3.2.2 The immune system

What is primary non-specific defence

The first line of defence that prevents the entry of pathogens. It’s non specific as the response is the same irrespective of the type of pathogen or whether it’s a first or 2nd attack.

NSP - Skin

• mechanical

• physical, protective barrier

• Secretes sebum that contains fatty acids with anti microbial properties

• Has anti microbial proteins on surface that change the structure and function of microbial csm

• Skin has an outer layer of dead, dry, hardened cells that provide an inhospitable environment for growth of microorganisms.

NSR - Blood clotting

• mechanical

• blood clotting cascade seals breaks in skin

NSR - mucous membranes

• chemical

• Lines airways, reproductive systems, gut

• Has goblet cells that secrete mucin that forms mucus

• Mucus traps pathogens and cilia wafts them back up the trachea to be expelled or swallowed

• Mucus also covers ciliated epithelium and prevents trapped pathogens reaching alveoli

• Has lysozymes that breakdown cell wall of bacteria

• Has phagocytes to destroy bacteria

NSR - HCl

• chemical

• HCl produced by parietal cells in stomach lining

• HCl in stomach kills swallowed pathogens

NSR - tears

• chemical

• Lysozymes that destroy cell wall of bacteria

NSR - cilia

• reflux expulsion - coughing/sneezing

• Ciliated epithelium beat and waft trapped pathogens up trachea to be swallowed or expelled

NSR - role of histamines in inflammation

Released by activation of MAST CELLS

• vasodilation - more blood flow to wound site - localised heat and redness (higher temp inhibits pathogen reproduction)

• Arterioles more leaky - more plasma forced out - more tissue fluid is formed - swelling / pain

What is an inflammatory response

A localised response to pathogens at site of wound that causes redness, pain, odema (swelling) and heat

NSR - role of cytokines in inflammation

Released by mast cells

• IL-1 and IL-6 attract phagocytes to wound site - phagocytosis occurs and pathogens engulfed and destroyed

• Stimulation of liver to release proteins that bind to surface of bacteria and damaged host cells to promotes phagocytosis by macrophages

NSR - role of serotonin and prostaglandins in inflammation

• make arterioles more leaky

• Vasodilation

How do fevers help defend against pathogens

• many pathogens reproduce at 37 degrees or lower, so higher temp inhibits pathogen reproduction

• Specific immune responses work faster at higher temp

3 types of phagocytes

• neutrophils

• Macrophages

• Dendritic cells

Role of neutrophils

• circulate in blood plasma

• Short lived - die after phagocytosis

• Rapid response

• Chemicals released by pathogen or infected cell attract neutrophils. (Chemotaxis)

• neutrophils have receptor proteins on surface that bind to antibodies attached to antigens on pathogen

• once attached, pathogen is engulfed and destroyed

Role of macrophages

• long lived

• These are monocytes that leave the bloodstream and enter tissues

• Process and present antigens to the lymphocytes instead of killing pathogens directly.

• Macrophages digests the pathogen and combines the antigens form pathogen’s csm with glycoproteins called major histocompatibility proteins (MHC)

• This allows the macrophage to present the pathogens antigens to its surface

• Macrophage becomes an antigen presenting cell (APC)

• The exposed antigens can be recognised and destroyed by other lymphocytes

Dendritic cells

• long processes that increases surface area for the interaction with pathogens + lymphocytes

• Once they engulf pathogens they migrate to lymph nodes

Mode of action of phagocytes

• pathogen produces toxins

• damaged cells releases cytokines

• Phagocytes are attracted to cytokines and toxins and travel to site of infection via chemotaxis

• Antigens in surface of pathogens recognised as foreign

• Receptors on surface of phagocytes bind to antigens on pathogen via opsonins

• Phagocytes engulfs the pathogen via endocytosis to form a pseudopodia (where csm extends around pathogen) until the csm fuses with itself again

