# data[].attributes.body
Causes:
1. genetic factors
- lack of Treg cells
- defective -ve selection and self-reactive lymphocytes

2. environmental factors
- viral infections
- tissue damage
- intake of drugs

mechanisms:
1. altered autoantigens
--> self peptide mutated

2. lack of T cells
- deficient or malfunctioning regulatory CD4+ T cells --> loss of regulation or inhibition to loss of tolerance
- T regular cells --> inhibits helper or cytotoxic T cell activation by self antigens

3. polyclonal activation
- proliferation of numerous clones of B cells including autoreactive ones which produces antibodies

4. release of sequestered antigens
- not recognised as self antigens
- antigens released into circulation which induces immune respond
- via accidental trauma or infection

5. escape of lymphocytes during selection
- defect in -ve selection

6. APC with cross-reactive Ag
- activation of autoreactive T or B cells
- sensitized T helper cell reacts with cross reacting self antigen -> tissue damage
- activation of B cells of cytotoxic cells

causes for tissue damage
- complement mediated lysis
- opsonization
inhibition of receptor function
- activation of receptors
- blockage of biological function
- ADCC

classification of autoimmune diseases
1. organ specific autoimmune diseases
- directed primarily against a single organ or glands

2. systemic autoimmune diseases
- directed against a broad spectrum of tissues and manifest in a variety of organs

# data[].attributes.body
Antibodies are specialized, Y-shaped proteins that bind like a lock-and-key to the body's foreign invaders like viruses.
An antibody structure has 2 heavy chains and 2 light chains, and the heavy and light chains are held together by interchain disulphide bonds.
The 5 types - IgG, IgM, IgA, IgD, IgE - (isotypes) are classified according to the type of heavy chain constant region, and are distributed and function differently in the body.
*IgG is the main antibody in blood.
Functions of Antibody

1. IgG provides long term protection because it persists for months and years after the prescence of the antigen that has triggered their production.

2. IgG protect against bacteris, viruses, neutralise bacterial toxins, trigger compliment protein systems and bind antigens to enhance the effectiveness of phagocytosis.

3. Main function of IgA is to bind antigens on microbes before they invade tissues. It aggregates the antigens and keeps them in the secretions so when the secretion is expelled, so is the antigen.

4. IgA are also first defense for mucosal surfaces such as the intestines, nose, and lungs.

5. IgM is involved in the ABO blood group antigens on the surface of RBCs.

6. IgM enhance ingestions of cells by phagocytosis.

7. IgE bind to mast cells and basophils wich participate in the immune response.

8. Some scientists think that IgE’s purpose is to stop parasites.

9. IgD is present on the surface of B cells and plays a role in the induction of antibody production.

# data[].attributes.body
Antibodies:
2 large polypeptide chain
Tertiary structure

Homodimer -> quaternary
held tgt by disulfide bonds
Forms Y shape
Fab - antigen binding
Fc - CRYSTALisable
Fab bind to antigen,
where? epitopes
ABAG complex
Antibody-Antigen
E on AG -> AB
epitope -> binding site on ag

editting of ag - heat, cutting, inhibitors
changes shape of antigen, epitopes shape lost = cannot bind to receptors and infect cell
Antibodies bind -> phagocytes clean up
Conti epi - binding site does not change, cannot be destroyed
Discon epi - can easily be destroyed

Non-covalent interaction - van der waals etc. (reversible, non perm)

# data[].attributes.body
-The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen's cell membrane.
-Complement can be activated through three pathways: classical, lectin, and alternative.
Classical Pathway
-This pathway involves complement components C1, C2 and C4. The pathway is triggered by antibody-antigen complexes binding to C1, which itself has three subcomponents C1q, C1r and C1s. The pathway forms a C3 convertase, C4b2a, which splits C3 into two fragments; the large fragment, C3b, can covalently attach to the surface of microbial pathogens and opsonise them; the small fragment, C3a, activates mast cells, causing the release of vasoactive mediators such as histamine.
Alternative Pathway
-This pathway involves various factors, B, D, H & I, which interact with each other, and with C3b, to form a C3 convertase, C3bBb, that can activate more C3, hence the pathway is sometimes called ‘the amplification loop’. Activation of the loop is promoted in the presence of bacterial and fungal cell walls, but is inhibited by molecules on the surface of normal mammalian cells.

Mannose-binding Lectin Pathway

-This pathway is activated by the binding of mannose-binding lectin (MBL) to mannose residues on the pathogen surface. This in turn activates the MBL-associated serine proteases, MASP-1 and MASP-2, which activate C4 and C2, to form the C3 convertase, C4b2a.

# data[].attributes.body
Pathways
-classical
-lectin
-alt
what does it do
- opsonizes and kills pathogen
-activated by antigens
- c1 complex forms between c1q and c1molecules + ab
- complex form on surface of patho, forming a pore
- disrupting and increasing osmotic pressure causing the cell to lyse
- salt goes out water goes in

when talking about bacteria - describe what it does e.g
commensal round bacteria...
opportunistic bacteria...

funfact: When finding out if there is an infection, the amount of c molecules can help determine if there is one or not.

