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ImmunologySPP 3341

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Tolerance

Good or bad?

For which cells?

Where?

Central tolerance

Positive selection

Negative selection

for B cells: receptorediting

Peripheral tolerance

anergy

clonal ignorance

activation-induced celldeath

suppression

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Hypersensitivity

Good or bad?

Types based onimmunological

mechanisms: Antibody mediated

Type I IgE mediatedreaction

Type II cytotoxic reaction

Type III immune complexreaction

T-cell mediated

Type IV cell mediatedimmunity reaction/delayed

type hypersensitivity

Examples

hypersensitivities

allergy

transfusion reactions,rhesus incompatability

serum sickness

Arthus reaction

autoimmune Link to autoimmune

diseases?

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Autoimmunity

Good or bad?

Definition

Mechanisms how it

develops:

molecular mimicry

polyclonal activation

(superantigens)

presentation of hidden

self antigen

modification of cell

surface

Link to tolerance?

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Autoimmune Disease

Good or bad? Types:

Organ-specific

Systemic

Types based on

immunological

mechanism: Type II: autoimmune haemolytic

anaemia, Graves, myasthenia

gravis

Type III: SLE

Type IV: Type I DM, rheumatoid

arthritis

General therapy: anti inflammatories:

corticosteroids

immunosuppressive:

cyclosporin

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Tumour Immunology

Good or bad?

Controlling tumourgrowth

CTL NK, NKT

antibody & complement

cell lysis

antibody

ADCC

cytokines

TNF

Tumour evasion/escapefrom immune system

tumour doesnt providesuitable target

no antigenic epitope

reduced MHC I

does not provide signal 2

immune system doesntrespond well

poor antigen presentationby APC

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Transplantation

Good or bad?

transplantation

rejection

autograft, syngraft,allograft, xenograft

MHC

HLA Class I: A, B, C

HLA Class II: D [DP, DQ,DR]

polymorphic genes,codominantly expressed

Link to tolerance?

Rejection

host versus graft

hyperacute: preformed

ab/CROSSMATCHING

acute: 1o T cell activation/TISSUE

TYPING

accelerated: reactivation of

sensitised T cell

chronic

graft versus host bone marrow, skin, alimentary

tract, liver

privileged tissue

NO REJECTION

Immunosuppression

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Immunity towards infection

Good or bad?

Bacteria

Extracellular: antibody,

phagocytes Intracellular: CTL

Gram positive: not MAC

but phagocytosis

Gram negative: MAC,phagocytosis

Mycobacterium: DTH

Virus

Intracellular: CTL, NK,

Type I IFN

Extracellular virusparticle:

Fungi

phagocytosis

Helminths

IgE and eosinophil/mast

cell activation

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Immunodeficiency

Good or bad? Primary

B: X-linked

agammaglobulinaemia/Brutons

B: IgA deficiency

B: Hyper IgM syndrome

B: CVID

T: DiGeorge

B & T: SCID

Phagocytes: CGD, Chediak-Higashi

Complement

classical: lupus-like

lectin: increased infections

alternative: pyogenic, Neisseria sp

infections

Secondary drugs

HIV

burns

chemotherapy/radiation

chronic disease

splenectomy

malnutrition

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Immunisation

Good or bad?

Active

administration of an

agent that STIMULATES

immune system to

become protective

Passive

administration ofprotective immune

agents

Types of vaccines killed whole

attenuated

toxoids

subunit vaccines

Vaccination schedule &

their types

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Immunotherapy

Good or bad?

Active

tumour infiltrating lymphocytes

LAK

DC vaccine

Passive

cytokine infusion

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Aging and Immunity

Good or bad?

Definition

Changes to immune

system thymus

innate cells

adaptive cells

cytokine expression

haematopoiesis

Effects on immunity

infection

reduced response to

vaccination cancer

autoimmune diseases

inflammatory conditions