immuno Flashcards
What would a C1 protein deficieny cause?
C1 inhibitor (C1-INH) protein deficiency
causes hereditary angioedema
C1-INH is a multifunctional serine protease inhibitor
probable mechanism is uncontrolled release of bradykinin resulting in oedema of tissues
What would a C5 deficiency cause?
C5-9 deficiency
encodes the membrane attack complex (MAC)
particularly prone to Neisseria meningitidis infection
What does IL-6 do?
Endogenous pyrogen
Stimulates acute phase protein production
Also secreted by Th2
What is the major chemotactic factor for neutrophils?
IL-8
Describe the basic process of antigen recognition in the lymph node
Dendrite phagocytoses pathogen
Undergoes ‘licensing’ and upregulates CCR7 (chemotactic receptor) that sends them to the spleen or lymph node
In paracortex of spleen LN, activates the naive t-cell to either CD8 killer or memory cell or
CD4 (TH1, Th2, Th17, T-reg, or TFH)
What are the roles of, and cytokines required for differentiation of activated CD4+ T-Cells?
Th1 - activates macrophages via IFN-gamma, activates B-Cells. Requires IL-12 and IFN-gamma to become this.
Th2. Recruits and activates granulocytes. Requires IL-4 to become this.
TFH (T follicular helper). Allows B-Cells to differentiate, class switch, and proliferate with help of Th1 or Th2. Requires IL-6 alone.
T-Reg. Regulates T-cells by inhibiting immature dendrite entry into the lymph node. Requires IGF-B alone.
Th17. Secretes IL-17, causes epithelial cells to recruit more leukocytes to the affected area. Requires IGF-B and IL-6 to become this.
What does CD4+ Th1 do?
Th1 -
activates macrophages via IFN-gamma, activates B-Cells.
Secretes IFN-gamma and TNF-_beta_
Requires IL-12 and IFN-gamma to become this.
What does CD4+ Th2 do?
Th2.
Recruits and activates granulocytes (mast cells and eosinophils) and B-cells.
Secretes IL-4 (autocrine), IL-5 (eosinophils & mast cells), IL-6 (major inflam mediator) IL-10, and IL-13
Requires IL-4 to become this.
What does CD4+ Th17 do?
Secretes IL-17, causes epithelial cells to recruit more leukocytes to the affected area. Requires IGF-B and IL-6 to become this.
What does CD4+ T-reg do?
Regulates T-cells by inhibiting immature dendrite entry into the lymph node. Requires IGF-B alone.
What does CD4+ TFH (T follicular helper) do?
Allows B-Cells to differentiate, class switch, and proliferate with help of Th1 or Th2. Requires IL-6 alone.
What is the general mechanism of severe combined immunodeficiency?
Most cases of SCID are due to mutations in the gene encoding the common gamma chain (γc), a protein that is shared by the receptors for interleukins IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. These interleukins and their receptors are involved in the development and differentiation of T and B cells. Because the common gamma chain is shared by many interleukin receptors, mutations that result in a non-functional common gamma chain cause widespread defects in interleukin signalling. The result is a near complete failure of the immune system to develop and function, with low or absent T cells and NK cells and non-functional B cells.
OR
Janus kinase-3 (JAK3) is an enzyme that mediates transduction downstream of the γc signal. Mutation of its gene causes SCID
What are the general features of severe combined immunodeficiency?
- absence of functional t-lymphocytes
- defective antibody response as t-cells can’t kill or activate B-cell
- most severe form of primary immunodeficiency
- known as the ‘bubble boy disease’
- severe infections of all types
- BMT is tx, it’s rare.
What is the mechanism of the second most commonest form of SCID?
- defective enzyme, adenosine deaminase (ADA)
- necessary for the breakdown of purines.
- causes accumulation of dATP –> inhibition of the activity of ribonucleotide reductase, the enzyme that reduces ribonucleotides to generate deoxyribonucleotides.
Without functional ribonucleotide reductase, lymphocyte proliferation is inhibited and the immune system is compromised.
What does IL-3 do?
- stimulates myeloid progenitor cells or lymphoid (with IL-7) progenitors - works just like GM-CSF
- secreted by activated T-cells and basophils
Describe the process of B-cell activation in the presence of antigen
- B-Cell MHC2 presents antigen to T-helper cell TCR
- CD40 is coexpressed on the B-Cell and attaches to the CD40 ligand on the Thelper which stimulates B-cell proliferation and differentiation
- T-cell releases IL-4, IL-5, and IL-6 which also activates the B-cell in the dark zone of the germinal centre.
- The immature B-Cell undergoes somatic hypermutation (alteration of binding specificity and affinity of resultant antibodies) and affinity maturation (only the high affinity antibodies survive) and turns into a centroblast.
- The centroblast expresses CXRCR4 and CXCR5 which attract it to chemokines in the light zone where it becomes a centrocyte.
- Once in the light zone, they die if they’re of low affinity mutation, if high, the T-helper follicular cells will bind it and signal it to class switch, differentiate, and proliferate.
- Either becomes Memory B-Cell (IgG), or to plasma cell (which goes to the BM and secrete antibodies).
What are the three main roles of antibodies?
Neutralisation - prevents pathogen adhesion
Opsonization - promotes phagocytosis
Complement activation –> activates MAC destruction
What is Pathogen Associated Molecular Pattern (PAMP)?
All bugs have it, allows leukocytes to recognise it and start immune response.
Local mast cells will also release histamine in the presence of PAMP
Local macropahges will release cytokines too –> blood vessels will extrude monocytes into the tissues where they become macrophages, and neutrophils
What is diapedesis?
The process through which neutrophils extrude through the blood vessels (migrate)
How does opsonisation occur?
