Introduction to immune system (lecture1).ppt

Overview Of The Immune System

Immune System

[a] Defence System[b] Extremely adaptable

[c] Generates a variety of cells and molecules

Immune Response

Two interrelated activities

[1] Recognition

[2] Response

Recognition

D isc r im ina te b e tw e e n fo re in g p a th og ena n d o w n ce lls an d p ro te ins

D istin gu ish on e p a th og en fro m an o th er

Remarkably Specific

Response

Also known as effector function.

Eliminate or neutralize foreign organisms.

Later exposure to same foreign organism memory response heightened immune reactivity.

Immunity

S pe cif ic (A q u ired) N o nspe c ific (In na te )

Immunity

“State of protection from infectious diseases”

Nonspecific Immunity

In fla m m a to ry E n do c ytic o r P h ag o cy tic P hy s io log ic A n a tom ic

Nonspecific ImmunityBarriers

“Basic resistance to disease that a species possesses”

Anatomic Barriers

Skin Sebaceous Glands secrete sebum low pH (3-5) Inhibitory to growth of most microorganisms.

Mucous membranes of the respiratory/GI/Urogenital tracts

Secrete mucuc traps microorganisms and expels them by movement of celia.

Physiologic Barriers

Temperature

pH

Soluble factors

Gastric juice acidic organisms can’t survive.

Newborns less acidic gastric juice more susceptible to infections.

Soluble factorsComplement = serum proteins that are non active.

when pathogen enters activated membrane damaging reactions clear infections

Endocytic and Phagocytic Barriers

Endocytosis “Macromolecules in the ECF internalized by cells”

Phagocytosis “More specialised and involves plasma membranes expanding around macromolecules

Specialized phagocytic cells include: monocytes, macrophages and neutrophils.

Inflammatory Response

Signs

Redness (Ruber)Swelling (Tumor)Heat (Colar)Pain (Dolor)

Three major events

(1) Vadodilation(2) Increased capillary permeability(3) Influx of phagocytic cells (chemotaxis)

Specific Immunity

“Reflecting the presence of a specific and functional immune system”

Properties of self immunity

SPECIFICITY

MEMORY

DIVERSITY

SELF/NONSELF RECOGNITION

Cells and Organs of The Immune System

WBC or leukocytes development of immune response.

Cells of The Immune System

LYMPHOCYTES are CORE cells of the immune system. WHY?

SPECIFICITY

MEMORY

DIVERSITY

SELF/NONSELF RECOGNITION

Remaining WBC : @ Activate lymphocytes @ Increase effectiveness of antigen

clearance @ Secrete immune effector molecules

Cells of The Immune System

Cell Type Cells/ml %

RBC 5 x 106

Platelets 2.5 x 106

Leukocytes 7.3 x 106

Neutrophil 50-70

Lymphocyte 20-40

Monocyte 1-6

Eosinophil 1-3

Basophil <1

Haematopoiesis

“Formation and development of white blood cells and red blood cells from stem cells”

Begins in the yolk sac in the first few weeks of embryonic developments

Yolk Sac

Spleen/Liver

Spleen/Liver/Bone marrow

Bone marrowBirth

Stem Cells

1/104 bone marrow (BM) cells

Pluripotent (Differentiate along a number of pathways).

Two main lineages from stem cells:

Lymphoid stem cells

Myeloid stem cells

These further differentiate into committed progenitor cells.

Progenitor cells respond to particular growth factors differentiation to mature RBC’s and WBC’s.

Lymphoid Cells

Lymphocytes are WBC responsible for immune response.

Based on function and cell membrane components

Lymphocytes

Null

B

T

Effector cells:

B cells: Plasma cells

T cells: T helper cells (TH) and cytotoxic T cells (CTL)

Lymphocytes express glycoprotein as membrane cluster of differentiation (CD)

B Cells

Mature in the BM.

Mature B cells have antibodies (Ab) on their surface ( 1.5x105 molecules/cells).

All antibodies on a single B cell have identical binding sitesfor antigen (Ag).

B cells express CD45

B cells also express MHCII functions as antigen presenting cell (APC).

B Cells

R e m a in in B M un ti l seco nd ary A g e n co u nter

M em ory C e lls

S e cre te A b

P lasm a Ce lls

A g E xp o su re

Naive B cell

T Cells

Produced in BM. Matures in thymus.

Recognise Ag ONLY if presented on MHC complex.

Possess distinctive membrane molecules.

T Cell Subtypes

Express CD4 and are class II restricted.

T Helper Cells (TH)

Secrete lymphokines activation of B cells, cytotoxic T cells and other immune cells.

Cytotoxic T Cells (TC)

Express CD8 and are class I restricted.

Ratio of TH:TC is 2:1 in normal blood.

Altered in autoimmune diseases and immunodeficiency.

Suppressor T Cells (TS)

Not isolated yet.

May suppress humoral and cell-mediated immunity.

Null Cells

Lack CD4 and CD8.

Lack specificity and memory.

