Module 2 - Branches of the IS Flashcards
3 immune barriers of the innate immune system
physical, cellular, soluble
Physical immune barrier
made of every structure located at the interface between the inside and outside of the body
examples of physical barriers
skin, cilia, bodily secretions
Cellular immune barrier
made of the cells which play a role in the innate immune response
examples of cellular imune barriers
neutrophils, macrophages, dendritic cells, NK cells
soluble immune barrier
made of macromolecules that contribute to the mediation of an innate immune response
examples of soluble immune barriers
complement and cytokines
primary function of physical barrier
prevent or slow down the invasion of pathogens
physical components of the physical immune barrier
skin & mucous membranes
mucous membranes
-cover the cavities of the body including the respiratory, gastrointestinal, urinary and reproductive tracts
-contain specialized cells like cilia and produce mucous
primary function of cellular barrier
prevent or slow down the invasion of pathogens that have broken through the physical barrier
four major cell types that play a key role in innate immune response processes (imflammation and phagocytosis)
neutrophils, macrophages, dentritic cells and natural killer cells
Chemical components of the physical immune barrier
tears, saliva (activate antimicrobial substances like lysozyme) and gastric acid (destroys bacteria and toxins)
Neutrophils
-most common leukocyte found in mammals
-phagocytes that patrol the body to find, engulf and destroy pathogens
-circulate in blood for 12h before entering tissues via diapedesis
-recruited to site of infection by macrophages
-lifespan of 1-3 days after entering tissues
Diapedesis (extravasation
process by which blood cells (like neutrophils) move from blood to tissues by passing through intact vessel walls.
Macrophages
-phagocytes that patrol the body to find, engluf and destory pathogens
-can either take up residence in specific tissue or move freely
-contribute to tissue repair & present antigens to other immune cells (T-cells)
-activated after phagocytosing pathpgens or in response to cytokine signalling
Dendritic Cells
-phagocytes that are often in contact with the external environment
-engulf foregin antigens that have invaded initial barriers
-present antigens on their cell surface through peptide MHC complexes which can be recognized by helper T cells
-major link between adaptive and innate IS
Natural Killer Cells
-recognize abnormal cells lacking antigen specific receptors
-destroy abnormal cells of the body, which include tumourous and virus infected cells
-bind to cell surface of target cells and release chemicals causing pores to form in the cell membrane, leading to their lysis
two major categories of macromolecules in the soluble barrier
complement system and cytokines
Importance of soluble barrier components
developing inflammatory innate immune response, induced following penetration of infectious agent through physical barriers
what is the complement system made of
over 30 soluble proteins
where is the complement system
complement proteins circulate in the blood, normally in the inactive form
When is the compliment system activated?
directly activated in the presence of extracellular pathogens or indirectly by pathogen-bound antibody
How is the compliment system activated?
activation induces reactions between complement proteins, leading to the formation of a membrane attack complex (MAC) and complements the efficency of other immune functions such as inflammation and phagocytosis
Membrane Attack Complex
Structure made of activated complement proteins, which have the ability to destroy extracellular pathogens by creating holes in their cell membrane (can also damage host cells)
Complement system inflammation process
-attraction of various immune cells to the site of infection through release of chemotactic molecules (histamin and cytokines)
-activated complement proteins bind to receptors on immune cells and induce release of substances which enhance inflammation response
Complement System Functions
Inflammation, Phagocytosis and Membrane Attack Complex
which three major pathways can the compliment system be activated by
classical, alternaitave and lectin pathways
Chemotactic molecules
inducing the movement of cells towards the site where substance was originally released
Complement system phagocytosis process
activated complement proteins opsonize pathogens targetting them for destruction by phagocytes
complement system membrane attack complex
destory extracellular foreign invaders through the formation of membrane attack complexes. the MAC structures create holes in the pathogen which leads to lysis and death
