bt224 lec2 cells organs
TRANSCRIPT
Cell and organs of immune system
Chapter 2 Kuby
Key concepts from last lecture• Pathogen• Antigen• Antibody?• B cells (Plasma cells)• T cells (Th&Tc)• Innate immunity• Adaptive immunity• Passive immunity• Active immunity • History
• Overview of immune response• Cell mediated immunity• Humoral immunity• Phases of immune response• Adaptive immunity has memory• Primary and secondary
response• What happens on immunization
1. What are the main cell types of the immune response?
2. Where are they, where do they come from, what do they look like, what are their major functions?
3. How does this package fit together to give you a circulating immune system?
4. Describe the overall physical organization of the immune system and the different roles played by primary and secondary lymphoid organs.
Today’s Objectives
Blood composition– 55% Plasma (fluid matrix of water, salts, hormones,
proteins, Ab, metabolites, etc.)– 45% Cellular elements:
Red Blood Cells (RBCs): 5-6 million RBCs/ml of blood. Contain hemoglobin which transport oxygen and CO2.
White Blood Cells (WBCs also called leukocytes): 5,000-10,000 WBCs/ml of blood. Play an essential role in immunity and defense. Include:
Lymphocytes: T cells, B cells and NK cells Macrophages (phagocytes) Granulocytes: Neutrophils, basophils, and eosinophils.
Platelets/Thrombocytes: Cellular fragments. 250,000- 400,000/ml of blood. Important in blood clotting, release growth factors/cell differentiation/proliferation/blood cells/blood vessel/healing properties.
Name two types of fluid that circulate in our body?
1. Blood2. Lymph:
• Tissue fluid/interstitial fluid/intercellular fluid• Colorless, • composition similar to blood serum.• Collected from tissue into lymph vessels by diffusion• Along with it are collected Antigens (pathogens/toxins)• Added to blood in the heart
BloodBlood
Serum ProteinsSerum Proteins White Blood White Blood CellsCells
(Leucocytes)(Leucocytes)
•ImmunoglobulinsImmunoglobulins•ComplementComplement•Clotting factorsClotting factors• Growth factorsGrowth factors• Many othersMany others
Phagocytic/Phagocytic/dendritic cells dendritic cells (macrophages, (macrophages, dendritic cells, dendritic cells, NK cells etc)NK cells etc)
Lymphocytes (T Lymphocytes (T cells, B cells & cells, B cells & NK cells)NK cells)
Where are they (immune components)?
Where are they?
Lymphocytes15-40%
Neutrophil
Eosinophil
Basophil
Macrophage
Hematopoiesis
• The process of– proliferation – differentiation &– maturationof blood cell
• Mostly in bone marrow from stem cells• Regulated by cytokines & growth factors
Hematopoiesis
Blood Cell (RBCs and WBCs)
Self renewing
Differentiation and Maturation
Routes for hematopoietic stem cell (HSC)
HSC HSC
Stromal cells
Non-hematopoietic cells found in bone marrowForm a meshwork for HSC growthProvide microenvironment consisting of
cellular matrix + hematopoietic growth factors (these proteins/Growth factors induce differentiation and maturation)
Thus stromal cells support HSC differentiation
and maturationWhen infection occurs: Activated T cell and macrophages produce hematopoitic
growth factors stimulate hematopoiesis
MyeloidProgenitor
LymphoidProgenitor
HSC
Development of immune cells
B cellProgenitor
T cellProgenitor
B cell
TC cell
TH cell
Dendritic cell
Natural killer(NK) cell
Dendritic cell
Macrophage
Monocyte
Neutrophil
Eosinophil
Basophil
Platelets
RBC Erythroid progenitor
Megakaryocyte
Basophil progenitor
Eosinsophil progenitor
Granulocytemonocyte progenitor
Where do they come from?
Where do they come from?
Cytokines and Growth factors
IL = Interleukins
In Vitro Hematopoiesis
Adherent layer of stromal cells
Bone marrow cells added (HSCs)
Cell culture in semisolid agar
Used for detection and identification of HGFs Eg. Cytokine called colony stimulating factors (CSFs)
• Acidic glycoproteins• Induce the formation of hematopoitic cell lines
Eg. Cytokine Erythropoietin (EPO)• Glycoprotein involved in terminal development of RBCs
Growth of bone marrow cell colonies
Cells of the Immune System
Immune System
Myeloid Cells
Lymphoid Cells
Granulocytic Monocytic T cells B cells
NeutrophilsBasophils
Eosinophils
Macrophages
Dendritic cells
Helper cells
Cytotoxic cellsPlasma cells
NK cells
Bone marrow lymph
Lymphocytes
• Group of WBC (20 - 40%)• 99% cells in lymph• Three classes of lymphocytes• Morphologically similar • Each has distinct function• Circulate in blood and lymph• Migrate to tissue spaces and lymphoid organs
Lymphocytes ClassesClass Function
B Lymphocytes Antibody productionT lymphocytes a) Helper T cell
b) Cytolytic T cell
-Stimuli for B-cell growth and activation- Release cytokines for macrophage activation- Phagocytic, Lysis of pathogen infected cells
Natural Killer cells - Lysis of pathogen infected cells, virus infected cells, tumor cells etc
Lymphocyte subsetsCLP
CommonLymphoidProgenitor
NaiveT cell
TC cellCYTOTOXIC T
LYMPHOCYTESKill pathogeninfected cells
TH cellT HELPER CELLSActivate B cellsand macrophagesSecrete cytokines
NaiveB cell
B cellPLASMA CELLS
Produce antibodies
Antigen activation Antigen activation
TC cellCYTOTOXIC T
LYMPHOCYTESTH cell
T HELPER CELLSB cell
PLASMA CELLS
Adaptive immunityNaive Lymphocyte
Antigen activation
Effector cells Memory cells• Short life (days to weeks)• Eliminate antigen
• Long lived years• Give life long immunity against a particular antigen
Name and Maturation
B cell mature in bone marrow Called B cell (not true)
B cells got their name because B cell differentiation was first demonstrated in the bursa of Fabricius of chicken embryos.
