Innate Immunity Flashcards
Function of the immune system
Protective responses against external pathogens
What is the innate immune system ?
The first line of defence against external pathogens.
It is not specific.
What is adaptive immunity ?
Specific response
Can involve memory
State the 3 phases of response to initial infection
Innate Immunity
Early induced response
Adaptive Immune response
Innate immunity response time
Immediate : 0-4 hours
Early induced response time
Early : 4-96 hours
Adaptive Immune Response time
Late >96 hours
Describe innate immunity
Infection
Recognition of preformed non-specific effectors
Removal of infectious agent
Describe early induced response
Infection
Recruitment of effector cells
Recognition and activation of effector cells
Removal of infectious agent
Describe adaptive immune response
Infection
Transport of antigen to lymphoid organs
Recognition by native B and T cells
Clonal expansion of effector cells
Removal of infectious agent
How do pathogens get access ?
Mucosal surfaces
Describe the pathogen : influenza virus, neisseria meningiditis
Route of entry : Airway
Mode of transmission : Inhaled droplets
Disease : Influenza, Meningococcal disease
Describe the pathogen : salmonella typhi, rotavirus
Route of entry : GI tract
Mode of transmission : Contaminated food/ water
Disease : Typhoid fever, diarrhoea
Describe the pathogen : treponoma pallidum
Route of entry : GU
Mode of transmission : Physical contact
Disease : Syphilis
Describe the pathogen : flavivirus, plasmodium, borrelia burgdorferi
Route of entry : Insect bites
Mode of transmission : Mosquito, Ticks
Disease :Yellow fever, Malaria, Lyme disease
Describe the pathogen : tinea pedis
Route of entry : External surface
Mode of transmission : physical contact
Disease : Athletes foot
Describe the pathogen : bacillus anthracis, clostridium tetani
Route of entry : Wounds and abrasions
Mode of transmission : Minor skin abrasions, punctures
Disease : Anthrax, Tetus
State the 3 types of barriers to infection
Mechanical
Chemical
Microbiological
Mechanical Barrier
Tight Junctions between cells
Air and fluid flow across epithelium
Movement of mucus by cilia
Chemical Barrier
Fatty acids on skin
Enzymes : lysosome in saliva, sweat and tears
Low stomach pH
Antibacterial peptides
Name some antibacterial peptides
Defensins (skin and gut)
Cryptidins (gut)
Microbiological Barrier
Normal flora compete for nutrients and attachment, also produce antibacterial substances
Describe Innate Immunity
Recognition by phagocytic cells in the bloodstream/body : neutrophil/macrophage.
Phagocytosis - Engulfing and Destroying pathogen
State the anti-bacterial effects and agents produced by phagocytes
Acidification - pH 3-4, (low pH environment)
Toxic oxygen derived products
Toxic nitric oxides
Peptides
Enzymes
Competitors - depriving pathogen of nutrients
Where do all immune cells derive from ?
Haematopoietic stem cells
State the polymorphonuclear leukocytes
Neutrophils
Basophils
Eosinophils
Describe monocytes
Circulate in bloodstream, differentiate into macrophages in tissues.
(macrophage precursor)
Describe the action of macrophages
Phagocytosis and killing of microorganisms
Activation of T cells and initiation of immune reponse
Describe neutrophils
Most numerous & important granulocyte of innate immunity.
Phagocytosis and killing of microorganisms
What does neutrophil deficiency lead to ?
Overwhelming bacterial infections
Describe eosinophils
Evolutionarily important in parasite defence.
Killing of antibody-coated parasites through release of granule contents.
State the following about neutrophils :
Duration of Action :
Percentage of WBCs :
DOA : short : 12 hours, once in tissue 2 days
% WBCs = 70%
Neutropenia
Low numbers, may be genetic or the result of mediation including chemotherapy.
State some facts about eosinophils :
- Duration of action
- What the granules contain
DOA : short 12 hours, survive in tissues for 3 days
Granules : histamine, major basic protein
Describe basophils
Granulocyte
Function similar to eosinophils and mast cells
Describe mast cells
When activated release a number of substances that effect vascular systems.
