INTRODUCTION TO IMMUNOLOGY

Karachi King’s College of Nursing

Questions To Be Answered

• What is immunity ?

• What is structure or anatomy of immune system ?system ?

• What are functions of immune system ?

• How immune system works ?

History Of The Term “Immunity”History Of The Term “Immunity”

• Originally implied exemption from military service or taxes.

• Introduced into medicine to refer to those people who did not get further attacks of people who did not get further attacks of Smallpox or plague once they had had the disease .

• In wider sense the term refers to the resistance of a host to invasive pathogens or their toxic products.

Anatomy of Immune System

• Composed of various components

• Cellular

• Non-Cellular• Non-Cellular

• Scattered nature of various components.

• Not organized like other human body system e.g. Cardio Vascular system ,Respiratory System.

Cellular Components

• Lymphoid tissue

• Other Cells– Neutrophills– Neutrophills

– Monocytes Macrophages

– Natural Killer Cells

Non-Cellular components of Immune System

• Immunoglobulins

• Antigen

• Cytokines • Cytokines

• Complement

Lymphoid tissue• Primary or Central.

• Secondary or Peripheral.

• Cells of immune system -Lymphocytes (T-Lymphocytes ,B--Lymphocytes (T-Lymphocytes ,B-Lymphocytes, Null Cells )

-Plasma Cells.

Lymphoid tissuecontinued…..

• Primary Lymphoid tissue include Thymus ,Liver , Spleen and Bone marrow .

• Primary lymphoid tissues provide appropriate environment for lymphocytes maturation .environment for lymphocytes maturation .

• In primary lymphoid tissues progressive lymphopoieis occur ,independent of antigenic stimulation .

Lymphoid tissuecontinued…..

• Secondary lymphoid tissue include Blood , Lymph ,Pharyngeal and Gut associated lymphoid tissues.

• Secondary lymphoid tissue trap antigens and • Secondary lymphoid tissue trap antigens and make it available for mature lymphocytes .

• In secondary lymphoid tissues T & B cells further mature to become Memory and killer T-Cells and Plasma cells.

Cell of Lymphoid Tissue

Lymphocytes

• Lymphocytes are chief cell of immune system .

• Posses diversity ,specificity ,memory , self and non-self recognition .

• 20-40 % of cells in blood are lymphocytes • 20-40 % of cells in blood are lymphocytes

• 99 % of the cells and lymph are lymphocytes.

• Circulate in blood and have capability of migrating to tissue .

T-Lymphocytes

• There are different subsets of T-Cells T-Helper (TH ) ,T-Suppressor (T S), T- Cytotoxic (TC) and T-Delayed Hypersensitivity (TD).

• (TH ) & (T S)cells exercise are immunoregularity role over the • (TH ) & (T S)cells exercise are immunoregularity role over the whole specific immune system .

• Cellular interaction between (TH ) and B-Cell is essential for optimal humoral response to most Antigen .

• Antigen independent B-Cell maturation .

• Plasma cell are end cells with a life span of 2-3 days during which they continuously

B-Lymphocytes

2-3 days during which they continuously synthesized and secrete Antibodies .

• Antigenic stimulation through antigenic receptors on B-Cells surface (immunoglobulins).

Others Cells Of Immune System

NEUTROPHILS

• Mature in bone marrow and are released in circulation

• Circulate for 6-7 hours and then migrate into tissue survive for 3-4 days

Natural Killer Cells

• Lymphoid cells detected in circulation and spleen, lack convential surface markers.

• The number of NK cells in circulation • The number of NK cells in circulation decline with age.

• Damage viral infected tissues cells

• Cytotoxic to many tumors.

MONOCYTES - MACROPHAGES

Circulate as Monocytes for 1-3 days and when enter a tissue become MACROPHAGES.

Survive for a month.Link between innate and adaptiveLink between innate and adaptiveimmunity = ANTIGEN

PRESENTING CELL

Phagocytose pathogens and then Present the antigens on thesurface in special receptors

Antigen

• Antigen is any thing that can be recognized by the immune system.

• Thus immune system ca be either part of the • Thus immune system ca be either part of the host or can be foreign .(i.e Self Antigen or non Self Antigen)

• Epitome is the part of the antigen that is recognized by immune system .

IMMUNOGLOBULINS (Antibodies )

• Antibodies are glycoprotein's synthesized and secreted by plasma cells in response to antigenic stimulation of B-Cellsantigenic stimulation of B-Cells

• There are five serum immunoglobulins IgG,IgA,IgM,IgD and IgE .

