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Immunology, Antigen receptors, Cytokines, Significance, A form of acquired…
Immunology
Acquired immunity
Adaptive immunity
Significance
Lymphocytes are specially hand-picked to mature and defend during an attack depending in the specific infectious organism.
through processes referred to as clonal selection and clonal expansion
Plays a vital role to enable faster, and more effective defense against and during re-infections
Memory driven
Cell-mediated immunity
T-cells
T cell activation
TCR signal transduction
initiated by
Recognition of Peptide-MHC complex by TCR
Reception; CD3 signal molecules binds with the receptor
CD3 molecules are responsible for proximal signalling events
CD3 assembled with TCR possess characteristic sequence motif for tyrosine phosphorylation, immuno-receptor tyrosine-based activation motif (ITAMs)
Signal transduction; chemical signal results in a series of enzyme activations
facilitation of cell-cell and cell-extracellular matrix interaction
Adhesion molecules
classified by structure & function
Integrins, selecetins, cadherins, and immunoglobulin superfamily (IgSF) molecules
stabilise (or secure) the binding of T cells to respective APCs
Response (cellular): results in necessary cellular responses by T-cells
Co-stimulation
second signal activating T cells besides antigen presentation by MHC-TCR complex
costimulate TCR to activate T cells
support effector T cells
common costimulators
CD-80
Recognised by CD-28 on most of the T cells
CD-86
Differentiation to effector/memory cells
T helper cells (CD4+)
Th1, Th2, and Th17
leave secondary lymphoid organs to look for microbes found in other sites of the body
Th1
stimulate phagocyte-mediated ingestion & killing of microbes
produce interferon-gamma & IL-2
Th2
stimulate phagocyte-independent, eosinophil-mediated immunity -> effective against helminthic viruses
produce IL-4, IL-5 & IL-13
Th17
station at mucosal barriers to remove pathogens trying to enter at those portals of entry
produce IL-17 (pro-inflammatory)
Tfh (T-helper follicular cells)
remain inside the lymphoid organs to help B-cells in the production of antibodies
secrete cytokines
engage phagocytes
activates CD8+ cells for effector actions
aid in B cell activation for antibody production
Cytotoxic T cells (CD8+) or CTLs
CTLs recognise class I MHC-peptide complex leading to activation of signal transduction pathway -> exocytosis of CTL's granules
delivery of granule proteins via receptor-mediated endocytosis - bound to serglycin (sulphated glycoprotein)
granzymes
enzymes that cleave and activate enzyme, caspases which induce apoptosis
perforin
insert into endosomal membranes and facilitate movement of granzymes into cytoplasm
activated CTLs express Fasligand protein - binds to death-inducing receptor Fas(CD95)
remain long-term even after an infection is cleared
memory T cells
central memory cells
predominant in lymphoid organs eg. spleen
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effector memory cells
predominant in peripheral tissues
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tissue-resident memory cells
in skin & mucosal tissues
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T-cell mediated activation of macrophages
Classical pathway
Recognition of antigens
Macrophages express various pattern recognition receptors (PRRs) which can recognise specific molecular patterns associated with pathogen triggering a signalling cascade
Signal transduction
Binding of antigens to PRRs initiates intracellular signalling cascades -> activation of transcription factors
Gene expression and cytokine production
Activation of transcription factors leads to the expression of genes involved in inflammation and immune responses
Enhanced microbicidal activity
Activated macrophages increase their microbicidal activity, including phagocytosis, production of reactive oxygen species (ROS) and reactive nitrogen intermediates (RNI), and secretion of antimicrobial peptides
Antigen presentation
Activated macrophages also play a crucial role in antigen presentation, presenting antigens to T cells
activated by
IFN-gamma
Alternative pathway
Tissue damage or inflammation
The alternative pathway can be initiated by signals associated with tissue damage, inflammation or presence of foreign substances in the tissue
Activation of PRRs
While the alternative pathway does not rely on specific antigen recognition like classical pathway, macrophages still utilise PRRs to detect signals
Signal transduction
Activation of PRRs triggers intracellular signalling cascades within macrophages -> change in gene expression and functional properties
Gene expression and functional changes
Activated macrophages exhibit distinct gene expression profile -> produce anti-inflammatory cytokines
Tissue repair and remodeling
Macrophages play essential roles in tissue repair, remodelling and promote tissue healing
initiated by
IL-4/IL-36
Migration of T lymphocytes (transmigration/ diapedesis)
Rolling of lymphocytes
when lymphocytes roll around blood vessels (venules), a reaction is triggered between chemokines (in endothelial layer of venules) & their respective chemokine receptors (on lymphocytes)
Signalling
once connection is made (chemokines-chemokine receptors), an intracellular signalling happens
adhesion molecules of integrins is activated
Adhesion
this adhesion molecules cling onto walls of the vessels to congregate and pool lymphocytes at that area
regulated by
selectins, integrins & chemokines
NK cells
Phagocytes
Antigen presentation by APCs
engulf & process antigens -> dispplay fragments on cell surface with MHC
T cell activation
T cells recognise antigen presented by APC -> activate T cells
Clonal expansion
T cell undergo clonal selection followed by expansion to multiply rapidly
Effector functions
performed by T helper cells & cytotoxic T cells
Memory formation
some activated T cells differentiate -> memory T cells for rapid response upon re-exposure
Humoral immunity
Antibodies
Also known as immunoglobulins, they are proteins
Produced by B lymphocytes
they are glycoproteins that bind to anitgens with a high degree of specificity and affinity
Carry out two principal functions in the immune system
Recognise and bind to invading microorganisms.
