immune cells 3rd lecture
TRANSCRIPT
Immunology Lecture 3rd
Cells of Immune System
BY
Dr. Humera Kausar22thSep 2014
Cells of the Immune System
Cells of the Immune System
Leucocytes
Cells of the innate immune system:
• Phagocytes– Monocytes/macrophages– Neutrophils/PMNs/
• NK cells
• Basophils and mast cells
• Eosinophils
Phagocytic Cells Mononuclear PROMONOCYTES MONOCYTES MACROPHAGES (Fixed or Free)
Brain ---------Microglial cells
Lungs ------------Alveolar cells
Liver ----------------- Kupffer cells
Connective tisues-----Histocytes
Kidney ---------------------Mesangial cells
Bones ------------------------ Osteoclasts
Skin ------------------------Langerhans cells
Macrophages
• Characteristic nucleus• lysosomes• CD14 membrane
marker proteinMacrophage
Macrophages
Activated by variety of stimuli in the course of an immune response.
Activated macrophages are more effective then resting ones in eliminating potential pathogen.
Activated macrophages secreted various cytotoxic proteins that help to eliminate broad range of targets including
o virus infected cellso Tumor cellso Intracellular bacteria
Also act as antigen presenting cells
Macrophage as an antigen presenting cells
Granulocytes
Neutrophils
Polymorphonuclear (PMN) leukocyte.
Has multilobed nucleus and granulated cytoplasm.
Stains with both acidic and basic dyes.
Constitute 50% to 70% of the circulating leukocytes.
After release in to the blood, circulates 7 –10 hours before migrating in to the tissues.
Life span is few days. (3 days)
Neutrophils (PMNs)
• CD66 membrane marker protein
Geimsa stains
Neutrophil
Neutrophils
First cells to arrive at the site of inflammation.
In response to many types of infections the bone marrow releases increased number of circulating neutrophils called leukocytosis.
Act as phagocytic cells.
GRANULOCYTES
Neutrophils GRANULOCYTES
Lytic enzymes and bactericidal substances in neutrophils are contained within primary and secondary granules.
Larger denser primary granules are a type of lysosome containing
peroxidase, lysozyme, various hydrolytic enzymes
Smaller secondary granules contains,
collagenases, lactoferrin, lysozyme
Both primary and secondary granules fuse with phagosomes.
Neutrophil
Eosinophils
Stain with acid dye eosin red.
Has bilobed nucleus and granulated cytoplasm.
Constitute 1% to 3% of WBC population.
Like neutrophils, motile phagocytic cells that can migrate from blood into tissues.
Phagocytic role of eosinophils are less significant than that of neutrophils.
Play a role in the defense against parasitic organisms by secreting contents of eosinophilic granules, which damage the parasite membrane.
GRANULOCYTES
Eosinophil
Basophils
Basophil has a lobed nucleus and heavily granulated cytoplasm.
Stains with basic dye methylene blue.
Non phagosytic granulocyte.
Constitute <1% of circulating WBC.
Function by releasing pharmacological active substances from cytoplasmic granules.
Play a major role in certain allergic responses.
GRANULOCYTES
Basophil
Mast Cells
By hematopoiesis, released into the blood as undifferentiated cells.
Do not differentiate until they leave the blood and enter the tissues, including
skin, connecting tissue of various organs, mucosal epithelial tissues of respiratory, genitourinary & digestive tracts
Like circulating basophils, mast cells have large numbers of cytoplasmic granules that contains histamines and other pharmacological active substances.
Play an important role in the development of allergies.
MEDIATORS RELEASEDProstaglandin D2 Platelet Activating Factor TryptaseHeparin Histamin IL-4, IL-5, IL-6, IL-8 TNFɑ
CAUSINGVasodilation, increased vasopermeability, contraction of smooth muscles, bronchoconstriction, increased eosinophil, neutrophil & monocyte chemotaxis, anticoagulation, increased fibroblast proliferation, platelet activation
Dendritic Cells
Activation of T cells and initiate adaptive immunity
Found mainly in lymphoid tissue
Function as antigen presenting cells (APC)
Most potent stimulator of T-cell response
Dendritic Cells
Dendritic Cells
DC covered with long membranous extensions that resemble the dendrites of nerve cells.
Display class I & class II MHC.
B and T lymphocytes are the mediators of immunity, but their function is under the control of dendritic cells.
