Lecture 3 Tissues and Receptors Innate Immunity

What are the two primary lymphoid organs

bone marrow and thymus

What immune cells are made in the bone marrow

B cells

What immune cells are made in the thymus

T cells

Secondary Lymphoid tissues

Lymph nodes, spleen, MALT

What is the main purpose of all secondary lymphoid tissues

They expose lymphocytes to ags

What type of tissue are peyers patches found on

GALT

What are the three main sections of the thymus

Lobule, medulla and cortex

Traits of the thymic cortex

Dark staining, T cell maturation, + T cell selection

Traits of the thymic medulla

Lighter stain, T cell maturation, - T cell selection

A thymic lobule is made up of..

Thymic cortex and medulla

What cells express MHC 2

Only APCs

What cells express MHC 1

All cells except for RBCs

In the first step of T cell maturation what receptors are present (what are these t cells called?)

double negative thymocytes

Only CD3, CD4 and CD8 not present

T/F T cells begin in the thymus as double positive thymocytes

False

They start as double negatives

How do double negative thymocytes become double positive

The cells rearrange their T-cell receptor genes, starting with the beta chain.

What is positive selection

The first step of the T cell selection process

Takes place in cortex

Testing if the CD4 and CD8 receptors can recognize MHC1 and 2 (with self protein). If the T cell is unable to bind to these MHCs they will be killed via apoptosis

Why is it beneficial for defective T cells to be killed via apoptosis? Why not have macrophages or neutrophils take care of them?

To avoid inflammation - very bad

What is negative selection

The second step of the T cell selection process

Takes place in the medulla

Testing to see if the T cell will bind to MHC and self protein with too strong of an affinity. If the affinity is too high these cells will be killed via apoptosis

Why is a high binding affinity bad in negative selection

Because those T cells would attack normal healthy cells presenting self protein. We only want our T cells to bind with strong affinity to cells presenting ag peptide.

What type of T cells are released from the thymus

Naive T cells

How are naive t cells released from the thymus

Out of the medulla

T/F as you age your thymus becomes larger and more efficent

False - it shrinks and produces less naive t cells

How do lymphocytes enter lymph nodes

Through the blood stream - not lymphatic vessle

How do DCs enter lymph nodes

Via afferent lymphatic vesicles

Where do B cells reside in lymph nodes

Inside the cortex, specifically in lymphoid follicles

Where do T cells reside in lymph nodes

Inside the paracortex

What two structures make up the thymic medulla

Medullary sinuses and cords

Medullary sinuses

Lymphatic channels in medulla -

Medullary cords

lymphatic tissue in between channels, containing macrophages, DCs

Two parts of spleen

Red and white pulp

Red pulp function

In spleen - for RBC clearance

White pulp function

In spleen - Containing periarteriolar lymphoid sheaths (PALS) and lymph nodules

periarteriolar lymphoid sheaths (PALS)

Rich in T cells - located in the white pulp in spleen

What is special about the circulatory system of the spleen

It lacks HEV meaning it is an open circulatory system

sinusoid

Red blood cells will be forced to pass through sinusoid tissues to re enter the blood stream. Healthy and flexible RBCs will be able to pass back into the blood stream, old ones will not and will get removed

What is a peyers patch

Lymphatic tissue (GALT) found on small intestine. They contain B and T cells, ags enter through specialized "M" cells.

PAMPS

Pathogen associated molecular patterns - located on ags - recognized by innate immune cells

How are innate cells able to differentiate between self and ag cells while not having any specificity for one particular ag

They are able to recognize Pathogen associated molecular patterns (PAMPs) on ags with their Pattern recognition receptors (PRRs).

What are some examples of structures that can be PAMPs

Microbial nucleic acids

Microbial carbohydrates

Lipopolysaccharide

A toll like receptor is a type of ...

Pattern recognition receptors (PRRs).

What are TLRs transcription factors

NF-kBs and IRFs

What is the main purpose of NF-kBs

Acute inflammation

Adaptive immunity stimulation

What is the main prupose of IRFs

Antiviral state

IRFs are also known as...

Type 1 interferons

What cells secrete type 1 interferons vs what cells have type 1 interferon receptors

Virally infected cells produce type 1 interferon, however all cells have type 1 interferon receptors

What is the antiviral state? How does it occur

When a healthy cell has type 1 interferon bind to its type 1 interferon receptors it will enter an antiviral state. The antiviral state is characterized by Inhibition of viral gene expression and virus assembly, Increased viral RNA degradation, and Inhibition of viral protein translation

What are interferon stimulated genes? What do they do

They are genes that are expressed in response to type 1 interferon binding to it's receptor. They put the cell in an antiviral state

What are the three main characteristics of the anti viral state

Inhibition of viral gene expression and virus assembly, Increased viral RNA degradation, and Inhibition of viral protein translation

Plasmacytoid Dendritic Cell characteristics

•low numbers in blood and lymphoid tissues

•migrate into viral-infected tissue

•have extensive ER devoted to making IFN-a/b

master regulator of inflammation

IL-1b

Which cell makes IL-1b

macrophages

What is the inactive form of IL-1b called? where is it stored

pro-IL-1b in the cytoplasm in macrophages

Functions of IL-1b

Stimulates other macrophages to secrete a variety of other inflammatory cytokines,

Enhances monocyte differentiation

Induces fever

Induces the acute phase response

How is the production of IL-1b regulated

Signal 1 (PRR + PAMP) is needed to make NF-kB which makes proIL-1b.

Signal 2 is needed to produce an inflammasome

The inflmmasome will cleave proIL-1b into IL-1b

What do resident macrophages release to help respond to infection

They release inflammatory cytokines

What is the goal of the inflammatory cytokines released by macrophages

To recruit effector cells (Neutrophils, monocytes, NKs)

and plasma proteins (abs)

What is the earliest intracellular vesicle that contains material opsonized by macrophages

phagosome

What is needed to fuse with a phagosome to make a phagolysosome

lysosome

What is the vesicle called when lysosome and phagosome combine

phagolysosome