07. immunology

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1 Dr Alan Tuffery — Physiology Medical Science — 7 1 Slide 1 Lecture 7 — Immunology Structure Components Leukocytes Lymphoid tissue Recognition of self Innate Immunity Physical and chemical barriers Phagocytosis Inflammation Adaptive immunity Humoral responses (B cells) Cell mediated responses (T cells) Immune Disorders Autoimmune diseases AIDS Learning Outcomes 1. List the principal lymphoid tissues and outline their roles 2. List the differences between innate and adaptive immunity 3. Outline some key processes of innate immunity 4. Explain some key features of adaptive immunity 5. Explain the pathophysiology of some immune disorders. Dr Alan Tuffery — Physiology Medical Science — 7 2 Slide 2 A network of cells and tissues that: 1. Defends the body against invading pathogens 2. Removes ‘worn-out’ cells 3. Destroys abnormal/mutant cells within the body (e.g. control of cancer) Immune System can also have harmful effects: 1. Allergies / autoimmune diseases 2. Tissue rejection. Role of the Immune System (IS)

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Page 1: 07. immunology

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Dr Alan Tuffery — Physiology Medical Science — 7 1

Slide 1

Lecture 7 — ImmunologyStructure

• Components– Leukocytes– Lymphoid tissue– Recognition of self

• Innate Immunity– Physical and chemical barriers– Phagocytosis– Inflammation

• Adaptive immunity– Humoral responses (B cells)– Cell mediated responses (T

cells)• Immune Disorders

– Autoimmune diseases– AIDS

Learning Outcomes

1. List the principal lymphoidtissues and outline their roles

2. List the differences betweeninnate and adaptive immunity

3. Outline some key processesof innate immunity

4. Explain some key features ofadaptive immunity

5. Explain the pathophysiologyof some immune disorders.

Dr Alan Tuffery — Physiology Medical Science — 7 2

Slide 2

A network of cells and tissues that:1. Defends the body against invading pathogens2. Removes ‘worn-out’ cells3. Destroys abnormal/mutant cells within the

body (e.g. control of cancer)

Immune System can also have harmful effects:1. Allergies / autoimmune diseases2. Tissue rejection.

Role of the Immune System (IS)

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Dr Alan Tuffery — Physiology Medical Science — 7 3

Slide 3

FUNGUSEpidermophyton

floccosum(athlete’s foot)

VIRUS

Polio

PARASITETapeworm

BACTERIAStaphylococcus

aureus(causes sepsis)

Infection-causing organisms (Pathogens)

Dr Alan Tuffery — Physiology Medical Science — 7 4

Slide 4

Components — White Blood Cells

Lymphocyte

– B cells - secreteantibodies

– T cells - directly destroyforeign cells

– Natural Killer cells - fightviruses

Monocyte/macrophage

– Phagocytosis– Secrete cytokines

(signalling moleculesother than antibodies).

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Dr Alan Tuffery — Physiology Medical Science — 7 5

Slide 5

CENTRAL LYMPHATIC TISSUES– Bone marrow - site of B cell development (and pre-

T cell)– Thymus – site of T cell development

PERIPHERAL LYMPHATIC TISSUES– Spleen– Lymph nodes– Gut-associated lymphatic tissue (GALT)

[Peyer’s Patches]– Adenoids– Appendix– Tonsils.

Components — Lymphoid Tissues

Dr Alan Tuffery — Physiology Medical Science — 7 6

Slide 6

Components — self-recognitionMajor Histocompatibilty Complex

• MHC on every (nucleated) cell

– Also known as humanleukocyte associated antigens(HLA)

• Normally the body’s immunesystem does not attack cellsthat carry this ‘self’ markeri.e. MHC

• No two individuals, exceptidentical twins, will evershare identical MHC.

Transplant rejection

– Organ transplants and skin graftsmay be rejected due to presence ofMHC

– To minimise rejection, the MHC ofdonor and recipient are matched asclosely as possible i.e. tissue typing

– Siblings usually provide the closestmatch

– MHC do not play a role in transfusionreactions because red blood cells donot have MHC.

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Dr Alan Tuffery — Physiology Medical Science — 7 7

Slide 7

Skin & mucous membranesPhagocytosisInflammation

IMMUNE SYSTEM

INNATEINNATE IMMUNITY IMMUNITY(non-specific; natural)

ADAPTIVE IMMUNITY(specific; acquired)

HUMORAL-MEDIATED(antibody mediated)

B cells

CELL-MEDIATED

T cells

Organisation of the Immune System

Dr Alan Tuffery — Physiology Medical Science — 7 8

Slide 8

Innate vs Adaptive ImmunityInnate

(Phagocytosis, Inflammation)

• Nonspecific– Defends against any

pathogen upon firstexposure

– Responds to infectiousagents, chemical irritants,tissue injury, burns

Adaptive(Lymphocytes)

• Specific– Responds to specific

pathogens on 2nd orlater exposure

– Comes into play afternonspecific responseshave begun.

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Dr Alan Tuffery — Physiology Medical Science — 7 9

Slide 9

• Initial & immediate response against invasion by avariety of pathogens

• The response is rapid and non-specific

• Main mechanisms1. Interferon, NK cells and complement system2. Phagocytosis (by neutrophils & macrophages)3. Inflammation.

Innate Immunity

Dr Alan Tuffery — Physiology Medical Science — 7 10

Slide 10

Innate — 1. Interferon, Natural Killer Cells

Interferon• Released by virus-

attacked cells• Protects other cells

from any virus• Anti-cancer effects

– Slows cell division– Enhances action of

NK cells andcytotoxic T cells (qv)

Natural Killer cells

• Attack virus-infected cells…

• …Cause lysis

• NB Both IF and NKcells are non-specific— any virus.

