Immunophysiology Flashcards
What did Edward Jenner achieve?
What was his method?
- Invented the vaccine
- Pus taken from a cowpox pustule
- Inserted into the arm of a boy
- The boy was vaccinated
What are the two pathways of removing pathogens?
- Innate/Natural immunity
- Adaptive/Acquired immunity
Summary of natural immunity
- Cellular and humoral elements remove pathogens
- Not antigen specific
- Immediate reaction
- Activated by toll-like receptor
Summary of aquired immunity
- Production of specific antibodies
- Response can be humoral or cellular
Which type of antigen aren’t antibodies produced against
Major histocompatibility complex
Innate and active immune processes are divided into 3 phases:
- Afferent phase
- Central Phase
- Efferent Phase
What occurs during the Afferent phase of innate immunity?
Responsive immune cells are prepared
What occurs during the central phase of innate immunity?
Specific immunoglobulins (Abs) produced in large quanitites
What occurs during the Efferent phase of innate immunity?
Non-self matter is eliminated
Give the organs of the Primary immune system
- Thymus
- Bursa
- Embryonic liver
- Bone marrow (Red and yellow)
Give the organs of the secondary immune system
- Lymph nodes
- Spleen
- MALT (Mucosa assoicated lymph tissue)
- GALT (Gut associated lymph tissue)
Which long-term process is shown in the figure?
The involution of the thymus over a lifetime
What are macrophages derived from?
Monocytes
Which cells can kill viruses-infected and tumour cells without a previous encounter?
Natural killer cells
Natural killer cells don’t require binding to…
MHC-Ag complex
They can kill tumour cells that have low levels of MHC molecules
Which cell surface markers are absent from NK cells?
CD4 and CD8 antigens
NK cells posess … which prevent lysis of cells with MHC molecules
Killer inhibitory receptors
cells bind to these to avoid being eliminated
Which NK receptors cause lysis of target cells?
Killer activating receptors
Which cell is described as the bridge between the innate and adaptive immune system
Dentritic cell (Innate immune system)
contains TLRs
Describe the immune system activation via the Toll-like receptor (TLR)
- Receptor acts as a sensor
- Recognises microorganisms by ligand binding
- Activates innate immune system
- Inflammation
If toll gene is mutated, the system wont work
How many toll-receptors have been identified?
10+
Give the varieties of toll-like receptor
External TLRs: On the cell surface
Internal TLRs: On endosomes
Why can’t the innate immune system be called ‘completely non-specific’?
TLRs recognise certain pathogenic substances
Therefore not specific
What is the main role of dendritic cells?
- Search for microorganisms
- Initiate inflammation
- Engulf microorganisms
- Process the microoganisms
- Express MHC receptors
List the main molecular components of the Innate immune response
- Complement factors
- Heat shock proteins
- FC receptors
- Inflammatory cytokines
- Histamine
List the main cellular components of the innate immune response
- Macrophages
- NK cells
- Granulocytes
- Dendritic cells
- Neutrophil
- Eosinophil
- Basophil
List the main molecular components of the Aquired immune response
- Antibodies
- MHC
- T+B cell receptors
- Lymphatic cytokines
List the main cellular components of the aquired immune response
- B+T Lymphocytes
- APCs
- Dendritic cell
- Follicular dendritic cell
List the main functional characteristics of the aquired immune response
- Antigen specific
- Immunological memory
- Activated after latency period
- Exponential amplification of reaction
Name the three pathways to activate the mechanism of the complement system
- Classic pathway
- Alternative pathway
- Mannose binding lectin activated pathway
Describe the clasic pathway to the complement system
- Previously produced specific antibody + antigen:
- Build a complex
- Complex initates the process
Describe the alternative pathway to the complement system
- Previously unknown antigen
- Appears and acts as a trigger
Describe the Mannose binding lectin activated pathway to the complement system
Mannose-binding lectin binds mannose on pathogen surface
What is the function of the complement system?
- Lysis of bacterial membranes
- Initiation of chemotaxis
- Stimulate opsonisation
After the complement system has been activated
- Autocatalytic process
- Complement protein activation in plasma
- Membrane-drill formed
- Pathogen membrane disturbed
- Death of pathogen
Chemotaxis
Complement factors attract phagocytes to the site of reaction
Membrane drill
The three complement activating pathways converge to the…
C3 complement component
What are the two major forms of aquired/specific immune response
- Humoral Immunity
- Cellular immunity
Clones of B cells
In secondary lymph organs
Ag stimulus
- Blastic transformation
- Plasma cells
- Helper
- Supressor
- Cytotoxic
Hematopoietic stem cells are produced in…
Bone marrow
Hematopoietic stem cells produce…
- Myeloid progenitor cells
- Lymphoid progenitor cells
Which inflammatory cells does the Myeloid progenitor cell produce?
- Neutrophil
- Basophil
- Eosinophil
- Monocyte
Which cells does the monocyte produce?