# data[].attributes.body
L5 (Gabriel)
-There are two types of Mature T cells which are CD4+ and CD8+ and TCR are all located on CSM.
Cytotoxic T cell=CD8. TCR= Binds to antigen. Helper T cell=CD4
What are the differences between TCR and BCR?
-TCR will bind to continuous epitopes located on the peptide Ag together with Class 1/2MHC.
-BCR binds to soluble cells such as Ag.
What are the similarities between TCR and BCR?
-They are both similar in terms of receptor diversity and both helps in cell fixation and survival.
What are Class 1 and Class 2 MHC?
-Both classes cannot bind to carbohydrates but they can only bind to peptide fragments that originates from protein antigens.
-Both classes will bind to various types of peptide: Class 1 bind to smaller peptides while Class 2 binds to bigger peptides, therefore this will result in various types of activation.
-Additionally, Class 2 MHC consists of two legs, while Class 1 MHC consists of one leg, and both are similar because they are both made up of alpha and beta proteins of the macroglobulin.

# data[].attributes.body
T cells have t cell receptors (antigen binding)
a chain + b chain form a unique tcr
tcr binds to mhc
mhc types: class 1 and class 2
class 1 - 3 alpha  1 beta
binds to peptides 8-9 amino acid long
class 2 - 2 of each
binds to peptides 12-20 long
Class 1 presents to CD8
Class 2 present to CD4
Dendritic cell engulf and take antigens to lymph node
cytosol - endogenous
extracellular - exogenous

Perforin/ granzyme
-in cytoplasmic granules
-discharged via exocytosis
Tc makes pore, granzymes enter
FasL are produced by Tc
FasL bind to Fas receptor, cell lyses

# data[].attributes.body
All T cells have T cell receptors (TCR) which is used for antigen binding. There are 2 types based on co-receptors CD4 and CD8
- Helper T Cell - CD4 T cells
- Cytotoxic T Cell - CD8 T cells
TCR have alpha and beta chains
Binds to:
- peptide antigens
- MHC class I or II
- continuous epitope on peptide antigens

B cell receptors (BCR) have a heavy and light chain and binds to diverse variety of antigens, both soluble and cell associated antigens.

Naive T cells develop into:
1. Cytotoxic T cells
2. Helper T cells

Tc cells help in killing pathogens (apoptosis)

Th cells helps in producing antibodies and development of memory B cells

# data[].attributes.body
Structure of monomeric antibody:

2 heavy chains (H) and 2 light chains (L).

H chain has one variable domain (VH) and multiple constant domains (CH).

L chain has one variable domain (VL) and one constant domain (CL).

H and L chains linked together via interchain disulfide bonds.

Constant and Variable domains are folded and held in place by intrachain disulfide bonds.

Ab can be cut by protease into Fragment-antigen-binding (Fab) and Fragment crystallizable (Fc) fragments.

Fab binds to antigens/epitopes

Fc binds to:

C1 complex complement proteins

Fc receptors on NK cells, macrophages, neutrophils and mast cells.

Antigen (Ag): molecule recognized by an antibody.
Epitope: Specific part of an antigen interacting with an antibody.

Epitope on Ag binds to Ab.

One B cell produce one specific antibody, antibody recognize one specific antigen.

Affinity: Strength of a SINGLE antibody-antigen interaction.
Avidity: Strength of COMBINED antigen-antibody interaction.

Resting B cell:
Membrane Ab acts as B cell receptor (BCR), BCR used in B cell activation and development.
After activation, will differentiate into plasma cells, secreting Abs. Abs performs Ag neutralization and pathogen elimination.

Functions of Antibodies:
Neutralization:
Neutralizing Ab directly prevents toxin/pathogen binding to its target, rendering it harmless. Antibodies can bind to viral receptors and prevent them from binding and entering host cells.

Opsonization:
Antibodies bind to antigen, promote recognition by phagocytes.
Phagocytes use Fc receptors to bind to Ab.

Agglutination of microbes:
Antibodies clump microbes together = easier to destroy large groups for phagocytes.

Precipitation of soluble antigen:
Abs bind to soluble antigens, form precipitates (deactivation). Can be phagocytized.

Antibody-dependent cellular cytotoxicity (ADCC):
Infected/tumor cells may display antigens on their surfaces. Ab binds to Ag and promote ADCC via NK cells.

Complement Activation:
IgM and IgG binds to pathogen surface to activate Classical pathway. Promotes direct lysis, opsonization and inflammation against pathogens.

# data[].attributes.body
3 Complement Pathways:

Classical

Alternative

Mannose-Binding Lectin (MBL)

Classical Pathway:

IgM and IgG on pathogen binds to C1 (Composed of C1q, 2 C1r and 2 C1s) to form C1qrs complex.

C1qrs complex cleaves C4 into C4a/b and catalyze C4b2 into C4b2a (C3 convertase).