Eliminate the invading microorganism.
2 types
Membrane bound antibodies
These antibodies are anchored to the surface of B cells.
Play a crucial role in antigen recognition and B cell activation. They bind to the antigens presented on the surface of pathogens, and initiate signaling pathways that leas to B cell activation, and/or differentiate into antibody-secreting plasma cells. The binding of antigens to membrane-bound antibodies triggers processing of antigens for presentation to helper T cells. This would make the immune response stronger against the attacker.
Secreted antibodies
B cells are stimulated to produce this type of antibodies these are referred to as immunoglobulin.
These antibodies are released into the bloodstream, and tissues by plasma cells. These are the soluble form of antibodies, which we refer to as immunoglobulins. They play a crucial role in humoral immunity. They are divided into various classes (Ig G, Ig A, Ig M, Ig D, Ig E). These antibodies contribute to the adaptive immune response by providing long-lasting immunity through memory B which attack the attacker quicker when they try to attack the body again.
Structure
Made up of 4 polypeptide chains (2 identical light chains and 2 identical heavy chain). Together they form a flexible Y-shape. The polypeptide chains are linked by disulfide bridges.
Different parts of the antibody explained:
Variable region: this is where the antibody binds with their antigen; highly specific
Constant region: this part of the antibody determines which class the antibody may belong to
Can also categories the structure of the antibody as:
Fab segment (Fragment of antigen-binding region)
Binds to antigens
Fc segment (Fragment crystallisable region)
2 Functions
Determine the class of the antibody
Activate the rest of the immune system
Classes (isotypes) of antibodies
Why do we need different types of antibodies?
Because it determines what immune cells and molecules are recruited by the antibody to help destroy and remove a pathogen.
Different isotypes appear at different stages of an immune response.
Each of them differ based on their differences in the amino acid sequences found in the constant region.
Antibody classes also differ based on their valency
5 classes
Ig G
Abundantly found in internal body fluids
Primarily produced in and during secondary immune response
Ig G1, Ig G2 and Ig G3 are found more than Ig G4 as Ig G1, Ig G2 and Ig G3 are responsible for activating the complement pathway
They also bind to the invading microorganisms so that they can be opsonised by macrophages and neutrophils to be phagocytosed and killed.
This is the only antibody capable of crossing the placenta to give passive immunity to fetus (all 4 subclasses are to cross into fetal circulation).
Subdivided into Ig G1, G2, G3, and G4
Ig A
Majorly found in external secretions
Secretory Ig A is safe from proteolytic lysis (due to the presence of the J-chain)
Secreted in breast milk
Ig M
Largest antibody (size-wise) in the human body
Key antibody for primary immune responses (high amounts in body could mean an infection)
Activates complement pathway
First antibody to be produced by the newborn
Ig E
Usually found in smallest amount in the body (on surface of mast cells and basophils)
Responsible for the trigger and release of inflammatory mediators in the body.
High numbers of Ig E are seen in people with allergies
Works together with mast cells to act as "gatekeepers" (regulating the exit of cells into extravascular sites).
Stages strong immune responses against parasitic infections.
