Immune System Flashcards
What are 3 types of granulocytes
Neutrophils
Eosinophils
Basophils
What is the major circulating white blood cell
Neutrophils
What is the major mechanism of granulocytes
Phagocytosis
What is the name of the enzymes which produce bleach
Myoperoxidases
What is a method used by Neutrophils to kill pathogens
conversion of oxygen into toxic oxygen free radicals
What is special about necleophiles when seen under a microscope
Polynucleated, with 1 nucleus in multiple lobes
Where are the granules kept in the granulacytes
Cytoplasm
What is the capsule in which the phagocyte engulfed into called
Phagosome
Which type of pathogen do Granulocytes focus on
bacteria
How do Nucleophiles move from the blood vessel into the non-immunological organs
Walls become sticky to slow down the cells
Cells squeeze through the epithelium cells towards the infection (extravasation)
What happens to the nucleophiles in the blood if there is no infection after 24hrs
The Cells die
What is the function of macrophages
Remove Debris from damaged tissues
How do macrophages perform their function
Phagocytosis
What is the name of Liver Specific Macrophages
Kuppfer Cells
What si the name of the precursor of the macrophage, and where is it found
Monocyte, found in blood
When are the macrophages used in the immunological defence against pathogens
2nd Wave, when the granulocytes fail. Have stringer killing mechanisms than granulocytes
What is the major cell of the adaptive immune response
Lymphocytes
What are the names of the 2 sub-populations of lymphocytes
T and B cells
Where do T Cells develop
Thymus
Where do B Cells develop
In the Bone Marrow
Which 2 locations do the lymphocytes circulate through
the Tissues and Blood
What is a typical feature of the Lymphocyte when seen under a microscope, unactivated
Almost No Cytoplasm
How long does it take for the T Cell to become highly activated
24hrs
What does a Plasma Cell Differentiate from
B Cells
What is typical for Plasma Cells
Packed with Endoplasmic Reticulum
How Long Lymphocytes live for
20-30 years
Where do Lymphocytes re-circulate through
Blood Vessels and lymphatics
Where do Effector T Cells leave to go to the tissues to control infection
Blood Stream
What do Naive and Memor cells leave the bloodstream to enter lymphoid tissue to search for
Antigens
Where does the primary immune response start
Lymph Nodes
What is the role of dendritic cells (2)
Sampling Antigens from the environment
Carrying samples to the lymph nodes
What are 3 types of dendritic Cell
Langerhan’s Cell
Veiled Cell
Interdigitating Dendritic Cell
Which Type of dendritic cell can be found in the skin
Langerhan’s Cells
Which 3 types of cell are in the innate immune system
Granulocyte
Macrophage
Dendritic Cells
Which 2 types of cells are in the Adaptive Immune System
T cells
B cells
What is the type of interaction in immune recognition
Receptor-Ligand Interaction
What is the name of the receptors of innate immunity
Patter Recognition Receptors
What is the name given to the ligands which are molecular components of the microbe
Pathogen Associated Molecular Patterns (PAMPs)
What does Toll-like Receptor 3 bind to
RNA
What does Toll-Like Receptor 4 bind to
Gram-negative Bacterial Lipopolysaccharide
What does Toll-Like Receptor 2 Bind to
Lipoteichoic Acid
Where are Pattern Recognition Receptors (PRR) Found (4)
Blood
Cell Surface
Within Cellular Organelles
Cytoplasm
What are 3 Innate Effector Mechanisms
Phagocytosis and intracellular Killing
Extracellular Killing
Interferons and Restriction Factors
How does complement act
In a proteolytic amplification cascade system
What is the central step of the complement pathway
C3 cleaved into C3b and C3a
What are the 3 major functions of complement
Opsonisation
Lysis
Inflammation
What is the opsonisation pathway of complement
C3b binds onto C3b receptors on phagocytes leading to Phagocytosis
What is the Cell Lysis pathway of complement (3)
C3b cleaves C5 in C5b and C5a
C5b, C9, C6, C7 and C8 form membrane attack complex
Attack Complex causes cell lysis
What does C9 Form
Pores in the bacterial cell membrane
What is the Inflammation pathway of complement (5)
C3a and C5a cause mast cell degranulation
Degranulation leads to increased vascular permeability
Neutrophils chemotaxis
Granulocytes attracted to the area of infection
Inflammation
What are the 3 ways o activate complement
Bacterial Surfaces (Directly activate complement)
Acute Phase proteins
Antibody
What are the 3 pathways which lead to the central step in complement