MBL Pathway:
Linked with CP

MBL is complexed with a serine protease ( MASP-1/2/3).

MBL binds to mannose located on the surface of a pathogen.

MBL is activated to cleave C4 into C4a/b and catalyzes C4b2 into C4b2a.

Alternate Pathway:

C3 is cleaved by C3bBb (Signal Amplification)/ C4b2a into C3a/b.

C3b + Factor B = C3bB + Factor D = C3bBb.

C3b + C3bBb = C3bBb3b (C5 convertase)

C5 convertase cleaves C5 into C5a/b.

C5b + C6 + C7 + C8 + C9 = Membrane Attack Protein (MAC).

Many copies of C9 forms a tube which allows free diffusion of water molecules into pathogen, lysing it.

# data[].attributes.headline
L05: Antigen Presentation and T cell functions

# data[].attributes.subject
L05: Antigen Presentation and T cell functions

# data[].attributes.body
Two types of T cells: CD4 Helper T, CD8 Cytotoxic T Lymphocytes. All T cells have T cell receptor (TCR) for antigen binding.

TCR ONLY binds to continuous epitopes on peptide antigens AND Class I/II MHC. Co-receptor CD4/8 required during TCR-antigen binding.

Class I MHC:

One transmembrane domain

Peptide binding cleft = Alpha Chain + Beta-2 microglobulin.

Alpha Chains: 3 domains

Beta-2: One domain

Closed peptide binding groove, binds to 8-9 amino acid long peptide.

Distributed to all nucleated cells except RBCs.

Obtained from endogenous peptide antigen  ( viral protein within infected cell).

Presents to CD8 T cells

Class II MHCL

two transmembrane domains

Similar Alpha and Beta chains.

Alpha: 2

Beta: 2

Open groove, binds to 12-20 amino acid peptide.

Distributed to Antigen-presenting cells (APCs, dendritic, macrophages, B cells)

Obtained from exogenous peptide antigen via phago/endocytosis.

Presents to CD4 T cells,

T cells will only recognize antigen together with MHC on APC. TRC does not interact with free/soluble/unbound antigens w/o MHC, binds only to processed peptide fragment presented on MHC.
Class I MHC is located on CD8 Cytotoxic T cells.
Class II MHC located on CD4 Helper T cells.

Dendritic Cells:

DCs capture antigens -> migrate to lymph node ->  Stimulate Naive T Cells.

DCs need co-stim signals to activate naive T cells. PAMP induces co-stim signal on DCs via PRR binding -> DCs also secrete cytokines, processes antigens and present on MHC.

3 Signals to activate naive T cells:

Foreign peptide antigens

Co-stim signal B7 binding to CD28.

Cytokines guide T cell differentiation process.

Naive T cell bind to antigen presented by DC to activate -> Cell division and diff -> Become effector and memory T cells.

Antigen Presentation via Class I:
Virus infects host cells -> Infected cell produces viral proteins in cytosol -> peptide fragments of viral proteins bounded by MHC I in ER -> MHC I transported to cell surface -> Endogenous antigens processed & presented on MHC I to activate Cytotoxic T cells (CD8).
Antigen Presentation via Class II:
Antigen taken from extracellular space into intracellular vesicle -> after phagocytosis, enzymes from lysosomes delivered to phagosome -> enzymes digest protein antigens into peptide fragments -> vesicles with peptides fuse with vesicles containing MHC II. -> transported to cell surface to activate Helper T cells (CD4).

DCs can cross-present processed peptide antigens to CD4/8 T cells.

Cytotoxic T cells (Tc) killing methods:

Perforin/Granzyme Killing: Tc have cytoplasmic granules containing proteins perforin and granzymes, released via exocytosis when Tc binds to target cell. Perforin insert into plasma membrane, forming pores -> granzymes enters, produces ROS/ activate apoptosis cascade enzymes, causing target cell to self-destruct.

FasL Killing: Tc expresses Fas ligand on their surface -> Tc Fas ligand binds to Fas receptor expressed by most target cells -> Induce apoptosis.

Subtypes of Effector T helper (TH) cells:
TH1: Formed when DC presents antigen to pre-TH cells. DCs secretes interleukin 12 (IL-12) and IFN-gamma. Cytokines by DCs stim TH1 cells to secrete lymphokines: Interferon-gamma and Tumor-necrosis factor-beta (TNF-beta).  Effector TH1 recognize antigens presented by macrophages.

TH1 secretes IFN-gamma which enhances macrophage phagocytosis activity.

Recruits other leukocytes to inflammation producing site.

Assists TC in their function and convert them into memory T cells.

Controls antibody class switching.

TH2:

Formed when APCs present antigens (allergens/ antigens of parasitic worms) to pre-TH cells TCR.

APC secretes IL-2./4

TH2 stimulated by APCs cytokines to secrete IL-4/5/13.

TH2 secretes cytokines to recruit mast, eosino/basophils to fight against parasitic worm infections.

