Host Immunity 2 Flashcards
What are the three complement pathways?
classical, alternative, and lectin
What is the common key product of the complement pathways?
C3b
What are the end effects of the complement pathways?
- cell lysis
- inflammation
- opsonization
- interact with other pathways
What activates the classical pathway of complement fixation?
C1 binding to C-reactive protein on the pathogen surface
also called binding of Ab to Ag
What are the steps involved in the classical complement pathway?
- > C1 binds to C-reactive protein on the pathogen surface
- > C1s cleaves C4 into C4b which binds to C1
- > C2 binds to C4b and is cleaved by C1s into C2a, which binds to the complex, and another fragment, C2b.
- > the combination of C4b2a (C3 convertase) cleaves C3 into C3b which binds to the complex and also releases fragment C3a
- When acted on by C3 convertase, C3 is cleaved into C3b which binds to C4b2a and a small fragment, C3a is released. The complex of C4b2a3b forms C5 convertase
What do bacteria induce macrophages to produce and what does it do?
IL-6 which acts on hepatocytes to induce synthesis of acute-phase proteins
What is IL-6?
a pro-inflammatory cytokine produced by macrophages and induces hepatocytes to synthesize acute-phase proteins
What does the liver (hepatocytes) produce in response to IL-6 specifically?
C-reactive protein, fibrinogen, mannose-binding lectin
What does C-reactive protein bind to and do?
binds to phosphorylcholine on bacterial surfaces, acting as an opsonin and as a complement activator
What does mannose-binding lectin bind to and do?
binds to residues on bacterial surfaces, acting as an opsonin and as a complement activator
What are the initial complement components of the classical pathway?
- C1q, C1r, C1s, C4, C2
What makes up C3 convertase in the classical pathway?
C4bC2b
What makes up C5 convertase in the classical pathway?
C4bC2bC3b
What is the activator of the lectin pathway?
mannan binding lectin (MBL), MBL-associated serine protease-2 (MASP-2)
What is the initial complement component of the lectin pathway?
C4, C2
What are the steps involved in the Alternative pathway ‘tick over’ phase?
- Fluid phase C3 and H2O creates C3i
- C3i acts with factor B and Mg2+ to create C3iB
- C3iB is acted on by factor D to create C3iBb and Ba
- C3iBb acts on C3 to create C3b and C3a
- C3b binds to normal cell surface or is hydrolyzed and inactivated in fluid phase
What are the steps involved in the activation phase of the alternative pathway?
- The spontaneous hydrolysis of C3 to C3b and the binding of C3b to microbial surfaces initiates the alternative pathway
- Factor B binds to C3b and factivates factor D
- When factor D acts on bound Factor B, the latter is cleaved into the fragments Ba and Bb;Bb binds to the complex, forming C3bBb (C3 convertase)
- This complex is then stabilized by the binding of properdin
- When acted on by C3 convertase, C3 is cleaved into C3b which binds to C4b2a and a small fragment, C3a is released. The complex of C4b2a3b forms C5 convertase
What is the activator of the alternative pathway?
contact of microbial cell wall with C3
What is the initial complement component of the alternative pathway?
C3
What makes up C3 convertase in the alternative pathway?
C3bBb
What makes up the C5 convertase in the alternative pathway?
C3bBbC3b
What makes up the C3 convertase in the lectin pathway?
C4bC2b
What makes up the C5 convertase in the lectin pathway?
C4bC2bC3b
What are the regulatory factors of the classical pathway?
CR1, C4BP
What are the regulatory factors of the alternative pathway?
Factor I, Factor H
What are the regulatory factors of the Lectin pathway?
CR1, C4BP
What is the classical pathway initiated by?
binding of C1q to complexes of antibioties with antigen, or by direct binding to some microbial structures
What is the alternative pathway initiated by?
when trace amounts of C3b formed by spontaneous breakdown of C3 bind to bacterial surfaces
What is the lectin pathway initiated by?
binding of mannose-binding lectin (MBL) or ficolins to bacterial sugars
What happens in the termination pathway?
- C5 convertase acts on C5, cleaving it into C5b which binds to the complex
- C6 binds to C5b and interacts with C7
- C7 binds to the C5bC6 complex and creates a binding site for C8
- C8 binds to the C7C6C5b complex
- When C9 binds to the C5bC6C7C8 complex, it forms the membrane attack complex (MAC)
What are the results of the complement activation pathways?
smooth muscle contraction, mast cell degranulation, vasodilation, local oedema, local influx antibody and complement, cell extravasation, neutrophil activation, and removal of particulate antigens
How are particulate antigens removed as a result of complement activation?
- particulate antigen randomly encounters IgG and C3b complexes or IgG alone
- the antigen gets coated with IgG and C3b
- circulating RBC has C3b receptor and binds to C3 bound to antigen
- They travel to the liver or spleen and are removed
What are the biological consequences of complement activation?
Lysis (MAC), Opsonization (C3b), Activation of inflammatory response (C3a & C5a), and Clearance of immune complexes
What are the steps involved in the lectin pathway?
- Mannose-binding lectin (MBL) binds to mannose residues on glycoproteins or carbohydrates on the surface of microorganisms; this molecule has activity similar to C1q
- Following binding of MBL to mannose residues, MBL-associated serine proteases (MASP) 1 and 2 (MASP-1 and MASP-2) become autocataclytically activated and behave like C1 in the classical pathway, cleaving C4
- Same as classical pathway from here on out
What are two types of adaptive immune responses?
- humoral immunity
- Cell-mediated immunity
What is humoral immunity?
an immunity mediated by antibodies secreted by antigen-activated B cells and their progeny plasma cells
What is cell-mediated immunity?
an immunity mediated by antigen-activated T cells and the cytokines they secrete
What do CD8 + T cells function as?
cytotoxic T lymphocytes (CTL)
What do CD4 + TH1 cells and activated macrophages function in?
delayed type hypersensitivity responses
What are the main differences between the primary and secondary humoral immune responses?
the secondary response has a shorter lag phase, greater magnitude, and class-switched IgG
What are the parts of immunoglobulin?
the antigen binding site, the hypervariable regions, and the hinge region. contained within the fab (first 2) and Fc respectively
What do antigens do?
- induce specific, adaptive immune responses
2. react specifically with the products of the response
What are paratopes?
the part of an antibody which recognizes an antigen, the antigen-binding site of an antibody
- a small region of 15-22 amino acids of the antibody’s Fab region
What have paratopes with specificity for a single antigenic epitope?
surface immunoglobulin or B-cell receptors, antibodies, and t-cell receptors
What do B-cell receptors and antibodies recognize?
native protein antigens without processing or MHC
What do T-cell receptors recognize?
processed antigens on MHC
- this means that the native protein antigen must be denatured, broken down into peptide antigens, and then the t-cell receptors bind to the peptide:MHC molecule complexes
How do dendritic cells present pathogens for T-cells?
- dendritic cell takes up pathogen for degradation
- pathogen is taken apart inside the dendritic cell
- pathogen proteins are unfolded and cut into small pieces
- peptides bind to MHC molecules and the complexes go to the cell surface
- T-cell receptors bind to peptide:MHC complexes on dendritic cell surface
What are the types of protective immunity employed in extracellular interstitial spaces, blood, and lymph infections?
antibodies, complement, phagocytosis
What are the types of protective immunity employed in extracellular epithelial surface infections?
IgA antibodies, antimicrobial peptides
What are the types of protective immunity employed in intracellular cytoplasmic infections?
cytotoxic T-cells, NK cells
What are the types of protective immunity employed in intracellular vesicular infections?
activated macrophages
