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72 Cards in this Set
- Front
- Back
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What are the characteristics of innate immunity (II)
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1)rapid response
2)independant of prior exp 3)specific to molecules shared by groups of microbes- doesn't react to non microbial substances 4)limited diversity- coded in germline 5)no memory 6)non reactive to self |
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what are the components of Innate Immunity
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1)cellular barriers
2)cells 3)plasma proteins 4)cytokines 5)complement system |
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what are the cellular barriers of the innate immune system
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1)skin
2)GIT 3)Respiratory tract continuous epithelia that provides physical and chemical barriers by producing peptide antibiotics and also contain intraepithelial lymphocytes |
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what are the main functional cells in innate immunity
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phagocytic cells - neutrophiles and macrophages
dendritic cells natural killer cells |
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neutrophil
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-leukocyte produced in marrow.
-Cytokines ^ production. -they ingest microbes in circulation and enter extravacular tissue at site of infection. -die a few hours after ingestion of microbes |
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monocytes
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-ingest microbes in circulation
-if they enter extravascular tissue they differentiate into tissue macrophages |
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macrophage
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tissue based phagocytic cell derived from blood monocyte
-phagocytose & kill microbes -secrete proinflammitory cytokines -present antigens to helper t cells - can be microglia, kupffer cells, alveolar or osteoclasts |
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T lymphocyte
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-mediates cell mediated immune response in the adaptive I
-mature in thymus then circulate in blood, populate secondary lymphoid tissues, recruited to peripheral sites of antigen exposure -express antigen receptors (t cell receptors)that recognise foreign proteins bound to self MHC molecules -functional subsets include CD4 helper T's and CD8 cytolytc T's |
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B lymphocyte
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only cell type capable of producing antibodies (humoural response)
-develop in marrow -mature b cells found in lyphoid follicles in the 2ndary lymphoid tissues -low numbers in circulation |
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Natural Killer Cells
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-bone marrow derived lymphocyte
-innate immunity -activate phagocytes by secreting interferon-y -kill microbe infected cells -don't express clonally stimulated antigens -activated by cell surface stimulatory and inhibitory(recognising MHC) receptors. |
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Antigen Presenting Cells (APC)
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displays peptide fragments of protein antigens in association with MHC to activate antigen specific t cells (peptide-MHC complex)
-must also express costimulatory molecules to optimally activate T lymphocytes |
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Helper T Cells
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-subset of t lymphocyte
activate macrophages in cell mediated immune responses and promote b cell antibody production in humoural I -mediated by secreted cytokines and by Tcell CD40 ligand binding tomacrophage or b cell CD40 -most express CD4 molecule |
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Cytolytic T cell
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recognise and kill infected host cells
-usually express CD8 and recognise peptides displayed by class 1 MHC. -kill cells by releasing cytoplasmic granules which include membrane pore forming proteins and enzymes |
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Defensins
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cysteine-rich peptides produced in epithelia and neutrophil granules
-act as broad spectrum antibiotics |
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What are the primary lympoid organs and what is their function
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1)thymus = t lymphocytes
2)bone marrow = b lymphocytes -site of development and maturation of lymphocytes -generation of receptor diversity -MHC restriction for t cells -development of self tolerance |
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what are secondary lyphoid organs and what are their function
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lymph nodes, spleen, mucosal lymphoid tissue
1) antigen uptake 2)antigen presentation and activation of T and B lymphocytes 3)maturation of B cells |
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plasma proteins otherwise known as the complement system
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system of serum and cell surface proteins that activate innate and adaptive I
-3 pathways 1)classical pathway 2)alternate pathway 3)lectin Pathway -each pathway consists of a cascade of proteolytic enzymes that generate inflammatory mediators and opsonins that lead to the formation of a lytic complex that inserts in cell membranes |
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opsonin
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macromolecule that become attached to microbes for recognition of neutrophils and macrophages to increase the efficiency of phagocytosis
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phagocytosis
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process where cells in the innate I engulf large particles leading to the formation of an ingested intracellular vesicle (phagosome)
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opsonization
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process of attaching opsonins suc as IgGor complement fragments
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cytokines
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secreted proteins that function as mediators of immune and inflammatory reactions.