Ig D
Minimally found in blood or body fluids
Contribute to immunity through 5 ways
Neutralisation
Opsonisation
Cell-mediated cytotoxicity
Complement pathway
Agglutination
Phases of humoral immune responses
Naive B lymphocytes recognised antigens
B cells activated to proliferate
Differentiated into antibody secreting plasma
2 types of B-cell activation
T- cell independent activation
B-cells respond directly to antigenic stimulation without antigen processing and presentation by APCs or T cell
Result in production of antibodies with lower affinity and shorter duration
Microbial antigens are: Polysaccharide, glycolipids, nucleic acids. Usually with multiple repeating epitopes
Steps
T-independent antigens
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T-cell dependent activation
3 signal process
Antigen recognition and binding
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T and B-cells interaction (CD40-CD40L complex)
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Release of Cytokine by T helper cells
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These antigens referred to as T dependent or Thymus-dependent (Td antigens)
No multiple epitopes
Antigen induced B-cell signaling
B cell receptors (BCR) like IgG and IgM recognised microbial antigen
Igα-Igβ complex associated with BCRs transmit intracellular signal to nucleus of B cells so that B cells can be activated now
The multiple Igα-Igβ complex cluster together to initiate signaling process. This clustering is referred to B-cell receptor cross linking
Signal transduction of BCR
: Once a foreign antigen is bound, tyrosine kinases found in ITAM are activated
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Class Switching process
Portion of antibody heavy chain locus are removed from chromosome
Gene segments surrounding deleted portion are rejoined
Double stranded break are generated at switch (S) region of DNA
The intervening DNA between S regions are deleted
Remove unwanted µ and δ heavy chain constant regions and replace α, γ or ε
Only one antibody class is expressed by B cell at a time
Affinity maturation
Refers to antibodies likening to a protein
Significance: When body faces same antigen again, the response time by antibodies quickened
Only seen in foreign antigens that express protein antigen, where T-cell dependent B-cell activation takes place
Primary Vs Secondary responses
Primary Responses
Naive B cells activated by T cells
B cells proliferate and undergo somatic hypermutation
Class-switch to other antibody types
Differentiate into plasma cells and memory B cells
Long-lived memory cells move to periphery
Secondary Responses
Long-lived memory B cells continue production of antibodies even after pathogen is removed
Only high-affinity antibodies are made like IgA, IgE, IgG
Attacking of pathogen is faster and more efficient
Antigen receptors
Maturation of Lymphocytes (T/B)
Maturation of lymphocytes from bone marrow stem cells involve 3 major processes:
Proliferation of immature cells
Expression of antigen receptor genes
Selection of lymphocytes that express useful antigen receptors
B cell development to Action
Early B cell development in the bone marrow
B cell development begins from hematopoietic stem cells (HSCs) in the bone marrow. Immature B cells, also called pro-B cells, undergo rearrangement of their immunoglobulin heavy chain (IgH) genes to form functional heavy chains. the successful rearrangement of the IgH genes leads to the expression of pre-B receptor (pre-BCR) on the surface of pre-B cells.
Late B cell development in the Bone Marrow
Pre-B cells that express functional pre-BCRs undergo further maturation into immature B cells. Immature B cells express both IgM and IgD on their surface and undergo an additional process of selection and maturation to become mature B cells. During this stage, immature B cells undergo negative selection .
Migration to peripheral Lymphoid organ
Mature B cells that successfully complete maturation in the bone marrow migrate from the bone marrow to peripheral lymphoid organs, including the spleen and the lymph nodes, via the bloodstream.
Action and Antigen Encounter
In the peripheral lymphoid organs, mature B cells encounter antigens derived from pathogens or foreign substances. Recognition of antigens by B cell receptors (BCR) leads to B cell activation, proliferation, and differentiation into antibody-secreting plasma cells or memory B cells.
Differentiation into Plasma or Memory B cells
Activated B cells differentiate into plasma cells, which are specialised to produce and secrete large quantities of antibodies specific to the encountered antigen. Some activated B cells differentiate into memory B cells, which have a longer lifespan and provide a rapid and enhanced secondary immune response upon re-exposure to the same antigen.
Antibody Production and Immune Response
Plasma cells secrete antibodies, which circulate in the blood stream and lymphatic system, targeting and neutralising pathogens or foreign substances. Memory B cells remain quiescent but can quickly respond to subsequent encounters with the same antigen, leading to a faster and more robust immune response upon re-exposure.
T cell development to Action
Thymus seeding
T cell development begins with the migration of progenitor cells from the bone marrow to the thymus via the bloodstream. Progenitor cells entering the thymus are called thymocytes.