IgG

• Constitute about 75% of total serum immunogloblins.

• Bacteriolytic, viricidal, and precipitating antibody.antibody.

• In an immune response it appears late and persists for longer duration

• Half-life is 18 to 23 days. • Carries the major burden of neutralizing

bacterial toxins.

IgM

• Accounts for 5 to 10 % of total immunoglobulins.

• Half-life is 5-days

• Can’t cross the placental barrier .• Can’t cross the placental barrier .

• The first one to appear in response to an antigen and also the first one to disappear from the serum .

• The first immunoglobulin ,synthesized by the neonates .

IgA

• 2 subclasses: IgA1 and 2.• It is present in 2 forms:• Serum IgA: monomeric, forms 15-20% of

serum Igs.serum Igs.• Secretory IgA: predominant in secretions

e.g. saliva,tears, colostrum, bronchial, genitourinary and intestinal secretions, has a protective role against invading pathogens.

• Less than 1% of total serum Igs.• Monomeric.• Present on B-cell membrane and acts as a

IgD

• Present on B-cell membrane and acts as a B-cell receptor.

• Exact function not known.

IgE

• Present in trace amounts in normal serum.• Monomeric.• Associated with atopic diseases, e.g. bronchial • Associated with atopic diseases, e.g. bronchial

asthma.• Homocytotropic, and plays a role in type I

hypersensitivity.• May be important in immunity to helminthic

parasites.

Cytokines

• Cytokines are polypeptides and sylcoprotens secreted from a range of cell types .T-Cell ,Macrophages ,Fibroblasts ,Bone marrow.

• Cytokines act as a messengers between those cell • Cytokines act as a messengers between those cell which secrete them and transmit cells

• Important Cytokines – Interferon's – Interleukins – Tumor Nervous Factor

COMPLEMENT – MAIN STRUCTURAL FEATURES

COMPLEMENT – MAIN STRUCTURAL FEATURES

�Consists of about 30 serum proteins marked by C and arabic number (C1q, C2, C3 etc.)

�Many C proteins are zymogens –�Many C proteins are zymogens –proenzymes requiring proteolytic cleavage

�Enzymes are often formed from several C molecules –eg. C4B2a cleaves C3

�Activation of C is controlled by regulatory proteins – eg. DAF

EFFECTS OF ACTIVATION OF COMPLEMENT SYSTEM

EFFECTS OF ACTIVATION OF COMPLEMENT SYSTEM

�Chemotaxis (attraction of cells to sites of infection

�Opsonization (facilitation of phagocytosis)�Increased blood flow�Increased blood vessel permeability�Damage to plasma membranes�Release of inflammatory mediators from mast

cells

BIOLOGICAL EFFECTS OF COMPLEMENT

BIOLOGICAL EFFECTS OF COMPLEMENT

�Promotion of killing of bacteria

�Clearing of immune complexes

�The induction and enhancement of �The induction and enhancement of antibody responses

�Detrimental if activated on a large scale, e.g. in Gram negative septicaemia, in tissue necrosis, in autoimmunity

Functions Of The Immune SystemFunctions Of The Immune System

�Defense against infections

�Defense against cancers

�Recognition of self , non-self and altered-self .

�Eliminate non-self, altered-self invaders . �Eliminate non-self, altered-self invaders .

�Preservation of genetic integrity of the individual

MAJOR FUNCTIONS OF CELLS

PARTICIPATING IN IMMUNE RESPONSES

MAJOR FUNCTIONS OF CELLS

PARTICIPATING IN IMMUNE RESPONSES

• B cells - recognize antigens and produce antibodies

• Plasma cells - produce antibodies• Th cells - help in immune response,

produce cytokinesproduce cytokines• Treg cells - inhibit immune response,

produce cytokines• Tc cell - kill target cells• NK cells - able to to kill virally infected

and transformed cells• Dendritic cells- present antigens to Th cells

NON-SPECIFIC TYPE

IMMUNITY

SPECIFIC TYPE

GENETIC BIOCHEMICAL

PASSIVE ACTIVE

OTHERS

PHYSICAL ,MECHANICAL

CELLULAR

PASSIVE ACTIVE

ARTIFICIAL

NATURAL NATURAL

ARTIFICIAL

INNATE IMMUNITY/NONSPECIFIC IMMUNITY

(Natural Resistance)

It operates through following factors :

• Genetic factors .