Plasmin and kinin activate complement cascade which then either opsonise the pathogen allowing easily elimination by phagocytes, or destroy the pathogen by rupturing it’s membrane.
How does the innate immune system recognise pathogens?
Specific PAMPs - only on pathogenic microbes - LPS, lipoproteins, peptidoglycans, lipoprotease, and lipotechoic acids (LTAs) are some examples.
They can be cell wall, flagella, or even DNA/RNA and are essential for pathogen survival.
via Pathogen Recognition Receptors
3 types - intracellular, extracellular, or secretory (for tagging) and all trigger the innate response (phagocytosis, opsonisation, complement, release cytokines and inflammatory mediators)
Describe the extracellular pathogen receptor protein
Sits on innate immune cells i.e. macrophages.
- binds PAMP (i.e. cell wall)
- tells cell to engulf pathogen and release lysosomic granules - this is done by mannose and scavenger receptors
- OR signals nucleus to release cytokines/IFNs (if virus has invaded the cell) via toll-like-receptors
Describe the intracellular cellular pathogen receptor protein
Sits inside innate immune cells i.e. macrophages.
- most famous is the nod-like receptor
- cell gets infected by pathogen ie virus
- releases cytokines
- aptoptoses if fully infected
Describe the secreted cellular pathogen receptor protein
Secreted by the liver and immune cells
Once secreted, no relation to those cells
Activates complement cascade via complementary receptors
What are the cytokines and receptors involved in diapedesis of neutrophils?
Macrophage releases TNF-a at site of injury
Activates endothelial receptors - selectins and Ig SuperFamily
Macrophages secrete CXCL8 or IL-8 which is a chemokine that shows the neutrophil the way to the site of injury
Neutrophil then passes through the vessel wall by binding the receptors. The neutrophil expresses a special carbohydrain chain, an IL-8 receptor, and an Integrin.
Rolling–> Adhesion –> Binding
Special carbohydrate chain binds to the selectin (it’s like a leg) - ‘adhesion’
and then
Integrin binds Ig Superfamily (I-CAM-1 and ICAM-2 (superfamilies are usually called ICAM)
IL-8 binds IL-8 which lead the way
What is the difference between MHC1 & MHC2?
MHC 1
All nucleated cells (so NOT red blood cells)
1 leg in phospholipid membrane
Binds small antigenic peptides which are tightly bound
B2 domain stays constant
4 microglobulins (alpha 1, 2, 3 and B2) - 1 never changes (B2 - represents MHC1), which the MHC1 molecule, other makeup the cleft (binding site). The alpha portion of the binding site will then change to fit the specific antigen.
Antigen sits in cleft, CD8 receptor on T-cell ‘checks’ if the MHC is class 1 (via the beta domain)
Cell mediated immunity is then activated.
MHC 2
Antigen presenting cells only (phags, macrcophage, dendritic cell)
2 legs in phospholipid membrane
Binds large antigenic peptides which are loosely bound
Presents antigen to T-helper cell so it can get help
4 microglobulins - alpha 1&2 (different to MHC1 alpha), B1&2 - specific to a particular antigen
Binds CD4 D1-D2 domain (which binds the beta 1&2) after checking if an MHC2 molecule.
T-Cell receptor then checks the antigen fits and then binds it
Initiates adaptive and cell mediated immunity.
How does MHC-1 present an antigen?
Bacteria ends cytosol via lipid membrane
Antigen winds up in the cytosol
Proteosome activated which chops up the bacteria into identical peptides
Peptides enter the ER within the cell via the TAP-transport channel
Calnexin sits inside the ER bound next to an incomplete MHC1 (missing a b2 domain) which allows B2 to attach.
Calnexin then dissociates after B2 has been attached
MHC1 then requires binding of calreticulin, ERPs and tapsin, which allows a peptide (the antigen) to load and attach to the alpha domains of the MHC1 molecule
MHC1 then leaves the ER in an endosome.
It then surfaces on the infected cell, ready to present to CD8 t-cells.
How does MHC-2 present an antigen?
Pathogen gets phagocytosed through a cell via endocytosis.
Pathogen sits in endosome
Lysosomes release acid into endosome, the pathogen is degraded into small peptides.
On the other side of the cell, the ER contains the MHC2 which is all synthesised and ready to go, but it’s binding site is blocked by a protein called Li.
Blocked MHC2 leaves in an endosome, and Li breaks down in the now acidic environment, leavning a fragment ‘CLIP’ still bound.
HLMDM then binds MHC2, releasing CLIP, completing the MHC2
The peptide containing endosome, binds to the endosome containing MHC2, and binds it
MHC2 then fuses with the cell membrane, now presenting the antigen to T-helper cells.
How do toll-like receptors work?
Pathogen recognition receptors found on cell membranes
Bind PAMPs
Signalling receptors with end result: Secrete cytokines/chemokines to ‘warn’ other cells in area, attract other mediators
TLR-4 main pathogen recognition factor, on macrophages.
- binds LPS (major cell wall component of g- bacteria)
- requires MD2 and CD14 (macrophage engulfing receptor) cobinding to function
- activates NFKB or IRF (interferon regulatory factor) –> cytokine transcription and production
Viruses get bound by the endosomal TLR (need 2 TLRs to activate lower domains) –> IRF –> IFNa and b get produced which target other cells in area, protecting them from taking in the virus
What are scavenger receptors?
Pathogen recognition receptor that binds PAMPs and different types of LDLs
Co-receptors of TLRs
Expressed on macrophages and assist in phagocytosis –> pathogen sits in phagosome stuck to SR –> lysosome fuses and acidifies ‘phagolysosome’, destroying pathogen
On platelets, macrophages, smooth muscle
Bind LDLs using scavenger receptor –> becomes foam cell, and attach to vessel wall
If this constantly occurs –> atherosclerosis
What does the complement pathway do?