-in innate I cytokines are produced by macrophages and NK cells -in AI produced mainly by T lymphocytes |
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what are the characteristics of AI
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1)slow
2)dependant on prior exposure 3)specific to antigens and non-microbial antigens 4)huge diversity 5)memory 6)non reactive to self |
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components of AI
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1) cells: B and T cells and unique membrane receptor on each clone
2)plasma proteins: antibodies produced from b cells |
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3 types of AI
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1)humoural- b cell with unique membrane receptor -> plasma cell ->ag specific antibodies
2)cellular immunity: t cell with unique membrane receptor -> activated t cell -> ag nonspecific cytokines 3)tolerance - specific inability of B or T to respond to antigen due to deletion of self-reactive B and T cells in lymphoid organs and other mechanisms |
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functions of innate I
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1) early protection
2)activate and shape AI 3)supply mechanisms for AI ie complement, phagocytosis, inflammation |
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Toll like Receptors TLR and their 4 main effects
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-recruit adaptor molecules and activate gene transcription
1)cytokine production - inflam 2)chemokine prod- cell recruit 3)activate bact killing mechanisms 4)activate dentritic cells |
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what do cellular pathogen recognition receptors do?
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1)activate cells via the membrane with TLRs and in the cytoplasm via NOD-like receptors
2)promote phagocytosis leading to bacterial killing by lyosomal enzymes and reactive oxygen and nitro intermediates |
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what are the main points of clonal selection theory
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1-random gene rearrangement gives lymphocytes unique antigen receptors
2)antigen binds to specific receptor -> clonal expansion 3)re-exposure activates memory cells 4)self antigen bearing lymphocytes are deleted |
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what are the phases of the adaptive immune response
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1)recognition
2)cell activation 3)antigen elimination 4)contraction -> homeostasis 5)memory |
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antibodies
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-glycoprotein produced by B cells that binds to antigens
-high specificity and affinity -neutralise antigens by preventing them from binding to cells -activate complement -promote phagocytosis and destruction of microbes |
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what are dendritic cells
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lineage of antigen presenting cells for naive Tcells found in epithelia and most organs in the body
-when mature (activated) they upregulate MHC1&2, produce cytokines, and migrate to draining LN to activate tcells |
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major histocompatibility complex (MHC) molecule
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peptide display molecule for recognition by Tc
-class 1 present on all nucleated cells that are infected and are recognised by CD8+ Tc (cytolytic T) -class 2 restricted to APCs, macrophages and Bc. Bind proteins from endocytosed proteins and are recognised by CD4+ Tc (helper T) |
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antigen presenting cell APC
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cell that displays peptide fragments of antigens in association with MHC 11.
must express costimulatory molecules to optimally activate Tc |
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how are dendritic cells activated by different pathogens
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they express receptors that bind microbes such as receptors for terminal mannose residues on glycoproteins which are a feature of microbial but not mammalian glycoproteins
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how can Tc recognise an infinite variety of protein antigens from microbes
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the expression of antigen receptors is initiated by somatic recombination of gene segments V,D,and J that code for the variable regions of the receptors and then even more diversity is gainded from further changes in the nucleotide sequence introduced at the junctions of V,D and J.
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how is activation of Tc regulated
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microbes activate APCs to express membrane proteins (costimulators)and to secrete cytokines that provide signals that function in concert with antigens to stimulate specific Tc. This ensures that the Tc respond to antigens and not to harmless non-microbial substances
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describe the structure of b cell receptor (BcR)
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core structure of antibodies consists of two heavy chains and 2 light chains forming a disulfide liked complex.
each chain consists of a variable region which is the part that recognises the antigen and a constant region which provides structural stability and in heavy chains performs the effector functions of the antibody. |
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what is the difference between surface and secreted antibodies
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suface is bound to the membrane of Bc - when the antigen binds to a surface receptor it signals the cell to become a plasma cell and create and secrete that antibody.