TH2 cytokines stimulate IgE production, for the development of allergies.

TFH (Follicular Helper):

TFH are CD4 cells located in B cell nests in lymph nodes.

When exposed to APCs (B cells) and cytokines -> TFH migrate into follicles.

Binding interactions stim B cell to: class switch with synthesis of other antibody classes except IgE. Undergo affinity maturation. Form plasma and memory B cells.

# data[].attributes.headline
L06: Tolerance and Organ Transplantation

# data[].attributes.subject
L06: Tolerance and Organ Transplantation

# data[].attributes.body
Self-tolerance: Immune system does not react antigens secreted from self tissues. Achieved via central and peripheral tolerance.

Central tolerance: Induced in bone marrow (B cells) and thymus (T cells). T cell progenitors migrate from bone marrow to thymus to undergo positive and negative selection.

Positive selection:

TCR successfully binds to self-MHC = Immunocompetent.

Binds to MHC I = CD8 T cell. Binds to MHC II = CD4 T cell.

TCR doesn't bind to self-MHC = Non-immunocompetent T-cell = Dies

Negative selection:

TRC recognize polymorphic residue of self-MHC = able to recognize foreign peptide bound by self-MHC = MHC-restricted Immunocompetent T-cell (Mature T cell).

TCR + self-MHC + self-peptide = self-reactive T cell = killed off or mature into T regulatory cells.

Self-reactive T cell will undergo: Clonal deletion OR Receptor editing.

Mature T cells exiting thymus are:

self-restricted/tolerant

Single positive for one MHC

T cells that recognize MHC II and self-peptides are self-reactive Th cells = Treg cells.
Treg cells detect self antigens on APC = secrete cytokines to suppress activation. (Peripheral tolerance)

Peripheral tolerance:

During infection, PAMP induces co-stimulatory molecule (B7) on DC.

DC activate naive T cells against antigens from pathogens.

DC + self-antigen - B7 = T cell inactivation (anergy) OR T cell clonal deletion.

B cell Tolerance
Central tolerance: Autoreactive BCR = Clonal deletion/ Receptor editing.
Peripheral tolerance: Autoreactive BCR = Clonal deletion/ Anergy

Immune Privileged sites: Brain, eyes, testis, placenta. High antigen tolerance, antigens not used during negative selection.
Sequestered antigens hidden by physical barriers to prevent T cells from reaching them. If T cells recognize sequestered antigens, they will not be deleted.
Tissues at immune privileged sites have high expression of FasL to induce apoptosis in Tc cells bearing Fas.
Organ transplantation:

Autograph (From same individual, histo-compatible)

Isograft/Syngraph (Genetically identical individual, histo-compatible)

Allograph (Genetically different individual, incompatible)

Xenograph (different species, incompatible)

Hyperacute rejection:

Pre-existing antibody (host) against donor blood group antigens

Complement activation and inflammation damages blood vessels

Prevention is to perform ABO-matching and cross-matching to determine existing antibodies in host against donor cells.

Acute rejection:

Occurs after days/weeks

Tc cells activated to kill graft cells with mismatched MHC molecules

Prevention is to perform MHC matching.

Chronic rejection:

Occur after months/years

May suddenly exhibit rejection symptoms

Accelerated rejection:

Skin graft rejected in 10-14 days

2nd graph with same tissue type will be rejected more quickly due to memory cell activation.

# data[].attributes.body
self-tolerance
- immune system does not react to antigens derived from self-tisses
- 2 processes: central and peripheral tolerance

central tolerance
- induced in bone marrow (B cells) and thymus (T cells)

peripheral tolerance
- induced in peripheral lymphoid organs (spleen, lymph nodes, tonsils)

thymus
- T-cells progenitors migrate to thymus, positive and negative selection occurs

CENTRAL TOLERANCE FOR T CELLS
positive selection - removal of non-MHC binding T cells, leaving behind T cells which be recognised by self-MHC
T cell --> MHC I --> CD8 T cell
T cell --> MHC II --> CD4 T cell

negative selection - removal/inactivation of T cells which binds to both self-peptides and self-MHC (self-reactive).
removal via clonal deletion
inactivation via receptor editing
Some T cells can escape negative selection to become mature Treg cells

this results in MHC restricted immunocompetent T cells - T cells which interacts with self-MHC and non self-peptides. They are self-restricted, self-tolerant and single positive (CD4 & CD8)

Treg
- self-reactive TH cells (CD4)
- detect self-antigens presented on APCs
- secrete cytokines to suppress activation

PERIPHERAL TOLERANCE
dendritic cells
- PAMP will induce co-stimulatory molecule (B7) on DC
- DC will activate naive T cells
- when DC presents self-antigen w/o co-stimulation signal, it will lead to T cell inactivation (anergy) or deletion of T cell (clonal deletion)

immune privileged sites  - high expression of FasL at these tissues (e.g. testis) to kill effector T cells through Fas

TRANSPLANTATION
histo-compatible - autograft & isograft/syngraft
histo-incompatible - allograft & xenograft