Opsonisation (C3b)
MAC (C3b)
Inflammation (C3a)
In general - activated complement mediators ending in B kill stuff, while those ending in A, enhance inflammation
How does the lectin and classical complement pathways differ from the alternative pathway?
- When the classical and lectin pathways activate C3b, they do so via the C4b2a variant of C3a convertase - this activates the alternative pathway.
- The aforementioned pathways are activated by antigen, the alternative is activated by C3b via C3b convertase
- The alternative pathway enhances the classical and lectin pathways.
- The C3 convertase produced by activated of the alternative pathway is C3bBb, not C4b2a.
How does the lectin and classical complement pathways differ from the alternative pathway?
- When the classical and lectin pathways activate C3b, they do so via the C4b2a variant of C3a convertase - this activates the alternative pathway.
- The aforementioned pathways are activated by antigen, the alternative is activated by C3b via C3b convertase
- The alternative pathway enhances the classical and lectin pathways.
- The C3 convertase produced by activated of the alternative pathway is C3bBb, not C4b2a.
What are the complement proteins specific to the classical complement pathway?
C1 q and R - these get activated to split C4
C2
C4 (which forms C3 convertase with C2a)
What are the complement proteins specific to the classical complement pathway?
C1 q and R - these get activated to split C4
C2
C4 (which forms C3 convertase with C2a)
What are the complement proteins specific to the lectin complement pathway?
Mannose binding lectin - binds mannose
Filcolin - binds oligosaccharides
C4 and C2 (which when activated form C4B2a or C3 convertase)
What are the complement proteins specific to the lectin complement pathway?
Mannose binding lectin - binds mannose
Filcolin - binds oligosaccharides
C4 and C2 (which when activated form C4B2a or C3 convertase)
What are the complement proteins specific to the lectin alternative pathway?
Factor D (classical pathway) - complexes with factor B and C3b to form C3bBb (convertase)
Properdin (lectin pathway) - complexes with Factor-B and C3b to form C3bBb
Factor B complexes with C3b as well as Factor D (classical) or Properdin (Lectin pathway)
Factor B is used from both classical and lectin pathways.
Both complexes form C3bBb which is a C3 convertase produced only by the alternative pathway
What are the complement proteins specific to the lectin alternative pathway?
Factor D (classical pathway) - complexes with factor B and C3b to form C3bBb (convertase)
Properdin (lectin pathway) - complexes with Factor-B and C3b to form C3bBb
Factor B complexes with C3b as well as Factor D (classical) or Properdin (Lectin pathway)
Factor B is used from both classical and lectin pathways.
Both complexes form C3bBb which is a C3 convertase produced only by the alternative pathway
Describe how the classical pathway activates C3
- Complement protein C1 binds antigen-antibody complex at the Fc part via C1q
- C4 and C2 are cleaved, forming the C4b2a complex or C3 Convertase
- C3 convertase splits C3a and C3b
- C3b then activates the alternate pathway, enhancing the classical
- Further C3 is split into C3a and C3b.
Describe how the classical pathway activates C3
- Complement protein C1 binds antigen-antibody complex at the Fc part via C1q
- C4 and C2 are cleaved, forming the C4b2a complex or C3 Convertase
- C3 convertase splits C3a and C3b
- C3b then activates the alternate pathway, enhancing the classical
- Further C3 is split into C3a and C3b.
Describe how the lectin pathway activates C3
- Mannose binding lectin binds mannose (single sugar) or Filcolin binds oligosaccharide
- This activates C1 to split C4 and C2, forming the C4b2a complex, or C3 convertase
- C3 convertase splits C3a and C3b
- C3b activates the alternative pathway which makes another C3 convertase, C3bBb which makes LOTS of C3 convertase
- Reaction ramped up, C3 begins to be split into C3a and C3b at a much higher rate
Describe how the lectin pathway activates C3
- Mannose binding lectin binds mannose (single sugar) or Filcolin binds oligosaccharide
- This activates C1 to split C4 and C2, forming the C4b2a complex, or C3 convertase
- C3 convertase splits C3a and C3b
- C3b activates the alternative pathway which makes another C3 convertase, C3bBb which makes LOTS of C3 convertase
- Reaction ramped up, C3 begins to be split into C3a and C3b at a much higher rate
Describe how the alternative pathway activates C3
- Small amount of C3b generated by activation of lectin or classical pathway.
- Properdin complexes with Factor B and C3b or, Factor D cleaves Factor B to form and stabilise C3bBb, a type of C3 convertase specific to the alternative pathway.
- Production of C3bBb ramps up C3 convertase production, enhancing cleavage of C3a and C3b.
Describe how the alternative pathway activates C3
- Small amount of C3b generated by activation of lectin or classical pathway.
- Properdin complexes with Factor B and C3b or, Factor D cleaves Factor B to form and stabilise C3bBb, a type of C3 convertase specific to the alternative pathway.
- Production of C3bBb ramps up C3 convertase production, enhancing cleavage of C3a and C3b.
Describe the role of C3a protein in the complement system
With C5a, causes mast cells to degranulate and release histamine
This attracts leukocytes (macrophages) and causes vascular permeability
Describe the role of C3a protein in the complement system
With C5a, causes mast cells to degranulate and release histamine
This attracts leukocytes (macrophages) and causes vascular permeability
Describe the role of C5a protein in the complement system
Causes mast cells to release histamine and attract leukocytes and icnrease vascular permeability
Attaches to the macrophage C5a receptor, allowing the macrophage to then bind an opsonised pathogen via it’s CR1 receptor (which binds the C3b that coats the pathogen).
Describe the role of C5a protein in the complement system
Causes mast cells to release histamine and attract leukocytes and icnrease vascular permeability
Attaches to the macrophage C5a receptor, allowing the macrophage to then bind an opsonised pathogen via it’s CR1 receptor (which binds the C3b that coats the pathogen).