• Physical and Mechanical Barriers .• Physical and Mechanical Barriers .

• Biochemical Factors

• Cellular Factors

• Miscellaneous Factors

Genetic Factors

• Genetic factors may make host more vulnerable or resistant to infections, certain cancers.

Physical And Mechanical BarriersBarriers

• Intact skin and mucous membrane play important role in immunity of the host.

• Works as a barrier

-Burns lead to infections

Biochemical Factors

• Hydrochloric acid of gastric secretions has antibacterial activity.

• Lysozyme in Sweat ,Saliva, Tears and Human milk ,give protection against grown +VE bacteria.

• Human milk has others antibacterial substances • Human milk has others antibacterial substances against E.coli and staphylococci called lactoferrttin

• Interferons are glyco-proteins produced by nucleated human cells in response to wide range of viral infections.

• Interferons inhibit viral replication and certain tumors.

Biochemical Factors continued……

• Complement system comprises of 18 distinct serum proteins .

• Complement activation can potentiate phagocytosis and stimulates the phagocytosis and stimulates the inflammatory reaction.

• There are two pathways of complement activation Alternate and Classical.

Cellular Factors

• There are two major cell types involved in innate immunity.

1)Phagocytic cells 2)Natural killer cells

Neutrophilic polymorphic Nuclear leucocytes (PMN)And Monocytic Macrophages.

Non PhagocyticLymphoid Cells.

Phagocytosis

• This is a process where by a single phagocytic cell engulfs objects such as unwanted or muted cells or invading unwanted or muted cells or invading infectious organisms.

• The various stages of phagocytosis are chemotaxis,Attachment,Ingestion,

Intracellular killing and Digestion.

ACQUIRED IMMUNITY

(SPECIFIC IMMUNITY )

• Specific response of body against Non-self or Altered Self or Foreign Agent.

• Immune products react specifically with the stimulating agent.the stimulating agent.

• Conventially divided into active and passive immunity ,both of which either may be natural or artificial.

NON-SPECIFIC TYPE

IMMUNITY

SPECIFIC TYPE

GENETIC BIOCHEMICAL

PASSIVE ACTIVE

OTHERS

PHYSICAL ,MECHANICAL

CELLULAR

PASSIVE ACTIVE

ARTIFICIAL

NATURAL NATURAL

ARTIFICIAL

Passive Immunity

• Involves either transfer of antibodies or in some cases sensitized white blood cells, from an Immune to an Non-Immune person.

• Natural passive immunity is transferred • Natural passive immunity is transferred from mother to baby through placenta or through colostrum .

• Artificial transfer is therapeutic use of Gamagloblins in treatments of Tetanus, Diphtheria ,Snake bite.

• Passive immunity is short lived

Active Immunity• When a foreign substance is encountered,

one of two responses is observed. • There is active immune response with

production of specific antibodies and sensitized cells. sensitized cells.

• -or Antigen specific unresponsiveness called immunological tolerance.

• There are three essential characteristic of Active Immunity ;

-Recognition -Specificity -Memory

Active Immunity continued………

• Recognition of foreign molecules is a prime characteristic of specific (Active) immunity .

• The substances so recognized are called Antigens. (The substances that stimulate immune response and react specifically with the resultant Antibodies or react specifically with the resultant Antibodies or sensitized cells )

• Immunogenicity is the capacity of an Antigen to stimulate immune response .

• The cells in the body that recognize Antigen are Lymphocytes called immunocompetent cells .

Active Immunity continued………

• Functionally there are two major sub-types of immunocompotent lymphocytes called T-Lymphocytes (Thymus Derived ) and B-Lymphocytes (Bone Marrow Derived)

• Antigen presenting cells (APC) • Antigen presenting cells (APC) Macrophages and denderatic cells process and present antigen to T-Cells.

• Expression of MHC molecules.• Cytokine secretion.

Hypersensitivity Reactions

• When an immunological sensitized individual comes in contact with same antigen second time it leads to secondary boosting of immune system .boosting of immune system .

• Secondary response may be excessive leading to tissue damage .

• Such a reaction is called hypersensitivity or Allergy .

Classification of Hypersensitivity

• Type I – Anaphylactic ,Atopic hypersensitivity.

• Type II –Antibody dependent cytotoxic hypersensitivity.

• Type III – Immune complex mediated hypersensitivity.

• Type IV –Cell mediated (Delayed type) hypersensitivity.

• Type V- Stimulatory hypersensitivity .

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