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what are the different classes of antibodies
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IgM, IgG, IgA, IgE, IgD
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what antibodies are predominant in the primary and then the secondary response. How can this be used clinically
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primary= IgM followed by IgG
secondary= IgG - faster,higher if they are recently infected then they will have high IgM but if they have developed immunity they will have high IgG |
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outline the Tc receptor structure
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consist of an alpha and a beta chain. each chain has both a V and a C region. both chains participate in antigen recognition which for most Tc are peptides displayed by MHC molecules
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diversity of antibodies
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the expression of antigen receptors is initiated by somatic recombination of gene segments V,D,and J that code for the variable regions of the receptors and then even more diversity is gainded from further changes in the nucleotide sequence introduced at the junctions of V,D and J. same as for TcR
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what is the role of co-stimulation in TcR
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the full activation of Tc is dependent on the recognition of co-stimulators (second signals) on APCs
Apc's that are exposed to antigens or to cytokines produced by the II produce high levels of these co-stimulators and thereby activate the Tc |
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how does the Tc respond to activation
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1-cytokine secretion
2-expansion of the antigen specific clones of lymphocytes 3-differentiation of naive Tc into effector cells 4-development of memory cells |
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what are the roles of cytokines IL-2 and IL-2R in Tc proliferation
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when the Tc is activated it produces IL-2 and express the alpha chain of the IL-2R which associates with the beta chain and y chains to form the high affinity IL-2 receptor. Binding of IL-2 to its receptor -> proliferation of the T cells that recognise the antigen
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what are Th1 and Th2 cells
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these are the subsets that CD4 helper cells can differentiate into. These subsets may produce restricted sets of cytokines and perform different functions.
Th1- activate phagocytes to eliminate ingested microbes and stimulate the production of opsonising and complement binding antibodies Th2- produce IL4 and 5 stimulate Ige production and activate eosinophiles which function mainly in defense against helminths |
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what are the two types of CD4 T cell lymphocyte response
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1)Th1- target intracellular parasites via activation of macrophages, pro inflammatory and IgG2a antiB
2)Th2- target parasitic infections responsible for type 1 allergic reactions by help Bc mature, recruit and activate specialised effector cells |
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What are the two types of cell-mediated
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1)CD4 Tc activate pagocytes to destroy microbes in the vesicles of these phagocytes
2)CD8 Tc kill any cell containing microbes or microbial proteins in the cytoplasm thus eliminating the resevoir of infection |
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Why do effector T lymphocytes migrate to sites of infection
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because these lymphocytes express high levels of adhersion molecules that bind to ligands that are expressed on endothelium on exposure to microbes and because chemoattractant cytokines are produced at the infection site
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What does Th2 cells do
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unctional subset of helper T that
1)help Bc mature 2)secretes cytokines IL-4 and IL-5 whos principal function is to stimulate IgE and eosinophil/mast cell immunity 3)down-regulate th1 responses |
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What does Th1 do
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functional subset of helper
1)secrete cytokines interferon Y 2)stimulate and activate phagocyte mediated defence, esp intracellular microbes |
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how do T cells contribute to antibody production
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1)cytokines IL-4 & IL-13
2)expression of CD40L by activated Tc activates CD40 on Bc *these actions cause isotope switch, affinity maturation, in Bc as well as the development of memory Bc *these all occur in the germinal centre of the secondary lymphoid follicle |
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what is affinity maturation
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the process that leads to increased affinity of antibodies for a protein antigen as a humoural response progresses. It results from somatic mutation of Ig genes followed by selective survival of the Bc producing the highest affinity antibodies
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what is an Eosinophil and what is it's main function
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bone marrow derived granulocyte that is abundant in the inflammatory infiltrates of immediate hypersensitivity late phase reactions.