Opsonize
making a foreign particle more susceptible to phagocytosis by binding to the antigen and marking for ingestion
Cytokines
-small proteins secreted by various immune cells in response to a number of different stimuli
-chemical mediators for cell-cell communication
where are cytokine receptors expressed
cell surface of various immune cells depending on needs/functions
Autocrine cytokines
the sending and recieving cell is the same
Function of cytokine signalling
regulate immune processes, such as immune responses, inflammation and hematopoiesis
Paracrine cytokines
the sending and recieving cells are near eachother
endocrine cytokines
the sending and recieving cells are distant from eachother (signal travels through bloodstream)
Specificity and affinity for cytokines
-bind to specific receptors on the membrane of their target cells
-cytokines and their receptors exhibit very high affinity for one another
Cytokines altering gene expressions
cytokines binding its receptor initiates a series of rxns that ultimately alter gene expression, which may affect cell growth and maturation and have roles in the host’s response to infection and disease
Pro inflammatory vs anti inflammatory cytokines
react opposietly to balance eachother out
Pro inflammatory cytokines
made by most immune cells, when secreted they will induce inflammatory response
Antiinflammatory cytokines
made by several immune cells, work to limit the inflammatory response within the body by inhibting pro-inflamatory cytokine production and activiting the immune cells that promote healing
when is inflammatory response initiated
when pathogen evades the physical barriers
what is inflammation
localized tissue response to injury or invasion and has both local and systemic effects within the body
signs of inflammation
redness, heat, pain, swelling
what happens during inflammation brief
-alteration of blood flow to the injured area
-influx of phagocytic and other immune cells
-removal of foreign antigens
-healing of damaged tissue
main purpose of inflammation
-bodys attempt at self-protection by removing harmful stimuli, including damaged cells, irritants, or pathogens.
-localize & eliminate the invading pathogen, in an effort to stop it from spreading and to remove damaged tissue
1st major event of inflammation
BREACH
-pathogens find a breach to enter body
2nd major event of inflammation
VASODILATION
-increase in the diamiter of blood vessels and permeabilization of the cappilaries near affected area
-induced by vasoactive and chemotactic factors secreted by damaged tissue and activited immune cells (macrophages and mast cells)
-vasodilation causes redness and heat due to higher blood volume around the area
3rd event of inflammation
PERMEABILIZATION
-increase capillary permeability facilitating entrance of fluids
-coupled with vasoconstriction of vessels carrying blood away from the area, this allows accumulation of access fluids at the site of infection called exudate
-accumulation of fluids is called edema
Exudate fluid
-exudate fluid contains proteins that contribute to mediation of inflammatory response
-it includes pro-inflammatory cytokines (chemokines) and complement proteins
4th event of inflammation
EXTRAVASATION
-chemotactic factors released by cells during the vasodilation and permeabilization steps induce the recruitment of more immune cells
(first type to arrive by chemotaxis are neutrophils)
-when neutrophils arrive they adhere to endothelial cell walls via margination and migrate between the capillary endothelial cells into the infected tissue by extravasation or diapedsis
5th event of inflammation
- PHAGOCYTOSIS: at infection site, neutrophils and other phagocytes engluf the pathogens
major events of inflammation: put these in order: chemotaxis, extravasation, vasodilation, permebilization, margination
vasodilation, permeabilization, chemotaxis, margination, extravasation
why is heat and swelling beneficial
-heat increases metabolic rates allowing cells to repair faster
-swelling leaks proteins, which help clot blood, form scabs and recruits phagocytes and lymphocytes to help destroy pathogens and clean up dead cells
How does innate recognize self from nonself
via pattern recognition receptors (PRRs) that recognize repeated molecular patterns of pathogens (ex. Toll-like receptors)
Are PRRs innate or adaptive
can be expressed by both innate and adaptive immune cells, however they are an integral signalling component of the innate immune system
what are Pathogen-associated molecular patterns (PAMPs)
molecular structures either expressed on the surface or found inside pathogens. patterns are specific for pathogens and not found in host cells
