2 - INNATE AND ADAPTIVE IMMUNITY Flashcards
Describe the general characteristics of innate immunity
Non specific
Do not require previous exposure
Present at birth
Immediate response, no memory cells
Recognises surface molecules that are common among many pathogens
Provides initial discrimination between self and non-self entities
Initially inhibits spread of invaders
Functions of the innate system
Initial defence against microbes - preventing spread, eliminates and controls
Eliminates damaged cells and initiates repair
Stimulates adaptive immune response
Innate defences: surface barriers
Physical barrier: skin and mucosal surfaces - to trap microbes and carried to external surfaces via ciliated epithelial cells
Cough reflex: prevents entry into the RT
GIT: acidic pH, proteolytic enzymes are not an ideal environment for microbial survival
Innate defences: internal defence
Specialist cells: destroy invading microbes
- Macrophages and neutrophils: phagocytosis and activation of bactericidal mechanisms
- Dendritic cells: antigen presentation in lymph nodes
- NK cells
Inflammation
Antibacterial peptides
- amino acids with anti-microbial activity
- defensins: kills a wide range of bacteria, some fungi and enveloped viruses
Secreted by neutrophils, epithelial cells and paneath cell
Disrupts the microbe membrane causing lysis
Describe the process of inflammation
Injury causes the release of inflammatory mediators
Acute inflammation removes damaging stimulus which can either result in:
- cell regeneration: restore normal function and structure
- no cell regeneration: healing by repair and scar formation
What processes begin inflammation?
Tissue/cellular injury
Attempt to prevent spread of agent
Disposal of debris and pathogens
Tissue repair
What are the signs of inflammation?
Redness Heat Swelling Pain Loss of function
What are the types of inflammatory mediators
Cytokines: proteins that are released by cells that affect other cells
Chemokines: proteins released by cells to attract other cells to the area
Acute-phase proteins: plasma proteins that increase in concentration with inflammation
Provide examples of acute phase proteins and their mechanisms
C reactive protein: binds microbes and activates complement
Kinins: locally induce vasodilation
Describe the process of phagocytosis
- Phagocytic cell recognises surface of microbe, adheres and takes in microbe
- Held within phagosome and fuses with lysosome to form a phaglolysosome
- Toxic substances kill and degrade microbe -
- nitric oxide
- superoxide anions
- hydrogen peroxide - Exocytosis to remove debris
Describe the mechanism of NK cells
NK cells recognise reduces MHC I molecules via receptors
ADCC: Antibody dependent cell mediated cytotoxicity - NK cells attach to abys via Fc receptor on cell surface
Direct cytotoxicity by release of perforin and granzymes
How does the inhibitory receptors of NK cells work
When inhibitory receptor is engaged
- NK cell is not activated = no cell killing
When inhibitory receptor is engaged
- NK cell is activated = cell killing
How is the innate system stimulated
PAMPs - pathogen associated molecular patterns
DAMPs - damage associated molecular patterns
Describe the mechanism of PAMPs
When the cells of the immune system, recognises a particular structure on a pathogen a response is stimualated
Give examples of the structures on pathogens that are recognised by PAMPs
Virus: nucleic acid - ssRNA, dsRNA, cpG
Bacteria: proteins - pilin, flagelin
GNB: cell wall - lipids
When cells of the innate system recognise lipids found on the cell wall on a GNB a response is stimulated
Describe the mechanism of DAMPs
Damaged cells will release molecules in response to trauma resulting in healthy cells releasing alarmins to enhance the innate response
Describe how pattern recognition receptors on cellular phagocytes work
Dendritic cells, macrophages and neutrophils have TLR that bind to PAMPs/DAMPs activates a signal transduction pathway to promote inflammation and anti-microbial activity
Provide examples of TLR, their location and the PAMP/DAMP they bind to.
TLR 1 - bacterial lipoproteins found on cell membrane binds to microbial molecules via LPS or viral nucleic acid
Provide examples of TLR found on cell membranes
TL-1: Bacterial lipoproteins
TL-2: Bacterial peptidoglycan
TL-4: LPS
TL-5: Bacterial flagelin
What are NOD-like receptors
NOD: nucleotide binding oliomerisation like receptors
Are specific for intracellular pathogens
These receptors are found in the cytosol of cells
Are activated by peptidoglycan, RNA, toxins and flagellin
They release pro-inflammatory cytokines: IL1, IL6, TNFa and IL8
What are the groups of interferons and what is their function
IFNa, IFNb and IFNy
IFNa and IFNb are produced in response to viral infection
INFy are inflammatory - macrophages, B cells and T helper cells
Describe the mechanism of interferons
Binds specific receptors of neighbouring cells
- neighbouring cell produces PKR: blocking virus entry
- Limits spread of viral infections
- Stops production of protein in cells -> inhibiting virus production
- Stimulates endonuclease production -> Degrades viral mRNA
What are APCs
Antigen presenting cells
Phagocytose antigens
APCs migrate to the lymph node and digests + presents antigens to T helper cells via MHC II
What are the types of APCs
Dendritic Cells
Macrophages
Describe the general characteristics of the adaptive immunity
Is stimulated once innate system has been overwhelmed More specific Has memory Mediated by lymphocytes Two branches: humoral and cell mediated
How is communication permitted between the innate and adaptive immune system
Via DCs and macrophages
List the characteristics of humoral immunity
Antibody mediated
Acts against extracellular invaders
Produced by B lymphocytes
List the characteristics of cell mediated immunity
Lymphocytes kill infected cells
Act against intracellular invaders
Cytotoxic T cells involved
Define somatic cell recombination
Multiple gene segments are combined and recombined to form variations in protein binding of antigen
What is the action of antibodies
Activate complement
Trigger phagocytosis
Neutralise viruses and toxins
Agglutination
List the classes of antibody isotypes
IgG IgA IgM IgE IgD
Describe each antibody isotype
IgG - monomer, most abundant in SERUM: long term immunity and can cross the placenta
IgA - monomer in serum and dimer in secretions, most abundant overall: found in saliva, mucosal surfaces, nasal fluids
IgM - pentamer and involved in primary response; first aby to appear during an infection
IgE - monomer, binds mast cells basophils and eosinophils causing granule release: anti-parasitic and allergy responses
IgD - monomer, attached to B cells and is the largest antibody
Describe the primary immune response
Has a lag of several days for B cell proliferation
Antibody levels peak and falls as the antigen is removed
The predominant antibody isotype: IgM
Describe the secondary immune response
Second exposure to the same antigen
The response is much quicker and larger, with a rapid rise in antibody levels
Memory cells become plasma cells much more quicker
Predominant antibody isotype: IgG
Define clonal selection
How a B or T cell is selected to destroy a particular antigen
Describe how clonal selection works
An antigen can only bind to an antibody specific to it, the antigen will select the antibody
The specific antigen binds to the variable region on the B cell surface
The B cell is stimulated
Clone is selected
Other antibodies on other B cells are not able to bind
Describe cell-mediated immunity
Mechanism acting against intracellular infections (viruses, mycobacteria) and cancer cells
T cells involved: Cytotoxic T cells which require T help cells
Describe the mechanism of cytotoxic T cells
Have a wide range of surface receptors against an antigen
Each Tc is specific for one receptor
Infected cells will express the antigen on their surface by MHC I
Tc via a T cell receptor binds and destroys the cells expressing the specific antigen with MHC I
Killing occurs by the release of toxic molecules effecting the membrane causing lysis and initiating apoptosis