- Dendritic cell
- Macrophage
Why is active immunity named as such?
The system actively responds to the antigen
Passive immunity
Individual made immune by recieving cells/immunoglobulins by an immunised individual
Acquired immunity is divided into which two groups?
- Active immunity - specific, creates memory
- Passive immunity - specific, no memory
What occurs during the Afferent phase of acquired immunity?
- Ly-repertoir express receptors
- Recognise Ags, Ag and LyR interactions
- Ag activation + processing
- Discrimination between ‘self’ and ‘non-self’
What occurs during the Central phase of acquired immunity?
Non-specific immune cells undergo:
- Activation
- Proliferation
- Differentiation
- B-cells → Plasma cells*
- T-Cells → Effector T-Lymphocytes*
What occurs during the Efferent phase of acquired immunity?
- Immune cells eliminate ‘non-self’ structures
- Protect/develop tolerance against ‘self’ structures
Major characteristics of humoral immunity
- Antigen recognition: by Antibodies or T/B-cell receptors
- Immunoglobulins specifically bind ligands
- Immunoglobulin production
Give the regions/chains of immunoglobulins
- Heavy chains
- Light chains
- Variable regions
- Constant regions
Heavy chain
Light Chain
Variable Region
Constant Region
Flexible Hinge region
Which part of the antibody binds to the antigen binding domain?
The aminoterminal end
Which part of the antibody binds to the surface receptors of cells
Effector region
Immunoglobulins can be cleaved by enzymes into…
- Antigen binding fragments
- Crystallisable Fragments
1: Monovalent
2: Bivalent
Which part of the antibody is in the red box?
FAB
(Fragment antigen binding)
Which part of the antibody is in the red box?
FC
Fraction crystallisable
(responsible for biological effect)
Which part of the antibody is in the red box?
2 x Hypervariable antigen binding sites
Each binds one antigen
Which part of the antibody is in the red box?
Joint region (‘hinge’)
Allow flexibility during binding
Variability in antibody class is known as…
Isotipia
Variability in individual antibodies is known as…
Allotipia
Variability in antibody Type is known as…
Idiotipia
Idiotype is determined by which region?
Variable region
Isotype is determined by which region?
Constant region
What forms antibodies?
Immunoglobin domains
Immunoglobulin domain
Loops form in the peptide chain
Caused by disulphide bonds
Complimentary Determining Region (CDR)
kappa
lambda
Mu
Gamma 1-4
Alpha 1-2
Delta
Epsilon
Neutrophil
Macrophage
Basophil
Mast cell
IgA dimer produced
Secreted into interstitial fluid
IgA binds to polymeric receptor
Contains secretory component
Secretory vesicle
Secretory IgA seperates
Secretory IgA binds to pathogen
Secretory-IgA
Pentamer IgM
Due to the size of Pentamer IgM, it causes a blockage in transplacental transfer of IgM, preventing…
Haemoblastosis fetalis
Monofunctional character of immunoglobulins is…
FAB dependent function
Polyfunctional character of immunoglobulins is a…
FC dependent function
Non-activated B-lymphocytes produce
IgM
becuase Cµ is next to VDJ
When is Monofunctional character of immunoglobulins activated?
Before antigen administration
When is polyfunctional character of immunoglobulins activated?
After antigen administration
Immunoglobulins are synthesised by…
B-lymphocytes
During the humoral immune response, B-lymphocytes with B-cell receptors (BCR) are called…
Recognising cells
As they bind to a specific antigen
Antigen binding to B-lymphocytes causes…
Cell differentiation:
B-lympocyte → Plasma cell
Plasma cell secretes antibodies
Primary antibody repertoire
A set of immunoglobulins produced by B-cells:
- 109 different antigen determinants
- No antigen stimulus
- B-cell recognises a single antigen
What is shown?
Model of clone selection theory
1
- Lymphocyte clones mature
- Specific for diverse antigens
2
- Lymphocyte clones contact with antigens
- Go to lymph organs
- Antigens are selecting appropriate lymphocytes
- Then activating antigen-specific clones
3
- Clones converted to plasma cells
Result: Antigen specific immune response
Clone selection theorises that B-lymphcytes specific to an antigen are…
Already present before infection
It can be deduced from the clone selection theory that…
Immunoglobulins against all antigens are produced, and are stored on the B-lymphocyte cell surface
What ensures genetic diversity of immunoglobulins?
Gene rearrangement
What is shown in the figure?
Gene structure of a mouse heavy chain locus
L=
Leader
First section of the proteins
V=
Variable region
of the heavy chain
D=
Diversity supporting region
J=
Joining region
C=
Constant region
What do the red numbers represent?
DNA section length
Describe immunoglobulin gene rearrangement
- Segments join randomly
- Can recognise millions of different antigens
- Isotype switching
- Antigen stimulus → H-chain changes
Which process is shown in the diagram?