cell surface example of a PAMP
Lipopolysaccharides found on the cell surface of gram-negative bacteria
inner pathogen PAMP example
double stranded RNA found inside dsRNA viruses
two major categories of molecular patterns that can be recognized by PRRs
-pathogen-associated molecular patterns (PAMPs)
-Danger-associated molecular patterns (DAMPs)
PAMPS associated with groups of pathogens that are recognized by immune cells that include:
-functional strucutres of a pathogen
-repeated sequences of protein, glycoprotein, lipoprotein, amino acids etc. that are conserved across specific groups of microbes
Examples of PAMPs
-lipopolysaccharides
-peptidoglycan
-flagellin
-viral nucleic acids
what are DAMPs
molecules released by stressed cells undergoing necrosis
-are host biomolecules
-indicate damage to the body
-initiate an inflammatory response
examples of DAMPs
-abnormal location of a cell structures (DNA found outside of mitochondria or nucleus)
-cell-stress indicator molecules (heat-shock proteins)
what are Toll-Like Receptors
a class of PRRs whose signalling plays an essential role in the innate immune response
where are TLRs expressed
depending on the type of PAMP or DAMP, they are either expressed on the plasma membrane or endosomal/lysosomal membranes of mammalian cells
upon activation of TLRs, these receptors initiate the transcription of genes encoding for:
-inflammatory cytokines
-chemokines
-costimulatory molecules
**these contribute to the activation of innate immune cells, which increase ability of phagocytes to engulf pathogens an enhance their ability to present antigens to the adaptive immune system
two MAJOR roles of TLRs
-recognize PAMPs and/or DAMPs
-induce expression of signalling to activate T-cells
step 1 of TLR signalling process
-TLRs sense the presence of an infection through recognition of PAMPs and/or DAMPs
-the bacterium will be engulfed through phagocytosis by the phagocytic cell, which in this case is a dendritic cell
step 2 of the TLR signalling process
-after engulfing the bacterium, the immune cell, also called an antigen presenting cell, will present pieces of the pathogen on its cell surface through the peptide: MHC complex
step 3 of the TLR signalling process
-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
Step 4 of the TLR signalling process
-an immunocompetent naive T cell specific for the antigen presented by the DC will bind to the peptide: MHC complex through its TCR
-this interaction will activate the T cell and initiate an adaptive immune response
when would Phagocytosis occur
once pathogens have penetrated epithelial barriers and enter tissues, an array of cells can trigger an immune response within innate immunity
what is phagocytosis
type of endocytosis, in which a cell takes up particulate material (bacteria) by invaginating its membrane to form a vacuole
major innate immune cells that are involved in maintaining cellular barrier and have phagocytic functions
macrophages, neutrophils, dendritic cells
Neutrophil
-first cell to arrive from the blood to site of infection
-perform early phagocytosis, eliminating pathogen quickly
-can initiate inflammatory response
Macrophages
-monocytes migrate from the blood to the tissues to become macrophages
-perform phagocytosis most efficently
-release cytokines that stimulate inflammation and recruit other immune cells
dendritic cells
-recognize microbes and initiate phagocytosis
-most efficent antigen-presenting cell
-play a major role in the initiation of the adaptive immune response
Step 1 of phagocytosis
ATTACHMENT: the pathogen becomes attached to the membrane evaginations called pseudopodia
step 2 of phagocytosis
INGESTION: the pathogen is ingested, forming a vacuole, called a phagosome, within the cell
Phagosome
a vesicle composed of cell membrane of a phagocyte, containing the phagocytosed material
setp 3 of phagocytosis
FUSION: the phagosome fuses with a lysosome, releasing lysosomal enzymes that degrade macromolecules and other materials, such as bacteria
step 4 of phagocytosis
DIGESTION: the pathogen is destroyed and digested by the lysosomal enzymes
step 5 of phagocytosis
RELEASE: the digestion products are released from the cell via exocytois, the process in which the vacuole membrane fuses with the cell membrane
Specificity of the adaptive IS
each cell recognizes one specific epitope of a pathogen. For each pathogen that the adaptive immune system encounters, it creates a unique immune reaction to eliminate the infectious agent
diversity of the adaptive immune system
because each cell is so specific, the adaptive IS is composed of countless numbers of cells to be able to fight any pathogen encountered