Describe the role of C3b protein in the complement system
- Opsonisation. Coats the bacteria in itself via it’s thioester bond, then attaches to the macrophage CR1 receptor with the help of the C5a-C5a-receptor on the macrophage, which then allows the macrophage to phagocytose the pathogen.
- Complexes with C4b2a (the main C3 convertase) to form C4b2a3b or C3-C5 convertase to cleave C5 into C5a and C5b (the terminal stage and beginning of the MAC attack)
Describe the role of C3b protein in the complement system
- Opsonisation. Coats the bacteria in itself via it’s thioester bond, then attaches to the macrophage CR1 receptor with the help of the C5a-C5a-receptor on the macrophage, which then allows the macrophage to phagocytose the pathogen.
- Complexes with C4b2a (the main C3 convertase) to form C4b2a3b or C3-C5 convertase to cleave C5 into C5a and C5b (the terminal stage and beginning of the MAC attack)
Describe the role of C5 protein in the complement system
Cleaved by C3/C5 convertase (C4b2a3b convertase)
C5a - histamine release from mast cells, binds macrophages to activate CR1 receptor to bind C3b opsonised pathogens –> phagocytosis
C5b - terminal stage of complement pathway - binds C6/7/8 and 9 proteins to form a pore that lyses the cell.
Describe the role of C5 protein in the complement system
Cleaved by C3/C5 convertase (C4b2a3b convertase)
C5a - histamine release from mast cells, binds macrophages to activate CR1 receptor to bind C3b opsonised pathogens –> phagocytosis
C5b - terminal stage of complement pathway - binds C6/7/8 and 9 proteins to form a pore that lyses the cell.
What are the key regulators of the complement pathway?
C1-inhibitor
C4bBp - blocks formation of C3 convertase in the classical pathway
Factor H - blocks formation of C3 convertase in the alternative pathway
Membrane cofactor protein (MCP/CD46) - Cell bound blocker of C3 convertase in classical and alt pathways
Decay Accelerating Factor (DAF) - membrane anchored, dissociates C3 convertase from both classic and alternate pathways
What are the key regulators of the complement pathway?
C1-inhibitor
C4bBp - blocks formation of C3 convertase in the classical pathway
Factor H - blocks formation of C3 convertase in the alternative pathway
Membrane cofactor protein (MCP/CD46) - Cell bound blocker of C3 convertase in classical and alt pathways
Decay Accelerating Factor (DAF) - membrane anchored, dissociates C3 convertase from both classic and alternate pathways
What is the main function of C1 inhibitor?
Inhibits the complement system to prevent spontaneous activation.
Irreversibly binds C1r and C1s proteases in the C1 complex of the classical pathway of complement, as well as the MASP-1 and MASP2 proteases in MBL complexes of the lectin pathway, thereby preventing downstream cleavage of C4 and C2.
Also inhibits proteases of fibrinloytic, clotting, and kinin pathways.
Most important inhibitor of plasma kallikrein, FXIA and FXIIa.
What is the main function of C1 inhibitor?
Inhibits the complement system to prevent spontaneous activation.
Irreversibly binds C1r and C1s proteases in the C1 complex of the classical pathway of complement, as well as the MASP-1 and MASP2 proteases in MBL complexes of the lectin pathway, thereby preventing downstream cleavage of C4 and C2.
Also inhibits proteases of fibrinloytic, clotting, and kinin pathways.
Most important inhibitor of plasma kallikrein, FXIA and FXIIa.
Which complement protein deficiency is most reliable in the diagnosis of acquired angioedema and why?
How can you distinguish it from hereditary angioedema?
Screening is conducted by determining the C4 level, which is decreased during the attack as well as in between the attacks.
If the C4 level was normal and suspicion is high, the test should be repeated.
When clinical suspicion of acquired angioedema is high, qualitative and functional values of C1-INH should be obtained at the same time.
Antigenic levels of C1q are usually low (in acquired) and are useful to distinguish hereditary angioedema from acquired angioedema.
Which complement protein deficiency is most reliable in the diagnosis of acquired angioedema and why?
How can you distinguish it from hereditary angioedema?
Screening is conducted by determining the C4 level, which is decreased during the attack as well as in between the attacks.
If the C4 level was normal and suspicion is high, the test should be repeated.
When clinical suspicion of acquired angioedema is high, qualitative and functional values of C1-INH should be obtained at the same time.
Antigenic levels of C1q are usually low (in acquired) and are useful to distinguish hereditary angioedema from acquired angioedema.
What cytokines do macrophages and dendritic cells secrete when bound to antigen, and what does each do?
IL-6 - activates B and T cells, stimulates liver to make more immune proteins
CXCL-8 (IL-8) - chemokine that attracts more leukocytes
IL-12 - activates NK and differentiation of naive CD4 cells into Th1 cell
TNF-a - stimulates the inflammatory response
IL-1b - vascular permeability
What cytokines do macrophages and dendritic cells secrete when bound to antigen, and what does each do?
IL-6 - activates B and T cells, stimulates liver to make more immune proteins
CXCL-8 (IL-8) - chemokine that attracts more leukocytes
IL-12 - activates NK and differentiation of naive CD4 cells into Th1 cell
TNF-a - stimulates the inflammatory response
IL-1b - vascular permeability
What immune components does the liver secrete?
Fibrinogen
CRP
Complement proteins
Mannose binding lectin
Usually does so after signalling from an activated macrophage
What immune components does the liver secrete?
Fibrinogen
CRP
Complement proteins
Mannose binding lectin
Usually does so after signalling from an activated macrophage
What are the actions of an activated macrophage?
