Immunology Lectures 1-4

NK cells kill microbes where?

Intracellular / cytoplasm

Innate immunity recognizes what?

Many structures not present on normal host cells.

Molecules expressed / produced solely by microbes

Pathogen associated molecular patterns (PAMPs)

TLR4 Binds to what?

Lipopolysaccharide

TLR3 Binds to what? Recruits what? Leads to production of what?

• Binds dsRNA

• recruits TRIF

• Production of IFNa/B

Recruitment of what adaptor proteins leads to activation of transcription factors and cytokine production

MyD88 and TRIF

MyD88 and TRIF is recruited by what? after it binds what? * ONLY receptor that recruits two.

TLR4 after it binds LPS

What receptor recognizes PAMPs?

PRR (Pattern recognition receptors) of innate immune system

NLRP3 Inflammasone assembly leads to activation of what?

Capase-1 activation, IL-1Beta release

Capase-1 activation results in?

Cleavage of pro-IL1B (inflam. cytokine) and Secretion of IL-1B

Secretion of IL-1B does what?

Recruits neutrophils through increasing adhesion molecules in veins.

Cell that is most abundant (1×10^11 / day) and is short lived (6 hours)

Neutrophils

Do neutrophils have lysosomes?

NO

Plasmacytoid Dendtric Cells produce what? Function?

Type 1 interferon (IFNalpha/B), possesses antiviral activity.

Plasmacytoid DC bind to what?

dsRNA via TLR3

NK Cells produce what interferon?

IFNy

IFNy Function?

Activates macrophages that leads to the killing of phagocytosed microbes

How do NK cells kill virus infected cells?

Releases Perforin / granzyme

Activated Mast cells release proteolytic enzymes that contribute to what?

Inflammation, histamine, prostaglandin, heparin, leukotrienes, TNFa.

what are the two signals lymphocyte activation requires?

• Signal 1: Antigen binding to antigen receptor

• Signal 2: Molecules provided by innate cells (costimulatory molecules)

Four symptoms of Inflammation

Increase in temp., redness, swelling, pain

Inflammation has what effect on capillaries?

Increases permeability allowing plasma proteins and phagocytes influx locally.

Role of cytokines?

Activate and mobilize other cells

TNFalpha and IL-1 both induce what?

Fever

Steps of Leukocyte Recruitment

Rolling, Integrin activation, stable adhesion, transmigration through endotheliu

Liver responds to what cytokines to produce plasma proteins that trigger phagocyotsis?

IL-1, IL-6, TNFa

What are the liver plasma proteins made in response to IL1,6 and TNFa?

SAP, CRP, MBL

Function of SAP, CRP and MBL

Function as Opsonins, targeting microbes for phagocytosis

Molecules coating a microbes surface

Opsonin

Process of marking a microbe for ingestion

Opsonization

Patients with high CRP levels are at risk of what?

Serious Gum disease

What liver plasma proteins are involved in the classical activation pathway?

CRP and SAP

What liver plasma proteins are involved in the lectin activation pathway?

MBL

All complement pathways lead to cleavage of C3 by what?

C3 convertase

C3 is cleaved into what?

C3b (opsonin) and C3a (anaphylatoxin)

What do C3a and C3b do?

C3a: Inflammation

C3b: coats pathogens

C3a and C5a have what effect on vascular permeability? Microbicidal activity?

INCREASE BOTH permeability (swelling) and Microbicidal activity (recruit monocyte & neutrophil)

Process of ingesting opsonin coated or receptor bound microbes

phagocytosis

Oxidative respiratory burst is mediated by what?

NADPH Oxidase

Generation of O2, and Reactive oxygen species has what effect on ingested microbes?

TOXIC

Two free radical systems produce what that is toxic?

ROS, NO, and reactive peroxynitrite

Neutrophils or Macrophages have MPO (WBC), Ocl and OH?

Neutrophil

Antigens are transported from tissue to where for recognition by T cells?

Lymphoid organs

Majority of Dendritic cells in tissues and lymphoid organs are what type?

Classical Dendritic cells

What type of DC captures and processes antigen?

Immature DC

What type of DC presents MHC antigens to T cells

Mature DC

What event turns a immature DC to mature DC? mediated by what interaction?

Interact with T cells, CD4-T cell interaction

TCR on T cells recognizes peptide antigens displayed by what?

MHC molecules on the APC

What MHC is an Alpha (a1,2,3) chain associated with a B2 microglobulin

MHC Class I

What MHC is alpha and beta chains with a groove for peptide binding

MHC Class II

What chains in MHC Class II are invariant?

a2 and B2

What type of cells only recognize peptides presented by MHC Class I

CD8 T cells. a3 binds CD8

What type of cells only recognize peptides presented by MHC Class II

CD4 T cells, B2 variant binds CD4

MHC Class II induced by what?

IFNy

MHC class I expressed on what cells?

All Nucleated cells. (all in body except RBC)

What is the benefit of CD8 T cells being activated and not on every cell?

Prevents autoimmune disease

MHC only binds peptides derived from what?

Protein antigens

If a protein is extracellular, how must it be processed so MHC Class II can recognize it?

processed in endosome / lysosome

Cytosolic proteins are processed by a proteasome and ER to be displayed on what?

MHC Class I to CD8 cells

CD4 and CD8 which intracellular / extracellular

• CD4: Extra cellular

• CD8: Intracellular

  (“Intra = I = MHC class I”)

CD 4 or 8 can cause periodontitis by destroying periodontium

CD4