Chapter 4: Adaptive Immunity

Innate Immune Cells

phagocytes, granulocytes

Innate Immune Recognition of Pathogens

PRRs recognize common PAMPs, unable to recognize novel pathogens

Innate Immune Receptors

have receptors for constant regions of immunoglobulins

Adaptive Immune Cells

B cells, T cells

Adaptive Immune Recognition of Pathogens

have diverse receptors specific for particular molecules on particular pathogens, capable of recognizing novel foreign molecules

Immune Memory

only the subset of B and T cells that recognize the pathogen with their receptors activate and proliferate; increased number of daughter B and T cells with same specificity serve to combat future infections by the same pathogen more quickly and efficiently

How Adaptive Immunity Differs from Innate

has immune memory, can target novel pathogens or pathogens expressing new antigens

How Pathogens are Recognized by Cells of the Adaptive Immune System

T cell receptors, B cells receptors, Humoral Immune response, cellular immune response

Timeline of Adaptive Immune Response

Dendritic Cells, Lymph nodes, Helper T cells, B cells, plasma cells

Dendritic Cells: Timeline

phagocytose proteins at infection site and migrate to lymph nodes

Lymph Nodes: Timeline

Present the peptide fragments to circulating T cells that interact via cell-adhesion molecules

Cytosolic Pathogen Proteins

processed in the cytosol, peptide fragments presented on class I MHC molecules

Extracellular Pathogen Proteins

processed in phagolysosomes, peptide fragments presented on class II MHC molecules

Helper T Cells

migrate to part of lymph node where they meet circulating B cells

B Cells

B cells that recognize the same pathogen as T cell become activated, divide, and differentiate; some turn into plasma cells, memory B cells, other undergo further refinements to their B cell receptor

Affinity Maturation

somatic hypermutation and selection generates B cells with higher affinity for the antigen

Isotype Switching

recombination of heavy chain constant region genes result in a different heavy chain type

Plasma Cells

secrete antibodies

V(D)J Recombination

recombination of different randomly selected variable gene segments; addition or removal of random nucleotides at junctions of recombined variable gene segments

VDJ Recombination Subunits

ɑ-chain and β-chain for T cell receptors; heavy and light chain for B cell receptors

Somatic Recombination

splices DNA segments; only occurs in developing T and B cells, only spliced gene segments are expressed

V and J Segments

T cell-receptor a-chain, immunoglobulin light chain

V, D, J

for T-cell receptor B-chain, immunoglobulin heavy chain

TCR: VDJ Alpha Chain

alpha-chain joins a single randomly selected Va to a single randomly selected Ja segment, Va + Ja

TCR: VDJ Beta Chain

rearrangement joins a Db and Jb segment, then joins a Vb segment to form many VbDbJb combos

BCR: VDJ Heavy Chain

VH combines with DH and JH to form many possible VHDHJH combos

BCR: VDJ Light Chains

two types: Kappa and lambda, each light chain recombines to form multiple different VKJK or VlambdaJlambda; each B cell expresses a unique heavy chain and a single unique light chain (either K or lambda)

VDJ Recombinase

RAG1 (recombination activating gene 1) and RAG2 bind and recognize recombination signal sequences (RSSs) that border V, D, J DNA segments; enzymes in the non-homologous end joining (NHEJ) DNA repair pathway are involved

VDJ Recombinase: RSSs

contain a heptamer, a nonamer sequence, and either a 12-bp or 23-bp sequence spacer between them

Diversity Mechanisms

RAG1/RAG2 recombinase cutting at the RSSs creates hairpins; nicking by Artemis creates single strand palindromic overhangs that create P-nucleotides; exonucleases and terminal deoxynucleotidyl transferase delete and add random nucleotides (N-nucleotides); junctional sequence diversity amplifies receptor diversity

Self-Tolerance Mechanisms

processes that generate receptor diversity create receptors that recognize self-molecules

Positive Selection

selects cells with functional receptors

Positive Selection Mechanism

TCR and immunoglobulin gene rearrangements proceed in defined sequence; after each recombination, the protein product’s function is tested

Positive Selection Mechanism Possible Results

if the protein is not functional, the developing B or T cell goes through apoptosis; if the protein is functional, the cell goes through the next step of development

Negative Selection

selects against cells with self-reactive receptors

Negative Selection Mechanism

lymphocytes with functional antigen receptors are tested for reactivity to self-molecules; cells in thymus express many self peptides on MHC molecules to test developing T cells

Negative Selection Mechanism Possible Results

T cells that recognize self-peptide MHC complexes too well undergo apoptosis; T cells that recognize self-peptide MHC complexes only moderately survive

Ultimate Goal of Positive and Negative Selection

tests developing lymphocytes for functional receptors that do not react with self-molecules; lymphocytes that pass both selections mature and enter circulation

MHC (Major Histocompatibility) I

most cells; present peptides from proteins made inside the cell, a transmembrane a-chain forms peptide binding pockets, plus beta2 microglobulins; proteins in the cytoplasm digested to peptide fragments by proteasome

Class I MHC Molecules

peptide fragments are presented into endoplasmic reticulum, peptide complexes exit ER and travel to plasma membrane via secretory pathway

MHC I: CD8 T Cell

recognize Class I MHC, peptide complex can be activated

MHC II

professional antigen-presenting cells; present peptides from extracellular proteins taken into phagolysosomes, transmembrane alpha and beta chains together form peptide binding pocket; peptide complexes travel to plasma membrane

MHC II: Phagolysosomes

proteases in phagolysosomes degraded endocytosed or phagocytosed proteins into peptide fragments; phaolysosomes then fuse with secretory vesicles that contain MHC Class II proteins,

MHC II CD4 T Cell

peptide complex can be activated

Role of T Cell Receptors

antigen recognition; each T cell responds only to the specific peptide presented by the specific MHC molecule; most T cells are able to recognize only a specific pathogen and only a particular peptide from that pathogen

TCR and MHC Co-receptor Engagement

results in signaling and T-cell activation

TCR and MHC Co-receptor Engagement: CD8 T Cells

differentiates into cytotoxic T cells, engaged with Class I MHC

TCR and MHC Co-receptor Engagement: CD4 T Cells

differentiates into various types of helper T cells, engaged with Class II MHC

Role of TCR: CD3 Complex

associate with other transmembrane proteins that form the CD3 complex; proteins of the CD3 complex have cytoplasmic tails with signaling motifs

Role of Immunoglobulins

antibodies, serve as B cell receptors expressed as a cell surface protein with a transmembrane domain; serves as soluble effector molecule when secreted by plasma cells; can activate classical pathway of complement system

Immunological Memory

the basis for vaccines and immunity after recovery from infection, developed after primary and secondary immune response; prevents further re-infection

Primary Immune Response

requires weeks; antigen processing, migration of dendritic cells to lymph nodes, presentation to T cells, activation and differentiation of T and B cells; antigen specific B and T cells proliferate into memory B and T cells

Memory Cells

increase the number of antigen specific T and B cells and are primed to response faster if/when the ssame antigen re-enters the body

Secondary Immune Response

memory cells encounter antigen faster, respond quickly and more strongly; memory B cells produce antibodies with better affinity, clears antigen within a few days