- stimulates hypothalamus, fat, and muscle to increase body temp
- cytokines target bone marrow epithelial cells to produce more neutrophils
- most importantly - secreted TNF-a stimulates dendritic cells to migrate into the lymph nodes to initiate adaptive immunity. Most important link between innate and adaptive system.
What are the actions of an activated macrophage?
- stimulates hypothalamus, fat, and muscle to increase body temp
- cytokines target bone marrow epithelial cells to produce more neutrophils
- most importantly - secreted TNF-a stimulates dendritic cells to migrate into the lymph nodes to initiate adaptive immunity. Most important link between innate and adaptive system.
In terms of dendritic cells, what does licensing refer to?
Dendrite attaches to antigen on it’s MHC complex
Starts expressing CCR7 which is like a magnet to chemokines (CCL21) coming from the lymph node
Makes the dendrite migrate to the lymph node where it can activate the dendritic cell.
In terms of dendritic cells, what does licensing refer to?
Dendrite attaches to antigen on it’s MHC complex
Starts expressing CCR7 which is like a magnet to chemokines (CCL21) coming from the lymph node
Makes the dendrite migrate to the lymph node where it can activate the dendritic cell.
How does an NK cell work?
Lymphocytes with no immune memory
Same lineage as t-cells (lymphoid progenitor)
Always activated, do not require Thelper involvement - like cops on the street!
Normal Cell
- MHC1 expressed normally and attaches to KIR (CD94)
- AR ligand on normal cell interacts with AR on NK cell
- nothing happens
Virus-infected or malignant cell
- MHC1 is downregulated or absent
(important)
- still express AR ligand
- NK cell attaches to AR ligand but no signal from MHC1
- NK cell starts secreting chemical mediators and kill the infected cell.
How does an NK cell work?
Lymphocytes with no immune memory
Same lineage as t-cells (lymphoid progenitor)
Always activated, do not require Thelper involvement - like cops on the street!
Normal Cell
- MHC1 expressed normally and attaches to KIR (CD94)
- AR ligand on normal cell interacts with AR on NK cell
- nothing happens
Virus-infected or malignant cell
- MHC1 is downregulated or absent
(important)
- still express AR ligand
- NK cell attaches to AR ligand but no signal from MHC1
- NK cell starts secreting chemical mediators and kill the infected cell.
How does an NK cell kill it’s target after it detects a target?
Fas pathway
Fas-ligand on the NK cell attaches to the cell Fas receptor, pulling the two together
NK cells release granzyme and perforin from cytoplasm are endocytosed onto infected cell
Perforin forms a pore
Granzyme B exits the vesicle with the help of perforin which initiates the killing mechanism
- makes the mitochondria release cytochrome C into the cytoplasm –> indicates the cell to apoptose
- THEN procaspase is disinhibited by granzyme to cleave Caspase 3 which causes apoptosis.
Cytotoxic killer T-cells do the same but need to be activated by Thelper cells. NK do not require this.
How does an NK cell kill it’s target after it detects a target?
Fas pathway
Fas-ligand on the NK cell attaches to the cell Fas receptor, pulling the two together
NK cells release granzyme and perforin from cytoplasm are endocytosed onto infected cell
Perforin forms a pore
Granzyme B exits the vesicle with the help of perforin which initiates the killing mechanism
- makes the mitochondria release cytochrome C into the cytoplasm –> indicates the cell to apoptose
- THEN procaspase is disinhibited by granzyme to cleave Caspase 3 which causes apoptosis.
Cytotoxic killer T-cells do the same but need to be activated by Thelper cells. NK do not require this.
Describe the process of T-cell development
- Lymphoid progenitor moves from BM to thymus (cortex)
- At this stage it is ‘double negative 1’ (DN1). Thymic epithelial cell helps it become a precursor T-cel (DN2), at which point it loses its ability to become anything else.
- Then it becomes a thymocyte and expresses a TCR (DNIII)
- Then it becomes DN4 and proliferates into a double positive thymocyte (CD4+CD8
- It then has one of three fates
a) The thymic epithelial cell ignores it and it dies from neglect (the majority)
b) the thymic epithelial cell expresses MHC but it doesn’t recognise it ‘self’ and it apoptoses
c) the thymic epithelial cell expresses MHC (either one or 2) and it differentiates into a single positive naive T-Cell - If the thymic epithelial cell expressed MHC2 it becomes a CD4+ T-cell in the medulla
- If the thymic epithelial cell expressed MHC1 it becomes a CD8+T-cell in the medulla
- In the medulla a dendritic APC will either present an antigen (the t-cells will be scanning for it), or, more commonly, the T-cell will then migrate to a peripheral lymphoid organ ie the LN or the spleen.
Describe the process of T-cell development
- Lymphoid progenitor moves from BM to thymus (cortex)
- At this stage it is ‘double negative 1’ (DN1). Thymic epithelial cell helps it become a precursor T-cel (DN2), at which point it loses its ability to become anything else.
- Then it becomes a thymocyte and expresses a TCR (DNIII)
- Then it becomes DN4 and proliferates into a double positive thymocyte (CD4+CD8
- It then has one of three fates
a) The thymic epithelial cell ignores it and it dies from neglect (the majority)
b) the thymic epithelial cell expresses MHC but it doesn’t recognise it ‘self’ and it apoptoses
c) the thymic epithelial cell expresses MHC (either one or 2) and it differentiates into a single positive naive T-Cell - If the thymic epithelial cell expressed MHC2 it becomes a CD4+ T-cell in the medulla
- If the thymic epithelial cell expressed MHC1 it becomes a CD8+T-cell in the medulla
- In the medulla a dendritic APC will either present an antigen (the t-cells will be scanning for it), or, more commonly, the T-cell will then migrate to a peripheral lymphoid organ ie the LN or the spleen.
