Immune System Flashcards
What is the immune system
A versatile defence system that protects us from pathogenic microbes
With 3 main lines of defence
First line of defence
“Innate immunity”
Physical barrier ie skin & mucous membranes
Second line of defence
“Innate immunity”
Non-specific response when pathogens pentrate first line of defence
includes:
Complement system
Transferrins
Phagocytes
NK cells
Inflammation
Cytokines (eg interferons)
Fever
Third line of defence
“Specific/adaptive immunity”
Activated by innate immune system, producing a response towards a specific pathogen
What is a pathogen
An infectious agent that can cause disease in a host
What aRe antigens
A protein (hence specific 3D shape) with an identifiable genetic code
That can be recognised by leukocytes
2 main types of antigens
- Foreign (eg microbes, food, drugs)
- Self-antigens (present on cell membranes) - transmembrane proteins
What are antibodies
Proteins produced in response to a specific antigen
Combine with specific antigens reading identifiable code
Where are IgA found
Saliva, sweat, tears, breast milk, mucous secretions
Immunoglobulin - aka antibody - first layer of defence on surface
Stress compromised
How does the skin act as a first line of defence
Physical barrier with tightly packed epithelial cells
Outer epidermis consists of dead epithelial cells & sheds which remove microbes
Dermis contains accessory structures sebaceous & sweat glands which have immune functions
Immune function of sebaceous glands
Contains fatty acids which inhibit microbial growth as well as waterproofing the skin
mucous membranes as first line of defence
Digestive, respiratory & urogenital, conjunctiva
Contain IgA & lysozomes
Saliva, tears, mucous Wash away microbes & are antimicrobial
Mucous traps microbes & foreign bodies eg mucociliary escalator take down to stomach to be swallowed
What are transferrins
Iron-binding proteins in blood
Act to inhibit growth of certain bacteria, by reducing the amount of available iron
Why is excess iron problematic
Feeds bacteria if pathogens present
Increases favourable environment
What is the complement system
A defensive system of proteins that help to destroy microbes
made of over 30 proteins produced by the LIVER
Proteins Identified by a letter with a number eg C3
Proteins are inactive & only become active when split by enzymes into active fragments eg C3 > C3a + C3b
What is the classical pathway
Most common mechanism through which complement system is activated
Whereby antigen-antibody complexes are formed
When activated they act in a cascade -amplified
What is opsonisation
Where complement fragment C3b ‘coats’ a microbe causing phagocyte to attach
What complement fragments contribute to inflammation
C3a & C5a bind to mast cells & cause release histamine
What complement fragments contribute to cytolysis of a microbe
C5, 6,7,8,9
Join & create hole in cell, which causes it to take in fluid & ultimately bursts microbe
What are cytokines
Protein hormones that act as chemical messengers, stimulating or inhibiting immunity cell functions
Group of non-antibody proteins secreted by leukocytes
What are interleukins
Group of cytokines
Act as mediators between leukocytes
Released by macrophages
What are interferons
Grouped under cytokines
Produced by cells that are infected by a virus
Involved in anti-viral responses
Messenger tells surrounding uninfected cells to stop dividing & induce synthesis of anti-viral proteins that prevent viral replication
What are Tumour Necrosis Factor (TNF)
Grouped under cytokines
Promote accumulation of neutrophils & macrophages to cause cell death
Two main types of phagocytes
- Neutrophils
- Macrophages
Non-selective in targets
‘Antigen presenting cells’
Two types of macrophages
Aka Monocytes in blood, macrophages in tissue
Fixed = watch over specific tissues
Wandering = migrate to sites of infection & enlarge
Digests, excretes, sticks small amount onto its own cell membrane to then present to T-lymphocyte helper cells to learn specific antigens
‘Antigen presenting cells’
Two main antigen presenting cells
Macrophages & B-lymphocytes
Present to T-lymphocytes
Main types of fixed macrophages & where they are found
• histiocytes - connective tissue
• kupffer cells - liver & erythrocytosis
• alveolar macrophages -lungs
• microglia - nervous tissue
• langerhans cells - skin
• tissue macrophages - spleen, bone marrow & lymph nodes
What is a granuloma
Pathogens resistant to adherence in phagocytosis are instead surrounded by macrophages & immune cells to try & contain microbe
Eg tuberculosis
What are NK cells
Non-specific lymphocytes
Attack anything not recognised, including abnormal body cells
Bind to a target cell & release granules containing protein ‘perforin’
Present in blood, lymph nodes, spleen & bone marrow
What is perforin
A protein released by NK granules when binding to a target cell
Perforin inserts into target cell membrane & creates a channel for tissue fluid to flow into the cell = cytolysis
Main cardinal signs of inflammation
• redness
• heat
• pain
• swelling
• loss of function
How do histamine & heparin promote inflammation
Cause vasodilation & increased permeability
Released by mast cells & basophils
Leukotrienes as inflammatory mediator
Attract phagocytes & increase vessel permeability
Released by basophils & mast cells
Kinins as inflammation mediators
Proteins that induce vasodilation & increase permeability. They also attract phagocytes & induce ‘pain’
Prostaglandins as inflammatory mediators
Lipids released by damaged cells
Enhance effects of histamine & kinins (& so intensify pain)
What does the cytokine interleukin-1 increase
A hormone protein that enters the blood & resets hypothalamus thermostat
Increases body temp/induces a fever
Positives of elevated body temp
- makes interferons more effective
- inhibits growth of some microbes
- speeds up reactions that aid repair
When reaching beyond 39 degrees becomes dangerous
