Clinical Immunology and serology Practice

MLIS-201

Prof. Dr. Ezzat M HassanImmunology Dept.,Med. Res. Inst., Alex. Univ.

OutcomesBy the end of the lecture the students will be

able to• Recognize Structure of the immune system.• Enumerate the Cell Frequency of Different

Leukocytes in Blood of Healthy Individuals

Structure of the immune system

C ells O rgans

Im m un e sys tem

1-Cells of the Immune System

Cells of the Immune System

BasophilsNeutrophils

EosinophilsLangerhans &Macrophages

Kupffer cellsDendritic cells?

Monocytic

CytotoxicHelper

Suppressor

T-cells

Plasmacells

B-cells Dendriticcells?

Myeloid cells

~ 60% neutrophils (50% - 70%) ~ 3% eosinophils (>0% - 5%) ~ 0.5% basophils (>0% - 2%) ~ 5% monocytes (1% - 9%) ~ 30% lymphocytes (20% - 40%)

Cell Frequency of Different Leukocytes in Blood of Healthy Individuals

Myeloid LineageGranulocytes

Neutrophils Eosinophils Basophils

Monocytes MegakaryocytesErythrocytes (RBC)Dendritic cells (APC)

Macrophages

Platelets

Neutrophils60-70% of WBCsMulti-lobed nucleusGranulated cytoplasmLife span is 2-3daysProminent in inflammatory responseLeukocytosis is marker for infectious

processDead neutrophils make up a large

proportion of pus.Actively phagocytic

Eosinophils~2% of WBCsBi-lobed nucleusGranulated cytoplasmStains red with acid dye (eosin)Prominent in response to parasitic

infections Phagocytic

Basophils

<1% of WBCsLobed nucleusHeavily granulated cytoplasmStains blue with basic dye Prominent in allergic responsesNon-phagocyticSecrete allergic & inflammatory mediators

Monocytes and MacrophagesMonocytes:Large WBCsMonocytes are circulating precursors of Macrophages.MacrophagesFound in the organs, not the blood.Made in bone marrow as monocytesCalled macrophages once they reach organs.Long livedPhagocyticInitiate immune responses as they display antigens to

the lymphocytes (APC). Activated by cytokines and gamma interferonSecretes numerous immune response factors

Macrophages

Liver

Kuppfer cells

Skin

Denteritic cells

CNS

Microglia

Spleen,lung

Macrophages

Bifunctional

Phagocytosis

Antigen presentation

Mast Cells

Found in many different tissuesContains granules which release histaminePlay role in allergic reactions

Dendritic CellsHave long “dendrites”Major role as APCStimulated by innate responseHave constitutive MHC II expressionPhagocytic

APC INTERACTING WITH T CELL

T cell

APC

N K (N a tu ra l k ille r ce lls)

T -ce lls B -ce lls

L ym p h o id ce lls

Lymphoid Lineage

Lymphocyte ProductionLymphocytes are produced in:

lymphoid tissues (e.g., tonsils)lymphoid organs (e.g., spleen, thymus)Bone marrow

Make up 20–30% of circulating leukocytesMajority are stored in lymphoid organs, not

circulating (remember that only about 1% of your WBCs are in the blood)

Classes of Circulating Lymphocytes

T cells: thymus-dependentMake up 80% of circulating lymphocytes

B cells: bone–marrow derivedMake up 10–15% of circulating lymphocytes

NK cells: natural killer cellsMake up 5–10% of circulating lymphocytes

Lymphocytes1-T Lymphocytes

Mature in thymus Have T cell receptors (TCRs) Recognize Ag on cells onlyCELL-MEDIATED IMMUNE RESPONSE

T cell subclasses:1. Cytotoxic T cells

Attack cells infected by viruses & malignant cells2. Helper T cells

Stimulate function of T cells and B cells3. Suppressor T cells

Inhibit function of T cells and B cells4. Regulatory T cells

Regulate the functions other T cells5. Memomry T cells

For secondary immune responses

Lymphocytes2-B Lymphocytes

Mature in bone marrowHave membrane-bound Ab(~10,000 per cell)Go from “naive” to activated.Differentiate into plasma cells, which produce

and secrete antibodies (immunoglobins)HUMORAL IMMUNE RESPONSEPlasma cells are Ab secretors

