Adaptive Immunity Flashcards
What are the 2 types of adaptive immunity?
Humoral immunity - mediated by CD4 and B-lymphocytes
Cellular immunity - mediated by CD4 and CD8+ cytotoxic T-lymphocytes
*both branches are mediated by CD4+ helper T cells
What are the primary and secondary lymphoid organs?
Primary
- red bone marrow
- Thymus gland
Secondary
- spleen
- gut
- lymph nodes
What is an epitope?
The binding site on the Ag for the Ab
Describe what Ab T cells are
Helper T cells expressing CD4 and CD3
- secrete cytokines when activated
- aid immune responses
- can become memory cells
- TH1 and TH2 subgroups
Summarise Humoral immunity
Via fluid
Following infection, produces antibodies in plasma to neutralise specific infectious agent
What are the 2 types of MHC?
MHC class I : HLA-A, B and C
- expressed on all nucleated cells
- presents peptide to CD8 T cells
- signals for cytotoxic T cell response
MHC class II : HLA-D
- expressed on ‘professional’ APCs
- Presents peptide to CD4 T cells
- qualifies immune response: cellular/humoral
What is the role of IgM?
IgM is a functional Ig expressed on cell surface membrane
Acts as a B cell receptor associating with tyrosine kinases
Binding of anitgens to IgM activates tyrosine kinases and their signal transduction pathways
What is the difference between the different Ig classes?
Differ slightly in heavy chain constant region amino acid sequence producing different functions
What affects the binding of antigens and antibodies?
The complex binding is dependent on the Ab binding site being 100% complementary to the
Ag surface site
What are the different subsets of T cells?
- Ab T cells
- Cytotoxic T cells
- Regulatory T cells
- g/d T cells
Describe the structure of Antibodies (Ig)
Ig proteins are Y shaped tetramers composed of
- 2 identical light chains
- 2 identical heavy chains
Held together by non covalent interactions and disulphide cross links between Cysteine
residues
Each Ig molecule has 2 antigen binding regions
What are the dendritic cell sub types?
Langerhans cells (skin)
Interdigitating
Plasmacytoid
Follicular DCs (fibroblasts)
Approximately how many B cells are produced?
The body produces over 100,000,000 B cells each producing different Ig’s randomly
Each B cell can only make one Ig type specifically
Descendants of the original activated B cell produce clones of the Ig
How are antigens processed and presented to CD8 via MHC class I?
- Production of proteins in cytosol
- Proteolytic degradation of proteins (ubiquitylation)
- Transport of peptides from cytosol to ER via TAP
- Assembly of peptide Class I complexes in ER by ERAP
What are the 2 types of antibody light chains?
Kappa (ϰ)
Lambda (ℷ)
How does the thymus alter during humans lifetime?
Thymus enlarges during childhood and atrophies at puberty
Outline the antigen processing and presenting to CD4 for MHC class II expression
- uptake of extracellular proteins to vesicular
compartments of APC - Processing of internalised proteins in endosomal /
lysosomal
3. Biosynthesis and transport of MHC class II molecules to
endosomes
- Association of processed peptides with MHC II
molecules in vesicles
(w/ CLIP & HLA-DM) - Expression of peptide MHC complexes on cell surface
How are B cells activated?
- Ag binds to IgM (B cell receptor)
- Stimulation of tyrosine kinase signal transduction
pathway - Co-stimulation via T cells
Outline the key features of CD8 activated Cytotoxic T cells
Express CD8 co receptor
Eliminate intracellular infections
Produce Il-2 TNFα and gIFN
Involved in anti-tumour immunity and transplant rejection
How is the antibody-antigen complex formed?
Antibodies bind to antigens via the following non covalent interactions
- Electrostatic
- Hydrophobic
- Van der Waals
- Hydrogen bonds
What is CLIP in MHC II formation?
CLIP is a Class II associated invariant chain peptide
How does T cell development occur?
In the thymus
Immature T cells mature in the bone marrow
Migrate to thymus to encounter self antigen
Many T cells undergo apoptosis during this process
Leave behind cells that generate useful immune response only
What is so significant about dendritic cells?
They are the only APC that can present to naive T cells
What are the different classes of Ig?
α - IgA β - IgM Ɣ - IgG δ - IgD 𝜺 - IgE
What is the exclusive role of Regulatory T cells?
Inhibit effector functions of CD4 and CD8 T cells
Inhibit antigen presentation function of B cells and other APCs
How do progenitor cells decide whether to differentiate into B or T cells?
In early develpmental stage, cells either pass to Thymus (T cells) or Bone marrow (B cells)
Describe the essential features of CD4 activated Regulatory T cells?
Express co receptors CD4, CD25, snd FOXP3
Maintain immune tolerance and suppress immune responses
Produce anti inflammatory cytokines IL-10 and TGF-β (SMAD receptor)
Contact dependent immunosuppressive effect
Describe the role of IgM
Produced by B cells during primary response
Initially made as membrane bound protein on B cell surface
Activates B cell signal transduction
Later made in secreted form
-> activates complement
-> acts as opsonin
Name some APCs
- Dendritic cells
- B cells
- Macrophages
- Endothelial cells under certain conditions
How can Fab and Fc fragments be produced from antibodies?