Cortical Selection and Positive Selection
Thymocytes then undergo positive selection. Positive selection ensures the survival and maturation of thymocytes expressing T cell receptor (TCRs) that are capable of weakly recognising self-antigens. This is so that they don't attack upon normal body cells expressing such self-antigens. Thymocytes that successfully undergo positive selection differentiate into CD4+ helper T cells or CD8+ cytotoxic T cells.
Medullary Selection and Negative Selection
After positive selection, Mature thymocytes undergo negative selection. Negative selection involves the elimination of thymocytes that strongly recognises self-antigens. Those negatively selected under programmed cell death referred to as apoptosis.
Differentiation and Exit from the Thymus
Thymocytes that successfully pass through positive and negative selection differentiate into mature T cells with diverse TCR specificities. They exit the thymus and migrate to peripheral lymphoid organs, such as lymph nodes and the spleen, via the bloodstream.
Peripheral Activation and Effector Functions
In the peripheral lymphoid organ, mature T cells encounter foreign antigens presented by antigen-presenting cells (APCs) such as dendritic cells. Recognition of such antigens by TCRs, together with co-stimulatory signals, leads to T cell activation, specialised differentiation of T-cells to helper T cells (Th1, Th2, Th17) or cytotoxic T cells (CD8+ T cells).
Memory T cell formation
Some activated T cells differentiate into memory T cells, which provide long-term immunity against previously encountered pathogens or antigens.
Antigen recognition
How does antigens recognition help in immunity?
Initiates an immune response:
When an antigen enters the body, B and T cells are activated. These cells have specialised receptors in their surface designed to recognise specific antigens. When a B or T cell encounters its matching antigen, it activates and immune response.
Specificity:
Antigen recognition is highly specific. Each B and T receptor has a unique shape that can only bind to a particular antigen. This ensures that the immune system only attacks foreign invaders, and not the body's own healthy tissues.
Adaptivity:
The immune system can adapt and remember past encounters. when a B or T cell is activated by an antigen, it clones itself to generate a large army of identical cells to target that particular antigen. this creates immunological memory, allowing the immune system to respond swiftly, and efficiently in the future if the same pathogen tries to enter the body.
First step in empowering our immune cells to recognise foreign invaders
Variable regions
Antigen-recognising areas
Highly specific areas referred to as hypervariable regions (aka complementarity-determining regions (CDRs))
Why is there a diversity
T cells recognise peptides displayed on APCs bound to MHC molecules
Membrane-bound antibodies act as antigen receptors of B lymphocytes
VDJ recombination
Players
DNA segments
Gene encoding antigen receptors are split into multiple segments: Variable (V), Diversity (D - only present in T cells), and Joining (J) segments. Each cell has a large pool of these segments.
Recombination Activating Genes (RAG)
Enzyme complexes (RAG1 and RAG2) that act like molecular scissors, initiating the recombination process
Recombination Signal Sequence (RSS)
Specific DNA sequences flanking the V,D, and J segments that guide RAG where to make the cuts.
Steps
Initiation and cleavage
RAG proteins recognises the RSS flanking the V, D, and J segments. They introduce precise double-stranded breaks at specific location within these sequences. This creates "signal ends" and "coding ends" on the cleaved DNA segments.
Hairpin Formation
The coding ends (where the variable region of the antigen receptor is encoded) undergoes a unique modification. They bend and fold back onto themselves, forming hairpin structures. This step is crucial for the proper joining of the segments later.
Joining and Re-sealing
The coding ends from different V, D (for T cells), and J segments are brought together. The cellular machinery recognises them and precisely joins them. Meanwhile, the signal end, which lacks the hairpin structure, are rejoined with minimal modifications.
Diversity at Junctions
During the joining process, enzymes can insert or delete a few nucleotides at the junctions where the V, D (for T cells), and J segments come together. this slight randomness adds another layer of diversity to the antigen receptor.
Selection and Functionality
Not all rearrangements are successful. the cells checks if the joining process resulted in a functional antigen receptor sequence. If not, the process might be repeated with different segments. Only lymphocytes with functional antigen receptors will mature and contribute to the immune response
B cells
B cell receptor (BCR)
How antigen diversity happen
Diversity is primarily generated through a process called V(D)J recombination
Genes encoding the variable (V), diversity (D), and joining (J) regions of the BCR light and heavy chains undergo rearrangement.