T cell mature in thymus therefore called T cell
B cell• Membrane bound Immunoglobulins (Ig)/Antibodies (Ab) on surface• These are receptors for Ag: recognize free Ag• ~1.5 x 105 Ab on B-cell surface • Other molecules on B-cell surface are
CD40 (interaction with TH cell), MHCII (APC), (Major histocompatibility complex)CR1 and CR2 (receptor for complement products)
• B cell Ab binds to Ag and also interacts with TH/macrophages• Activation of naïve B-cell• B cell divides and differentiate• Plasma cells + Memory cells• Plasma cells secrete Ab and die in 1-2 weeks
T cell• Membrane bound T cell receptor (TCR) on surface• TCR receptor for Ag• Does not recognize free Ag• Recognizes Ag bound to MHC molecules on self-cells• TH cells express CD4 = CD4+T-cell • TC cells express CD8 = CD8+T-cell• CD4+T-cell recognize Ag bound to MHC II• CD8+T-cell recognize Ag bound to MHC I• CD4+T-cell: CD8+T-cell/TH:TC = 2:1
TH cellsAg on MHCIIActivatedEffector cells Secrete cytokinesCytokines activate Bcell, Tcell and macrophages
Tc cellsAg on MHCIInteraction + Cytokines =ActivatedEffector cells= cytotoxic Tcell (CTL)Recognize and eliminate infected cells
• The immune system must discriminate between self and non-self. • When self/non-self discrimination fails, the immune system destroys cells and tissues of the body and as a result causes autoimmune diseases (AID). • Autoimmunity against hematopoietic stem cell causes Aplastic anemia• Bone marrow transplant /Stem cell transplant
• Regulatory T cells actively suppress activation of the immune system and prevent pathological self-reactivity, i.e. autoimmune disease.
• The critical role regulatory T cells play within the immune system is evidenced by the severe autoimmune syndrome that results from a genetic deficiency in regulatory T cells.
Regulatory T cells (Treg)
Also known suppressor T cells (Ts)
CD4+CD25+Foxp3+ regulatory T cells, or "Tregs"
1. Prevention of autoimmune diseases by establishing and maintaining immunologic self-tolerance .
2. Suppression of allergy and asthma.3. Induction of tolerance against dietary antigens, i.e. oral
tolerance.4. Induction of maternal tolerance to the fetus .
Functions of T reg cells
Still research is ongoing?
A third kind of lymphocytes
Release lytic granules that kill Virus infected cells
+ Tumor cells
•Granules contain porins and granzyme (serine) proteases•Cause lysis or apoptosis of infected/tumor cells
Natural Killer cells
Tumor cells and virus infected cells display Ags on surface Antibodies (produced against these Ags by immune system) bind to theses Ags on the surface of infected cells CD16 receptor on NK cells recognizes antibodies (Fc) Destroys the target cell Process is called Antibody dependent cell mediated cytotoxicity (ADCC)
NK cells also recognize abnormalities on infected or tumor cells• Reduction in display of MHCI on surface• Unusual profile of surface Ags
NK cells recognize potential target cells by the following ways
White Blood CellsWhite Blood Cells
Other WBCsOther WBCsLymphocytesLymphocytes
The cells of the immune system
PhagocyticPhagocyticPhagocytic Phagocytic APCAPC SecretorySecretoryB, T, NKB, T, NK
Dendritic Dendritic MacrophagesMacrophages
NeutrophilNeutrophil EosinophilEosinophil
Basophil Basophil Mast cellMast cell
Most abundant WBCsMigrate to infection siteskill the invader
Big in sizeFix or movingProfessional APCSecrete hydrolytic Enz.Innate immunity
Professional APCPresent to TH cells
Phago = “eating”Cyte = “cell”
Phagocytic
Read from Kuby
Non-phagocyticAllergic responsesHeparin (stop blood coagulation)+Histmine (allergic reaction)
PhagocyticMotileDamage parasite memb
Non-phagocyticMC Precursor in Bone marrowMigrate blood tissueDifferentiate in tissueRole in allergic reactions
White Blood CellsWhite Blood Cells
Other WBCsOther WBCsLymphocytesLymphocytes
The cells of the immune system
PhagocyticPhagocyticPhagocytic Phagocytic APCAPC SecretorySecretoryB, T, NKB, T, NK
Dendritic Dendritic MacrophagesMacrophages
NeutrophilNeutrophil EosinophilEosinophil
Basophil Basophil Mast cellMast cell
Organs of the immune system
Lymphatic system: It is a network of lymph vessels
that collects the fluid and lymphocytes that escape into
the tissues from blood capillaries and returns these
back to the circulating system.
