Complement, MHC, And Antigens Flashcards
What are the three complement pathways?
Classical
Lectin
Alternative
What are the main outcomes of the complement system?
Recruitment of inflammatory cell
Opsonization of pathogens
Killing via pores in membrane
What are the three ways the classical pathway is activated?
Bind directly to surface of bacterial components
Binds C-reactive proteins that binds to phosphocholine residues on bacterial polysaccharides
Binds to antigen-antibody couples on pathogen surface
How is the lectin pathway initiated??
Binding of carbohydrate-binding protein (mannone-binding lectin or Ficolins) on surface of pathogen
How is the alternative pathway initiated?
Spontaneously derived plasma C3b to pathogen surfaces
Activation of C1 in the classical pathway is caused by?
C1 binding to Fc region of the antibody
C1- cleaves C4 to C4a and C4b
What are the steps of classical complement cascade?
- C1 cleaves C4 to C4a and C4b
- C1 cleaves C2 to C2a and C2b
- C4b and C2a bind and form C3 convertase
- C3 convertase cleaves C3 to C3a and C3b
- C3b binds to C3 convertase to make C5 convertase (C4b2a3b)
- C5 convertase cleaves C5 to C5a and C5b
- C5b recruits C6 and C7 to form C5b67 compelx
- C8 joins complex with hydrophobic tail that is inserted into membrane
- C9 recruited (9-10copies) to form pore in membrane (MAC)
How is C3 convertase formed in the lectin pathway?
Mannose binding lectin binds to surface of pathogen, becomes activated, and cleaves both C4 and C2.
C4b and C2a bind to form C3 convertase
Describe the alternative pathway of the complement system.
- C3b spontaneously hydrolyzes
- C3b binds to Factor B on microbe surface -> C3bB complex
- Factor D cleaves C3bB to C3bBb (C3 convertase)
- C3 convertase cleaves C3 to C3b and C3a
- C3b combines with C3 convertase (C3bBb) to form C5 convertase (C3bBb3b)
- C5 cleaved
- C5b recruits C6, C7, C8, and C9 to form MAC
If a C3b (spontaneously lysed) binds to a host cell, what is the outcome?
Sailic acid promotes binding of C3b to Factor H
Factor H and I degrades C3b
Prevent lysis of host cells
How does C1 inhibitors prevent the complement cascade?
Inactivates C1r, C1s, and MASPs (classical and lectin pathways)
How does decay-accelerating factor control the complement pathway?
Accelerates the decay of C3 convertase (alternative)
How does Protectin contro the complement pathway?
Binds to C5b678 and prevents C9 recruitment and MAC formation
What are the possible outcomes of the complement pathway?
Direct target lysis Tissue inflammation Endothelial activation Chemotaxis Opsonization Immune complex clearance
The genes responsible for survival or rejection of a graft are called ______________________
Tissue or histo-compatibility genes
Each MCH cluster of genes has at least _____ classs of gene loci
3
Class I MHC are expressed on ?
All nucleated cells
Class II MHC are expressed on?
Professional antigen presenting cells
B cell
Macrophage
Dendritic cells
MHC class III genes encode proteins which function as?
Complement proteins
Not antigen presenting molecules
MHC genes are ____________ expressed, therefore each individual will have ______ MHC I genes
Co-dominantly
Six
What is the main role of MHC I and II in adaptive immunity?
Antigen presenting
MHC I present antigens to __________ T lymphocytes
CD8+
MHC II presents antigens to ________ T lymphocytes
CD4+
What is the structure of MCHi
Heterodimer - a (a1, a2, and a3) and B2-microglobulin
Extracellular domain makes up antigen binding groove
Transmembrane domain
Cytoplasmic domain
The T cell co-receptor binds to the _____ region of MHC I
a3
What is the structure of MHC II?
a (a1 and a2), B (B1 and B2)
Peptide binding groove made of a1 and B1
What cytokines increase expression of MHC I
IFNa, IFNB, or IFNy
What cytokines increases expression of MHC II?
IFNy
How does the immune response differ between animals with heterozygous and homozygous MHC alleges
Heterozygous-able to bind a large variety of antigenic peptides
Homozygous - able to bind few antigenic peptides
If MHC is unable to bind an antigen -> no immune response
What are the two subcategories of antigens?
Immunogens
Haptens
Immunogens are?
Substances capable of stimulating an immune response
Haptens are?