# data[].attributes.body
Background info.
-Foreign Antigens/Heteroantigens examples include viruses, while Self-Antigens/Autoantigens examples include body cells and consist of cell surface molecules.
-Self-tolerance of immune system means that will not destroy its own tissues because it will not be initiated when it detects antigens made by its own tissues, and instead protect those tissues against other antigens.
-Central tolerance occurs in the bone marrow and thymus where B and T cells are present, while for Peripheral tolerance it occurs in the peripheral lymphoid organs like the spleen and tonsils.
T cell and TCR interaction process.
-During Maturation, each T cell will shuffle the TCR leading to a unique TCR combination, Developing T cells have positive and negative selection for mature cell selection, Self-MHC is immunocompetent hence it can interact with the polymorphic residues of self-MHC which leads to positive selection.
Positive selection.
-Binding strength moderate for survival,
No interaction with MHC I or MHC II molecules [apoptosis], Immunocompetent (surviving T cells) can interact with self-MHC which allows them to interact with polymorphic residues of self-MHC, Non-immunocompetent T cells will undergo deletion to be removed.
Negative selection
Clonal deletion and Receptor editing occurs, T cells which binds to self-peptide with self-MHC will be removed/inactivated, Immunocompetent  means they interact with self-MHC and not with the self-peptide or they bind to foreign peptide instead of self-peptide, Non- immunocompetent cells (self reactive) are removed or inactivated, Treg which are regulatory T cells survive negative selection, but won’t proliferate, for Immunocompetence, T cells must pass both positive and negative selection to leave the thymus

# data[].attributes.body
Histocompatible
Autograft - same individual
Isograft - another similar individual
non histocompatible
Allograft - different individual
Xenograft - totally different individual/species

What prevents T cells in thymus from apoptosis? Constant signal to not die 💀
Without this --> death by neglect
Who? non regulatory T cells

Tolerance - Central (BM & Thy)
Peripheral (spleen, lymph nodes)
Low tolerance = big immune response = more cytotoxic t cells = diseases such as autoimmune --> NK kills normal bodily cells

Central
+ select ( t cell - mhc 1 - CD8) (t cell - mhc 2 - CD4)
- select (self reactive mhc - clonal deletion)
Peripheral
> B7 on DC induced
> Naive t cells activated

# data[].attributes.body
Herd immunity is defined by the vaccination or natural immunity in a population.

Acquired immunity – long lasting protection, proteins recognise and destroy pathogen.

Can prevent from spreading to other people during a second exposure.

If enough people from a population become immune, the rest of the population is protected by proxy which establishes herd immunity

Herd immunity works by the number of immunized individuals in the population

No immunized, disease spreads through population

Partial immunized, disease spreads through some of the population

Most immunized, disease spread is contained but still able to infect nonimmunized.

Active immunity - recognize pathogen, apc -> tcell, mhc-> tcr
passive - eg. blood plasma transfusion = pathogen being killed by additive antibodies in plasma.

Vaccines dont last very long -> booster shots required - increase number of antibodies and memory t cells

Attenuated - Live weakened
Inactivated - killed in culture
Subunit - Uses proteins or polysacc instead of virus
mRNA - mRNA to synthesize protein normally found on pathogen
Toxoid - Purified and inactivated

# data[].attributes.body
Natural Active Immunity: Exposure to a diseased organism that triggers immune system to produce antibodies to counter to that disease.
Artificial Active Immunity: Activation of adaptive immunity by deliberate exposure of weakened/inactive pathogens. (Vaccination)
Natural Passive Immunity: Natural passage of antibodies from mother to fetus. IgG can cross via placenta, IgA via breast milk.
Artificial Passive Immunity: Transfer of antibodies from donor (Human/Animal) to recipient. Can be used to prevent disease after pathogen exposure or to treat active infection.
Herd Immunity: Humans can either be immune or susceptible to a disease, if a population has drastically more immune individuals than vulnerable, the vulnerable individuals are protected  via herd immunity. The disease is unable to spread effectively to the vulnerable as there are too few of them and too many immune individuals.

Types of vaccines:
Live attenuated: weakened strain of entire pathogen. Long lasting, cellular and humoral immunity.
Inactivated: Pathogen killed/inactivated with heat/chemicals/radiation. No risk of infection.
Subunit: Immunogenic antigens. Low risk of side effects.
Toxoid: Inactivated bacterial toxin, Humoral immunity.
Conjugate: Capsule polysaccharide conjugated to protein. T-dependent response to capsule

# data[].attributes.body
Passive Immunity.
-Passive natural immunity is naturally given like when a mother is breastfeeding her child, antibodies (IgA) are transferred into the child
-Passive artificial immunity (Short span) is artificially obtained like vaccine injection will help immunize antibodies.
Active Immunity.
-Active immunity can be naturally obtained when antigens go into the body which will activate a primary response like infection.
-Active immunity can be artificially obtained when antigens go into the body after a vaccine is given, which will activate the primary response.
-Both will help to produce memory T and B cells and provide Immunity.
Difference between Active and Passive Immunity.
For active immunity:
- T and B memory cells are produced.
- Antibodies are formed by the acquired immune system in the hosts’ body.
- Antibodies are formed naturally by an infection, or can be artificially by vaccination.
-Provides long term protection.
For passive immunity:
- No memory cells are included in the process.
- Antibodies will be transferred from  donor into the body.
- Antibodies can be purified from a recovered patient or can be grown from a cell culture.
- Quick response however, it is short lasting until all the antibodies are used up, so this can be used to treat diseases.