IgE mediated triggering in allergies
Describe lymphocytes
Either B or T cells
Within these populations lie adaptive immune response
Describe B cells
Produce antibodies
Describe T cells
Become cytotoxic T cells or helper T cells
Plasma cells
Fully differentiated form of B cell that secretes antibodies.
Describe natural killer cells
Large granular lymphocytes
Recognise virus infected cells non-specifically
Describe dendritic cells
Most important immune cell
Bridges the innate and adaptive immune responses.
Specialised in antigen uptake and presentation.
State the 3 functions of natural killer cells
(IMP EXAM Q)
Induce resistance to viral replication in all cells
Increases MHC class 1 expression and antigen presentation in all cells.
Activate NK cells to kill virus-infected cells.
What do Natural Killer cells secrete ?
(IMP EXAM Q)
Interferon alpha
INterferon beta
State the difference between NK cells and CD8 T cells
NK cells are not antigen specific
They do not require to undergo the lengthly expansion of T cells in lymph nodes when the virus is detected.
Describe the green curve of NK cells
Production of interferon alpha and beta, tumour necrosis factor.
Peak of chemical signals which indicate infection, help cells become resistant to viral infection.
Describe the blue curve of NK cells
NK-cell killing of infected cells.
Helps get rid of and control virally infected cells during the initial stages of an infection.
Role of NK cells in immune reponse
Provide initial coverage to allow the adaptive immune response to get going over a period of time.
Keeps things under control until you start making your highly effective antibody response.
Describe the red curve of NK cells
Antibody response
T-cell killing of infected cells.
(secondary immune response)
Describe the yellow curve of NK cells
Amount of virus you could detect in the bloodstream of a person.
Interaction of NK cell with uninfected healthy cell
No killing of healthy cell
Interaction of NK cell with target cell in which MHC class 1 expression is lost
Killing of virus infected cell in which MHC class 1 expression is inhibited
Interaction of NK cell with healthy cell in the presence of anti-MHC class 1 antibodies
Anti-MHC class 1 antibody prevents interaction between the inhibitory receptor and the MHC class 1.
What is the complement pathway ?
A cascade of activated proteins that are pre-formed floating in your bloodstream and are available for immediate activation to fight off pathogens
What are the 3 main ways to trigger the complement cascade ?
Classical Pathway
Lectin Pathway
Alternative Pathway
Describe the Classical Pathway
Antibody binds to specific antigen on pathogen surface
Describe the lectin pathway
Mannose-binding protein binds to pathogen surface.
Describe the alternative pathway
Pathogen surface creates local environment conductive to complement activation.
Describe complement
Comprises a large number of distinct plasma proteins
Describe the outcomes of complement activation
Recruitment of inflammatory cells
Opsonisation of pathogens, facilitating uptake and killing by phagocytic cells
Lysis and death of pathogens
C3b
Membrane binding protein and OPSONIN
Opsonin
Coats bacteria and enhances phagocytic effects
C3a
Direct peptide MEDIATORS of INFLAMMATION
What is the classical pathway initiated by ?
Activation of the C1 complex
Describe C3a and C3b in the classical pathway
C3a - floats away and helps other phagocytic cells come to the site of infection
C3b - sticks on the surface of the pathogen, helps it be opsonised and phagocytosed
Difference between classical and alternative pathways
Alternative pathway : activation of C3b directly on the surface, you don’t need C1 component to start with (no pre-existing antibody response)
Trigger of the alternative pathway
Bacteria
Describe the assembly of the membrane attack complex (MAC)
Activation of C8 and C9 leads to formation of a pore which punctures through the membrane of the bacterial cell wall.
These pores are big enough to allow internal components of the bacteria to escape and kills the bacteria.
Activation of C8 and C9
Great way of directly killing bacteria
Function of regulation of the complement activation
Protects host cells from damage
Series of inhibitory molecules floating around in the bloodstream.
DAF
Decay accelerating factor
MCP
Membrane cofactor protein
CR1
complement receptor 1
How do you stop the membrane attack complex (MAC) from punching holes in your own cells ?
Exam Q
CD59 stops the membrane attack complex from forming on your own cells.
Complement deficiencies
Repeated bacterial infections
C2 - inflammatory disease
C3 - recurrent bacterial infections