J.

IMMUNITY
Immune system = bodys defense system
Antigen = any molecule that body recognises as foreign
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Learning Objective / Outcomes:

Phagocytes & lymphocytes: Structure, origin, maturation & mode of action To explain meaning of the term immune response T & B lymphocytes : mode of action, origin, function Role of memory cells in long-term immunity Molecular structure of antibodies related to their function Active & passive immunity Natural & artificial immunity Vaccination
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4 components of blood???
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White Blood Cells/ Leucocytes (0.5%):

Lifespan: (varying) Contents: Eosinophils, basophils
Phagocytes Lymphocytes
Monocytes/macrophages neutrophil

Function: Immunity
- inflammation - phagocytosis - antibody production
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Blood cells
:: how to tell them apart::
WBCs Granulated Eosinophil - 2 x RBC - multilobe nucleus Basophil - 2 x RBC - bean nucleus Neutrophil - 2 x RBC - multilobe nucleus Agranulated Macrophage - 2.5 x RBC - bean nucleus Monocyte - 2 x RBC - bean nucleus Lymphocyte - same as RBC - oval nucleus 5

RBC - 7 m wide - no nucleus - biconcave

Functions of WBCs

White blood cells

Origins - Cells of the immune system

The cells of the immune system originate from the bone marrow. There are 2 groups of these cells: i) phagocytes (e.g. neutrophils and macrophages/ monocyte) ii) lymphocytes (T and B cells)

 Phagocytes

Phagocytes & phagocytosis (Non specific immune response)

- produced & stored in bone marrow before distributed in blood circulation

- feed like Amoeba on bacteria, viruses and dead body cells.

Neutrophils
60% of WBC in blood (most abundance)

Macrophages
Larger than neutrophils found mostly in lung, liver, kidney, spleen, & lymph nodes, rather remain in blood

travel throughout the body (blood)

squeeze through the capillary wall and into the infected tissue, engulf and leave the bone marrow & travel in digest offending bacteria blood as MONOCYTES then develop into MACROPHAGES once short-lived cells released in large settle in organs numbers during infection long-lived cells which initiate immune response by displaying antigens to be recognised by 9 lymphocytes

Phagocytosis

ingestion of invading microorganisms by certain type of white blood cells which are phagocytic / phagocytes
Phagocytes attach to microbes via microbes surface receptors Phagocyte engulfs the microbes, form a vacuole that fuses with a lysosome Lysosomes destroy microbes by 2 ways: 1. Nitric oxide & other toxic forms of oxygen contained in lysosomes poison the engulfed microbes 2. Lysozyme & other enzyme degrade the microbial components However, some microbes can evade from the attachment & destruction of phagocytes because their receptors are surrounded by outer capsule. Some resistant to lysosomes.
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Phagocytosis - Neutrophils
Cells under attack respond by releasing histamine, attract passing neutrophils (chemotaxis) neutrophils move towards the pathogen & its plasma membrane engulf the pathogens & trap it to form a phagosome. Inside the vacuole, digestive enzymes are secreted to kill the pathogen

After killing & digesting the pathogens, the neutrophils die.

Dead neutrophils often collect at a site of infection to form pus
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Phagocytosis - Neutrophils
1. Attraction (chemotaxis)

2. Recognition & attachment

3. Endocytosis 4. Bacteria within a phogocytic vacuole 5. Fusion of lysosomes & phagocytic vacuole

6. Killing & digestion

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Phagocytosis - Macrophage

Cut antigen up that it can be recognised by lymphocytes

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Phagocytosis of bacteria by a macrophage

bacteria

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Lymphocytes
Smaller than phagocytes, with a large nucleus fills most of the cell 2 types:
1. B lymphocytes ( B-cell) 2. T lymphocytes ( T-cell)

Similarities: Both B & T cells are produced before birth in bone marrow Only mature lymphocytes can carry out immune response. When mature, all B & T cells circulate between blood & lymph
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Lymphocytes: B cells and T cells

Differences:

B cells remain in bone marrow until they are mature then spread throughout the body concentrating in lymph nodes & spleen Y-shape and 4 polypeptide chain Bind with 2 antigen Immune system- humoral respond