Alternative Pathway
Classical Pathway
Lectin Pathway
What do all the complement activation pathways lead to
Cleaving of C3 into C3a and C3b
What is the main defence against viruses
Interferons
What cells can produce type 1 interferons
All Nucleated Cells
What do Interferons induce
A potent anti-viral state
How do interferons act
Via the up-regulation of many restriction factors
What does the resistant state mean for a cell infected by a virus
Unable to perform regular functions as all energy put into viral defence
What is the virus protected from when inside the cell (2)
Complement and Phagocytes
What is inflammation
Pathologicalequivalent of a normal immune response
What are the cardinal signs of inflammation, aka the symptoms (5)
Heat Redness Swelling Pain Loss of Function
What is inflammation caused by (2)
Cellular recruitment
Activation of neutrophils followed by macrophages
How is redness caused during inflammation (2)
Lots of Cells were recruited, resulting in more blood
More blood results in vasodilation and redness
What Causes the swelling in inflammation (2)
Lots of Cells are recruited, which increases the leakiness of the vessels
This causes vasopermeability, which results in swelling
What Causes Loss of function
Hypoxia
What does Interleukin 6 act on
Acts on tissues around the body to activate proteins found in the blood, such as complement compounds
What is the role of Interleukin 8
Main Attractor of Neutrophils
What is the function of Tumour Necrosis Factor
INcreases the stickiness of the vessel walls to attract neutrophils
Which proteins are up-regulated in the blood during the acute phase response (4)
Inflammatory cytokines, especially IL6
Soluble PRRs
Complement compounds
Coagulation factors
What can the proteins present during the acute response phase be a useful indicator of
Marker of Inflammation
Which common diseases are affected by chronic inflammation (5)
Arthritis Atherosclerosis Diabetes Dementia Cancer
Which immune cell ism mostly responsible for Chronic Inflammation
Macrophages
What are the sections of the antibody (Chains and Regions)
Heavy and Light Chains
Variable and Constant Regions
What are the complementary determining regions called (3)
CDR2
CDR3
CDR1
What are the types of bonds involved in antibodies (1+4)
Non-Covalent Interactions
Electrostatic
Van der Waals
Hydrophobic
Hydrogen Bonds
What is the name of the region of the antibody which recognises and binds to the antigen
Paratrope
What is the name of the antigen which binds to the antibody
Epitope
Where, and during which cells development, is diversity generated in antibodies
During B Cell Development in the Bone Marrow
What is the name of the random selection of Variable, Diversity and Joining regions which cause diversity in antibody generation
VDJ Recombination
What are the 2 types of Light Chains fromed during recombination
Lambda
Kappa
What is somatic hypermutation
Introduction of addition mutations after antigen recognition
What is the equivalent antibody on the T Cells Called
T-Cell Receptor (TCR)
What is one way in which TCR is different to antibody
TCR not secreted, only acts as a receptor
During the generation of TCR Diversity, which process is notably absent but present in Antibody Diversity generation
Somatic Hypermutation
What are the 3 independent sets of antigen receptors
Antibody
TCRab (alpha-beta)
TCRyd (gamma delta)
What is the name of the enzymes involved in the rearrangement of the VDJ Regions
Recombinase Enzymes (RAG)
What is the benefit of the large diversity of antibodies
Almost any pathogen, including those which can mutate, can be recogised
What is the difference between Transmembrane antibody and secreted antibody
Secreted antibody does not have the part which anchors the antibody to the cells
What are the differences between the primary (PIR) and secondary Immune Response (SIR)
More antibodies in SIR (More specific B Cells)
SIR Faster than PIR
the Antibody in SIR have a stronger affinity than those produced in PIR
What are the Different Antibody Isotypes and there Heavy Chain specific gene
IgG - y (Gamma) IgA - a (alpha) IgM - u (mu) IgD - d (delta) IgE - e (epsilon)
What is the most common Antibody Isotype
IgG
Which Antibody is found on mucosal surfaces
IgA
Which is the main antibody produced during PIR
IgM
What is the antibody expressed during the start of life in B Cells
IgM
Which is the Antibody isotype expressed in Naive B Cells
IgD
What is the main Antibody Isotype expressed in allergy
IgE
What type of polymer is produced by IgA