Substances that by themselves do not stimulate an immune response, but can do so when complexed with larger molecules (eg host protein)
What are the two cardinal features of an antigen?
Immunogenicity
Antigenicity
____________ is the ability of an antigen to induce an immune response
Immunogenicity
__________ is the ability of an antigen to bind with products of the immune system
Antigenicity
What is an epitope?
Aka antigenic determinant
Part of an antigen that is actually responsible for inducing the immune response and binding to the immune system products
What 8 factors can affect the immunogenicity of antigens?
- Foreignness
- Size
- Chemical composition
- Physical properties
- Degradability
- Genetic Factors
- Age
- Chemical nature of antigens
How does forigenness affect immunogenicity of antigens?
Self vs non-self
Only non-self substances are immunogenic
How does size affect immunogenicity of an antigen?
Larger the antigen, the more immunogenic
How do the physical properties of an antigen affect its immunogenicity?
Particulate antigens- more immunogenic than soluble antigens
Denatured antigens are more immunogenic than native forms
How does degradability of an antigen affect its immunogenicity
Antigens that are phagocytose and easily degraded are more immunogenic
How can age and genetics affect immunogenicity ?
Species variation and severity to particular antigens
Different genes encoding antigen receptors on T or B cells
Very young and old individuals are less capable to mount immune response.
How does the chemical nature of an antigen affect immunogenicity?
Protein- highly immunogenic
Polysaccharide - good immunogens
Nucleic acid- weak antigens, highly immunogenic when conjugated with protein
Lipids- generally not immunogenic (Haptens)
What is an adjuvant?
Substance that enhances the body’s immune response to an antigen
What are T-independent antigens?
Directly stimulate B lymphocytes to produce antibodies (no Helper Tcells needed)
Eg lipopolysacchride - polymeric structure with repeating epitope
What are T-dependent antigens?
Indirectly stimulate B lymphocytes
Require helper T cells
Eg. Proteins - various epitope
What is a superantigen?
Antigens that can activate a large number of lymphocytes at a time (Usually form bacteria or virus)
Bind to variable domain of the TCR and a chain of MHC -> induce strong signal to activate many Tcells
What are autoantigens?
Natural part of body
Play a role in autoimmunity
Do dendritic cells present to CD4+ or CD8+ Tlymphocytes?
Trick question- both
Macrophages and B lymphocytes present antigens to ________ T lymphocytes
CD4+
What are two important functions of antigen presenting cells?
- Convert protein antigens to peptides and they display peptide-MHC complexes to be recognized by Tcells
- Provide stimulus to Tcells called co-stimulation
What is the processing of endocytosed antigens for presentation by MHC?
- Uptake into vesicular compartments (receptor mediated)
- Process proteins in endosomal and lysosomal vesicles (proteolytic enzymes-cathepsins)
- MHC II synthesized in ER and transported to endosome
- Associated of MHC II and peptide
- Expression of MHC II with peptide at surface
How are cytosolic antigens processed?
- Cytosol location of foreign proteins
- Proteolytic degradation of cytosolic proteins in proteosome (ubiquinated proteins)
- Transport of peptides from the cytosol to the ER by “transporter associated with antigen presentation” (TAP)
- Assembly to peptide to MHC I in the ER
- Pass through golgi and expressed on the surface
Exogenously acquired proteins will generate peptides that activate _________ T cells
CD4+
Endogenously acquired proteins will generate peptides that activate ________ Tcells.
CD8+
What are the two classes to T Cell Receptors (TCR)
TCR aB
TCR y&
What TCR recognizes antigen in an MHC dependent manner?
aB TCR
What TCR recognizes an MHC in an independent jammer?
y& TCR
What is the purpose of the CD3 complex?
The CD3 compels is necessary for cell surface expression of TCR
Transduces activation signals to the cell nucleus following antigen interaction with the TCR.
T lymphocytes recognize specific _______________, and only respond when they are attached to the surface of an APC with appropriate MHC
Peptide sequences (anchor residue)
What antigens can be recognized by B cells?
Soluble antigen Antigen exposed on cel surface Peptide Protein Nucleic acid Polysaccharide Lipid
Lipid antigens are presented by _______________________ which are found on APC’s and some epithelial cells
Class I like non-polymorphic molecules (CD1)
Present lipid to Tcells that are non MHC restricted (NKTcells)
