Lecture 4: Principles of Adaptive Immunity

adaptive immunity

the response of antigen-specific lymphocytes (T cells and B cells) to antigen, including the development of immunological memory

features of adaptive immunity

• acquired

• highly specific and efficent

• long lasting memory cells

• increases recognition of pathogens by innate immune system

innate vs adaptive: speed of response

innate: immediate response

adaptive: gradual response

innate vs adaptive: specificity

innate: targets a group of pathogens with common patterns

adaptive: targets specific pathogens

innate vs adaptive: memory

innate: no memory

adaptive: has memory

innate vs adaptive: maximum response

innate: immediate maximum response

adaptive: lag between exposure and the maximum response

advantages of adaptive immunity

• precise: targets small differences in pathogens

• memory: B & T cells are retained for a quicker response in case of recurrent infection

• adapts: keeps pace with rapidly evolving organisms

cell mediated immunity (CMI) pathogen

targets intracellular pathogens (viruses)

cell mediated immunity (CMI) mediator

mediated by cytotoxic C cells

cell mediated immunity (CMI) transferability

not transferable

humoral immunity (HI) pathogen

targets extracellular pathogens (bacteria)

humoral immunity (HI) mediator

antibody mediated

humoral immunity (HI) transferability

transferable

antigen

any molecule, macromolecule, viral particle or cell that contains a structure recognized and bound by an Ig or TCR

antibody determinant (epitope)

portion of the Ag recognized by the Ab

CD4T (AKA helper T cells)

triggers the immune system and picks the path of attack (HI vs CMI)

keystone cell

CD4T cell (aka helper T cell)

BCR

B cell receptor, binds native proteins on pathogen

soluble form of BCR

Antibody

TCR

T cell receptor, binds peptide fragments from degraded pathogen

soluble form of TCR

no soluble form

antibody

made by our bodies to bind a specific epitope and prevent re-infection

variable region

constant region

antigen-binding site

light chain

heavy chain

transmembrane region

antibody repertoire

the total number of antibody specificities in an individual (hundreds of billions!

antigenic processing

dendritic cells degrade pathogen, producing short peptides

clonal selection postulate 1

each cell has one receptor for one antigen

clonal selection postulate 2

activation occurs when a cell binds tightly to antigen

clonal selection postulate 3

differentiated effector cells are exact copies

clonal selection postulate 4

cells that bind tightly to self are destroyed

what links adaptive and innate immunity?

dendritic cells

two major steps linking adaptive and innate immunity

1. antigens carried to lymphoid tissue by dendritic cells

2. dendritic cells activate T cells

antigenic presentation

display of antigen as peptide fragments bound to MHC on cell surface

MHC

major histocompatibility complex, where peptides are presented

MHC class I

presents peptides from intracellular pathogens

MHC class I location

present on all nucleated cells

MHC class II

presents peptides from extracellular pathogens

MHC class II location

only on pAPCs

pAPC

professional antigen presenting cells

3 pAPCs

1. macrophages

2. dendritic cells

3. B-cells

co receptor for an intracellular infection

Tc TCR

co-stimulatory molecule for an intracellular infection

CD8

binding site of intracellular antigen recognition

APC MHC I

location of intracellular antigen recognition

AOC and cytotoxic T cells

co receptor for an extracellular infection

TH TCR

co-stimulatory molecule for an extracellular infection

CD4

location of extracellular antigen recognition

APC and helper T cell

binding site of extracellular antigen recognition

APC MHC II

APC

antigen presenting cell

to become activated, TCRs must bind to:

1. antigen and self protein on APC (with co-receptor)

2. co-stimulatory molecules

neutralization

prevents pathogen growth, replication or interaction with host cells

opsonization

aids in engulfment and destruction by phagocytosis

immunoglobulin

soluble form of antibody

clonal selection

selection of clones specific for Ag

clonal expansion

proliferation of selected clones

basic activation of B cells

1. surface Ig of B cells bind bacteria, the cell engulfs and degrades them, producing peptides

2. bacterial peptides are bound by MHC class II in vesicles

3. the bound peptides are transported by MHC class II to the surface of the cell

4. helper T cell recognizes the complex and activates the B cell

to become activated, a B cell must bind to:

• free antigen

• helper T cell (B cell acts as APC)

isotypes of antibodies

• IgA

• IgD

• IgE

• IgG

• Igm

somatic recombination process

non-functional DNA is cut by enzymes to join the segments in the light chain or heavy chain, to be later transcribed and translated

segments in light chain

V (variable) and J (joining)

segments in heavy chain

V (variable), J (joining) and D (divsersity)

somatic recombination benefits

increases diversity and specificity of antibody response

junctional diversification process

random addition or subtraction of nculeotides at the junction between V, D and J segments

junctional diversification benefits

increases diversity and specificity of antibody response

isotype switching process

by altering the heavy chain the isotype is changed on the antibody

isotype switching benefirs

improves specialization of function and ability to recruit effectors

somatic hypermutation process

random mutation that selects for for antibodies that bind more tightly to pathogen

somatic hypermutation benefits

improves Ag binding by the Ab