• Phagosome is formed

• Phagosome fuses with a lysosome to form a phagolysosome

• Lysosomes contain hydrolytic enzymes that digest and destroy pathogens

• Harmless products released into cytosol of phagocyte

Role of cytokines in phagocytosis

• acts as cell signalling molecules that attract phagocytes to site of infection/inflammation

• Increases core body temp - inhibits pathogen reproduction

• Stimulates a specific immune response

Role of opsonins in phagocytosis

• extracellular proteins that induce phagocytosis

• Bind to pathogens and ‘tags’ them so they’re recognised by phagocytes

• Phagocytes have receptors on surface that bind to opsonins allowing the pathogen to be engulfed.

site of production and maturation of T-lymphocytes/B-lymphocytes

• both produced in bone marrow

• T = matures in thymus gland

• B = matures in bone marrow

Role of T-lymphocytes in SPECIFIC immune response - CELL MEDIATED IMMUNITY

• CLONAL SELECTION - T-helper cells have CD4 receptors on their csm that bind complementary to antigens on surface of antigen-presenting cells, which causes t-cells to be activated

• CLONAL EXPANSION - activated t-cells proliferate and divide by mitosis to produce many clones (different types of T-cells)

  • T-HELPER

  • T-KILLER

  • T-MEMORY

  • T-REGULATORY

Role of T-HELPER CELLS

T-helper:

• releases interleukins (type of cytokine) that activate B-cells

• attract and stimulate macrophages to engulf pathogens

• stimulate production of other types of T-lymphocytes

Role of T-Killer cells

• recognise foreign antigens on csm of infected host cells and attaches to them

• releases toxic chemical PERFORIN which punches holes in csm of infected host cell so it becomes freely permeable and dies via lysis

T-MEMORY CELLS

• Long lived cells that remain in blood

• if same antigen is recognised again in a secondary attack, t-memory cells rapidly divide by mitosis to produce large numbers of clones of t-killer cells to destroy the pathogens

T-REGULATORY cells

• ensure body recognises self-antigens so an autoimmune response isn’t carried out

• stops immune response once pathogen is destroyed

B-LYMPHOCYTE specific immune response - HUMOURAL IMMUNITY

• CLONAL SELECTION - B-cells are activated by interleukins produced by t-helper cells

• CLONAL EXPANSION - activated B cells proliferate and divide by mitosis to form clones

• some clones differentiate into B-PLASMA cells and others into B-MEMORY cells

role of B-PLASMA CELLS

PRIMARY IMMUNE RESPONSE

• short lived cells

• secrete antibodies (immunoglobulins) that are specific to the antigens on csm of pathogen into the plasma

role of B-MEMORY CELLS

SECONDARY IMMUNE RESPONSE

• Long lived cells

• remain in body after infection to provide immunological memory

• if same antigen is encountered again, they divide rapidly by mitosis + differentiate to produce lots of clones of plasma cells so there’s a faster and higher production of Ig (before symptoms appear)

what will plasma cells have more of

• ribosomes - increased protein synthesis of Ig

• golgi apparatus - more proteins need to be packaged and processed

• RER: increased protein synthesis

• mitochondria - supply energy for Ig synthesis

why do we get symptoms for disease when first exposed to a pathogen

• there’s a delay in the primary immune response if we’re exposed to a new pathogen

• it takes time for clonal selection/expansion of T/B-cells to occur

• it takes time for antibodies to be produced and released into teh blood

why do we still experience symptoms when re-infected with the same pathogen as before?

• some diseases are caused by multiple different strains i.e common cold/flu

• each strain has different antigens, so a primary immune response must be carried out each time before immunity is achieved

structure of antibodies

• Y-shaped globular glycoproteins called immunoglobulins

• quaternary structure

• 2 heavy polypeptide chains bonded to 2 light polypeptide chains via disulphide bonds

• hinge region allows flexibility so antibody can bind to the antigens at an angle and bind to more than one antigen at a time

• constant region - same for all Ig in the same class (5 classes of antibodies)

• variable region - different for each antibody

  • has an antigen-binding site that’s specific to the epitope (part of antigen that binds to antibody) on an antigen

