Module 2 Flashcards
what are the 4 coomponents of the innate immune system?
- immune barriers
- inflammation
- pattern-recognition
- phagocytosis
what are the three types of innnate immune system barriers?
- physcial barrier
- cellular barrier
- soluble barrier
innamte immune system: physical barrier
- made up of every structure located at the interface between the inside and outside of body (physcial and chemical components)
- primary function is to prevent or slow down invasion of pathogens
- prison analogy: prison walls and cells (first thing prisiners needs to get through to break out)
innamte immune system: cellular barrier
- made up of various cells which play a role in inate immunes system response
- prison analogy: prison guards (monitor and make sure eveything is in order)
innamte immune system: soluble barrier
- made up of macromolecules whihc contribute to the mediation of innate imune response
- prison analogy: communication system inside prison which include radios and cameras
examples of physical barriers: physcial component
- skin
- mucous membranes
examples of physical barriers: chemical components
- tears and saliva because they contain active antimicrobial substances (ex: lysozomes)
- gastric acid (destroys bacteria and toxins)
cellular barrier: neutrophils
- most common leukocyte found in blood in mammals (~45-70%)
- phagocytes that patrol the body to find, engulf and destroy pathogens
- circulate in the blood for ~12hrs before entering tissues by diapedesis (process by which blood cells, such as neutrophils, move from the blood to tissues by passing through intact vessel walls)
- recruited to a site of infection by resident macrophages that have encountered pathogens
- lifespand 1 to 3 days after entering tissues
cellular barrier: macrophages
- phagocytes that patrol the body to find, engulf and destroy pathogens
- can either take up residence in a specific tissue, or move freely/patrol throughout a larger area of tissues
- contribute to tissue repair and present antigens to other immune cells such as T-cells
- become activated after phagocytosing pathogens or in response to cytokine signalling
cellular barrier: dentritic cells
- phagocytes that are often in contact with the external environment
- engulf forgeing antigens that have evaded the initial barriers of the innate immune system
- present antigens on theti cell surgace through peptide: MHC compleses, which can e recognized by helper T-cell
- major link between the innate and adaptive immune systems
cellular barrier: natural killer cells
- recognice abnormal cells lackinf antigen-specific receptos
- destroy abnormal cells of the body, which include tumorous 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
Soluble barrier: complemement system
- made up of over 30 soluble proteins
- circulate in the blood, normally in an inactive form
- directly activated in the presence of extracellular pathogens or indirectly by pathogen-bound antibody
- activation induces a cascade of reactions between various complements proteins, leading to the formation of a membrane attack complex (MAC) and in parallel, enhances or compliments the efficiency of other immune functions such as inflammation and phagocytes
- can be activated through three major pathways: classical, alternative and lectin pathways
what are membrane attach complex (MAC)?
structures made of activated complement proteins, which have the ability to destroy extracellular pathogens by creating holes in their cell membrane.
- side effect: might damage host cells
Soluble barrier complement system functions: inflammation
- includes attraction of various immune cells to the site of infection through the release of chemotactic molecules such as histamine and cytokines
Soluble barrier complement system functions: phagocytosis
- activate complement proteins, predominintaley C3b opsonize (making a foreign particle more susceptible to phagocytosis by binding to the antigen and marking for ingestion) pathogen therby targetting them for destruction by phagocytes
Soluble barrier complement system functions: membrane attack complex
- one of the ultimate complement system functions is to destroy extraclellular foreign invaders through the formation of membrane attack complexes
- the MAC structures create holes in the pathogen which leads to its lysis and death
soluble barrier: cytokines
- small proyeins 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
- large variety exist
- they have a strong affinity for specific types of cytokine receptor which are expressed on the cell surface of various immune cells depending on their needs/functions
- function of cytokine signaling is to regulate (increase or decrease strength of response) immune processes, such as immune responses, inflammation and hematopoiesis
characteristics of cytokines (4)
- autocrine vs paracrine vs endocrine
- specificity and affinity
- alter gene expression
- pro-inflammatory vs anti-inflammatory
autocrine vs paracrine vs endocrine
- these terms characterize the location of action depending on the site of secretion of cytokines by immune cell
- autocrine: sending and receiving cell is the same
- paracrine: sending and receiving cells are near to each other
- sending and receiving cells are distanct from each other
how can inflammation be characterized?
- redness
- heat
- pain
- swelling
what happens during inflammation?