-contribute to many of the pathological processes in allergic diseases. -important in defense against extracellular parasites |
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What are Treg cells
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regulatory Tcells regulate the activation of effector functions of other T cells and may be necessary to maintain tolerance to self antigens.
They act via cytokines & direct cell contact -most Treg cells express CD4, CD25,& FoxP3 |
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what are the Tc associated with the CD8 response and what do they target
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1)cytolytic T - lysis or apoptosis of target cells
2)pro-inflammatory cytokines - CD8 Tc target Virus infected cells and Tumour cells *cytolytic T begin as naive Tcells until they are activated |
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what are the 2 main ways that Cytolytic Tc kill virus infected or tumour cells
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1)secrete perforin (pore forming protein)& Granzymes (enters throughperforin created holes and cleaves substrates and cause apoptosis)
2)via cell contact through Fas ligand/ FAS (initiates a signalling cascade leading to apoptosis) |
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apoptosis
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process of cell death characterised by DNA cleavage. nuclear condensation and fragmentation, plasma membrane plebbing which in turn lead to phagocytosis of the cell
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what are the main functions of type 1 interferons alpha and beta
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1) inhibit viral replication in neighbouring cells
2)activate NK cells 3)increase MHC class 1 expression -> increase CTc function 4)anti-proliferative effect (can be used for cancer therapy) |
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what are Natural Killer Cells
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bone marrow derived granular lymphocyte
-function in the innate response (non-specific)to kill microbe infected cells and activate phagocytes by secreting interferon Y. because they don't express clonally distributed antigen receptors their activation is regulated by cell surface stimulatory and inhibitory receptors. The inhibitory receptors recognise self MHC molecules |
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why is the humoural response more effective in defending against microbes with capsules rich in lipids and polysaccarides
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because Tcells only recognise protein antigens
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What classes of antibodies do naive Bcells express
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IgM and IgD
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what are the two forms of antibody responses
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1)T-dependent - protein antigens
2)T-independent- poysaccaride, lipid and other non protein antigens |
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What are the main characteristics of T-independent antibody response
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1)respond to polysaccaride, lipid and non-protein antigens
2)relatively little heavy chain switching and affinity maturation 3)antibodies are largely low affinity IgM 4)minimal if any memory |
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what are the main differences between primary and secondary antibody responses
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1)time lag: P=5-10days, S=1-3
2)peak response:P-small, S=big 3)antibody isotope: P=usally IgM>IgG, S=increased IgG sometimes in IgA or IgE 4)affinity:P=low & variable S=higher average (affinity maturation) |
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what are the phases of antibody response
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1)recognition-in secondary lymph organs
2)activation- receptor cross linking causing signal transduction and activation 3)expansion of Bc clon 4)antibody secretion 3) |
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Receptor cross-linking
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occurs when two or more antigen molecules in an aggregate protein, or repeating epitopes of one protein antigen molecule bind to adjacent Ig molecules in the membrane of B cells which leads to signal transduction
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What occurs in signal transduction of Bc via Bc receptors
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cross-linking of IgM and IgD receptors by antigen triggers signals that are relayed across cemm membrane by Igalpha and Igbeta
2)phosphorylation of ITAMs initiates cascade 3)activates enzymes and transcription factors initiating novel gene 4)Bc is activated |
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what are the characteristics of activated Bc
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1)proliferation
2)low level IgM secretion 3)increased expression of B7 costimulators - activate Th 4)migrate from follicles 5)express cytokine receptors |
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what is the purpose of IgM secretion by activated Bc
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1)is greatest when antigens are multivalent(eg polysaccaride)
2)activates eliination mechanisms(eg complement activation) |
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what type of antigens require Tc help to elicit efficient antibody production
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Protein antigens because they elicit a poor IgM response
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how do antigen-specific T helper cells and B cells get together
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after the helper T is activated by the protein antigen and proliferation and differentiation has occured some of the effector T cells migrate toward follicles where naive Bc recognise antigens become activated and then migrate from follicles to Tc zones. T meets B at edges of follicles
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