Humoral immunity components (2)
- B-cells
- Antibodies
Cell mediated immunity component
T -cells
B -cell characteristics
-key component of humoral response
-mature in the bone marrow
-surface receptor : B-Cell receptor (BCR)
-function: antibody factory
plasmocyte
-effector cell
-produce large quantities of antibodies
memory B cell
-memory cell
-express BCR on their cell surface
T-cell
-key component of cell-mediated response
-mature in thymus
-surface receptor: T-cell receptor (TCR)
-function: cytotoxic activity or help the activation of immune response
subsets of T-cells
CD4 Helper T cell
CD8 Cytotoxic T cell
Memory T cells
Subsets of B - cells
Plasmocyte and memory B-cell
CD4 Helper T cell
-effector cell
-help the activation of the adaptive immune response
CD8 Cytotoxic t cell
-effector cell
-kill infected cells
memory T cells
-memory cells
-express TCR and CD4 or CD8 on their cell surface
what happens when antigen presenting cells engulf pathogens
can present the antigens to naive CD4 Helper t cells and depending on the type of antigen it encounters, helper T cells can differentiate into two subsets
Two subsets depending on type of antigen helper T cell encounters
- Cell mediated immunity: activated helper T cells will differentiate into TH1 subset
- Humoral immunity, activated helper T cells will differentiate into a TH2 subset
1st step of hummoral immuntiy (antibody- mediated)
activated and differentiated TH2 cells activate B cells and induce their differentiation into plasmocytes
1st step of cell-mediated immunity (cytotoxic-mediated)
activated and differentiated Th1 cells activate CD8 cytotoxic T-cells and induce their differentiation into cytotoxic T lymphocyte
2nd step of hummoral immunity (antibody-mediated)
plasmocytes produce antibodies specific for invading the antigen
2nd step of cell-mediated immunity (cytotoxic-mediated)
cytotoxic T lymphocyte recognize and eliminate any cells displaying the specific antigen presented at their cell surface by MHC class I complex
What are antibodies
aka immunoglobulin, is a large Y shaped protein that is highly specific and recognizes one epitope
Where do antibodies come from
-produced by B cells and exist in 2 forms: surface antibodies and soluble antibodies
-one B-cell will produce one specific antibody for one specific epitope
Surface antibodies
membrane-bound on B-cells, forming part of the B-cell receptor
soluble antibodies
secreted by B cells and circulate freely in the blood
why are antibodies Y shaped
they are two heterodimetric proteins that are held together by disulfide bonds
Light Chains (2)
the light chain is a protein subunit that, as one of a pair, forms part of the main antigen-binding region of an antibody
Heavy chains (2)
the heavy chain is a protein subunit that makes up the majority of the structure of the antibody. It forms part of the antigen-binding region and forms the Fc region
Parts of the antibody
2 light chains
2 heavy chains
2 antigen binding regions
1 Fc region
Antigen Binding regions (2)
-variable and changes from one antibody to another, but remain the same on one antibody
-responsible for the diversity and specificity of immunoglobulins
Fc region (1)
fragment crystallizable region is constant for every antibody of the same class. it is the part that interacts with immune cell surface receptors, called Fc receptors
5 classes of antibodies within serum of the the human body
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
**only important to know that the unique heavy chain is what differentiates between the classes
purpose of varyation in heavy chain polypeptides
allows each antibody class to function in a different type of immune response or during a different stage of the bodys defence response
IgM roles
-forms a pentamer (5 Y chains) from IgM monomers when secreted by B cells
-1st antibody to be formed in an immune response
-activates the complement which then amplifies the inflammatory and adaptive immune response
IgG roles
-monomer when secreted by B cells
-coats oathogens to promote phagocytosis and immune cell recruitment
-only l=class that can cross the placental barrier
IgA roles
-generally forms a dimer ( double Y chain) from IgA monomers when secreted by B cells
-first line of defense and predominant antibody class located in the bodys mucosal membranes
IgE role
-monomer when secreted by B cells
-produced in excess during allergic reactions
-has a role in immunity against certain parasites
IgD role
-monomer when secreted by B cells
-found in large quanitiy on the surfaces of mature b cells
-function or importance is unclear, thought to have a role during B cell develpment