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Dr Alan Tuffery — Physiology Medical Science — 7 11

Slide 11

Innate — 1. Complement System

Many very complex actions

• Innate response is recognition of micro-organisms

• Lysis of invading micro-organisms• Also reinforces other inflammatory

responses [hence name!].

Dr Alan Tuffery — Physiology Medical Science — 7 12

Slide 12

Innate — 2. Phagocytosis

Stages of Phagocytosis1. Attachment2. Internalisation (0.1 s)3. Degradation4. Exocytosis.

SEM macrophage engulfing bacteria

S&G. 23.3

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Dr Alan Tuffery — Physiology Medical Science — 7 13

Slide 13

Innate — 3. Inflammatory Response

1. Bacteria enter tissue/damage2. Release of histamine

– Increased blood flow– Increased vascular

permeability3. Increased leucocytes at site

Results– Destroy or inactivate invaders- Remove débris- Prepare for healing & repair.

Atopic_Dermatitis www.gcarlson.com

Animation of allergic (atopic) response

Dr Alan Tuffery — Physiology Medical Science — 7 14

Slide 14

Adaptive Immunity1. Specificity

• Lymphocytes (B and T cells) bind and respond to foreignmolecules known as antigens via antigen receptors

1. Diversity• The body possesses millions of lymphocytes that can recognise

and respond to millions of antigens (one each)

• Memory• 1st exposure to an antigen generates lymphocytes & long-lived

memory cells – next exposure to the same antigen, memory cellsreact more quickly & stronger response

• Self-Tolerance• Lymphocytes can distinguish ‘self’ (our normal antigens) from

‘non-self’ (antigens from foreign material).

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Dr Alan Tuffery — Physiology Medical Science — 7 15

Slide 15

Adaptive Immunity— humoral (antibody-mediated)1. B Cells — Clonal Selection

• Antigen fits B cell’s receptors• Proliferation and differentiation

into …

1. Plasma cells• Produce antibodies in blood

• (immunoglobulins IgG, IgM, IgE, IgA, IgD)• Short-lived

2. Memory cells (clone)• With same receptor• Long-lived.

S&G

23.7 (see Sherw

ood 12-11)

Dr Alan Tuffery — Physiology Medical Science — 7 16

Slide 16

• T cells must becomeactivated before theycan attack pathogens

• The antigen is‘presented’ to the Tcell by an ANTIGENPRESENTING CELL(e.g. an infectedmacrophage) via itsMHC

Adaptive — Cell-mediated Immunity

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Dr Alan Tuffery — Physiology Medical Science — 7 17

Slide 17

• CYTOTOXIC T CELLS– kill infected cells by lysis (direct action)

• HELPER T CELLS (~70% of T cells)– secrete cytokines that enhance the activity of cytotoxic T cells;

enhance phagocytosis– stimulate development of B cells into plasma cells (indirect action)

• SUPPRESSOR T CELLS– secrete cytokines that suppress the activity of B cells, helperT cells and cytotoxic T cells; inhibit phagocytosis.

Activated T cell enlarges & divides into:

Dr Alan Tuffery — Physiology Medical Science — 7 18

Slide 18

Adaptive Immunity

Natural

ACTIVE PASSIVEAntibodies or

lymphocytes are produced as a

result of infection

Antibodies are passed to foetus

via placenta or colostrum

Artificial

ACTIVE PASSIVE

Antibodies areproduced as a

result of immunisation with a vaccine

Antibodies that have been produced

by another animal or given artificially.

Adaptive Immunity can beNATURALNATURAL or ARTIFICIALARTIFICIAL

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Dr Alan Tuffery — Physiology Medical Science — 7 19

Slide 19

DISEASEDISEASE

• Systemic lupuserythematosus (SLE)

• Rheumatoid arthritis (RA)

• Multiple sclerosis (MS) (p116)

SYMPTOMSSYMPTOMS

• fever, arthritis, mouth ulcers,

• inflammation and damage tothe cartilage and bone of joints

• T cells attack myelin:Blurred vision,Muscle weakness,Ataxia

If immune system does not recognise its ‘self’ (e.g.MHC), it reacts against normal cells and tissues

Immune Disorders – Autoimmune Diseases

Dr Alan Tuffery — Physiology Medical Science — 7 20

Slide 20

• AIDS is caused by Human Immunodeficiency Virus (HIV)

• HIV binds to the surface of helper T cells and its nucleic acids(RNA and DNA) enter the T cell

• Inside the cell, HIV uses the cell to make copies of itself

• HIV slowly destroys helper T cells in the body(Helper T cells = 70% of all T cells)

• When T cell function is impaired, immune responses weaken andother diseases develop.

Immune Disorders - AIDS

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Dr Alan Tuffery — Physiology Medical Science — 7 21

Slide 21

SYMPTOMS

HIV Fatigue, fever, swollen glands, headache

AIDS Swollen lymph nodes, decreased T cell count;Susceptibility to pneumonia and Kaposi sarcoma;AIDS dementia

TRANSMISSIONThrough blood, semen, vaginal secretions and breast milk.

Immune Disorders - AIDS

Dr Alan Tuffery — Physiology Medical Science — 7 22

Slide 22

Learning Outcomes1. List the principal lymphoid tissues and outline their roles

• Thymus (T cell dev.); Gut —B cells)

2. List the differences between innate and adaptive immunity• Specificity, 1st exposure, cell-mediated, speed

3. Outline some key processes of innate immunity• phagocytosis, inflammation, immune memory, self recognition)

4. Explain some key features of adaptive immunity

5. Explain the pathophysiology of some immune disorders.