One V segment, one D segment (in the heavy chain), and one J segment are randomly selected and joined together to form the variable region of the Ig gene.
B cells undergo somatic hypermutation
Variable regions of the Ig genes undergo random mutations
T cells
T cell receptor (TCR)
How antigen diversity happen
Through V(D)J recombination, but it occurs during T cell development in the thymus.
Genes encoding the variable (V), diversity (D), and joining (J) regions of the TCR alpha and beta chains undergo rearrangement.
One V segment, one D segment (if present), and one J segment are randomly selected and joined together to form the variable region of the TCR gene for both the alpha and beta chains
TCRs do not undergo somatic hypermutation, but TCR diversity is further enhanced by the combinational diversity resulting from the pairing of the alpha and beta chains
Immunoglobulin (IG) or TCR molecules recognise antigens
Signals are delivered to the lymphocytes
B cell receptor (BCR) and TCR complexes are formed
Constant regions
Conserved/constant portions
Class switching
An extension from VDJ recombination (through which the DNA of the immunoglobulin is created) wherein through class switching the isotype of the immunoglobulin is being chosen to be either IgM-IgD, IgG, IgE or IgA
Naive lymphocytes first need to recognise their own specific antigens to initiate special responses.
Cytokines
Haematopoietic cytokines
Stimulate haematopoietic cells to differentiate into specialised cells
Cytokines:
Interleukins (ILs)
Colony-stimulating factors (CSFs)
Interferons
erythropoietin (EPO)
Thrombopoietin (TPO)
Bind to receptors on haematopoietic stem cells (HSCs) and regulate functions like quiescence, self-renewal, differentiation, apoptosis and mobility
-Small proteins, not antibodies Definitions: Hormone like secreted proteins that function as mediators of immune and inflammatory reaction
5 types:
Chemokines
Interferons
Interleukins
Lymphokines
tumour necrosis factor
Functions:
Act through cell surface receptors for an immune response
Moderate balance between humoral and cell-based immune response
Regulate development and production of certain other immune cells
Interactions:
Pleiotrophic - different effects on different type of target cells
Redundant - multiple cytokines have same effect
Synergic- cooperative effect of multiple cytokines
Antagonistic- Inhibition of 1 cytokines effects by another
Cascade induction- step-feed forward mechanism for amplified production of particular cytokine
Cytokines in Innate:
TNF-α
IL-1
IL-10
IL-12
INF-α
INF-g
Cytokines in Adaptive:
IL-2
IL-4
IL-5
TGF-β
IL-10
IFN-γ
Significance
Natural immunity one is born with
Innate immunity
How does the natural and adaptive immunity work together to defend and protect us?
Abnormal situation is detected
Immune system is triggered to start an immune response
An immune response is then responsible for inflammation in the body which is usually represented with 4 body signals:
Pain
Swelling
Redness
Warmth
This is then followed by a healing mechanism to help the body recover.
Major immune components
Epithelial barriers
Physical barrier
secrete anti-microbial peptides as chemical barriers
Intraepithelial T lymphocytes kill microbes and infected cells
Dendritic cells
Produce cytokines
Act as antigen presenting (APC) cells to T cells
Bridge between innate and adaptive immunity
Mast cells
produced in bone marrow, released to systemic circulation with granules inside
Granules contain histamine and proteolytic enzymes
Natural Killer cells
Classified as Group I Innate lymphocytes (ILCs)
Kill viral infected cells, control cancer
Secretes IFNγ and TNFα cytokines
Complement system
Proteins produced by hepatocytes (liver cells).