Isotype switching
List the stages of gene rearrangement
- Somatic recombination D-J joining
- Somatic recombination V-D-J joining
- Deleted DNA collapses in nucleus
List the stages of isotype switching
- Linear deletion (proliferation/differentiation of B-cells)
- Transcription + Translation
- Final product
Switching of Immunoglobin class happens due to…
Alternative splicing
at an mRNA level
List the stages of Alternative splicing
- Rearranged DNA → Transcription
- Primary RNA transcript → Splicing
- mRNA → Translation
- M heavy chain/ IgM produced
What regulates class-switching?
Cytokines
Which different ‘Constant region’ RNA transcripts exist?
Which isotypes do they produce?
- Cµ → IgM
- Cγ → IgG
- Cα → IgA
- Cδ → IgE
- Cε → IgD
Give the major characteristics of the immune response
- Specificity
- Diversity
- Memory
- Self restriction
- Differentiation of self fron non-self
What is an antigen?
- Substance recognised by T/B cell receptors
- Induces active immune response/tolerance
Immunogen
Fine chemical structure, which can induce specific immune response
Epitope
Region of the antigen molecule recognized by Ig/BcR or TcR
Paratop
Ligand pair of the epitope
Hapten
- Antigen
- Can’t induce immune reaction itself
- Recognised by immunoglobulins
Carrier
- Holds hapten molecules on the surface
- Doesn’t participate in the anti-hapten immune reaction
No AB
Anti-BSA
- Anti-T4
- Anti-BSA
- Anti-T4/BSA
Immunogenicity
The capacity to create immune response
Immunogenicity is determined by…
- Grade of fereignness
- Molecular weight
- Structure complexity
Antigenicity is determined by…
- Binding force
- Specificity
Immune reaction followed by a repeated immunisation by the body is called…
Secondary immune response
Give the steps of the secondary immune response
- Antigen stimulus
- Lymphocyte proliferation and increase
- Antibody + memory cell production
Which cells allow for faster, more efficient immune responses?
Memory cells
Which molecules are responsible for ‘self’ and ‘non-self’ differentiation?
- Immunoglobulins
- B cell receptors (BcR)
- T cell receptors (TcR)
- MHC class I and II molecules
MHC molecules are genetically determined, true or false?
True
What is shown in the figure?
Class I (Left) and Class II (Right) MHC molecules
After the APC binds to the T-helper cell, what occurs
- Cytokine production in APC (importantly, dentritic cells)
- Interleikin-2 production in T-helper cell
- Activating T-helper cell proliferation
MHC II can be found in…
- Langerhans cell
- Interdigital cell
- Dendritic cell
- B-lymphocytes
- Macrophage cells
Fc Receptors can be found in…
- Langerhans cell
- Dendritic cells
- B-lymphocytes
- Macrophage cells
C3b receptors can be found in…
- Langerhans cell
- Dendritic cells
- B-lymphocytes
- Macrophage cells
Phagocytosis can be found in…
- Dendritic cells
- Macrophages
In which two phases does humoral acquired immunity develop?
- Antigen-independent (Preparatory)
- Antigen dependent
Antigen-independent phase of humoral aquired immunity
- Pre-B-lymphocytes → virgin-B-lymphocytes
- IgG-like molecule appears on the cell surface
- Enter the blood
Antigen-dependent phase of humoral aquired immunity
- Virgin-B-lymphocyte binds to compatible Antigen on APC
- Virgin-B-lymphocyte is activated by interleukins
- May be T-helper cell independent or dependent
- B-lymphocytes undergo blastic transformation in secondary lymph organs
- Eventually, immunoglobulins are released into blood
Antigen-independent phase of cellular aquired immunity
- Pre-T-lymphocytes → virgin-T-lymphocytes
- IgG-like molecule (TCR) appears on the cell surface (becomes Ti cell)
- Enter the blood
Antigen-dependent phase of cellular aquired immunity
If Ti cell carries CD4 antigen:
- Cell can recognise an antigen on an APC with an MHC-II antigen
- Link between APC and Ti-cell = Primary stimulation
- Ti cell activation → blastic transformation
- T helper cell produced
Ti-cells with a CD8 antigen…
Recognises antigens expressed beside MHC-1 antigen
Tumour and virus antigens
Leads to Cytotoxic T-cells being produced
Cytotoxic T-cell
Immediately kills cells with tumor and virus antigens
Give the stages of T-lymphocyte maturation in the thymus
- T-lymphocyte receptors appear
- Immature lymphocytes can bind to MHC structures
- Positive selection: Only lymphocytes that can bind survive
- Negative selection: Lymphocytes which recognise both MHC and Self-Ag must die.
CD8+ cytotoxic T cells
- Kill virally infected cells
- Kill tumor cells
- Kill cells with cytosolic bacteria
CD4+ T cells (TH)
- Cytokine production
- TH1: Activates macrophages
- TH2: Activates B cells → Antibody production
Latency
Log-phase
Plateau
Decrease
Primary response
Secondary response
What is shown in the diagram
The interactions vetween the nervous, endocrine and immune systems
