Cells and Organs 1

Components of the Immune System

Learn on your own:Spleen structure and functionMast cells and NK cells

Self-Test Questions:A1: all C1: allA2: 1 - 4 C2: noneA3: 1 - 3, 5 C3: allA4: 1, 2, 4 D1: bothA5: all D2: 2 & 3A6: both D3: noneB1: noneB2: 1, 2, 4, 5

Cells and Organs 2

“Hematopoiesis” = Formation of blood cells

Stem cells self-renewing

multipotent (less differentiated)

progenitor cells (more differentiated

vs blast cells vs mature (naïve) cells

vs effector cells

Site of hematopoiesischanges during development

Cells and Organs 3

Why is apoptosis (programmed cell death) also Important?

-- a normal and essential process

Apoptosis vs Necrosis (cell lysis)

Occurs during B- & T-cell development

Also an important killing mechanism

Prevents triggering of inflammation Apoptosis

Cells and Organs 4

How can different cells be identified and separated?

Flow cytometry and “fluorescence activated cell sorting” (FACS) can be used to count, sort and separate cell types

See appendix 5

Cells possess different

CD antigens

With ImmunofluorescenceCD antigens can be stained

with antibodies tagged with fluorescent molecules

Cells and Organs 5

What are the 2 major categories of immune cells?1- Lymphoid cells

-- B- & T- cells-- NK cells

2- Myeloid cells-- Granulocytes-- Monocytes, macrophages, DC

Lymphoid cells

B-cells -- naïve carry B-cell receptor (membrane Ab)activated plasma cells secrete Ab

T-cells -- Carry T-cell receptor (TCR)Tc cells are MHC-I restricted

activated become CTLs

TH cells are MHC-II restrictedactivated secrete cytokines (TH1 vs TH2)

Cells and Organs 6

Myeloid cells

A. Granulocytes-- degranulation

Neutrophils-- multilobed-- rapid response

Eosinophils-- bilobed-- eukaryotic parasites

Basophils -- densely granular-- eukaryotic parasites-- type I hypersensitivities

Neutrophil chase

Cells and Organs 7

Granulocyte abnormalities can underlie disorders

Eosinophilia-- too many eosinophils

CausesAllergiesParasitic infections

Neutropenia -- too few neutrophils

CausesLeukemiaCongenitalDrug-induced

Cells and Organs 8

B. Other myeloid cells

Macrophages

Develop from monocytes (in blood)-- within tissues

Go by various names; e.g.:-- Kumpfer cells, Langerhans cells, microglial cells, etc-- tissue type specific

How do macrophages kill pathogens?-- external & internal mechanisms-- enzymes and reactive molecules

Act as “Professional-APCs” -- only to memory T-cells

Cells and Organs 9

Dendritic Cells

Functions: antigen…CaptureProcessingPresentation

Antigen + T-cell interaction… “licensed DC”

Only licensed DC can activate naïve T-cells

Take on specialized functions-- determined by cytokines-- generate different types of T-cells

Cells and Organs 10

What are the organs of the immune system?

Primary lymphoid organs(naïve immune cell development)

Bone marrow

Thymus

Secondary lymphoid organs(immune cell activation)

The “Nude Mouse”

Cells and Organs 11

Structure and function of 2O lymphoid tissues

“Follicle”-- basic organizational unit-- may be within specialized organ

2O tissues carry outsurveillance of systems

-- respiratory : tonsils & MALT-- digestive : GALT-- circulatory : spleen-- lymphatic : lymph nodes-- skin : SALT

What happens in these tissuesAG presentationcell : cell interactionscell activation

Cells and Organs 12

Leukocyte Rolling Leukocyte Homing

Immune Surveillance

Circulation of cells and Interstitial fluid

-- antigens / pathogens-- immune cells

Cell extravasation-- Chemokines-- post-venous capillaries-- receptors-- adhesion proteins

Cells and Organs 13

Structure and function of lymph nodes

Lymphatic vesselsafferentefferent

CortexFollicles & Germinal centers1O vs 2O

B-cell activation

ParacortexAG-presentation & T-Cell activation

MedullaPlasma cell accumulation

Cells and Organs 14

Mucosal-Associated Lymphoid Tissue (MALT)

Widely distributed-- More about MALT in Chapter 12

e.g., Peyer’s patches (GALT)-- Protects Intestinal track-- M-cells

Cells and Organs 15

Recent findings show effect of HIV on GALT

Destruction of T-cells in gut

Leads to destruction of GALTIleum of:

Uninfectected person HIV infected person

Image by Daniel Douek from Science (2005) 307: 1395

GALT