Breakdown into 2 during enzymatic cleavage:
-smaller subunit-a
-bigger subunit-b
Except for C2 (smaller-b, bigger-a)
Common steps found in 3 pathways:
Recognition
Enzyme activation
Expression of biologic activities
3 pathways
Lectin
Not initiated by antibodies, but mannose binding-lectin (MBL) to microbes
MBL changes conformation
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Classical
C1q bind to IgG and IgM
Activate C1r, then C1s subunit
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Alternative
Triggered by spontaneous hydrolysis of C3 in plasma
In presence of microbe, C3b attaches to it and form C3b-microbe complex and bind to factor B
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4 Main functions
Opsonisation- Microbes coated by C3b are recognised by phagocytes for phagocytosis
Cell lysis- MAC induces osmotic lysis of microbe-coated cells
Inflammation -residual fragments like C3a and C5a act as chemotactic agents for neutrophils, release inflammatory mediators
Initiates-B cell responses and antibody production- complement proteins bound to antigen-antibody complexes are recognised by APCs for B-cell activation and selection of high affinity B cells
Phagocytes
2 types
Neutrophils (polymorphonuclear leucocytes= PMN)
-most abundant in the body, stimulated by colony stimulating factors
-first to arrive at infectious site
-arrive at sites where tissue damages are rampant
monocytes (aka macrophages)
Differentiate into macrophages during inflammation
Functions:
ingest and destroy microbes
clear dead tissues and initiate tissue repair
produce cytokines
Classical activation(M1 macrophages) or alternative activation (M2 macrophages)
Evolutionally driven
Plays a vital role in fighting/controlling infections in the first 7 days of primary infection (and or incubation period)
Many of the cells in innate immune system activate the adaptive system
A form of acquired immunity one develops in their lifetime
Key features
Immunological memory
Adaptivity
Made possible through somatic hypermutation and VDJ recombination
Functions of adaptive immunity
To develop the immunological memory of the individual
To make sure that the immune cells can clearly distinguish between normal and abnormal antigens
Immune cells
develop from the bone marrow and become different types of cells
Neutrophils, Eosinophiles, Basophiles, Mast cells, Monocytes, Macrophages, Dendritic cells, Natural Killer cells, Lymphocytes (B cells and T cells)
Form the first line of defense in the immune response
Primary functions
Act as a physical and chemical barrier to infectious agents e.g. skin, clotting
Identify and remove foreign substances with the help of white blood cells
Engage immne cells to reach infectious sites in the body by producing cytokines
Activate the complement system
Activate the adaptive immunity to get involve in the fight against invading microorganisms
early T cell response
Cytokine secretion
activated T cells produce IL-2 which activates clonal expansion
Foreign antigen binds to MHC on surface of APC
provided by costimulatory molecule
polygenic; several different MHC I & II genes -> unique specificity
Major histocompatibility complex (MHC)
binds onto peptide fragments of pathogens and display them on APC surface for T cell recognition
expressed on all nucleated cells
MHC class I
peptide-binding cleft between a1 and a2
CD8 T cell co-receptor binding site -> a3
processes
endogenous proteins (common in viruses)
3 polymorphic classes
HLA-A
HLA-B
HLA-C
Antigen presentation
Signal 1
Interaction between CD8+ on surface T cell & non-peptide binding regions on MHC I
Signal 2
Interaction between CD80/86 on APC & CD28 on T cell surface
Signal 3
Includes production of cytokines by APC which fully activates the T cell to provide a specific response
found on APCs only
MHC class II
peptide-binding cleft between a1 and β1
CD4 T cell co-receptor binding site -> a2 and β2
processes
extracellular proteins (common in bacteria)
encodes 3 proteins
HLA-DP
HLA-DQ
HLA-DR
Antigen presentation
Antigen uptake
Antigens, eg. proteins from pathogens, are taken up by APCs, through phagocytosis, endocytosis or pinocytosis
Antigen processing
Once inside the APC, antigens are degraded by enzymes within specialised cellular compartments - endosomes/lysosomes
MHC II synthesis & transport
MHC II molecules are synthesised in the endoplasmic reticulum (ER) & then transported to endosomes within the cell. In the compartments, MHC II molecules bind to a protein - invariant chain (li) to stabilise & prevent premature binding of self-antigens
Removal of invariant chain
Within the endosomal or lysosomal compartments, the invariant chain is cleaved, leaving a
small fragment called the class II-associated invariant chain peptide (CLIP) bound to the MHC II binding groove.
Loading of peptide onto MHC II
Meanwhile, the processed antigen peptides generated from the degraded pathogen proteins bind to MHC II molecules in place of the CLIP fragment. Loading process facilitated by protein complex - HLA-DM molecule. HLA-DM catalyses the exchange of CLIP for antigenic peptides, ensuring that only peptides with high affinity for MHC II are presented.
Expression on cell surface
The MHC II molecules, now bound to antigenic peptides, are transported to the cell
surface and expressed on the APC's plasma membrane. Here, they present the antigenic peptides to CD4+ T cells,
also known as helper T cells. This is then followed by T cell activation.
polymorphic; multiple combinations, variance -> unique specificity
steps
granule proteins
sequence
characteristics
every individual inherits 1 from each parent :
every individual inherits 2 separate genes from each parent
each made up of 1 α & 1 β coding chain
