Immunology

[John]

Immunology

 

 

Non-specific resistance

A wide range of defences against pathogens

 

External barriers: Mechanical

Skin, mucous membranes, Tough keratin & normal flora

Hair, saliva, urine, mucus & Mucociliary escalator Filter, trap & wash

 

External barriers: Chemical

Lysosomes: Enzymes which destroy bacterial cell walls in tears , perspiration, saliva, nasal secretions, colostrum & tissue fluid

Acid: In skin, gastric juice, urine, vaginal secretions

 

Internal defence mechanisms

Phagocytes

Engulf foreign particles

These are White blood cells

Neutrophils & macrophages.

Inflammation

(-itis)

Confines & destroys microbes & repairs tissue. Mediated by cells & inflammatory chemicals.

Begins when basophils & mast cells secrete bradykinin, histamine & other substances

This causes vasodilation which causes increased blood flow (heat, redness) and increased capillary permeability (swelling).

Phagocytes activated. (margination, diapedesis, chemotaxis).

Complement activated.

Clotting reaction walls area off. Regional temp increases.  Specific defences activated.

Pain arises from damaged nerve endings, bradykinin, prostaglandins or bacterial toxins.

 

(Flow diagram from “Marieb” is excellent. Copy in other BB folder, but it uses lots of computer memory (& aids your memory?))

  

Fever

Promotes interferon activity & phagocytosis,

Inhibits microbial growth,

Speeds up enzyme activity & body reactions that aid repair.

 

Interferon

Produced by virus infected cells

Protects uninfected host cells from viral infection,

activates NK cells & macrophages,

destroys cancer cells.

 

Complement

Destroys bacterial cell walls by;

making holes causing cell lysis,

attracts phagocytes (chemoattraction)

enhances phagocytosis (Opsinization)

stimulates inflammation by stimulating mast cells & basophils.

Made of 20 or more plasma globulins (proteins)

 

NK (natural killer) cells

Large lymphocytes who destroy body cells if cancerous or contain virus

Null cells

 

Specific Immunity

Production of a specific antibody or T lymphocyte against a specific antigen or toxin

A learned response

 

Antigen

Any substance (usually protein) which causes an immune response.

Bacteria display several different ones

Usually a macromolecule

Small haptens escape identification unless they join a protein & become ‘visible’

Autoimmune diseases; body regards own cells as antigenic

 

Antibody

Immunoglobulin

Produced by lymphoid tissue

In response to an antigen

Is specific to that antigen

 

Specific immunity

Involves recognition of the antigen as different from self

Response is specific to that antigen

Develops memory of that antigen

May be either; Humoral or cell mediated

 

Humoral immunity

B cells or B lymphocytes

Found in blood, lymph nodes, lymph glands, spleen and bone.

Become plasma cells when activated & produce antibodies

Antibodies eliminate the pathogen

Macrophages or B cells with complementary receptors injest the antigen

Antigen fragments are displayed on the cell surface

Roaming helper T cells which discover the displayed fragments release lymphokines (chemical signals) like interleukin-2

This actives B cells to multiply rapidly. Some become memory cells. Most become plasma cells.  Plasma cells produce antibodies (2000/cell/sec)

 

Antibodies

Neutralise antigenic toxins by covering

Neutralise antigen by covering pathogenic sites & binding sites thus preventing attachment to cells (virus)

Agglutinate. Bind antigens together in clumps. Limiting mobility

Form antigen-antibody complexes (immune complexes). These enhance phagocytosis & trigger complement activation

There are 2 million different antigen binding sites for specific antigens

There are 5 different types of antibody: IgA, IgD, IgE, IgG, IgM

 

IgA; Protects external surfaces

Found in breast milk, colostrum, saliva, mucus, tears, GI tract & plasma

 

IgG; Most plentiful (80%) in plasma. Can cross the placenta

 

IgM; first produced after initial exposure

 

Cell mediated immunity

Immature T lymphocytes (T cells) migrate from bone to thymus

(gain immunological competance) to lymphoid tissue

 

Several different T cells:

Cytotoxic T cells; CD8 or T_C. Especially good at destroying transplant tissue,

                                 cancer cells & host cells infected with virus

Helper T cells:      CD4 or T_H. Assist all aspects of immunity (B & T cells)

Memory T cells

 

Cell mediated immunity

Macrophages, B cells (APCs) or host cell harbouring a virus, display antigen fragments

 

These are recognised by CD4 & CD8

 

CD4 releases lymphokines that

Promote the inflammatory response

Attract neutrophils

Stimulate macrophages to enhance phagocytosis

Stimulate production of more CD4 & CD8

 

CD8 recognise antigens & lock on.

They then release perforins which perforate cell membrane or Lymphotoxins

Which destroy target cells DNA

 

Primary Response

Occurs on first exposure to antigen.

Takes several days for the immune system to develop antibodies

  & lymphocytes specific to a new antigen.

Peak antigen production occurs around 10 days after exposure.

During the primary response memory B and memory T cells develop

Memory may last years

 

Secondary response

Occurs when antigen is recognised from a previous exposure.

Immune response is quick (hours)

Response is more intense and prolonged than the primary response

 

Example

A skin graft from an unmatched donor looks good for a week.

Because there are no antibodies or Tcells which recognise it as non-self

A second graft from the same donor would die in 1-2 days.

As memory B cells immediately produce antibodies and memory T cells produce large numbers CD8s

 

Types of Immunity

Innate: Genetically inherited resistance

Active: Memory cells develop

Passive: Donor antibodies given

Natural: As a result of the disease process

Artificial: By injection of antigens or antibodies

 

Innate immunity

Influenced by your species, race & family

Species: Being human provides resistence to plant & many animal diseases

Race: Develops over centuries of exposure

Family: Age, sex, nutrition, stress, hygiene

 

Active Immunity

Individual develops their own B & T memory cells

Either

1. By contracting the disease & recovering

Or

2. By innoculation with a vaccine or toxoid

 

Active natural immunity

By contracting the disease both humoral & cell mediated immunity is stimulated

Memory cells develop

These can last a life time

If about 70% of a population is immune (by either natural or artificial immunity)

  the entire population is usually protected (herd immunity)

 

Artificial Active immunity

Using vaccination

Usually given to children & travellers

Altered antigens are injected to stimulate an immune response

Antigens may be:

 

Artificial Active immunity

 

1. Micro-organisms which are killed by heat or chemicals without altering their antigenic properties. Large numbers needed.

These are phagocytosed & a primary immune response occurs where memory B & T cells are produced after 7 - 14 days

May need 3-4 innoculations to produce enough memory cells for immunity

Boosters may be needed every few years

Typhoid, Whooping cough, Polio (Salk)

 

    2. Living attenuated vaccines

Weakened micro organisms with reduced virulence produce a mild or subclinical disease.

A primary immune response produces B & T Memory cells

Immunity is as good as naturally aquired immunity

Polio(Sabin), measles (both rubella & rubeola), mumps, smallpox & tuberculosis

 

    3. Toxoids

Where disease is caused by exotoxins;

Toxins are inactivated by heat or chemical to produce toxoids

Immunisation produces a primary immune response similar to killed vaccines

Boosters are needed

Tetanus, diptheria

 

4. Recombinant DNA

Part of the hepatitus B virus that codes for its antigen is cloned into yeast

Yeast produces Hep B antigenic components used as a vaccine

Allergic reactions can occur to vaccines containing albumin, antibiotics or preservative

 

Natural Passive Immunity

IgA antibodies are passed to another through milk or colostrum

IgG antibodies are passed to baby across the placenta

Protection is immediate and temporary

Immunity lasts 3-6 months as no memory cells develop

 

Artificial Passive Immunity

Antibodies are administered by injection

As antiserum

Protection is immediate and temporary

Immunity lasts 2 – 3 weeks

Used to treat or protect from after exposure to; tetanus, gangrene, botulism, diptheria, Rhesus disease, Hepatitis B, Venoms.

Serum sickness (an allergic reaction) can occur