Dendritic cells in the periphery capture and process antigens.
Dendritic Cells
Express lymphocyte co-stimulatory molecules, (B7, CD40)
Migrate to lymphoid organs and secrete cytokines to initiate immune responses.
They not only activate lymphocytes, they also tolerize T cells to antigens that are innate to the body (self-antigens), thereby minimizing autoimmune reactions.
Cells of the immune system: APC
• Cells that link the innate and adaptive arms– Antigen presenting cells (APCs)
• Heterogenous population with role in innate immunity and activation of Th cells
• Rich in MHC class II molecules
– Examples• Dendritic cells• Macrophages• B cells• Others (Mast cells)
Cells of Adaptive Immune System
T cells and B cells
Cells of the Adaptive Immune System:• Lymphocytes (Lymphoid Cells)
– B cells• Plasma cells (Ab producing)• Memory cells
– T cells• Cytotoxic (CTL)• Helper (Th)
– Th1
– Th2
– Null cells (NK cells)
Lymphoid Cells
Contributes 20-40% of body’s WBCs,
Naïve or unprimed cells are small, motile, non-phagocytic cells.
Can not be distinguished morphologically.
Resting cells are in G0 phase of cell cycle.
Small lymphocytes are 6 um in diameter.
Cytoplasm barely covers the rim around nucleus.
Lymphoid Cells
Have,
o densely packed chromatin
o few mitochondria
o poorly developed endoplasmic reticulum
o Golgi apparatus
Life span of effector cell is few days to few weeks.
B-Lymphocytes
Derived its name from its site of maturation in the Bursa of fabricius in birds and Bone marrow in humans
•Plasma cells (Ab producing)
•Memory cells
B-CELL RRECEPTORS
Membrane bond Ig molecules i.e.,1.5 x 105 molecules/cell
CD 45 (Marker B220)MHC II(Antigen Presenting
receptor)CD35 (Complement receptor)CD21 (Complement receptor)CD32 (Fcɤ RII)
T-CELL RRECEPTORS
TCRThy 1 (1st receptor remains throughout life span of the cell)CD4 (T- helper cell)CD8 (T- cytotoxic cell)
Ratio of Th : Tc = 2:1
T- helper cell vs T cytotoxic cell)
Specificity of adaptive immune response
• Resides with Ag Receptor on T and B cells
• TCR and BCR – both specific for only ONE antigenic determinant
• TCR is monovalent• BCR is divalent
T cellTCR Ag
B cellBCR
Ag
Ag
Cytotoxic T cells (Tc) and Class I MHC proteins
The cell-cell interaction betweenthe infected cell and the Tccell is mediated by theMHC/antigen complex and TCR
The Tc cell produces cytotoxic proteinsperforins—produce holes or pores in thetarget cell and granzymes enter thevirus infected cell causing apoptosis orprogrammed cell death
The cytotoxic proteins only affect thosecells to which the Tc cell has specificallyinteracted
T helper cells and (TH) Class II MHC proteins
Specialized TH cell involved inthe inflammatory response
Cell-cell interaction mediatedby the TCR and the class IIMHC-antigen complex activatesThe TH cell which produces
cytokinesTNF-alpha (tumor necrosis factor)IFN-gamma (interferon)GM-CSF (granulocyte-monocytecolony stimulating factor)
These cytokines further stimulate macrophages to increase phagocyticactivity and to in turn produce cytokinesthat promote inflammation
NATURAL-KILLER CELLS
Fails to express membrane molecules that distinguished B and T cells.
Fails to express antigen binding receptors.
Constitute 5% - 10% of lymphocytes in human peripheral blood.
NK cells have ability to recognize tumor or virus infected cells.
NK cells express membrane receptor CD16 for a specific region of antibody molecule (ADCC).
NATURAL-KILLER CELLS
Human red blood cells (red), activated platelets (purple) and white blood cells - monocyte (green) and T lymphocyte (orange).
Colorized-SEM (scanning electron micrograph)
Magnification:-1200x--(Based on an image size of 1 inch in the narrow dimension)
Cells of the Immune System
وقت ایک پھر کیا پیدا سے مٹی تمہیں نے جس ہے وہی اللهبھی پھر تم ہے مقرر مدت ایک کےہاں اس اور دیا کر مقرر
ہو کرتے (2) شکَع(ام الاٴن ُة. َعر ۡوو ُةس