Antigen captuer & presentation

antigenic determinant/epitope

the specific portion of a macromolecular antigen wo which an antibody/peptide binds to MHC for recognition by the TCR (epitope = immunologically active region of antigen)

antigenicity

ability to combine with antibodies or TCR

Immunogen

a substance that induces a specific immune response

immunogenicity

ability to induce a humoral and/or CMI response

haptens

haptens are antigens, but do not indice specific immune responses unless coupled w/ a carrier protein (haptens LACK immunogenicity)

Immunization w/ hapten-carrier conjugate produces antibodies to:

hapten determinant, unaltered epitopes on carrier protein, new epitopes formed by region of both the hapten and carrier molecule (rationale: require hapten-specific B cells and carrier protein-specific T cells)

Characteristics of good immunogens

foreignness, molecular size, stability, chemical composition/heterogeneity (proteins>CHO>lipids), susceptibility to antigen processing and presentation, genotype (MHC), dose & route

Sequestered antigens

ex: eye, sperm, are immunogenic to the same animal from which they are derived

Antigen recognition by T cells

T cell receptors recognize peptides derived from proteins presented by MHC molecules (conventional), T cells do not recognize soluble antigens

MHC (major histocompatibility complex)

a membrane protein that displays peptides for recognition to T cells (class I and class II)

APC

antigen-presenting cells (DC, macrophage, and B cell); contain both MHC class I and class II

Antigen-recognition by T cells is MHC restricted

CD8 cells will recognize MHC class I + peptide from nucleated cells; CD4 T cells will recognize MHC class II + peptide from APCs

Significance of costimulation for T cell activation

need an APC for CD4 T cell to receive signal 1 (MHC on APC) and signal 2 (APCs expressing costimulatory molecules: causes activation by binding CD28 on T cell)

Function of dendritic cells for antigen presentation

Naive T cell activation, clonal expansion and differentiation into effector T cells (only dendritic cells present antigens and bind CD28 to activate naive T cells)

Function of macrophage for antigen presentation

Effector T cell response: macrophage activation (cell-mediated immunity)

Function of B cells for antigen presentation

Effector T cell response: B cell activation and antibody production (humoral immunity)

Lifecycle of dentritic cells

immature DC in tissues, mature during transit in vessels, complete maturity in lymph node

Classical dendritic cells (cDC2)

major location: tissues, produce TNF, IL-6, IL-2 and induce T cell response against most antigens

Plasmacytoid dendritic cells

Major location: blood and tissue, produces type I interferons and stimulate antiviral innate immunity and induction of T cell responses against viruses

mature DCs

antigen presentation to T cells, expression of T cell activting molecules, long half life, increased number of surface molecules

mature DCs

antigen presentation to T cells, expression of T cell activting molecules, long half life, increased number of surface molecules

Properties & functions of dendritic cells

constitutive express of class II MHC, constitutive expression of costimulators

properties & functions of macrophages

low or negative expression of class II MCH and low expression of costimulators that is inducible

properties and functions of B lymphocytes

constitutive expression of class II MHC and induced expression of costimulators

cross-presentation/cross-priming of microbial antigens

presents tumor and transplant antigens, similar to viral antigens; cDC1 (best CD8 instructors) present antigens of another cell by engulfing infected cells and presenting the antigen on its surface

Types of MCH classes

class I, class II, class III

What is MHC class I encoded to do?

receptors for endogenous antigens, found on most nucleated cells

what is MHC class II encoded to do?

receptors for exogenous antigen, found only on antigen-presenting cells

How many loci on a chromosome encode for class I MHC?

three

How many loci on a chromosome encode for class II MHC?

eight

MHC haplotype

complete set of alleles that encodes for MHC

common structures of MHC proteins

floor of groove that binds peptides to present, sides and tops that are contacted by TCR

structures of MHC class I molecules

peptide groove accommodates 8-11 aa (groove is closed), alpha1 and alpha 2 are most polymorphic regions; alpha3 is the binding site for CD8 receptor

structures for MHC class II molecules

1–30aa (groove is open) alpha1 and beta1 are polymorphic, but most polymorphisms are found in beta1; beta2-non-polymorphic, a binding site for CD4 coreceptor

polymorphism

no two individuals in an outbred population have exactly the same set of MHC genes/molecules (issue for tissue matching)

significance of MHC polyphorphisms

ensures that all microbial peptides will be recognized by at least some individuals in a population

codominant expression

both the maternal and paternal genes are equally expressed

significance heterozygosity

heterozygous individual will express more alleles and thus can bind to a greater variety of antigenic peptides than a homozygote

HLA-linked immunological diseases in cattle

bovine leukemia virus (resistance & susceptibility), resistance to mastitis

Presentation pathways for MHC class I molecules (cytosolic antigens)

antigen taken up by DC, processed in proteasomes, MHC class I receptors on ER will assemble with peptide inside the ER (TAP & Tapasin), then travels to the cell membrane to present to CD8 cells

Presentation pathways for MHC class II molecules (internalized pathogens)

endocytosis of extracellular protein → digestion of protein in proteosome → associate with MHC class II receptors outside ER in vesicle (CLIP & DM)→ go to membrane for presentation to CD4 cells

functional outcome of antigen recognition by CD4 T cells

APC (extracellular antigens) → MHC II/peptide → CD4 T cells → cytokines

functional outcome of antigen recognition by CD8 T cells

nucleated cells (antigen inside cell) → MHC I/peptide → CD8 T cells → direct killing of infected cells

antigen recognition by gamma-delta T cells

direct regocnition of bacteria ,recognition of lipids via DC1c (class I-like molecule), direct recognition of stress proteins

antigen recognition by B cells

direct recognition of antigens on microbial surface or soluble antigens without processing; FDC (follicular dendritic cells in lymph node) lack MHC class II molecules and display to B cells, b cells can present iccosome to T cells

functional outcome of antigen recognition by B cells

B cells → plasma cells (activated) → antibody production