T cells T cells mature once migrated from the bone marrow to the thymus gland. 2 polypeptide chain bind with 1 antigen. Immune system- cell mediated respond
Thymus- a gland lies in the chest just beneath the sternum Double in size between birth & puberty

Shrinks after puberty

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Adenoid Tonsil Lymph nodes Right lymphatic duct, entering vein Thymus Thoracic duct Thoracic duct, entering vein Lymph node Masses of lymphocytes and macrophages Valve Lymphatic vessel Blood capillary Tissue cells Interstitial fluid

Appendix

Spleen

Bone marrow

Lymphatic vessels Lymphatic capillary

Human lymphatic system consists of lymphatic vessels, through which lymph travels, & various structures that trap foreign molecules. These structures include the adenoids, tonsils, lymph nodes, spleen & appendix. Macrophages are either residents permanently in the spleen, lymph nodes & other tissues of lymphatic system to combat infectious agents or migrate 17 throughout the body.

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???
State the sites of origin & maturation of B cells & T cells.
Origin: bone marrow B cell mature in bone marrow; T cell mature in thymes gland

Suggest why the thymus gland becomes smaller after puberty.

By puberty, T cell have matured and left the thymus gland. Thus, thymus has

no further use so it decrease in size.

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Cytotoxic T-cells (Killer T-cells) Only B-cells can secrete antibodies.

Immunity

There are 2 major kinds of defense: 1. Innate Immunity

External defenses & Internal defenses

NKC work by undergoes apoptosis which is burst together with the bacteria NKC- non phagocytic WBC, patrols in body, performs apoptosis

2. Acquired Immunity
Overview of vertebrate defenses against pathogens

Phagocytes & NKC Lymphocytes

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How do lymphocytes work? Antigen Recognition

2 main types of lymphocytes: B lymphocytes (B cells): helper B cell T lymphocytes (T cells): cytotoxic/ killer, helper T Both circulate through blood & lymph, concentrated in lymphoid tissues Posses many identical antigen-specific receptors which embedded in their plasma membranes can recognize same epitope(name) of antigens or closely related antigens
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B Cell Receptors
A Y-shaped molecule Consist of 4 polypeptide chains: 2 identical heavy chains 2 identical light chains These chains linked by disulfide bridges Tail portion of molecule is the transmembrane region anchors receptor in the cells plasma membrane Short region at the end of tail extends into cytoplasm Variable regions amino acid sequences vary extensively from 1 B cell to another Remainder of the molecule made up of constant (C) regions Each B cell receptor has 2 identical antigen-binding site Interaction with antigen stabilized by multiple non-covalent bonds between chemical groups on molecules
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Slide 28

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Immunoglobulins
An antibodies secreted by lymphocytes

Structurally similar to B cell receptors

But lack of the transmemberane regions that anchor receptors in plasma membrane Thus, B cell receptors also called = membrane antibodies / membrane immunoglobulins

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T Cell Receptors
Consists of 2 different polypeptide chains ( and chains) linked by disulfide bridge Transmembrane region anchors the molecule in the cells plasma membrane Out tip of these chain are variable (V) regions, form a single antigen binding site Remainder of the molecule is constant (C) regions

B Cell Receptors vs T Cell Receptors

B cell receptors recognize intact antigens T cell receptors recognize small fragments of antigens that bound to normal cells surface proteins (MHC molecules)
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Interaction of T cells with MHC molecules

MHC

Antigen presentation

MHC Major Histocompatibility Complex

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Acquired Immune Response

Cell-mediated immune response
involves the activation & clonal selection of cytotoxic T cells, which directly destroy certain target cells

Humoral immune response

involves the activation & clonal selection of B cells, causes the production of secreted antibodies which will circulate in

blood & lymph

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 T cells develop surface receptors called T-cell receptors where they become programmed for the antigen of their specific enemy If an antigen is presented to a T cell with a complementary shaped receptor, the T cell is stimulated, increases in size and starts to divide cytotoxic T cells/ killer cells + helper T cells memory cells T cells reproduce rapidly, however they do not produce antibodies like B cells Cell-mediated immunity
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Chemical substances

Only Active helper Tcell will release chemical substance

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T Helper
recognise the non-self antigen (from the foreign cells) that the macrophages display on their outer surface. release a powerful group of chemicals called cytokines to stimulate B cells to proliferate

Cytotoxic T cell /Killer T

Cytotoxic (kill cell) attack & kills body cells that have been infected by virus, bacteria or fungus.