Ig treated briefly with proteases which cleave antibody at hinge region
When is TH17 most effective?
TH17 response is effective against extracellular bacteria and fungi
It is effective in
- promoting neutrophil mediated inflammation
- helping TH1 cells induce phagocytosis
- killing of pathogens
What are the essential features of cytotoxic T cells ?
Express CD3 and CD8 - kill infected targets when activated - become memory cells - cytotoxic in nature - release toxic contents of granules to kill
Outline how activated B cells carry out their function
Activated B cell secretes soluble IgM
- B cells multiply rapidly & differentiate into Ig secreting
cells - Produce IgM
3. Undergo class switching to produce specific Igs with
antigen specificity & different heavy chain constant
regions (e.g. IgG, IgA etc.)
What happens to lymphoid progenitor cells when stimulated by Antigens?
Upon stimulation by Ag, progenitor cells become one of 2 types of effector/memory cells:
- B cells
- T cells
What is the role of regulatory T cells?
Express CD4+ and some CD3+
- affect immune responses by supression/activation via
direct cell contact or indirect cytokine secretions
- 2 types of regulatory T cells:
- Natural
- Inducible
What is an immunoglobulin protein?
Antibodies are a glycoprotein (carbohydrate added to protein molecule in golgi
How are T cells activated by Dendritic cells?
Via 3 signals
- Peptide bound in MHC I or II ligates cognate TCR
- Co stimulation by ligation of CD80/86 to CD28
- Modulation of signal by cytokine secretion
How does positive or negative selection of CD4 or CD8 occur?
T cells in thymus enter as thymocytes - not expressing CD4 or CD8 (double -ve)
They go through a stage of expressing both CD4 and CD8 (double +ve)
Followed by a decision to either become CD4+ or CD8+
Positively selected to bind to MHC molecules
Negatively selected if they bind self peptides
Describe the structure of secreted IgM molecules
5 molecules of basic Ig tetramer polymerise to form a pentamer
What are g/d T cells?
TCR (T cell antigen receptors) formed from g/d chain
recognise lipid antigens
How do antibodies fight infection?
- Antibody coats and neutralises pathogen preventing
virus’ from binding to receptors on the cell surface - Antibodies activate complement which blows holes in
bacterial cell membranes - Ab also cause opsinosation so phagocytes with Fc
receptors on their membranes can bind to pathogens
coated with Ab faster to phagocytose them
What is the role of CD4 T cells?
Recognise peptides in MHC II binding grooves
Helper T cells (TH1 or TH2)
- produce cytokine profile directing the immune response
to a particular outcome
Regulatory T cells
- responsible for ending an immune response
What is TAP in MHC class I production?
Transporter associated with Antigen Presentation
What does the presence of IgM antibodies on an antigen indicate?
There’s been a recent primary response to that specific antigen so there is a current primary infection occurring
What is the role of memory B cells?
Allow a very rapid response for a second exposure
- immediate IgG production rather than IgM
What is the major role of cytotoxic T cells?
Kill infected cells in an antigen specific and cell contact dependent manner
Describe the features of lymphoid progenitor cells
- Give rise to lymphocytes
- 20-30% peripheral WBCs
- 6-10um in diameter
- large nucleus and small halo of cytoplasm
What is the killing mechanism of cytotoxic T cells?
Cell contact delivers lethal hit
CTL detaches and targets another cell
Releases cytolytic molecules from intracellular stores
Triggers apoptosis in target cell
What is meant by natural immune responses being polyclonal?
More than one Ig type and B cell clone is synthesised due to:
- multiple antigens on organisms
- multiple epitopes on each anitgen
- more than one Ig can recognise same epitope
What is the function of CD4 TH17 cells?
Express co receptor CD4
Help protect gut mucosa
Produce IL-17 and IL-22
Recruit neutrophils to infection sites
How does the strcuture of IgA differ in serum and secretions?
In serum - IgA occurs as single Ig molecule
In secretions - IgA present as dimer of 2 Ig molecules and accessory proteins
Describe the structure of TCRs
Dimetric molecule composed of ab or g/d chains covalently linked by disulphide bonds
Each chain has a variable & constant region
Variable region has hypervariable regions (Ag binding sites)
TCRs are associated with CD3 which idnetifies T cells
What is the constant region on antibodies?
The portion of amino acid sequence on Ig heavy or light chains determining effector function
=> determines mechanism used to destroy antigen
e.g. activating complement, binding to phagocytes
Describe the essential features of Dendritic cells
- APCs
- Irregularly shaped
- myeloid derived (can be lymphoid)
- Immature DCs capture antigens and migrate to
lymphoid tissues to mature and effectively present
antigens to T cells
In MHC class I formation what is ERAP ?
ER aminopeptidase - trims longer precursors to antigenic peptides on MHC Class I molecules
What does the presnece of IgG antibodies indicate?
May be due to past antigen exposure
Outline lymphocyte development in bone marrow
Haematopoietic stem cell HSC
- Common myeloid progenitor
- neutrophils RBC, platelets etc.