Why are vaccines important in the virus pandemic?
-Vaccines contain a weaker form of the pathogen like for example, measles vaccine contains weakened measles virus.
-The pathogen in the vaccine has either been killed off /weakened so much that it does not have the capability of making a person become ill.
-A vaccine will activate the immune system and cause it to form antibodies, so after getting a jab, a person will built up immunity to that particular pathogen and next time when the body encounters it again, the memory B and T cells lymphocytes will know how to kill them.
-Memory B and T cells are very long-lived, so a vaccine should be jabbed every once a year.
-However, immuno-compromised patients like HIV patients should consult their doctor for advise when deciding to be vaccinated, because their immune system is already compromised and weakened, so a vaccine type like a live-Attentuated vaccine that uses a living but weakened version of the virus may be dangerous to them as it may overcome the immune system of the patients and kill them.
-The 3 main approaches of creating a vaccine is using a whole virus/bacterium, parts that trigger the immune system, and the genetics material itself.

# data[].attributes.body
IMMUNITY

Active immunisation
- Antigens are introduced
- Antigen specific response is produced by body's immune system
- Memory T cells specific to the antigen is produced

Passive immunisation
- Antibodies are introduced
- Antigen specific response is not produced
- No memory T cells produced

Natural active immunity
Production of one's own antibodies or T cells as a result of infection or natural exposure to antigen
Artificial active immunity
Production of one's own antibodies or T cells as a result of vaccination
Natural passive immunity
Temporary, fetus acquires antibodies from mother via placenta or breast milk
Artificial passive immunity
Temporary, injection of preformed antibodies in immune serum

VACCINE

Attenuated
- Weakened live virus
- Cultivated in conditions that disables their virulent properties
- Less dangerous
- Elicit strong cellular and antibody response
- Lifelong immunity after 1 or 2 doses

Toxoid
- Made from inactivated toxic compounds that causes the illness rather than the microorganism
- Toxins inactivated with formalin
- Toxoids are able to trigger an immune response
- Safe as they cannot cause the disease
- Require booster jabs

Subunit
- A fragment of the virus is introduced to create immune response
- Blocks transmission
- Does not interfere with immunodiagnosis

Conjugate
- Bacterial pathogens
- Recognises the polysaccharide outer coat of bacteria cells
- Immune system recognise the polysaccharides as protein antigen

Recombinant Vector
- Combining physiology of one pathogen and the DNA of another
- Created for diseases with complex infection process

DNA
- Created from pathogen's DNA
- DNA very stable, sequence can be changed easily in the lab
- No immune response to vector as it contains no protein components

Dendritic Cell Vaccine
- Combination of DC with antigens
- Presentation of antigen to body's WBC
- Shown some positive preliminary results for treating brain tumors  and are also tested in malignant melanoma.

Recombinant vector, DNA and dendritic cell vaccine are experimental vaccines

# data[].attributes.body
Primary Immunodeficiency (PID): Inherited immune disorders caused by genetic mutations, present at birth.
B cell (adaptive): Mutations in genes producing B cells lead to loss of antibody production -> recurrent bacterial infections.
T cell (adaptive): Mutations in T cell genes may lead to decreased T cell count or with disrupted function -> affects B cell functions.
Severe Combined Immune Deficiencies (SCID, adaptive): Lack of T and B cells -> no immune function, -> minor infections can be deadly.
Phagocyte disorder (innate): Mutations affect phagocytes ability to phagocytose certain bacteria/fungi. Certain bacteria/fungal infections may cause severe harm or death.
Secondary Immunodeficiency (SID):
Caused by external or environmental factors.
Malnutrition: T cell count and function decrease due to protein deficiency -> susceptible to GI tract infections.
Drugs: Suppresses immune systems which leads to opportunistic infections.
Chronic infections: HIV = AIDS, HIV virus attacks CD4+ T cells to decrease numbers, high risk of recurrent infections.

