3.1 Immune system overview

PRIMARY LYMPHOID ORGANS

development and maturation of lymphocytes

SECONDARY LYMPOID ORGANS

trap antigens, allow lymphocytes to interact and react, promotes activation and differentiation of lymphocytes

Primary and secondary lymphoid organs are connected by

Blood and lymphatic systems join two organ types

Blood and lymphatic systems

Allow transfer of lymphocytes from point of origin to point of action

HEMATOPOIESIS

Process of blood cell formation in the bone marrow

HEMATOPOIESIS involves

differentiation of HEMATOPOIETIC STEM CELLS (HSC)

Differentiation of HEMATOPOIETIC STEM CELLS (HSC)

Self renewing and maintain entire blood cell population by cell division

When does hemotopoeisis begin

in embryonic yolk sac for mammals

Initially HSCs differentiate exclusively into

RBCs

IN the 3rd month of development

HSCs migrate to  spleen and liver

In the 7th month of development

primarily develop in bone marrow

HEMATOPOIETIC STEM CELLS (HSC) first differentiate into

SHORT TERM HSC (ST-HSC

The SHORT TERM HSC (ST-HSC) differentiate into

differentiates MULTIPOTENT PROGENITOR (MPP),

2 possible lineages of multipotent progenitor cells

are myeloid and lymphoid.

 LYMPHOID PROGENITOR CELL

gives rise to T cells, B cells, dendritic cells, and natural killer cells (NK or Innate Lympoid Cell (ILC))

 MYELOID PROGENITOR CELL

gives rise to macrophages, neutrophils, eosinophils, basophils, mast cells, RBC, and platelets, and dendritic cells

Committal step of hematopoiesis

when MPP choose myeloid or lymphoid lineage

Both myeloid and lymphoid progenitors no longer have what

No longer have capacity for self renewal

All blood cells begin devleopment in

the bone marrow, then may hone somewhere else for final maturation

How do stem ells know what to develop into

CYTOKINES

Cytokines

small signaling glycopolypeptide molecules to tell HSCs what to do

Cytokines bind to

receptors on the surface of HSC, activate transcription factors, mediate alterations in patterns of gene expression

Which 2 cell types regulation HSC differentiation

cytokines and stromal cells

STROMAL CELLS

present in bone marrow and thymus which regulation differentiation and development

Stromal cells generate

HEMATOPOIETIC-INDUCING MICROENVIRONMENT

HEMATOPOIETIC-INDUCING MICROENVIRONMENT

matrix with bound or diffusible growth factors (cytokines)

How are cells of IS identified

•Historically identified by morphological differences observed by microscopy, staining methodologies assisted identification

Hematoxylin

•stains basophil nucleic acids blue

Eosin

stains granules in eosinophils red

Identification of cell specific surface markers

led to rapid advancements in IC identifications

fluorescently labeled antibodies

can stain cells types

flow cytometry

can rapidly identify all cells in a given sample

Cells Derived from Myeloid Progenitor Cell

•Encompasses majority of cells involved in innate immune response, significant role in inflammation

MPC cells

•First cells to respond to immunological challenge, active within minutes to hours post challenge

Granulocytic Cells

named due to presence of granules in cytosol, all have multilobed nucleus

4 types of granulocytic cells

neutrophils,
eosinophils,
basophils,
mast cells,

NEUTROPHILS

•multi-lobed nucleus, granules stain with both acid and basic dyes, also called polymorphic neutrophils (number of lobes in nucleus varies)

EOSINOPHILS

bi-lobed nucleus, granules stain red with eosin

BASOPHILS

lobed nucleus, granules stain blue with methylene blue

Professional phagocyte

neutrophils

Which granulocytic cells are phagocytic

neutrophils and eosinophils.

Which granulocytic cells are NOT phagocytic

basophils and mast cells

Major circulating white blood cell (WBC)

neutrophils (50-70%)

infections usually stimulate increased production of WBCs like neutrophils, process called

LEUKOCYTOSIS

EXTRAVASATION of neutrophils

Circulating neutrophils enter tissues within 7-10 hrs of being released into circulation

Factors produced by neutrophils during inflammation

CHEMOTACTIC FACTORS

Once neutrophils arrive at infection, they function is similar to

MO, phagocytic cells

Neutrophils destroy bacteria with

lytic enzymes and other antimicrobial substance

Difference between neutrophils and MOs

lytic enzymes stores in granules with neutrophils (not lysozyme)