Kill the infected cells by secreting proteins (perforin) that punch holes in the membrane of the cell, and the stimulate macrophages to carry out contents ooze out. phagocytosis more vigorously.

In addition to helper & killer cells, memory T cell are produced which remain in the body & become active quickly during secondary response
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A T cell

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Cytotoxic T cells attacking a cancer cell

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A human helper T cell (green) under attack by HIV (red spheres)

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 When the pathogen first enter the body, macrophages engulf and digest microbes (including their antigens) through a process of called phagocytosis. Some of the digested antigens are then displayed on the surfaces of the macrophages. This is called antigen presentation T-helper cells antigen presentation B cell OR any B cells whose cell surface receptors fit the antigens, can respond directly

B cell dividing repeatedly by mitosis & after several generations will differentiate into plasma cell (antibodies) + memory B cells
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Humoral Immunity response

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of Humurol Cell-Mediated pond by antigen, gnition e mitosis matured es(receptor)

ween Humurol Cell-Mediated pond T cell MHC molecule destroy infected cell directly (KillerT cell produced perforin)
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Memory Cells
Remain circulating in the bodies for long time/ life time If antigens reintroduce after 1st infection, memory cells divide rapidly & develop into plasma cell (B cells) or killer cells (T cells) + more memory cells Thus, infection can be destroyed & removed before any symptoms of disease develop

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Changes in antibody concentration in blood

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Primary response: 1st response at 1st infection Slow Why?

Very few B cells are specific to the antigen at this stage Take times to replicate more plasma cell (give antibodies) ~15 days ~8 days

Secondary response 2nd exposure to antigen Faster Why?

Many memory cells available Can quickly divide & differentiate into plasma cells Give antibodies

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What is antibody?
Antibodies are globular glycoproteins and form the group of plasma proteins called immunoglobins.

A protein made by the immune system in response to the presence of an antigen & targeted specifically at it

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Antibody Structure
Four polypeptide chains
two light chains two heavy chains

All the chains are joint by disulphide bond Each chain has a variable region
Made up of different amino acid Bind to same Antigen Different Antibody has different variable region
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Hinge region.. Spring like..

The hinge region gives the flexibility for antibody to bind to antigens that are differently spaced
antigen microorganism

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Fab and Fc Regions

Fab (Fragment antigen binding) region contains the antigen-binding site Different antibody has different antigen-binding sites Fc (Fragment crystallisable) region Different Antibodies have same Fc region

Fab
Disulphide bridges

Fc

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(1) Prevent entry

How do Antibodies Work?

(2) prevent movement (3) agglutination

(4) lysis

(5) opsonisation

(6)neutralisation

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Four Classes of Antibodies

monomer

pentamer

Ig GAME

dimer

monomer
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Antibody (Recap)!!!!
Definition of antibody
Globular glycoprotein, immunoglobulin

Molecular structure of antibody

4 chains: 2 light & 2 heavy chains disulphide bridges Antigen-binding sites : variable regions Fab (Fragment antigen binding) region & Fc (Fragment crystallisable)
region

4 classes of antibody
IgG, IgA, IgM, IgE

6 functions of antibody
(1) Prevent entry (2) prevent movement (3) agglutination (4) lysis (5) opsonisation (6)neutralisation
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???
Why polysaccharides would not be suitable for making antibody molecules?
-Polysaccharides are made from only a small number of different sugar unlike
protein that are made from 20 different amino acid. - Polysaccharides would not give the same huge number of different molecule shape as is achieved with protein in the variable region of antibodies.

There are many different strains of the rhinovirus, which causes the common cold. Explain why people can catch several different colds in the space of a few months.
-Immunity to one strain does not provide immunity to all of them as they do not all share the same antigens.
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Why people are often ill for several weeks after they catch a disease, even though they can make antibodies against the disease?
- Because the primary respond to an antigen is slow. - It take several weeks (usually~16 days) to produce enough antibody to fight the infection effectively - During this time, we usually shows the symptoms of the disease concerned.

