Introduction to the Immune System Learning Objectives: - Understand the role of the cells in the innate and adaptive immune system - Describe the

Introduction to the innate and adaptive Immune System

The Innate Immune System

First line of defense - physical barriers

• Non-specific general barrier

→ Skin - sebaceous glands, hairs, keratinised cells

→ Epithelia - pH in stomach, cilia of the respiratory system, mucus on the GIT, lysozomes in tears

• Second line of defense - Innate Immune cells

• Non-specific but rapidly acting and efficient

• comes to the aid of anyone that needs help no matter what the danger is

• No memory

• Neutrophils, macrophages, etc. → phagocytose biomateral and pathogens

• Engulfs foreign bodies and activates the Adaptive Immune System

Adaptive Immune System

• Third Line of defense

• Slower to act, more specific

• Has memory

• Relies on ifnormation from the innate immune system

Macrophages and dendritic cells are communicating cells between innate and adaptive immune system.

→ are antigen presenting cells, they engulf foreign particles and present to adaptive immune cells for them to respond

Cells of the Innate Immune System

Neutrophils

• 40-60% of all white blood cells

• Neutral cytoplasm, multi-lobed nucleus

• Primary cell in acute inflammation

• Phagocyte - destroy bacteria

• Short life span (few days)

• Neutropenia seen after chemotherapy - low neutrophil numbers, chemo patients at highest risk of infection

• Most abundant, without would be very sick

• Travel rapidly to site of inflammation

  

Basophils

• Rapid first line of defense

• Contains granules consisting of proinflammatory molecules and cytokines (INCLUDES HEPARIN AND HISTAMINE)

• Recruits eosinophils and neutrophils

• Short life span

• Responsible for acute and chronic allergic disease e.g. Asthma, atoptic dermatitis, hay fever, and anaphylaxis

  

Eosinophils

• Cytoplasm stains red with H&E

• 1-3% of WBCs

• Granules contain enzymes and proteins to attack parasites

• High levels of eosinophils can indicate a parasitic infection

• Implicated in allergic diseases such as asthma

  

Mast cells

• Contains granules rich in histamine and heparin these protect against bacteria and parasites

• Also commonly associated with allergic reactions

• Mast + Basophils responsible for local irritations, anaphylaxis, and athsma attacks

• → process is done by increasing vascular permeability and bronchocontriction

• Treatments for asthma include mast cell inhibitors

  

Cells of the Innate Immune System - Antigen Presenting Cells

Monocytes

• the largest leukocyte

• consist of 2-10% of all leukocytes

• Non-granulated cytoplasm, uni-lobar nucleus

• Respond to inflammation and travel to the site of tissue injury within 8-10 hours of infection

• At the site of injury they differentiate into macrophages or dendritic cells (precursor to these)

• These are crucial antigen presenting cells that are messengers between the innate and adaptive immune system

  

Macrophages

• originate from monocytes

• main role - phagocytosis (e.g. of foreign bodies, cancer cells)

• present antigen to t cells and initiate inflammation by releasing inflammatory cytokines

• t cells can recognise these better now

• produce reactive oxygen species e.g. nitric oxide which kills phagocytose bacteria

Dendritic cells

• Professional antigen presenting cells

• Present antigen on the cell surface to T cells in the lymph nodes (migrates here)

• DC’s have characteristic long processes that “taste” their environment, can stretch and contract

• can sample gut lumen

• Harmful bacteria would be sampled and then taken to T cells

• Important in tolerance

  

T Cells/T lymphocytes - Cell mediated response

• originate in bone marrow

• mature in the thymus before entering the circulation

• 4 main types of T effector cells

→ T helper cells

→ Cytotoxic T cells - cells infected by virus

→ Memory T cells

→ Regulatory T Cells

• removal of infection

Cells of the Adaptive Immune System

B Cells - Antibody Mediated Response

• B cells originate and mature in bone marrow

• B cells are activated by T cells

• Once activated they proliferate into plasma cells (antibody production) and memory cells

Function of Antibodies

• Neutralise bacteria/virus

• Agglutination - foreign cells clump together

• Clumps become targets for phagocytosis

• 5 Main types of antibody: IgM, IgA, IgG, IgD, IgE

• IgM - first response to infection

• IgG - bacteria and virus

• IgE - helminths and worms, involved in allergic reaction

Conditions of the Immune system

Hypersensitivity reactions

• Caused by an antigen that wouldn’t normally trigger an immune response

• More damage results from the immune response than from the antigen itself

• Tissue damage

• 4 types of hypersensitivity reactions

• Type 1, 2, 3, 4

• Immune system is triggered and maintained inappropriately to exogenous (peanuts, beestings) or endogenous antigen (autoimmune disease)

Type 1

• Allergy - Immediate allergic reactions

• food, pollen, asthma, anaphylaxis

• Antibody mediated - IgE

• Damage caused by T cells, IgE antibodies, mast cells, and other leukocytes

• Characterised by repeat exposure to antigen

sequence

• dendritic cell presenting antigen to T cell, activating B cell

• B cell differentiates into IgE secreting plasma cell

• IgE binds to mast cell, sensitising mast cell to allergen

• repeated exposure of allergen, mast cell releases all of granules

• mediators include vasoactive amines, fast acting cause vasodilation, increased vascular permeability, smooth muscle contraction, increased secretion of mucous and inflammation → redness, swelling, runny nose

• produce cytokines in late phase reaction: recruit and activate leukocytes and amplifies immune reaction

Type 2

• Antibody mediated destruction of cells

• Cytotoxic

• IgM or IgG antibodies bind to antigen on cells and target these for phagocytosis (macrophages do this), causing tissue injury

• Destruction of cells seen in hemolytic disease of the fetus, where the mothers antibodies cross the placenta and attack the RBC of the foetus

Type 3

• IgG antibodies bind to circulating antigens

• Antigen-antibody immune complex formation and deposition in tissue

• Deposits in tissue activate acute inflammation

• Attracts neutrophils results in neutrophilic lysis or phagocytosis of cells

• E.g. Systemic Lupus Erythematosus

Type 4

• T cell mediated diseases

• Delayed type hypersensitivity

• Antigen presenting cells activate T cells that have been pre-sensitised to a specific antigen

• T cells release cytokines > activation of macrophages > inflammatory response

• Or activation of cytotoxic T cells

• Eg. Rheumatoid arthritis, Multiple Sclerosis, Type 1 Diabetes, IBD