# data[].attributes.body
Immunodeficiency
Primary - gene defect (inherited)
Secondary - Underlying diseases (Acquired)
Lower B cell count - lower antibody prod
HIV --> AIDS  - kill CD4+ t cell
Infected CD4+ will be killed by cytotox or NK
T cell affected --> ADA defi or digeorge
B cell affected --> XLA XG HYPO
gammaglobulin - igG
Hypo - less
Congenital - NO (no thymus, no naive b cells, no t cells)
Hyper - more
since no igG nothing can happen
SCID - combined = both b and t all wiped out (happens in stem cell or smth, higher up)
One thing happened to anything, all downstream affected
Adhesion - binding

# data[].attributes.body
Immunodeficiency disease

primary immunodeficiency
- caused by congenital birth defect (intrinsic), young age

B cell defect (specific)
- results increased susceptibility to recurrent infections with bacteria (S. aureus)
- Defective antibody response due to B cell function failure and failed signalling from T to B cells

Poor T cell function (specific)
- results in susceptibility to opportunistic infections due to defective cell-mediated immunity
- may result in SCID or MHC-II deficiency.

Phagocytic cell deficiency (non-specific)
- lack of phagocytic cells (NK cells, macrophages etc.)

Complement deficiency (non-specific)
- results in lack of any complement proteins (C3, C4, C5 etc.)
secondary immunodeficiency
- caused by external factors/diseases (extrinsic) , any age

common causes - HIV, cancer treatment, metabolic diseases (e.g. diabetes), malnutrition and immunosuppressant drugs

# data[].attributes.body
Causes of autoimmune diseases
- genetic factors (inherited)
- environmental factors (acquired)

Possible mechanism that leads to autoimmune diseases.
- release of sequestered antigens from immunoprivileged sites
- escape of lymphocytes reactive
towards self-antigen
- altered autoantigens
- lack of Treg cells
- polyclonal activation
- cross-reacting antigens

How does autoimmune disease cause tissue damage?
- complement mediated lysis
- opsonization
- receptor inhibition
- receptor activation
- biological function blockage
- ADCC

Classification (refer to images attached)

# data[].attributes.body
Types
I : Allergy (igE)
II: Cytotoxic (AB mediated) ADCC
III: Immune complex (ab-ag, comp, phag)
IV: Delayed (T cell) not adcc

mast cells degranulate to release histamine
anaphylaxis - cannot breathe, swelling,

# data[].attributes.body
When some components of the immune system is defective, this will weaken the body's ability to fight off foreign invaders like fungi, hence leading to Immunodeficiency, which refers to a state in which the immune system's ability to fight infectious diseases and cancer is compromised / absent.
2 types of Immunodeficiency:
-Primary (Inherited genetically) and Secondary (Acquired).
Primary Immunodeficiency (Obtained at early age).
-Most primary immunodeficiency sufferers are born missing some of the body's immune defenses or with the immune system not working properly, which leaves them more susceptible to invaders like bacteria that can cause infections.
-Examples include: DiGeorge syndrome, Ataxia-telangectasia, and Chronic granulomatous disease.
-Primary immunodeficiencies can only affect one component of the immune system / multiple cells and proteins.
-They can lead to antibody deficiency like IgM and IgG, combined immunodeficiency, complement deficiency, and phagocytic cell deficiency.
-Primary immunodeficiency includes the development of B-lymphocytes, T lymphocytes, or both.
-The affected lymphocytes may not be present, not enough, or may not be working properly.
Classification.
There are 4 groups:
1.T cell deficient (Specific Immunodeficiency which includes T cell of the adaptive immune system).
2.B cell deficient (Specific Immunodeficiency which includes B cell of the adaptive immune system).
3.Phagocytic cell deficient (Non-specific Immunodeficiency).
4.Complement deficient (Non-specific Immunodeficiency).

Secondary Immunodeficiency (Obtained at any age).
-This is caused by disease or environmental factors, like HIV, malnutrition, or medical treatment (e.g. Chemotherapy), which will weaken the body's immune response.
Examples include: Malnutrition which will cause immune cell activation and systemic proinflammatory mediator levels to increase, and this will impair immune priming by DC and monocytes, and impairs effector memory T cell function.

# data[].attributes.body
-Hypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity.
-They are usually referred to as an over-reaction of the immune system and these reactions may be damaging and uncomfortable.
-Type I: Allergy (IgE mediated)
-Type II: Cytotoxic hypersensitivity (antibody-mediated)
-Type III: Immune-complexes (antibody-antigen immune complexes, complement and phagocyte mediated)
-Type IV: Delayed type (T cell mediated: Th and Tc )
Type 1.
-IgE is formed as a result of prior sensitization (i.e., previous contact with the antigen) and coats mast cells and basophils.
-Subsequent encounter with antigen results in an IgE-mediated reaction by preformed IgE antibodies: free antigen binds to two adjacent IgE antibodies(crosslinking) → degranulation of cells
-Release of histamine and other mediators (e.g., prostaglandin,
platelet-activating factor, leukotrienes, heparin, tryptase), leading to:

1.Smooth muscle contraction →
bronchospasm
2.Abdominal cramping
3.Peripheral vasodilation and ↑ vascular permeability.
4.Extravasation of capillary blood → erythema
5.Fluid shift into the
interstitial space → edema, pulmonary edema
6.Pruritus

7.Mast cell secretion of
cytokines and other proinflammatory mediators →eosinophil and neutrophil
chemotaxis → late-phase reaction → inflammation and tissue damage.
Type 2.
-IgM and IgG mistakenly bind to surface antigens of the cells in the body, which results in:
1.Cellular destruction:
Antibody-dependent cell-mediated cytotoxicity,(NK cells or
macrophages), Target cell
opsonization→ phagocytosis and/or complement activation.