- alteration of blood flow to the injured area
- influx of phagocytic and other immune cells
- removal of foreign antigens
- healing of damaged tissue
- physical response during inflammation can result in a loss of function, another common physcial characteristic of inflammation
Events of inflammatory response (in order 1 to 5)
- Breach
- Vasodilatation
- Permeabilization
- Extravasation
- Phagocytosis
Breach
- pathogens enter through a breach (ex: a cut)
- prison analogy: prisoner finds a way through the cell door
Vasodilatation
- increase in diameter of blood vessels, and permeabilization of the capillaries near the affected area
- induced by vasoactive and chemoactive factors secreted by damaged tissues and activated immune cells such as maxcrophages and mastc ells
- redness and heat are consequences of vasodilatation inducing a higher blood volume around the infected tissue
- prison analogy: prison guard telling everyone once a prisoner has esscaped their cell
Permeabilization
- excess fluid collects at site of infection, called exudate
- excudate contains proteins that contribute to the mediaction of the inflammatory response. it includes both pro-inflammatory cytokins (chemokines) and complement proteins activated by the presence of extracellular pathogens. function of these proteins is to attract the cellular barrier key players to the site of infection
- swelling characteristic of inflammation is a consequence of accumulation of fluids at the infection site, forming what is called edema
- prison anaology: first thing security team will do is order a lockdown
Extravasation
- chemotactic factors released by cells during the vasodilatation and permeabilization steps induce the recruitment of more immune cells to the site of infection are neutrophils
- when nuetrophils that are circulating in the blood arrive to an infection site, they adhere to the endothelial cell walls via a process called margination and migrate between the capillary-endothelial cells into the infected tissue by a process called sxtravasation or diapedesis
Phagocytosis
- engulf and destroy cells
pattern recognition receptors (PRRs)
- innate immune cells have them
- capable of recognizing repeated molecular patterns of pathogens
- various families of PRRs
- in this class we will focus on the Toll-Like Receptors (TLRs)
- can also be a part of the adaptive immune system
molecular pattern
- repeated molecular patterns recognized by PRRs are conserved motifs and certain subsets can be found. in various groups of pathogens, where they are called pathogen-associated molecular patterns (PAMPs) which are molecular structures either expressed on the surface of or found inside pathogens
- theese patterns are specific to pathogens and not found in the host cells, which gives the ability to innate cells to distinguish non-self from self
what are the two major categories of molecular patterns
- pathogen-associated molecular patterns
- danger-associated molecular patterms
pathogen-associated molecular patterns (PAMPs)
- associated with groups pf pathogens that are recognized by immune cells
- inlcude: functional structure of a pathogen and repeated sequences of protein, glycoprotein, lipoprotein, amino acids, etc. that are conserved across specific groups of microbes
danger-associated molecular patterms (DAMP)
- molecules released by stress cells undergoing necrosis (morphologic changes that accompnay death of cells and that release large amounts of intracellular components to the environment)
- they: are host biomolecules, indicate damage to the body and initiate an inflammatory response
Toll-Like Receptors
- class of PRRs
- signalling plays important role in innate immune system
- either expressed on the plasma membrane or endosomal/lysosomal membrane of mammalian cells depending on type of RAMP or DAMP i recognizes
- initiate transcription of gene encoding for: inflammatory cytokines, chemokines, costimulatory molecules
2 major roles of toll-like receptors
- recognize PAMPs or DAMPs
- induce expression of signalling to activate T-cells
Secquence of events of how toll-like receptors work (4 steps)
- sense presence of an infection through PAMPs and/or DAMPs, bacterium will be engulfed through phagocytosis
- after englufing, immune cell will present pieces of pathogen on its cell surface through peptide : MHC complex
- antigen presenting cell will also increase its production of costimulatory molecules, which are involved in the strength and the stability of antigen presenting process
- an immunocompetent naive T cell specific for the antogen presented by the dentritic cell will bind to the peptide: MHC complex through its TCR, the interaction will activate the T-cell and initiate and adaptive immune response
which immune cells are involved in maintaining cellular barrier and have phagocytic functions? (3)
- neutrophil
- macrophages
- dendritic cells
5 steps of phagocytosis
- attachment
- ingestion
- fusion
- digestion
- release
adaptive immune system
- second line of defense
- specificity and diversity
specificity
each cell of the adaptive immune system recognizes one specific epitopeof a pathogen - for each pathogen, it creates a unique reaction to eliminate the infectious agent
diversity
composed of countless numbers of cells to be able to fight any pathogen encountered
adatptive immunity can be further subdivided into ___ and ___
- cell-mediated immunity (T-cells)
- humoral immunity (C-cells and antibodies)
B-cells can be differentiated into specialized subsets following their activation (2)
- plasmocyte
- memory B-cell
B-cell characteristics
- key component in humoral response
- mature in the bone marrow
- surface receptor: B-cell receptor (BCR)
- function: antibody factory
plasmocyte characteristics
- effector cell
- produce large quantities of antiobodies
memory B-cell characteristics
- memory cell
- express BCR on their cell surface
cell-mediated immunity is characterized by ____ which can differentiate into specialized subsets following their activation
T-cells
T-cell specificity
- key component of the cell-mediated response
- mature in the thymus
- surface receptor: T-cell receptor (TCR)
- function: cytotoxic activity or help the activation of immune response
T-cell disversity (3 kinds)
- CD4+ Helper t-cell
- CD8+ cytotoxic t-cell
- memory t-cell
CD4+ Helper t-cell
- effector cell
- helps the activation of the adaptive immune response
CD8+ cytotoxic t-cell
- effector cell
- kill infected cells
memory t-cell
- memory cells
- express TCR and CD4 or CD8 on their cell surface
humoral immunity is characterized by ___ and is an _____-_____ response
- b-cells
- antibody-mediated
cell-mediated immunity is characterized by ___ and is an _____-_____ response
- t-cells
- cytotoxic-mediated
what are antibodies?
- large Y-shaped protein
- highly specific and recognizes one epitope
- prison anaology: like a security face-recognition software system. If the security system identifies the faces of people who shouldn’t be where they are, their location will be flagged to the prison guards
where do antibodies (aka immunoglobulin) come from?
- produced by b-cells
- one b-cell will produce one specific antibody for one specific epitope
what 2 forms do antibodies exist in?
- 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
what are the functions of antibodies?
- play role in humoral immunity
- help eliminate a pathogen through various processes
what are the 4 processes in which an antibody eliminates a pathogen? and descirbe them
- 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 cell’s effector functions
antibodies are two heterodimeric proteins that are held together by ____ _____
- disulfide bonds
