Cells

Abdul Ghaffar Microbiology and Immunology

"When the mind is ready,a teacher appears.“ Chinese Proverb

Development of the Immune System ery pl

neu

mφ

CD8+

nk

CTL

CD4+ TH1

thy TH2

mye lym

Cells of the Immune System

Myeloid cells

lymphoid cells

Granulocytic

Monocytic

T-cells

B-cells

Neutrophils Basophils Eosinophils

Macrophages Langerhans & Kupffer cells Dendritic cells?

Helper Cytotoxic Suppressor

Plasma cells

Dendritic cells?

Components of the Immune System

Nonspecific Humoral complement, interferon, TNF etc.

Cellular macrophages, neutrophils

Specific Humoral

antibodies

Cellular T cells; other effectors cells

Balance between Infection and Immunity infection

Disease =

immunity

Bolus of infection x virulence immunity

Response to Infection infection

Innate immunity

x

disease

no disease

adaptive immunity

Significance of the Immune System 



Beneficial: 

Protection from Invaders



Elimination of Altered Self

Detrimental: 

Discomfort (inflammation)



Damage to self (autoimmunity)

Characteristics of Innate and Adaptive Immunity Innate Immunity

Adaptive Immunity

Antigen independent

Antigen dependent

No time lag

A lag period

Not antigen specific

Antigen specific

No Immunologic memory

Development of memory

Components of Innate and Adaptive Immunity Innate Immunity

Adaptive Immunity

physical barriers skin, gut Villi, lung cilia,etc

soluble factors many protein and non-protein secretions

cells phagocytes, NK cell eosinophils, K cells

non e Immunoglobulins (antibody)

T and B lymphocytes

Physical Barriers to Resistance

Effector mechanisms in Innate Immunity -1 Site Skin GI tract Lung

Component

Functions

squamous cells sweat

desquamation flushing, fatty acids

columnar cells

Peristalsis, low pH bile salts, fatty acids

tracheal cilia

mucociliary elevator surfactants

Effector mechanisms in Innate Immunity -2 Site

Component

Functions

Nasopharynx and eye

mucus, saliva, tears

flushing, lysozyme

Blood and Lymphiod organs

Phagocytes

phagocytosis and intracellular killing

K, NK & LAK cells

direct and antibody dependent cytolysis

Effector mechanisms in Innate Immunity -3 Site Serum and other serous fluids

Component

Functions

lactoferrin, transferrin

iron deprivation

interferons, TNF-

antiviral proteins phagocyte activation

lysozyme Fibronectin & complement

peptidoglycan hydrolysis

opsonization, enhanced phagocytosis, inflammation

Phagocytes are the Most Important Cells George Bernard Shaw wrote: “There is at bottom only one genuine treatment for all

diseases,…to stimulate Influenced by the work of phagocytes.theDrugs are a

Eli Metchnikoff,

delusion. …(when) the

phagocytes are stimulated; they devour the disease…”

Phagocytes: Macrophages

 phagocytosis, intracellular and extracellular killing, tissue repair, antigen presentation for specific immune response  characteristic nucleus and CD14 membrane marker.

Characteristics of Neutrophil Granules primary granules

secondary granules

azurophilic; characteristic of young neutrophils;

specific for mature neutrophils

contain cationic proteins, lysozyme, defensins, proteases and myeloperoxidase

contain lysozyme, NADPH oxidase, lactoferrin and B12binding protein

Phagocyte Response to Infection

 The SOS Signals –N-formyl methionine –Clotting system peptides –Complement products

 Phagocyte response –Vascular adherence –Diapedesis –Chemotaxis –Activation –Phagocytosis and killing

Initiation of Phagocytosis Attachment via ScavengerR IgG FcR

CR Toll-like R

Respiratory Burst

Oxygen Dependent Myeloperoxidase Independent Reactions Glucose +NADP+ G-6-P-dehydrogenase NADPH + O2 Cytochrome b558

Pentose-P + NADPH +

NADP + O2

-

-

2O2 + 2H+

Superoxide dismutase -

2O2 + H2O2

H2O2 + 1O2

.OH + OH- + 1O2

Respiratory Burst Oxygen Dependent Myeloperoxidase dependent reactions -

H2 O2 + Cl

myeloperoxidase -

2OCL + H2O

OCl- + H2O 1O -+ Cl-+ 2

H2O

-

2O2 + 2H+ Superoxide dismutase 2 H2 O2 catalase

H2O2 + O2

H2O + O2-

-

Pathways of Intracellular Killing

Intracellular Killing oxygen-depenedent myloperoxidase-independent

oxygen-independent

myeloperoxidase-dependent

Mediators of Oxygen Independent Killing in the Phago-lysosome Effector Molecule

Function

Cationic proteins (cathepsin)

Damage to microbial membranes

Lysozyme

Hydrolyses mucopeptides in the cell wall

Lactoferrin

Deprives pathogens of iron

Hydrolytic enzymes (proteases)

Digests killed organisms

Nitric Oxide Dependent Killing

TNF TNF

Nitric Oxide Nitric Oxide

Non-specific Killer Cells

NK and LAK cells ADCC (K) cell Activated

macrophages Eosinophils

They all kill foreign and altered self targets

Natural Killer (NK) cells  also known as large granular lymphocytes (LGL)  kill infected and malignant cells  are identified by the presence

of CD56 & CD16 and absence of CD3  activated by IL2 and IFN-γ to become LAK cells

Lymphokine Activated Killer (LAK) cell kills kills transformed malignant and malignant cells cells

Regulation of NK Cell Function MHC I KIR

No Killing

KAR KAL

Killing

K Cells  morphologically undefined  have IgG Fc receptor  recognize antibody coated targets  could be NK cells (IgG), macrophages (IgG), eosinophils (IgE) or other cells (IgG)