Lect 1 introduction to immunology by dr. naeem

Introduction to Immunology

MICROBES IN

ENVIRONMENT

AirWater Soil

HUMAN

Attack

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Microorganisms are found everywhere in the

environment human encounter is inevitable

Among thousands of microbial species

probably 300-400 cause diseases in humans

Immunology

• Is the study of our protection from foreign macromolecules or invading organisms including viruses, bacteria, protozoa or parasites and our responses to them

• The host response consists of:o Non-specific or innate immunity. o Specific or adaptive immunity.

In addition, we develop immune responses against our own proteins (and other molecules) as in

autoimmunity against our own aberrant cells as in tumor immunity

exaggerated immune response to foreign molecules as in hypersensitivity

NON-SPECIFIC IMMUNITY

• Resistance that exists prior to the exposure to the antigen

ELEMENTS

• Anatomical barriers: Skin & MM

• Secretary molecules

• Cellular components

• Involves processes like phagocytosis and inflammation

Protective Characteristics of the Skin

Outer (dermal) layers

• Keratin layer: physical barrier to microbial penetration

• Sloughing of outer layers removes attached bacteria

• Dry & acidic conditions limit bacterial growth

Hair follicles, sweat & sebaceous glands

• Production of acids, toxic lipids & salts

that limit bacterial growth

• Skin-associated lymphoid tissue

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Secretary Molecules

• Skin

o Organic acids, toxic lipids & salts in secretions

• GIT

o Thiocyanate & lysozymes in saliva: degrade peptidoglycan in bacterial cell wall

o Low pH in stomach: bactericidal

o Fatty acids & bile acids in the lower GI tract

Defenses after invasion bymicrobes

Non-specific DefencesPhagocytes : ingest & destroy bacteria.

Inflammation : if microbes survive

encounter with phagocytes:

Natural Killer Cells

Interferon

Specific DefensesAntibody-mediated immunity

Cell-mediated immunityNaeem

Secretary Molecules • In serumo Transferrin & lactoferrin: sequester iron required for

bacterial growth

o Interferons: Inhibit viral replication

o Complement: Cause bacterial killing

o Acute phase proteins: ‘CRP’ bind to bacteria and activate complement

o Defensins: create pores in bacterial cello Primarily located in GIT (α-defensin) & LRT (β-defensin)

o Lysozymes in tears & secretions: bactericidal

Cellular Components Phagocytic cells

Neutrophils (polymorphonuclear: PMN)o Are the most important cellular components in bacterial

destruction

o Are relatively large and most abundant WBCs with lobed nucleus and cytoplasmic granules (lysosomes) containing degradative enzymes

•Mononuclear Phagocytes: Include o Monocytes in circulation

o Histiocytes in tissues

o Microglilal cells in the brain

o Kupffer cells in the liver

o Macrophages in serous cavities and lymphoid organso Participate in both innate (bacterial killing) & acquired immune

responses (APC)


Monocyte Neutrophils

Monocyte with ingested

malarial parasite

Macrophages

attacking E. coli

• All phagocytic cells have receptors for a variety of molecules like:

o IgG Fc

o Complement

o Interferon

o TNF

o Certain bacterial components

• Receptor interactions with these ligands promote phagocytosis and activation for efficient killing of pathogens


Non-specific Killer Cells

NK and LAK cells

ADCC (K) cell

Activated macrophages

They all kill foreign

and altered self

targets

Natural Killer (NK) cells

• Named NK cells because:

they are active without prior exposure to the virus

are not enhanced by exposure and

are not specific for any virus

• Are large granular lymphocytes (LGL)

• Up to 15% of blood lymphocytes

• Do not need thymus for development

• Lack T-cell receptor

• Lack T CD3 proteins and surface IgM & IgD


• Kill virus-infected cells

Killing is non-specific and is not dependent on foreign antigen

presentation by of class I or II MHC and

kill by secreting perforins and granzymes

• Kill malignant cells by recognizing a protein MICA on many

cancer cells which is not found on normal cells

• Interaction of MICA with receptor on NK cells triggers

secretion of cytotoxins and death of tumour cell


Can kill without antibodies but IgGenhances their activity, a process called Antibody-Dependent Cellular Cytotoxicity (ADCC)

Activated by IL2 and IFN-γ to become LAK cells

NK Cells Activation

• Three groups based on cells of origin Alpha INF by leucocytes

Beta INF by fibroblasts

Gamma INF by lymphocytes

• Alpha & Beta INFs are induced by viruses

• Gamma INF is induced by antigens and is one of the effectors of cell mediated immunity

INTERFERONS

Alpha & Beta Interferons

• Are group of proteins produced by human cells primarily after viral infection

• DNA & RNA viruses are competent inducers

• dsRNA are better inducers: dsRNA poly (rI-rC) is one of the strongest inducers and was under consideration as antiviral agent but toxic effects prevented its clinical use.

Other Inducers

• Intracellular bacteria and protozoa

• Bacterial endotoxins

Alpha & Beta Interferons

• Are non-specific for any particular virus

• Inhibit intracellular viral replication without effect on normal cells : selective toxicity Is due to presence of dsRNA in virus infected cells and

not in uninfected cells

• Have no effect on extracellular virus particles

• Are typically host specific : other animals can not be used as source of INFs for human therapy

Alpha & Beta Interferons• INF binds to cell surface receptor and induce the cell to

produce three proteins : are activated by dsRNA in virus-infected cells Oligo A synthetase activates RNAse

RNAse that degrades viral & cellular mRNA

Protein kinase that inhibit protein synthesis

• Inhibit viral & cellular protein synthesis and leads to death of infected cell and no viral replication and no spread

• Are produced within a few hours of viral replication and act in early phase of viral infection

• Alpha INF: Chronic active hepatitis due to HBV & HCV and condyloma acuminatum

• Beta INF : Multiple sclerosis

• Gamma INF : Chronic granulomatous diseases

• Anti-cancer uses: Kaposi’s sarcoma and hairy cell leukoplakis which are due to oncogenic viruses

Alpha & Beta InterferonsClinical Uses

Differences between the two types of immunity

Specific ImmunityNon-specific Immunity

Highly specificNon-specific

Response is antigen dependentResponse is antigen-independent

There is a lag time between exposure and

maximal response (in days)

There is immediate maximal response

(within minutes)

Antigen-specificNot antigen-specific

Exposure results in immunologic memoryExposure results in no immunologic

memory

Physico-chemical barriers to infections

Effector MechanismActive componentSystem/Organ

Desquamation; flushing, organic

acids

Squamous cells; SweatSkin

Peristalsis, low pH, bile acid,

flushing, thiocyanate

Columnar cellsGI tract

Mucocialiary elevator, surfactantTracheal ciliaLung

Flushing, lysozymeMucus, saliva, tearsNasopharynx and eye

Phagocytosis and intracellular

killing

Direct & antibody dependent

cytolysis,

IL-2 activated cytolysis

Phagocytic cells

NK-cells, K cells &

LAK

Circulation and lymphoid organs

Iron bindingLactoferrin and TransferrinSerum

Antiviral proteinsInterferons

antiviral, phagocyte activationTNF-alpha

Peptidoglycan hydrolysisLysozyme

Opsonization and phagocytosisFibronectin

Opsonization, enhanced

phagocytosis, inflammation

Complement

Lect 1 introduction to immunology by dr. naeem

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