Lymph organs + lymph
Based on Function:
MALT: Mucosal associated lymphoid tissue: (less organized compared to lymph nodes, includes: small Intestine – Peyer’s Patches, tonsil, appendix,)
• Far fewer lymphocytes• Assumes an immune role only when challenged with antigens• Generally result in inflammation. • It achieves this by importing the lymphocytes from blood and lymph
The tertiary lymphoid tissue
CALT (Cutaneous Associated Lymphoid Tissues)
Thymus:
• Site for Tcell dev and maturation• Flat• Bilobed organ• Situated above the heart• Each lobe has two compartments
Cortex: outerMedulla: inner
• Cortex: densely packed with immature T cells called thymocytes• Medulla: few thymocytes
Thymus
•Cortex+Medulla has stromal cell network • Stromal cell network help in differentiation and maturation of T cells• Composed of epithelial cells, dendritic and macrophages• Thymic epithelial cells called Nurse cells
Nurse cells form membrane extensions surround many thymocytes form multicellular complexes
Selection process in thymus• Only 5% of T cells recognize Ag on MHC complex of APC• Rest 95% die (these cannot recognize Ag/or recognize self Ag)
Thymus does not work, No T cells, no cell mediated immunity, infectious diseases inc.
Thymus
With age cell content of thymus decreases Size decreases Fat content increases Decline in thymic function Leads to decline in immune function
Age and Thymus
Birds (Bursa), primates+ rodents (primary lymphiod organ), cattle+sheep (spleen) different site of B cell maturation
Largest lymphatic vessel in the body.
Collects most of the lymph in the body Empties it into left subclavian vein
•Blood flowing with pressure•Plasma seeps through the walls of capillaries• This fluid is called interstitial fluid• Most of it returns back to blood• Rest of this interstitial fluid is called lymph• Lymph collected by lymphatic capillaries network• Flows to large lymph vessels• Largest lymph vessel called Thoracic duct empties it in heart vein • Flow in the lymph achieved by muscles in the body
•Ag is picked by lymph syst and carries to secondary lymphoid organs: lymph nodes and traped there• Lymph system also transports immune components to various sites
• Bean shaped structure• divided into three regions• Outer most: Cortex
Contains lymphocytes
( B-cells mostly), Mac + dendritic cells = Primary follicle (PF) Ag challange PFs enlarges to Secondary follicles (SFs) Each SF has a germinal centre (GC) GC where B cell proliferate
• ParacortexContains ( T-cells mostly + dendritic cells APC:MHCII) to Th cells
• MedullaFew cells mostly Plasma cells secreting Ab
•Afferent vessel carries lymph containing pathogens to lymph nodes into Cortex, paracortex medulla. •Macrophages/dendritic cells of lymph attack and present Ag by MHC molecules. •Activate B cells and T cells
•Efferent vessel carries lymph away from the lymph nodes •Lymph leaving the lymph node is rich in Abs secreted by Plasma cells in medulla and other activaed lyphocytes
Spleen • Mounts immune response in blood• Large ovoid secondary lymphoid organ
• traps blood born Ag• not connected with lymphatic vessles• Ag supplied by splenic artery• It has a capsule• Projection from capsule goes to the interior of spleen• compartments are formed• Two compartments
•Red pulp (old RBCs removed here) •White pulp
•Red pulp: Mac+RBCs• White pulp: mostly T cells, DC and few B cells, forms PALS• Marginal zone Primary follicles + GC
Self-reading
MALT intestineMucosal membrane of gastrointestinal tract (stomach+intestine)
•Loose clusters:B cells,Plasma cellsTh cellsMacrophages
•Ab are secreted in the lumen
M-cellsEpithelial cells specialized for Ag transport
M cells
M cells lie aboveInductive site:
Self-reading
• Innate immunity found in invert. + plants
• Addaptive immunity mediated by Ab+Tcells found in vertebrates• All lyphoid tissues are not present in all vert.• With evolution new lymphid organs were added• Retains the old ones• Eg B and T cells not present in jaw less fish (Lamprey = GALT gut associated) • Shark is has jaws and it also has B and T cells
Evolution and lymphoid cells and organs
Break
Clotting factors in serum