Dimer (Dimeric Secretory IgA)
What type of polymer is produced by IgM
Pentamer (Pentameric Circulating IgM)
What si the name of the chain which holds together the monomers in the IgA and IgM Polymers
J Chain
Antibody-antigen reactions are … and as a result are able to reach … (2)
- Reversible
2. Equilibrium
What is Avidity
the overall binding strength of the antibody to the antigen
During an immune response, which antibody is released at the start of the infection and why
IgM, due to its high avidity
During an immune response, which antibody is released second and in larger amounts
IgG
Why is IgM production turned off during an immune response after the release of IgG (2)
High Affinity better than Avidity
High Avidity can form large complexes, which could block blood vessels
What is the Effector Function of IgM
Complement
What are the effector functions of IgG (3)
Neutralisation (toxins and viruses)
Direct opsonisation
Phagocytosis
How is antibody involved in the neutralisation of toxins
The Binding of antibodies prevents the toxin from being able to bind to the receptor and create pathology
What are 2 examples where toxin neutralisation is required
Tetanus
Diptheria
How is antibody involved during virus neutralisation
Viral Particles bind to the antibody, which prevents it from binding to the receptor and entering the cell, causing disease
What is the name of the receptors which allow phagocytes to bind to antibody
Fragment C Receptors (Fc Receptors)
How is antibody involved during opsonisation and phagocytosis (3)
Encapsulated Bacteria (usually resistant to phagocytosis) are coated with antibody (IgG)
IgG has Fragment C (Fc) Receptor, which binds to the Fcy (gamma) on phagocytic neutrophils
Bacteria able to be destroyed by the neutrophils
Which complement pathway is activated by antibody
Classical Pathway
Simply, what are monoclonal Antibodies
Antibodies of a single specificity
Monoclonal antibodies are used as drugs to treat which diseases (3)
Inflammatory Disease
Viral Infections
Cancer Treatments
What are the 3 subsets of the T Cells
CD4 Helper Cells
CD8 Cytotoxic Cells
CD4 Regulatory Cells
Which MHC Class do CD8 Cells Recognise
Class 1
Which MHC Class do CD4 Cells Recognise
Class 2
What are 2 pathways used by CD8 Cells to kill pathogens
Fas/FasL Pathway
Granzyme/perforin Pathway
How does the Fas/FasL Pathway work
FasL on the CD8 cell binds to the Fas receptor on the pathogen, causing caspase signalling
How does the Granzyme/Perforin pathway work (3)
Antibody recognises antigen
Perforin makes small holes in the membrane of the pathogen
Granzymes are released into the pathogen, leading to caspase signalling
What does Caspase Siganlling cause
Apoptosis
Why are innate lymphoid cell less precise
no TCR (T Cell Receptor)
What are the 6 types of cytokines
Interleukins Chemokines Interferons Tumour Necrosis Factor Colony-Stimulating Factors Growth Factors
What is meant by Cytokine Pleiotropism
One cytokine acts on several different types of cells, with different outcomes
What is meant by Cytokine redundancy
Several cytokines have similar effect on target cells
What is meant by Cytokine Synergism
Combined effect on two cytokines is greater than additive effect on each
What is meant by Cytokine Antagonism
Effect of one cytokine inhibits/cancels
Which receptors are expressed on the Helper T Cells
CD4
Which branches are controlled and amplified by the helper T cells (5)
Macrophages and Intracellular pathogens Eosinophils and mast cells in parasite immunity Neutrophils and extracellular pathogens B cells, antibodies and humoral immunity Cytotoxic T Cells and Viral Immunity
What are the important Th subpopulations (4)
Tfh (follicular cells)
Th1
Th2
Th17
What do Tfh (follicular cells) help with
Help B Cells make specific antibody
What do Th1 Cells activate (2)
Macrophages
Cytotoxic T cells
What do Th2 Cells activate (3)
Mast Cells
eosinophils
IgE
What does Th17 activate (1)
Neutrophils
How do T-B Interactions work (linked help) (5)
Costimulatory molecules B7 (B Cell) bind with CD28 (T Cell)
B cell presents peptide of antigen on MHC Class 2
T Cell Receptor recognise peptide
CD40 on the B Cell binds with CD40L on T Cell
Cytokines released by the T Cell, acting on the the B cell
What is Linked Help essential for (3)
Class Switching
Somatic Hypermutation
Memory
How do Th1 Cells activate macrophages to kill intracellular pathogens (5)
Peptides from intracellular pathogens presented on MHC Class 1 on the macrophages
TCR recognises the peptide
CD40 on macrophage binds to CD40L on T Cell