What are the different parts of a peripheral lymphoid organ and what lives in them?
Medulla - plasma cells and macrophages
Paracortex - naive T-cells
Cortex - Naive b-cells, germinal centre/follicle
What are the different parts of a peripheral lymphoid organ and what lives in them?
Medulla - plasma cells and macrophages
Paracortex - naive T-cells
Cortex - Naive b-cells, germinal centre/follicle
How do the acute phase proteins work?
CRP and SAP - opsonins
SAA - recruits immune cells, induces ECM degrading enzymes
Fibrinogen, prothrombin, factove VII, VWF - trap microbes in clots
Plasminogen - degrades the clots
Ferritin - binds iron, inhibits microbe iorn uptake
Hepcidin - internalises ferroportin, stops release of iron bound by ferritin within intestinal enterocytes and macrophages
Haptoglobin - binds haemoglobin, inhibits microbe iron uptake
Alpha1-antitryupsin - downregulates inflammation
How do the acute phase proteins work?
CRP and SAP - opsonins
SAA - recruits immune cells, induces ECM degrading enzymes
Fibrinogen, prothrombin, factove VII, VWF - trap microbes in clots
Plasminogen - degrades the clots
Ferritin - binds iron, inhibits microbe iorn uptake
Hepcidin - internalises ferroportin, stops release of iron bound by ferritin within intestinal enterocytes and macrophages
Haptoglobin - binds haemoglobin, inhibits microbe iron uptake
Alpha1-antitryupsin - downregulates inflammation
What are ‘negative’ acute phase proteins?
They go down inflammation
Albumin, transferrin, transthyretin, retinol binding protein, antithrombin, transcortin
Downregulation saves amino acids to produce positive acute phase proteins more efficiently
What are ‘negative’ acute phase proteins?
They go down inflammation
Albumin, transferrin, transthyretin, retinol binding protein, antithrombin, transcortin
Downregulation saves amino acids to produce positive acute phase proteins more efficiently
How do ESR and CRP differ?
CRP - short T1/2, returns to normal with treatment.
ESR - longer T1/2, will stay elevated longer.
I.e. Lupus - raised ESR but normal CRP in active disease.
May also indicate liver failure.
How do ESR and CRP differ?
CRP - short T1/2, returns to normal with treatment.
ESR - longer T1/2, will stay elevated longer.
I.e. Lupus - raised ESR but normal CRP in active disease.
May also indicate liver failure.
What are Witebsky’s postulates?
For a disease to be regarded as an autoimmune disease it needs:
- Direct evidence from transfer of pathogenic antibody or pathogenic T cells
- Indirect evidence based on reproduction of the autoimmune disease in experimental animals
- Circumstantial evidence from clinical clues
- Genetic architecture clustering with other autoimmune diseases
What are Witebsky’s postulates?
For a disease to be regarded as an autoimmune disease it needs:
- Direct evidence from transfer of pathogenic antibody or pathogenic T cells
- Indirect evidence based on reproduction of the autoimmune disease in experimental animals
- Circumstantial evidence from clinical clues
- Genetic architecture clustering with other autoimmune diseases
Which acute phase protein rises first and gets the highest?
CRP
Which acute phase protein rises first and gets the highest?
CRP
What is the pathophysiology of sarcoidosis?
- increased macrophage and CD4 helper T-cell activation, resulting in accelerated inflammation
- paradoxical immune response to antigen challenges such as tuberculin is suppressed - suggests a state of anergy.
The anergy may also be responsible for the increased risk of infections and cancer.
The regulatory T-lymphocytes in the periphery of sarcoid granulomas appear to suppress IL-2 secretion, which is hypothesized to cause the state of anergy by preventing antigen-specific memory responses.
What is the pathophysiology of sarcoidosis?
- increased macrophage and CD4 helper T-cell activation, resulting in accelerated inflammation
- paradoxical immune response to antigen challenges such as tuberculin is suppressed - suggests a state of anergy.
The anergy may also be responsible for the increased risk of infections and cancer.
The regulatory T-lymphocytes in the periphery of sarcoid granulomas appear to suppress IL-2 secretion, which is hypothesized to cause the state of anergy by preventing antigen-specific memory responses.
What is a surrogate light chain?
Light chain that sits on the Pre-B IgM until real ones are made
What is a surrogate light chain?
Light chain that sits on the Pre-B IgM until real ones are made
What is the role of somatic hypermutation?
Somatic hypermutation –> higher affinity antibody. Occurs in germinal centre after activation.
What is the role of somatic hypermutation?
Somatic hypermutation –> higher affinity antibody. Occurs in germinal centre after activation.
What do eosinophils do?
Degranulate to release an array of cytotoxic granule cationic proteins. These include:
major basic protein (MBP)
eosinophil cationic protein (ECP)
eosinophil peroxidase (EPO)
eosinophil-derived neurotoxin (EDN)
Major basic protein, eosinophil peroxidase, and eosinophil cationic protein are toxic to many tissues.
Eosinophil cationic protein and eosinophil-derived neurotoxin are ribonucleases with antiviral activity.
Major basic protein induces mast cell and basophil degranulation
What do eosinophils do?
Degranulate to release an array of cytotoxic granule cationic proteins. These include:
major basic protein (MBP)
eosinophil cationic protein (ECP)
eosinophil peroxidase (EPO)
eosinophil-derived neurotoxin (EDN)
Major basic protein, eosinophil peroxidase, and eosinophil cationic protein are toxic to many tissues.
Eosinophil cationic protein and eosinophil-derived neurotoxin are ribonucleases with antiviral activity.
Major basic protein induces mast cell and basophil degranulation
What is C3 nephritic factor?
C3 nephritic factor is an autoantibody to the alternate complement pathway’s C3 convertase, C3bBb.