Natural killer cells (NK).

5 - 10 % of lymphocyte population.

Display cytotoxicity towards a variety of tumours, in absence of previous immunisation

Natural Killer Cells

S p ec if ic(A b-d ep en de n t ce ll m ed ia te cy to tox ici ty)

N o nsp ec if ic(D ire c t co n ta ct w ith tu m o ur ce ll m e m b ran e)

NK Cells

Mononuclear Cells

Mononuclear Cells

Mononuclear Cells

Macrophage(Tissues)

Macrophage(Tissues)

Monocyte(Blood)

Monocyte(Blood)

Macrophages

Either fixed or free.

Motility by amoeboid movement.

Nomenclature depends on locationKidney:Mesangial cellsLiver: Kupffer cellsConnective tissue: HistiocytesLung: Alveolar macrophagesBrain: microglial cells.

Macrophages

Activation by IFN from TH cells.

Activated Macrophages:

a) Secrete more inflammatory mediators.

b) Increased microbicidal activity

c) Increased activation of T cells

d) Increased expression of MHCII better as APC.

Phagocytosis

GranulocytesNeutrophilNeutrophil

BasophilBasophil

EosinophilEosinophil

Neutrophils

Stain with both acidic and basic dyes.

Increased number indicated infection.

First arrival at site of inflammation.

Possess phagocytic properties

Eosinophils

Stain with Eosin Y (acidic dye).

Less phagocytic than neutrophils

Important in fighting parasitic infections.

Basophils

Stain with methylene blue (basic dye).

Non phagocytic

Major role in allergic reactions

Mast Cells

Skin and connective tissues of organs.

Granules containing histamine development of allergies.

Dendritic Cells

Express high levels of MHCII good APC.

Capture Ag in tissue then travel to lymphoid organs wherethey present it to T cells.

Organs Of The Immune System

Sites of maturation of lymphocytes.

Primary Organs

Thymus: T cell maturationBone marrow: B cell maturation

Lymphocytes then become IMMUNOCOMPETENT

Trap antigens

Secondary Organs

Sites of interaction between immunocompetent cells and theantigen.

Lymph nodes: Trap antigen from intracellular fluids

Spleen: Trap antigens from blood

Mucosal-Associated Lymphoid Tissue (MALT): Trap antigensentering from several mucous membrane surfaces.

Cortex: Densely packed with thymocytes maturation begins.

Thymus

Medulla: Sparsely populated with thymocytes fully mature.

Exit thymus via postcapillary venules.

T cell receptor diversity generated by a series of randomgene rearrangements.

T cells recognizing self MHC molecules are released from thymus.

Positive Selection

Negative Selection

Self-reactive thymocytes (i.e. recognise MHC + self antigen)are eliminated.

Lymph is produced from plasma seeping through thincapillary walls.

Secondary Lymphoid Organs

Lymph Nodes

Contain Lymphocytes, macrophages and dendritic cells.

Cortex, paracortex and inner medulla.

Cortex = B lymphocytes and macrophages B cells differentiate into plasma and memory cells.

Paracortex = T lymphocytes and dendritic cells.

Medulla = Plasma cells secreting antibody.

Humoral and Cell-Mediated Immunity

“Immunity conferred on a nonimmune individual by administration of serum antibodies from an immune individual”

Humoral Immunity

Antibodies produced interact with antigens and the antigenis then eliminated.

Cell-Mediated Immunity

“Immunity only transferred on by T cells”

Cytokines secreted by TH cells activate phagocytic cells + B cells.

Recognition Of Antigen by B and T Lymphocytes

Lymphocytes recognise DISCRETE sites on the antigen called EPITOPES.

B cells recognise epitopes alone.T cells recognise epitopes in association with MHC moleculeon the surface of a self cell.

Humoral branch: Recognise enormous variety of epitopeson bacteria, viruses and soluble proteins from invading pathogens.

Cell-Mediated branch: Recognise altered self cells such asa virus-infected self cell and a cancerous cells.

Generation of Lymphocyte Specificity and Diversity

Mature immunocompetent humans contain large numbers ofantigen-reactive clones of B and T cells.

Specificity of each clone is determined by random rearrangements in the bone marrow during maturation of the lymphocytes.

Antigen processing and Presentation

Processing “Conversion of proteins into MHC-associated peptide fragments”

Presentation of antigen with MHCI or MHCII molecules is determined by route of entry of antigen into the cell.

Exogenous Antigens

Produced outside host cell.

Enters cell by endocytosis or phagocytosis.

Associated with MHCII on APC.

Endogenous Antigens

Produced within the host cell.

Degraded endogenously into peptide fragments.

Associated with class MHCI molecule.

Examples are viral proteins within cells and unique proteinssynthesized by cancerous cells.

Clonal Selection

Role of antigen is to SELECT for and EXPAND populationof lymphocytes with a given genetic specificity.

Humoral and Cell-Mediated Responses

Reading

Immunology. Janis Kuby. W.H.Freeman and CompanyChapters 1 and 3