Leukocytes are either
Granular or agranular
Most abundant leukocyte
Neutrophils 60%
Phagocytic cell
Release lysozomes that digest
What cells release histamine & heparin & roles
Basophils & mast cells
Histamine = vasodilation/increase permeability
Heparin = anticoagulant
Involved in inflammation - easy flow to prevent stagnation
Express receptors for IgE & hence involved in allergies & hypersensitivity
Main leukocyte involved in asthma
Eosinophils
Also destroy parastitic worms via phagocytosis (less efficient cell)
Main antigen presenting cells
Macrophages
Also b lymphocytes
What mediates the connection between ‘innate’ immune system & the ‘adaptive’
Cytokines & antigen presentation
T & B lymphocytes are usually at rest unless activated for specific antigens
What is the MHC
Major Histocompatibility Complex
Group of cell surface proteins that are required for recognising self-antigens vs non-self
Formed of four polypeptide chains & display a protein produced by the cell (‘self’) on its binding groove
Two types
MHC-I
MHC-II
Class I MHC role
Located on all body cells except erythrocytes
Cell produces its own proteins that combine with MHC-I & are displayed on the cell membrane indicating whether ‘self-antigen’
If damaged/abnormal this shows in the proteins produced
Allows leukocytes to differentiate between healthy body cells from abnormal/infected
Class II MHC role
Located only on membrane of ‘antigen presenting cells’
Eg B-lymphocytes & macrophages
Displays the foreign antigen on its binding groove after ingestion to then present to T helper cells
What involved in cell-mediated immunity
T-cells / T-lymphocytes
Each have a unique T-cell receptor
CD4 receptor
Produced in bone marrow but mature in thymus
What involved in antibody-mediated immunity
B-cells / B-lymphocytes
CD4 cells
CD4 protein present on surface
T-helper cells & macrophages
CD8 cells
Cytotoxic T-cells
What traits are T-cells tested for in the thymus
- Ability to recognise self-antigens
- Not react to self-antigens “self tolerance” - loss leads to autoimmunity
Tested against thymus epithelial cells
Only 1-5% make through the process
B-cells undergo similar screening process in bone marrow
Role of interleukin 2 in antigen presentation
When antigen fragment binds with T helper cell it secretes the cytokine interleukin2
This causes T-lymphocyte proliferation & stimulates “clonal selection” of B-lymphocytes
This creates the active attack as well as immune memory
What does cell mediated clonal selection produce
- Cytotoxic T-lymphocytes - protein digests via perforin & granzymes
- Memory T-lymphocytes
- Helper T-lymphocytes - release cytokines increasing immune cell activity
Or suppresses when threat removed
Role of regulatory T-cells
De-activate immune cells when response no longer required
Maintining immune system homeostasis & tolerance to self-antigens
Why lock and key analogy for antibodies
Because they only bind specifically with the antigen that stimulated their production
“Antibody-antigen complexes” formed
What ways can antibodies inactivate antigens
- Neutralising
- Immobilising - binding
- Agglutination & precipitating - both binding sites can cause clumping
- Activating complement cascade
- Enhance phagocytosis
Concept of a vaccine
Immunological memory is the basis
Contain weakened, whole or partially dead portions of microbes - are immunogenic but not supposed to be pathogenic!
B & T cells activated can take several day
Naturally acquired active immunity
Natural exposure to a disease
Naturally acquired passive immunity
Transfer of IgG antibodies across the placenta from mother to child
Transfer of IgA from mother to child via breast milk
Artificially acquired active immunity
Vaccination
Encourages bodies immune process
Artificially acquired passive immunity
Injection with immunoglobulins eg anti-venom for snake bite
Immunity without body doing anything as remedy given
Hypersensitivity means
An excessive immune response produced by normal immune system
Hypersensitivity type I, II, III are mediated by
Antibody-mediated
Hypersensitivity type IIII mediated by
Cell-mediated
T-cell aka cytotoxic
What is type 1 hypersensitivity
Aka allergy
IgE antibody mediated (produced by plasma cells) that bind to mast cells causing degranulation
Immediate onset/rapid
Reactions eg hay fever, eczma, irritant contact dermatitis or serious reaction eg anaphylaxis & shock
What is type 2 hypersensitivity
As seen in blood transfusions & haemolytic disease of newborn
IgG antibody mediated as can cross placenta
Bind to antigens on cell surface activating complement system
Rapid onset
What is type 3 hypersensitivity
As seens in glomerulonephritis, RA & SLE (lupus)
Antibody-antigen complexes are formed and deposit in capillaries, skin, kidneys, joints which activates complement system triggering immune response eg inflammation
IgG, IgM, IgA mediated
Onset 4-8 hours
What is type 4 hypersensitivity
Involved in skin graft rejection, allergen contact dermatitis & MS
Cell-mediated, over reaction of T-lymphocyte cells to an antigen
Large number of CD8 (cytotoxic) & cytokines released, damagining normal tissues
Delayed type, 48-72 hours
What is anaphylactic shock
Severe, systemic allergic response within 5-10 mins of antigen exposure
IgE antibodies activate mast cells & basophils causing degranulation & histamine release
Bronchoconstriction, vasodilation & oedema of tissue
Danger because can occlude airways
Epinephrine treatment aka adrenaline - Epipen reverses histamine
Structure of an antibody
Y shaped made up of 4 polypeptide chains
Containing a variable region & a constant region & 2 binding grooves
What does antibody mediated clonal selection produce
Antigen binds to B cell where it is broken down and then expressed on the MHC-II
Helper T cells recognise the antigen complex on B membrane & release interleukin 2 which triggers B-cell clonal selection
Plasma cells (secrete antibodies) & Memory B cells are produced