2.Inflammation.
-Fc-receptor mediated
immune cell activation
-Antibodies bind to cellular surfaces → activation of the
complement system.
3.Impaired cellular function.
-Antibodies bind to cell surface receptors → inhibition or activation of downstream signaling pathways → impaired cellular function.

# data[].attributes.body
Type I:  Allergic Anaphylaxis Atopy

Upon first exposure to antigen, APC processes and presents antigen to TH2 cell.

TH2 releases IL-4 and IL-12 to activate B cells.

B cells proliferate and differentiate into plasma cells to secrete IgE.

IgE binds and sensitize mast cells by Fc region.

Mast cells with IgE bind to antigen and release inflammatory molecules upon subsequent exposures.

Mediated by: Eosinophils, neutrophils, lymphocytes.

Type II: Antibody-dependent cell mediated cytotoxicity

Mediated by: IgG/M

IgG/M binds to host cells to activate complement cascade, lying the host cells.

Type III: Immune complex

Mediated by: IgG

IgG binds to antigen to form immune complex and deposited on tissues.

Neutrophil and mast cell degranulation causes localized tissues damage.

Type IV: Delayed

Mediated by: T cells

APC processes and presents antigen to CD4 cells, sensitizing them into memory TH1 cells.

Subsequent exposures will stimulate sensitized TH1 cells into releasing cytokines to recruit macrophages, resulting in inflammation.

# data[].attributes.body
Mechanisms of Autoimmunity
Release of Sequestered Antigens: Sequestered antigens are those that can not interact with the immune system during development as they are anatomically sequestered and hence the lymphocytes specific for such sequestered antigens are not deleted. These are treated as foreign when introduced into the circulation, and elicit both humoral and cellular responses.
Altered Autoantigens:
Self-peptide Mutated
Molecular Mimicry:
Antigens of certain bacteria/viruses mimic self-antigens (Cross-reacting antigens). Microbe Antigens may activate autoreactive T and B cells. Antibody/ Sensitized T cells react with CRA and may produce tissue damaging reactions.
Polyclonal Activation:
Viruses/Bacteria can induce non-specific polyclonal B-cell activation. that express IgM in the absence of TH cells. Autoreactive B cells can be activated via polyclonal activation, thus they may produce autoantibodies.
Absence of Treg cells:
Deficient or malfunctioning Treg cells result in loss of regulation or inhibition of T cells against self-antigens, leading to loss of tolerance. This may be a result of a genetic disease or acquired from an infection (e.g. HIV).
Defective negative selection of self-reactive lymphocytes :
During the development of tolerance, and removal of self-reactive lymphocytes, some self-reactive lymphocytes escape negative selection, and are able to mount an immune reaction against self-antigen in the body.

Autoimmune Classification:

# data[].attributes.headline
are there any treatment available for Renoir's autoimmune disease?

# data[].attributes.subject
are there any treatment available for Renoir's autoimmune disease?

# data[].attributes.body
Autoimmune
Causes: genetic & environmental
Mech: Mimicry, T reg deficiency, polyclonal, sequestered ag

Tissue dmg:
1. Cleavage of various complement components in the classical pathway which form mac and consists of C5b, C6, C7, C8 and several C9 molecules​

2. Autoantibody binds to autoantigen -> antigen forms an ab – ag complex which is then engulfed by a phagocyte​

3. ADCC – Autoantibodies bind to the target cells which is then recognised by NK cells and cause the cell to lyse.

# data[].attributes.body
-Autoimmunity can be caused by genetics (inherited) or environment (acquired).
-Genetics examples include insufficient regulatory T cells and defect in negative selection.
-Environment examples include smoking, drugs, and vitamin D deficiency.
Mechanisms that cause autoimmune diseases include:
1.Sequestered antigen from immuo privilaged sites are released. Caused by accident injuries or viral infection.
2.Lymphocytes reactive towards self antigen gets out and becomes defective in - selection.
3.Altered autoantigens can lead to new ones not being tokerated by immune system cause autoimmunity.
4.The lack of regulatory T cells cause Treg cells to inhibit helper or cytotoxic T cell activation by self antigens.
5.Polyclonal activation initiate many lymphocyte clones such as autoreactive ones.
6.Cross reacting antigens result in pathogen being specific to T or B cells that recognise self antigens.
Classification of autoimmune diseases.
Organ specific autoimmune disease: it is concentrated on one organ / glands
Systemic autoimmune disease: it is concentrated on many tissues and occur in many types of organs.
Autoantibodies can destroy or injure tissues by:
1.Complement meditated lysis
2.Opsonization.
3.Disruption of receptor function
4.Receptor activation.