C3NF stabilises this enzyme leading to an increase in the rate that C3 is activated.
The outcome of this is a markedly reduced C3 serum level.
Presence of the autoantibody leads to uncontrolled activation of C3 leading to very low C3 levels but normal C4. The presence of this complement profile (very low C3 normal C4) in patients with appropriate renal symptoms is almost characteristic of the presence of C3 Nef.
The antibody can be seen in membranoproliferative glomerulonephritis, MPGN and partial lipodystrophy.
This assay is only indicated in patients with very low C3 levels.
What is C3 nephritic factor?
C3 nephritic factor is an autoantibody to the alternate complement pathway’s C3 convertase, C3bBb.
C3NF stabilises this enzyme leading to an increase in the rate that C3 is activated.
The outcome of this is a markedly reduced C3 serum level.
Presence of the autoantibody leads to uncontrolled activation of C3 leading to very low C3 levels but normal C4. The presence of this complement profile (very low C3 normal C4) in patients with appropriate renal symptoms is almost characteristic of the presence of C3 Nef.
The antibody can be seen in membranoproliferative glomerulonephritis, MPGN and partial lipodystrophy.
This assay is only indicated in patients with very low C3 levels.
What does ‘C3 tickover’ refer to?
Activation of the alternative complement pathway.
It is initiated by the spontaneous hydrolysis of C3, which is abundant in the blood plasma. “Tickover” occurs through the spontaneous cleavage of the thioester bond in C3 to form C3(H2O).
This change in shape allows the binding of plasma protein Factor B, which allows Factor D to cleave Factor B into Ba and Bb.
What does ‘C3 tickover’ refer to?
Activation of the alternative complement pathway.
It is initiated by the spontaneous hydrolysis of C3, which is abundant in the blood plasma. “Tickover” occurs through the spontaneous cleavage of the thioester bond in C3 to form C3(H2O).
This change in shape allows the binding of plasma protein Factor B, which allows Factor D to cleave Factor B into Ba and Bb.
In the complement cascade, what does Factor I do?
Inactivates C3b and C4b
Deficiency = low levels of C3 due to unregulated activation of alternative pathway
- recurrent bacterial infections in kids and implicated in HUS
In the complement cascade, what does Factor I do?
Inactivates C3b and C4b
Deficiency = low levels of C3 due to unregulated activation of alternative pathway
- recurrent bacterial infections in kids and implicated in HUS
What does the CD79 protein do?
The CD79a protein together with the related CD79b protein, forms a dimer associated with membrane-bound immunoglobulin in B-cells, thus forming the B-cell antigen receptor (BCR). This occurs in a similar manner to the association of CD3 with the T-cell receptor, and enables the cell to respond to the presence of antigens on its surface.
It is associated with agammaglobulinemia.
What does the CD79 protein do?
The CD79a protein together with the related CD79b protein, forms a dimer associated with membrane-bound immunoglobulin in B-cells, thus forming the B-cell antigen receptor (BCR). This occurs in a similar manner to the association of CD3 with the T-cell receptor, and enables the cell to respond to the presence of antigens on its surface.
It is associated with agammaglobulinemia.
What is CD3?
This is the T-Cell receptor!
What is CD3?
This is the T-Cell receptor!
Three main points of membranoproliferative (mesangiocapillary) GN
- Glomerular hypercellularity and basement membrane deposition on top of deposits ‘tram tracking - nephrotic, low complement, poor prog.
- Main Hep-C associated nephropathy (type 1), also: hep B, SLE, chronic infection - circulating immune complexse activate complement
- Type 2 ‘dense deposit disease’ due to C3 nephritic factor stabilising C3bBb convertase –> excessive complement
Three main points of membranoproliferative (mesangiocapillary) GN
- Glomerular hypercellularity and basement membrane deposition on top of deposits ‘tram tracking - nephrotic, low complement, poor prog.
- Main Hep-C associated nephropathy (type 1), also: hep B, SLE, chronic infection - circulating immune complexse activate complement
- Type 2 ‘dense deposit disease’ due to C3 nephritic factor stabilising C3bBb convertase –> excessive complement
What are the anti-TNF-a drugs?
Four monoclonal antibodies (MAbs) (infliximab, adalimumab, golimumab, and certolizumab pegol)
One recombinant TNF-α decoy receptor, etanercept, have been developed to inhibit TNF-α signaling.
What are the anti-TNF-a drugs?
Four monoclonal antibodies (MAbs) (infliximab, adalimumab, golimumab, and certolizumab pegol)
One recombinant TNF-α decoy receptor, etanercept, have been developed to inhibit TNF-α signaling.
What is a thymus independent antigen?
Antigens lacking a peptide component; cannot be presented by MHC to T cells (e.g., lipopolysaccharide from cell envelope of gram-negative bacteria and polysaccharide capsular antigen). Stimulate release of antibodies and do not result in immunologic memory.
What is a thymus independent antigen?
Antigens lacking a peptide component; cannot be presented by MHC to T cells (e.g., lipopolysaccharide from cell envelope of gram-negative bacteria and polysaccharide capsular antigen). Stimulate release of antibodies and do not result in immunologic memory.
What is a thymus dependent antigen?
Antigens containing a protein component (e.g., diphtheria vaccine). Class switching and immunologic memory occur as a result of direct contact of B cells with Th cells (CD40-CD40 ligand interaction).
What is a thymus dependent antigen?
Antigens containing a protein component (e.g., diphtheria vaccine). Class switching and immunologic memory occur as a result of direct contact of B cells with Th cells (CD40-CD40 ligand interaction).
Which two inhibitors prevent spontaneous activation of the complement cascade on self-cells?
Decay-accelerating factor (DAF) and Cl esterase inhibitor help prevent complement activation on self cells (e.g., RBC).
