Antigen Recognition & Activation of Adaptive Immune System Flashcards
Explain the role of lymph nodes and spleen in capture of epithelium and connective tissue antigens and blood-borne antigens, respectively
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Describe the process by which dendritic cells capture antigen and become effective antigen-presenting cells (APCs)
- immature dendritic cells capture antigens and move to lymph
- mature dendritic cells are efficient antigen-presenting cells that reside in T cell-rich areas of lymph nodes and spleen
- there is high expression of MHC proteins and expression of costimulatory molecules during maturation
Explain the recognition of peptide-MHC complexes by T cell receptors (TCR)
- TCRs have binding receptors for top and sides of the peptide displayed by MHC
- MHC has pockets for anchor residues of peptide
Describe key properties of human class I MHC genes
- expressed on all nucleated cells (extracellular and intracellular antigens)
- heterodimer: transmembrane alpha chain + soluble beta 2 microglobulin
- alpha 1 & 2 are polymorphic
- alpha 3 is invariant and binding site for CD8 protein
Describe the class I MHC pathway
- production of proteins in the cytosol (and ubiquitinized)
- proteolytic degradation of proteins
- transport of peptides from cytosol to ER
- assembly of peptide-class I comlpexes in ER, using TAP
- surface expression
Explain how segregation of the class I MHC and class II MHC pathways of antigen processing enables the adaptive immune system to respond differently to extracellular and intracellular pathogens
Class I: defense against intracellular pathogens
Class II: defense against extracellular antigens and pathogens
Compare and contrast the structures, antigen-binding characteristics and functions of the B cell antigen receptor (antibody) and T cell antigen receptor (TCR)
BCR/antibody – “look” at antigens
-heterodimer of immunoglobin – 2 heavy and light chains (H2L2)
-Vh and Vl are variable –> form antigen binding site
-2 isotypes: IgM and IgD
TCR (alpha-beta)
-membrane bound on surface of T cells
-heterodimer of alpha and beta transmembrane chains
-Va and Vb: variable domains, form antigen binding site
[helper T and cytotoxic T cells]
TCR (gamm-sigma)
-recognize protein and non-protein antigens
-abundant in epithelia
On NK-T cells
-express alpha beta and surface markers of NK T cells
-recognize lipid antigens in nonpolymorphic class I MHC-like molecules
MAIT cells
-20-40% of human liver cells
-express alpha beta with limited diversity
some recognize bacterially derived vitamin B metabolites bound to a MHC-like protein
Distinguish the roles of membrane-bound and soluble antibodies in the immune response
Secreted
-mediate effector functions
-constant domain determines effector function
Membrane bound
-bind to macromolecules and small chemicals
Explain the steps of a T cell response to antigen including the general features of T cell activation and the concepts of costimulatory signaling, clonal expansion and differentiation of effector and memory T cells
- Antigen recognition –> naive T cell binds APC
- cytokine secretion and cytokine receptor expression
- proliferation/clonal expression
- differentiation to CD4 helper, CD8 CTL, CD4 memory T cell, or CD8 memory T cell
- effector functions –> CD4 helper (activation of macrophages, B cells, etc), CD8 CTL (kill infected targets & macrophage activation
Distinguish between T cell-dependent and T-cell independent antibody responses
Dependent
-require T cells to help B cells
-elicited by protein antigens
-involve follicular B cells (in secondary lymphoid organs)
Independent
-do NOT require T cells to help B cells
-elicited by polysaccharide, lipid, & nucleic acid antigens
-involve B-1 B cells (mucosal tissues & peritoneum) and marginal zone B cells (spleen)
Describe the general features and results of signaling through the B cell antigen receptor, including co-receptor signaling
- must have coreceptors for signaling
- CR2 is complement receptor that binds to C3d (fragment of complement system)
- CD19/CD81 are the signaling complex
- protein antigens require signaling 2…polysaccharide, lipid, & nucleic acid antigens do not
- B cell can simultaneously recognize antigen via BCR and C3d via CR2
- engagement of CR2 leads to signaling that greatly enhances antigen-dependent B cell activation (not necessary)
- bridges innate and adpative immunity
Explain the steps of a T cell-dependent antibody response including the general features of B cell activation and the concepts of T cell help, clonal expansion, isotype switching and affinity maturation
- Antigen recognition (signal 1)
- Activation of B lymphocytes (signal 2) –> T cell help … activated B cell
- proliferation
- differentiation –> antibody-secreting plasma cells, IgG-expressing B cells, high-affinity Ig-expressing B cells
- outcomes:
- antibody-secreting plasma cells = antibody secretion
- IgG-expressing B cells = isotype switching (germinal center event)
- high affinity Ig-expressing B cells = affinity maturation and memory B cells (both germinal center events)
Describe the general roles of CD4+ helper T cells, CD8+ cytotoxic T cells, plasma cells and memory B and T cells
CD4+ helper T cells: interaction of CD40-ligand
with CD40 (on B cells); cytokines secreted; interact with class II MHC molecules
CD8+ cytotoxic T cells: kill class I MHC presenting cells
Plasma cells: secrete antibodies
Memory B & T cells: create faster response in future infections
Desccribe Antigen-presenting cells (APCs)/antigen presentation
- capture antigens
- express MHC on cell surface
- display peptides from protien antigens bound to MHC proteins to T cells
Describe immature dendrtic cells
- reside in tissues (including epithelia)
- form cell network with interdigitating process
- capture antigen and migrate via lymph
