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