- Common lymphoid progenitor
- > Pre T-cell -> further development in thymus
- > Pre B-cell -> immature B cell
What are the cytolytic proteins found in CTLs?
- Perforin
- Granzymes
- FasL
Describe the structure of membrane bound IgM
Formed form a single Ig tetramer
Outline the key features of ab chains in TCRs
- ~90% of blood MNC
- CD4 and CD8 expression
- MHC I or MHC II restriction
- Total Repertoire of ~10¹⁷
a chain consists of:
- germline variable
- joining region
- constant region
b chain consists of:
- germline variable
- joinign region
- constant region
- diversity regions
What is the variable region?
Each antibody chain has a variable region in which the amino acid sequence varies from one
Ig molecule to another
The variable region binds antigens
What is the role of CD4 TH1 cells?
Express co receptor CD4
Help activate cellular immune response (cytotoxic)
Produce g-interferon
Activates Mf and cytotoxic T cells
What is Perforin?
A pore forming cytolytic protein found in the granules of cytotoxic T cells
Forms pores in target cell membrane allowing the entry of granzymes
How does Class switching in B cells occur?
Once a B cell starts making an Ig which binds a specific Ag it can switch to make Igs with same Ag binding site but different constant regions to carry out different functions in the body
Outline the essential features of NK cells in cellular immunity
Express T cell markers and Nk cell markers
Have large cell population
Restricted TCR usage
Show antigenic specificity
Respond to glycolipids such as α-galactosyl-ceramide
Restricted by CDId
What is meant by Light chain restriction in terms of immunoglobulin proteins?
Any B cell will only produce one type of light chains, never both
This is known as light chain restriction
What are Granzymes?
Serine proteases released from cytoplasmic granules of cytotoxic T cells, inducing apoptosis in target cells
What is the role of IgE?
Physiological role in protection against parasitic worms
- binds to Fc receptors on mast cells and basophils
- triggers histamine release
When is TH2 response especially significant?
TH2 response is effective against extracellular cellular infections e.g.
Bacterial, protozoal and viral
It is also effective in IgE production against helminth infection
What is the role of TH2 CD4 cells?
Express co receptor CD4
Activate humoral response
Produce interleukins 4,5 and 13
Activates B cells to produce antibodies
What is the Fc fraction of the antibody?
Fragment crystalline is the tail end of the antibody which interacts with cell surface receptors
(Fc receptors) and some complement proteins
How do Granzymes induce apoptosis in target cells?
Act as a specific synapse between CTL and target cell reducing collateral damage
Involves cytoskeletal rearrangement and organelle release
Granzymes activate capases which cause apoptosis
Granzyme B specifcally activates the mitochondrial apoptic pathway
Describe the main features of IgG
Major class of Ig in circulation
Very good opsonin and at activating complement system
Formed of a single Ig tetramer
How does FasL eliminate infected cells?
FasL on CTL ligates Fas receptor on target cells causing activation of capases leading to apoptosis
What is a clone?
A group of cells or organsims that are genetically identical
What is the role of MHCs?
MHC encodes for human leukocyte antigens (HLA)
Describe the role of IgE in allergic reactions
IgE produced in response to allergens (pollen, peanuts etc.)
histamine release causes allergy symptoms
Anaphylatic shock caused by over expression
What is the relationship between TH1 and TH2 CD4 cells?
Th1 and TH2 are mutually antagonistic
e.g. In Mycobacterium Leprae
TH1 in some patients - Tuberculoid leprosy
Defective Th1 and Th2 dominant => lepromatous leprosy
Describe what acquired immunity is?
Infection acquired once, patient recovers and becomes immune to that specific infection for many years/life
What is the role of IgA?
Most abundant class in external secretions e.g
- Milk, sweat, tears, gut secretions
Protects mucosal surfaces
Doesn’t activate complements
Binds Fc receptors triggering phagocytosis and inflammatory reactions
What are MHCs?
Major histocompatibility complex
Surface expressed molecules which bind to antigen derived peptides and present to T cells
During an infection how do B cells produce specific Ig?
A small no. of B cells will by chance, already be producing an Ig complementary to the foreign antigen
These B cells get selectively activated and begin to undergo clonal selection
Describe the key features of g/d chains in TCRs
~10% of peripheral blood MNC
<70% of mucosal T cells
- CD4 and CD8 expression
- CDIc & some NK receptor restriction
- Some recognise cell stress indicators (HSP)
- g/d recognise range of bacterial cells & small aliphatic
molecules (PAMPs)
- extensive junctional diversity increases g/d TCR
repertoire to ~10¹⁹
What is the function of IgD?
Low [IgD] in circulation
On B cell membrane
Role unknown
What are the key features of acquired immunity?
- Delayed response
- Highly specific
- Usually eliminates infection
- Memory (long term specific immunity to pathogen
produces rapid immune response to a repeated
infection)
What is the Fab fraction of an Ig molecule?
Antigen binding fragment of Ig
composed of one constant and one variable region of each of the light and heavy chains