Th1 Cell releases INFy (Interferon-gamma) to mediate macrophage
Macrophage releases TNFa (alpha) and IL-1
How do Th1 Cells help activate CTL
Th1 cell releases interleukin 2, which activates CTL Cells
Th2 helps during parasitic infections. Which interleukins does it release
IL3
IL9
IL5
IL13
IL4
How do IL3 and IL9 released by Th2 help (1+2)
Drive Mast Cell recruitment
Mast Cells:
Release of granules
Recruits Inflammatory Cells
how does IL5 released by Th2 help (1+2)
IL5 recruits and activates eosinophils
Eosinophils:
Release of Granules
Cause Parasite killing
How does IL13 release by Th2 help (1+1)
IL13 induces epithelial cell proliferation and stimulates mucus production
Epithelial cells hinder parasite colonisation
How does IL4 released by Th2 cells help (1+1)
IL4 favours IgE production
IgE arms mast cells and eosinophils
How do Th17 Cells work in bacterial and fungal infections (2)
IL17 activates myeloid (immune) and stromal (non-immune) cells to produce GCSF and IL8
This recruits and activates neutrophils, which release granules that kill
What determines the Th type
the microenvironment around the antigen-presenting cells at the time the T cell is activated
On Th1 Cells … (2) causes … (1) to be presented during activation
- IFNy (gamma) and IL12
2. IFNy (gamma)
On Th2 Cells … (1) causes … (3) to be presented during activation
- IL4
2. IL4, IL5 and IL13
On Th17 Cells … (3) causes … (2) to be presented during activation
- TGFb (beta), IL6 and IL23
2. IL17 and IL22
On Th21 Cells … (1) causes … (1) to be presented during activation
- IL6
2. IL21
What is the qualitative regulation of the T Cell
Co-Stimulation via cytokines
What is the gatekeeper of the T cell
Antigens/MHC
What is the Quantitative regulation of the T Cell
Co-Stimulation via cell-to-cell contact
Increased co-stimulation = increased response
What is Excessive T Cell help associated with
the underlining of many pathologies
What holds the peptide onto TCR
Major Histocompatibility complex
Where is the peptide held in TCR
the peptide binding groove
How is CD3 involved in the T cell antigen receptor
CD3 transducer signal and aids in the decision of what happens to the binded cell
What is involved in T cell activation, other than the antigen (5)
Co-stimulation CD28 and CD80/86 (positive signals)
Negative signals CD28/CTLA4; PD1/PDL1
Professional and non-professional presenting cells
Dendritic Cells
The innate adaptive interface
What are the names of the 2 pathways peptides are loaded onto MHC, and which class are they specific to
Endogenous - Class 1
Exogenous - Class 2
What is Endogenous Processing (4)
Protein (usually viral) is broken into peptides by a proteasome Peptides enter the endoplasmic reticulum via the TAP gene and transporters Peptide join MHC class 1 and enter Trans-Golgi vesicle MHC class 1 and peptide expressed on the cell surface
What is Exogenous processing
Protein broken into peptides by protease enzyme-containing endoscope
MHC Class 2 and peptide join in MHC Class 2 loading compartment
MHC 2 expressed on the cell surface
What is the target for MHC class 2
CD4
What are the purposes of specialised lymphoid tissue (3)
Reticular meshwork to trap antigens
Facilitates cellular communication by slowing cells down
Separate T and B Cell areas for specialised differentiation pathways
What is the scaffolding built around lymphoid tissue built of
Collagen fibres laid down by fibroblasts
What binds naive T and B cells from the blood into the lymphoid tissue
High Endothelial Venules (HEV)
Where are B Cells differentiated
Germinal Centre
Where is the germinal centre located
Within the outer cortex of the kidney
What are the steps in B cell Differentiation (3)
Antigen-Specific B Cell undergoes Clonal amplification
Follicular dendritic cells carry antigen in original conformation
Competition exists between B Cells to produce cells with the highest affinity
What happens in the Dark Zone (2)
Proliferation
Somatic Cell Hypermutation
What Happens in the light zone
B Cell Selection
What are 2 examples of specialised Mucosa-associated lymphoid tissue (MALT)
Gut-associated lymphoid tissue (GALT)
Bronchus-associated lymphoid tissue (BALT)
What is the receptor which transports secretory IgA across the mucosal barrier
Poly Ig receptor
How does IgA work in the mucosal surfaces
IgA prevents the adhesion of microbes to surfaces
If microbe enters coated in IgA, then it will be rapidly destroyed by granulocytes
Which organ is the main producer of the acute phase and complement proteins
Liver