Granule contents of neutrophils

contents include elastase, collagenase, defensin, lysozyme, a1-antitrypsin, and histamine

Congtents of neutrophil granules fuse with

phagosome, promote destruction of bacteria

Main cellular component of pus

neutrophils

Eosinophils

also phagocytic, also migrate into tissues, granules stain bright pink with hematoxylin and eosin protocols (H&E)

Eosinophil granules

contain cationic proteins (produces ROS for oxidative burst), ribonucleases (antiviral activity), cytokines (promote T_H2 response), and chemokines to attract other effector cells

Singificant role of eosinophils

in thwarting parasitic infections

How do eosinophils bind to organisms

through Abs to release granule contents on surface

Eosinophils have role in

hypersensitivity development

Basophils

Non-phagocytic granulocytes, granules stain blue with H&E protocols

Basophil granules

contain T_H2 specific cytokines, leukotrienes, and histamine

T_H2

a subtype of T helper cells that produce cytokines promoting the activation of eosinophils and basophils.

Basophils work with

mast cells and PMNs to contribute to inflammation

Basophils also have large role in

parasitic infections

Basophils attach to organisms via

antibodies then release granules to surface of pathogen

Which 2 immune cells are believed to contribute to hypersensitivites

basophils eosinophils

Mast Cells

Formed in bone marrow by hematopoiesis, released into circulation as undifferentiated cells

When do mast cells differentiate

when they leave circulation and enter tissues

Where are mast cells found

in epithelial cells, connective tissues of organs, all mucosal linings of respiratory, genitourinary, and digestive tracts

MAst cell granules

Heavily granulated, granules contain histamine, T_H2 specific cytokines, and leukotrienes

MAst cells heavily involved in

allergy development

the mononuclcear phagocytic system involves which cell

MONOCYTES
macrophages

INFLAMMATORY MONOCYTE

enters tissue rapidly in response to infection

 PATROLLING MONOCYTE

•move slowly along blood vessels, detects if repair is needed, serve as reservoir for tissue dependent monocytes if no infection present, may play role in down regulation of immune response

MACROPHAGES (MF)

monocytes may differentiate into MF when they exit the blood stream and enter into tissues

When mononuclear cells differentiate into macrophages the cell becomes

much larger (5-10 fold), increase in number and complexity of organelles, more hydrolytic enzymes, and production of cytokines

IL-1

pyogen that signal pituitary gland to vasocontrict in extremities and will cause shivering for FEVER

Cytokines produced by macrophage

include interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)

Which cells are the professional phagocytes

macrophages and neutrophils

Professional antigen presenting cells

include dendritic cells, macrophages, and B cells

Most efficient pAPC

dendritic cell bc it constantly expressed MHC class II very highly

CD80

is a co-stimulatory molecule expressed on antigen presenting cells that enhances T cell activation.

Myeloid derived pAPC

macrophage and sometimes dendritic cells

Lymphoid derived pAPC

always B cells and sometimes dendritic cells

Least efficient pAPC

is typically a macrophage that presents antigens with lower efficacy compared to other professional antigen presenting cells.

Criteria of pAPCs

•Secretion of proteins that attract and activate other immune effector cells

•

•Internalize pathogens, break down, present antigens to T_H cells in MHC Class II molecules

•

•Express costimulatory molecules to activate T_H cells (CD80/86)

•

ERYTHROCYTES

red blood cells, primary role in gas exchange, carry hemoglobin

Why do erythrocytes have no nucleus

expel nucleus during development in bone marrow

Avian, reptile, fish, and amphibian species RBC

retain nucleus

Damage to RBC releases effectors that

that impact innate immunity

RBCs express which receptors

complement receptors that allow participation in immune complex clearance

RBCs produce

reactive oxygen species (NO), contributes to oxidative burst

MEGAKARYOCYTES

large myeloid cells, give rise to thousands of platelets

Megakaryocyte nucleus

lost during development

Megakaryocyte have major function in

in cessation of hemorrhaging and containing pathogen in clot

Adaptive immune sysem

involves specific responses mediated by lymphocytes

Lymphocyte percentage in body

Comprise 20% to 40%

Lymphocyte percentage in lymph

99%

 Three broad classes of lymphocytes

T cells, B cells, Innate Lymphoid Cells (NK cells)

Surface markers of NK cells (innate lymphoid cells)

Null cells that express no distinguishing markers

B lymphocyte develop in

bone marrow

How to distinguish b cells from other lymphocytes

has Abs on surface and B cell specific CD markers