PHSC1312 Microbiology/Immunology Lecture 7 Innate Immune Cell Activation

macrophages and dendritic cells

recognize organisms based on PAMPs or DAMPs and begin phagocytic process

phagocytosis

process of cellular engulfing/eating

PAMPs and opsonin coated pathogens

What activates phagocytes?

C3b and Fc

receptors that enhance the phagocytosis process

opsonin and antibody

What triggers the C3b and Fc receptors respectively?

respiratory oxidative burst, proteases, DNases, and reactive nitrogen species

mechanisms of phagocytosis to destroy

respiratory oxidative burst

using reactive oxygen species to create a toxic environment for microbial substances involved

NADPH oxidase, superoxide dismutase, myeloperoxidase

three enzymes in respiratory oxidative burst

neutrophils

What has myeloperoxidase?

proteases and DNases

used in phagocytosis to digest nucleic acids and proteins into peptide fragments

nitric oxide synthase

produces nitric oxide

nitric oxide

vasodilator for humans but toxic to pathogens

TLR, C3b, Fc, cytokine

four receptors that when ligated result in immune activation and an intracellular signaling cascade

lysosomal enzymes and NOS, production of cytokines, membrane rearrangement for migrating cells, receptor expression

What four things get upregulated after PRR ligation and in immune activation?

antigens

substances recognized by immune system

tolerance

opposite of immune stimulating

size, chemistry or structure, genetics of host, and for delivered antigens dosage, route, and timing

What feature of antigens make them more or less immunogenic?

all nucleated cells

Which cells express MHC I?

professional antigen presenting cells

Which cells express MHC II?

macrophages, dendritic cells, b cells

antigen presenting cells

T cells

What is the target for antigen presentation?

cannot see antigens without presentation

Why are T cells the target for antigen presentation?

CD8 markers

found on cytotoxic T cells, respond to antigens on Class I MHC proteins

cytotoxic T cells

Where are CD8 markers found on?

antigens on class I MHC proteins

What do CD8 markers respond to?

CD4 markers

found on helper T cells, respond to antigens on Class II MHC proteins

helper T cells

Where are CD4 markers found on?

antigens on class II MHC proteins

What do CD4 markers respond to?

T cell receptor

What is CD3?

bind to CD3 receptor complex and prepare cell for activation

What do both CD8 and CD4 markers do?

HLA A B C

Where are class I MHC genes coded for on chromosome 6?

HLA DP DQ DR

Where are class II MHC genes coded for on chromosome 6?

small cytosolic peptides

What do MHC I molecules display?

8-10 amino acids

length of MHC I cytosolic peptides

cut by proteasome

How do MHC I cytosolic peptides end up being 8-10 amino acids in length?

longer endocytosed peptides

What do MHC II molecules display?

18-20 amino acids

length of MHC II endocytosed peptides

closed

Is the peptide bonding cleft more open or closed for MHC I molecules?

open

Is the peptide bonding cleft more open or closed for MHC II molecules?

B cells and natural killer cells

don't require antigen presentation for activation

loss of MHC expression

a hallmark of infection to trigger immune response

presence or absence of MHC I

tips off natural killer cells when it is looking for presentation loaded from peptides

perforin and granzyme

What do natural killer cells use to kill?

antibody dependent cellular cytotoxicity

ability of natural killer cells to have activity enhanced by antibodies

antibodies bind virus infected cells, NK cell binds to antibodies with CD16 receptor, NK cells kill with cytotoxic granules and antiviral cytokines

steps to antibody dependent cellular cytotoxicity

using antibodies as opsonins and not phagocytosis but degranulation of cytoplasmic granules

What starts ADCC and what is the outcome?