells when bound to antigen and activate the cells effector functions
what is the basic structure of an antibody
are 2 heterodimeric proteins that are held together by disulfide bonds (s-s)
antibody structure: left chains
2 of them
- is a protein subunit that forms part of the main antigen-binding region of an antibody
antibody structure: heavy chains
2 of them
- majority of the structure of the antibody
- forms part of the antigen-binding region and forms the Fc region
antibody structure: antigen binding regions
2 of them
- is variable and changes from one antibody to another, but remain the same on one antibody
- these regions are responsible for the diversity and the specificity of antibodies
antibody structure: Fc region (fragment crystallizable)
- 1 of them
-constant for every antibody of the same class - it is the part that interacts with immune cell surface receptors, called Fc receptors
what are the 5 classes of immunoglobulins (antibodies)
- IgG have y-heavy chains
- IgM have u-heavy chains
- IgA have a-heavy chains
- IgE have e-heavy chains
- IgD have s-heavy chains
what differentitates between classes of antibodies
the unique heavy chain is what makes us able to distinguish between classes
what does the variation in heavy chain allows
- each antibody class to function in a different type of immune response
- specific amino acid sequences that confer these functional differences are located mainly within the Fc domain
serum
when blood is put into a centrifuge, the blood plasma or serum us the liquid that has been separated from blood cells in whole blood
where are the 5 classes of antibodies found
in serum
IgM
- forms a pentamer from IgM monomers when secreted by B-cells
what is the first antibody to be produces in immune response
IgM
what activates the complement
IgM antibody
- which then amplifies the inflammatory and adaptive response
IgG
- monomer when secreted by b-cells
- coats pathogens to promote phagocytosis and immune cell recruitment
- only class that can cross the placental barrier
placental barrier
the semipermeable layer of tissue in the placenta that serves as a selective membrane to substance passing from maternal to fetal blood
IgA
- forms a dimer from IgA monomers when secreted by B-cells
- first line of defense and predominant antibody class located in the body’s mucosal membranes
IgE
monomer when secreted by B-cells
- produced in excess during allergic reactions
- role in immunity against certain parasites (helminths)
IgD
- monomer when secreted by B-cells
- found in large quantity on the surfaces of mature B-cells
- function or importance is unclear (maybe role during b-cell development)