  • the antibody binds to the antigen to form an antigen-antibody complex

Function of antibodies

• agglutination

• opsonins

• lysis

• anti-toxins

• precipitations

role of agglutination

• Ig will bind to 2 identical antigens on 2 or more different pathogens

• Ig immobilises the pathogen, causing the bacterial cells to clump together

• this makes it harder for the bacteria to enter host cells

• harder for bacteria to spread through blood stream

• easier for phagocytosis as phagocyte can engulf multiple pathogens at once

role of antibodies as opsonins

• constant region of Ig binds to receptors on csm of phagocyte

• variable region of Ig binds to antigens on pathogen/damaged cell

• this allows the pathogen to be marked so phagocytes can identify them easier and destroy them

lysis - antibodies

• Ig binds to pathogen and attracts complement proteins

• these proteins creates holes in csm of pathogens

• bacterial cells becomes freely permeable

• water moves in via osmosis

• bursts (lysis) as cell contents leak out

role of anti-toxins

• Ig binds to toxins and neutralises them so they can’t prevent harm

Test for TB

• blood test carried out first to determine if person has Ig (if yes, test not needed)

• MANTOUX TEST

• tuberculin (from mycobacterium tuberculosis) is injected just below skin

• If Ig already present, inflamed and red area will appear

• Inflamed area is measured:

  • Big area = strong immunity (or active TB)

  • Small area = weak immunity - vaccine given

  • No area = no immunity - vaccine given

Importance of early screening for HIV

important as can lead to early diagnosis so early treatment can be given - people can get counselling/advice about how to limit spread of HIV

Test for HIV

1. Blood sample

   • tests for specific antibodies and antigens present in blood

   • Results in 2-14 days

   • More accurate test - less false +/-

   • if +, 3 follow up tests needed before diagnosis

2. Point of care test

   • finger prick or mouth swab

   • Results in 11-28 days

   • Chance of false +/-

3. ELISA testing

What does Elisa testing stand for

Enzyme linked immunosolvent assay

When is an ELISA test used and what’s it used for

• used to detect the presence of antibodies for a particular pathogen

• Used after an immune response has developed and antibodies have been produced

How does ELISA testing work

• first coat well with antigen that antibodies would be specific to

• Add patients serum and let sit in well for few mins to allow antibodies to bind to antigen - fixed capture molecule

• Wash away serum and unbound antibodies

• Add enzyme-linked antibody (secondary antibody) which is specific to human Ig

• Leave for few mins and wash away unbound secondary antibodies

• Add substrate and look for colour change (colour change = +ve result = antibodies specific to substrate)

• +ve result = antigen-antibody enzyme linked antibody antibody sandwich

Passive and active immunity differences

PASSIVE:

• no immune response

• B/T lymphocytes not stimulated - no memory cells

• Immediate response

• Temporary immunity

ACTIVE:

• immune response

• B/T lymphocytes activated - memory cells produced

• Longer lasting and greater immunity

• Time delay - antibody conc. takes time to increase

Passive natural immunity

• antibodies received across placenta via breast milk that’s rich in IgA

• Infants gut can absorb Ig into blood without being hydrolysed

• Only offers protection from diseases mother has had

Passive artificial immunity

• injection of Ig from external source

• As no memory cells are produced and Ig is eventually broken down by liver, boosters are needed e.g tetanus vaccine - acts as antitoxin and prevents spread of pathogens by preventing viruses from in entering host cells

Active natural immunity

• person exposed to live pathogen and gets infected

• Produces Ig themselves

• Experiences symptoms

• Memory cells produced - secondary infection means more Ig produced and at faster rate

• Not ok for people with compromised immune systems I.e HIV

Active artificial immunity

• antigens received from external source

• E.g vaccination

How is an allergic reaction triggered:

• person exposed to allergen

• Triggers an immune response

• IgE produced which binds complementary to receptors on mast cells

• Allergy molecules bind to IgE that are attached to the mast cells which triggers histamines to be released via exocytosis

• Histamines increase permeability of capillary walls - excess tissue fluid formation - inflammatory response