~1-2 week life span

P la sm a ce lls B -m e m o ry

B - ce lls

Immunoglobulins -Long lived-2ry immune response

B cells

Natural Killer (NK) Cells Also called large granular lymphocytes Responsible for immunological surveillanceLack T and B cell markersLack Ag receptorsInvolved with Ab-dependent cell-mediated

cytotoxicity (ADCC)Attack:

foreign cellsvirus-infected cellscancer cells

Lymphocyte DistributionTissues maintain different T cell and B cell

populations:T Cells: high in blood, thymus, marrow, spleen,

othersB Cells: high in nodes, spleen, others

Lymphocytes wander through tissues, migrating throughout the body to defend peripheral tissues (T cells move faster than B)

Have long life span (4 years+, up to 30!)Retain their ability to divide, which is

essential to immune system function

Hi ! Take short rest!!

Bone m arrow

Thym us gland

Prim ary

Spleen Lym ph nodes

Secondary

M ALT

Tertiary

Organs of Im m une System

Lymphoid Organs & Tissuesspleen, thymus

gland, Lymph nodes and

tonsilsPeyer’s patches and

bits of lymphatic tissue scattered in connective tissue

Figure 20.5

Primary lymphoid organs

ThymusSecretes hormones (thymosin and thymopoietin) that

cause T lymphocytes to mature It functions strictly in T lymphocyte maturation It does not directly fight antigensLocated in mediastinumDeteriorates after pubertyDivided into 2 thymic lobesSepta divide lobes into smaller lobulesEach lobule contains:

a dense outer cortex of dividing T cells a pale central medulla

T cells: divide in the cortex migrate into medulla leave thymus by medullary blood vessels

Secondary lymphoid organs

& tissues

Lymphoid FunctionsLymphoid tissues and lymph nodes:

Distributed throughout body to monitor peripheral infections respond before infections reach vital organs of trunk Lymph nodules in mucosa Lymph nodes monitor plasma/interstitial fluid Spleen Monitor blood

SpleenStructure

Gross Largest single collection of lymphoid tissue in the body Ovoid organ in upper left quadrant of abdomen

Microscopic Compartmentalized

Red pulp White pulp

Periarticualr lymphoid sheath Site of Ag presentation

Major cell types: Lymphocytes Macrophages Dendritic cells RBCs

Functions of the Spleen Filters the blood like lymph nodes filter the

lymph Phagocytes in the spleen remove abnormal

blood cells and other blood components by phagocytosis

• Storage of iron and other RBC products for later use or elimination

• Initiation of immune responses by B cells and T cells in response to antigens in circulating blood

• Site of lymphocyte proliferation Stores RBC’s & platelets

Lymph NodesStructure

Gross Bean-shaped structures Drains major segments of lymphatic system

Microscopic Major cell types

Lymphocytes Macrophages Dendritic cells

Cortex/paracortex/medulla Follicles

Primary Secondary

Peripheral Lymph Node StructurePeripheral Lymph Node Structure

Distribution•cervical region• axillary region• inguinal region• pelvic cavity• abdominal cavity• thoracic cavity• supratrochlear region

Lymph NodesFunctions:Filter potentially harmful particles from lymph Immune surveillance by macrophages and

lymphocytes Areas of lymphocyte production &

proliferation1st line of response to antigensSecondary follicle (Germinal center) is site of

B cell proliferation & differentiationAfter Ag stimualtion lymphocyte numbers

increase by 50X in efferent lymphatic vessel (Lymphadenopathy)

Tertiary lymphoid tissues

TonsilsFollicular structureContains lymphocytes, macrophages, mast

cellsGerminal centers appear in response to AgProtective role in URI

Appendix

Associated with intestinesResponds to AgRole in GI immune response

Mucosa Associated Lymphoid Tissues (MALT)

Lymphoid tissues below epithelium (Peyer’s Patches)

Presence of B cellsAg presented through unique cell (M cell)Preferentially responds with IgA antibody

Next Lecture: Innate immunity

Write assay aboutMucosa Associated Lymphoid TissuesLymph NodesFunction of spleen

Assignment:Cell Frequency of Different Leukocytes in Blood of Healthy and diseased Individuals.