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June 07 Paper 1

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June 07/P1

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N/04

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N/06

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J/08

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- Infection to disease - Maternal antibodies - Vaccination - Synthetic antibodies

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Active immunity
immunity gained following infection Because lymphocytes are activated by antigens on surface of pathogens that invaded into the body Activate B or T cells to give effective defense

1. Natural Active immunity body manufactures antibodies when exposed to an infectious agent. 2. Artificial Active Immunity injection of antigens into body, taking by mouth vaccination or immunisation Does it safe?
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 small dose of antigen is usually safe because the pathogen is either killed or attenuated (pathogen has being weaken) individual does not contract the disease itself, but is stimulated to manufacture antibodies against the antigen. second booster/ injection is given and this stimulates a much quicker production of antibody.
Long term immunity

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Vaccination
Is a preparation containing:
antigenic material (live/ dead/ harmless/ attenuated microbes), harmless toxin, or a preparation of surface antigen

Highly effective vaccines 1 injection may give a lifetimes protection

Less effective vaccines need booster injections to stimulate 2nd respond Does every single vaccine work?
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Problems with vaccines

1. Poor respond
Some people do not respond well / or not at all to vaccines Because of defective immune system: a) Inborn / Primary Immunodeficiency An immunodeficiency disease caused by a genetic or developmental defect in immune system Example: Severe combined immunodeficiency (SCID) both humoral & cell-mediated branches of acquired immunity fail to function b) Acquired / Secondary Immunodeficiency An immunodeficiency disease that develops later in life following exposure to various chemical or biological agents Example: Acquired immunodeficiency syndrome (AIDS)
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Poor respond also because of malnutrition

Especially protein energy malnutrition Do not have enough protein to make antibodies or clones of lymphocytes Higher risk to develop infectious disease

2. Antigenic variation Rhinovirus- colds- has at least 113 different strains Trypanosoma- sleeping sickness- has 1000 different antigens, & changes them every 4 or 5 days
Antigenic drift - minor changes in antigen structure, memory cells can work Antigenic shift - major changes
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3. Antigenic concealment

Some pathogens hide inside cells

Plasmodium enters liver cells or red blood cells, protected against antibodies in the plasma

Some parasitic worms cover their bodies in host proteins, invisible to immune system Some pathogens parasiting the macrophages & T cells

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Passive immunity
immunity gained by antibodies made other than in the host

1. Natural passive immunity

Antibodies made in one individual are passed into another individual of the same species. Mother fetus Antibodies from mother cross the placenta during pregnancy, remain in the infant for several months Example: Ig G ( circulates in the blood, prevent the growth of bacteria & virus)

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Explain the pattern of maternal & infant IgG.

Concentrations of antibody in the blood of fetus & an infant

fetus

Maternal IgG increases during pregnancy as it crosses the placenta (natural passive immunity) It decreases after birth as it is removed from the circulation Fetus does not produce its own antibodies because does not have mature T/B cells, & is kept in sterile environment Infant produces its own antibodies shortly after birth as it begins to encounter 64 infections

2.

Artificial passive immunity

Antibodies which have been made in one individual are extracted and then injected into the blood of another individual which may, or may not, be of the same species Tetanus: kills quickly, body needs immediate defense a prolonged contraction of skeletal muscle fibres, bacterial infection at wound contamination. Injection of antitoxin: provides immediate protection but only temporary. Why? Antibodies not produced by the bodys own B/T cells & therefore regarded as foreign Will remove from circulation by phagocytes in the liver & spleen (No memory cells) 65

Immunity

Antigen encountered

Immune respond

time before antibodies appear in blood Several week

Production of memory cells

protection

Active

yes

yes

yes

long term

Passive

no

no

immediate

no

temporary

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???
What are the difference between artificial active immunisation (vaccination) and artificial passive immunisation?

Artificial Active Imm

Artificial Passive Imm

Antigen are introduced into the Antibodies are injected into the body by injection/ by mouth body To stimulate an respond by B / T cells Gives a long term immunity (memory cells are generated) But respond not immediate Temporary /Short-term immunity, no immune respond Temporary/ short-term immunity, remove from circulation soon Gives an immediate respond
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Pass Year Questions - J

O/N 08/ P2 No.1 O/N 05/P2 No.4 (c) M/J 04/ P2 No. 6 O/N 03/ P2 No. 3, No.5 (c) and (d) O/N 02/ P2 No. 5

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