Which two inhibitors prevent spontaneous activation of the complement cascade on self-cells?
Decay-accelerating factor (DAF) and Cl esterase inhibitor help prevent complement activation on self cells (e.g., RBC).
What does IL-1-5 do?
“Hot T-Bone stEAk”:
IL-l: fever (hot).
IL-2: stimulates T cells.
IL-3: stimulates Bone marrow.
IL-4: stimulates IgE production.
IL-5: stimulates IgA production.
What does IL-1-5 do?
“Hot T-Bone stEAk”:
IL-l: fever (hot).
IL-2: stimulates T cells.
IL-3: stimulates Bone marrow.
IL-4: stimulates IgE production.
IL-5: stimulates IgA production.
What does IL-8 do?
“Clean up on aisle 8.” Neutrophils are recruited by IL-8 to clear infections.
What does IL-8 do?
“Clean up on aisle 8.” Neutrophils are recruited by IL-8 to clear infections.
What does IL-12 do?
Induces differentiation of T cells into Th1 cells.
Activates NK cells. Also secreted by B cells.
naturally produced by dendritic cells,[1] macrophages and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation.
What does IL-12 do?
Induces differentiation of T cells into Th1 cells.
Activates NK cells. Also secreted by B cells.
naturally produced by dendritic cells,[1] macrophages and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation.
Which cytokines do macrophages secrete?
IL-1, 6, 8, 12 and TNF-A
Which cytokines do macrophages secrete?
IL-1, 6, 8, 12 and TNF-A
Which two cytokines do all T-cells release and what do they do?
IL2 and IL3
IL2 - stimulates growh of helper, cytotoxic and reg t- cells.
IL-3 - supports growth and differentiation of BM stem cells - like GM-CSF
Which two cytokines do all T-cells release and what do they do?
IL2 and IL3
IL2 - stimulates growh of helper, cytotoxic and reg t- cells.
IL-3 - supports growth and differentiation of BM stem cells - like GM-CSF
What cytokine does Th-1 cells release and what does it do?
IFN-gamma
Activates macrophages and Th1 cells.
Suppresses Th2 cells. Has antiviral and antitumor properties.
What cytokine does Th-1 cells release and what does it do?
IFN-gamma
Activates macrophages and Th1 cells.
Suppresses Th2 cells. Has antiviral and antitumor properties.
What cytokines do Th2 cells release?
IL-4 - Induces differentiation into Th2 cells. Promotes growth of B cells. Enhances class switching to IgE and IgG.
IL-5 - Promotes differentiation of B cells. Enhances class switching to IgA. Stimulates the growth and differentiation of eosinophils.
IL-10 - Modulates inflammatory response. Inhibits actions of activated T cells and Th1. Also secreted by regulatory T cells. TGF-b has similar actions to IL-10, because it is involved in inhibiting inflammation.
What cytokines do Th2 cells release?
IL-4 - Induces differentiation into Th2 cells. Promotes growth of B cells. Enhances class switching to IgE and IgG.
IL-5 - Promotes differentiation of B cells. Enhances class switching to IgA. Stimulates the growth and differentiation of eosinophils.
IL-10 - Modulates inflammatory response. Inhibits actions of activated T cells and Th1. Also secreted by regulatory T cells. TGF-b has similar actions to IL-10, because it is involved in inhibiting inflammation.
What is the mechanism of interferons?
Interferons (a, b, y) are proteins that place uninfected cells in an antiviral state. Interferons induce the production of a ribonuclease that inhibits viral protein synthesis by degrading viral mRNA (but not host mRNA).
Interferes with viruses:
- a- and B-interferons inhibit viral protein synthesis.
- y-interferons increase MHC I and II expression and antigen presentation in all cells.
- Activates NK cells to kill virus-infected cells.
What is the mechanism of interferons?
Interferons (a, b, y) are proteins that place uninfected cells in an antiviral state. Interferons induce the production of a ribonuclease that inhibits viral protein synthesis by degrading viral mRNA (but not host mRNA).
Interferes with viruses:
- a- and B-interferons inhibit viral protein synthesis.
- y-interferons increase MHC I and II expression and antigen presentation in all cells.
- Activates NK cells to kill virus-infected cells.
What are the cell-surface receptors for T-cells?
TCR (binds antigcn-MI-IC complex)
CD3 (associated with TCR for signal transduction)
CD28 (binds B7 on APC)
T-helper: CD4, CD40 ligand
Cytotoxic: CD8
What are the cell-surface receptors for T-cells?
TCR (binds antigcn-MI-IC complex)
CD3 (associated with TCR for signal transduction)
CD28 (binds B7 on APC)
T-helper: CD4, CD40 ligand
Cytotoxic: CD8
What are the cell-surface receptors for B-cells?
Ig (binds antigen)
CD19, CD20, CD21 (receptor for EBV ), CD40 MHC II, B7
You can drink Beer at the Bar when you’re 21: B cells, Epstein-Barr virus; CD-21.
What are the cell-surface receptors for B-cells?
Ig (binds antigen)
CD19, CD20, CD21 (receptor for EBV ), CD40 MHC II, B7
You can drink Beer at the Bar when you’re 21: B cells, Epstein-Barr virus; CD-21.
What are the cell surface receptors for macrophages?
CD14, CD40
MHC II, B7
Fe and C3b receptors (enhanced phagocytosis)
What are the cell surface receptors for macrophages?
CD14, CD40
MHC II, B7
Fe and C3b receptors (enhanced phagocytosis)
What are the cell surface proteins of NK cells?
CD16 (binds Fc of lgG), CD56 (unique marker
for NK)
What are the cell surface proteins of NK cells?
CD16 (binds Fc of lgG), CD56 (unique marker
for NK)
What is anergy?
Self-reactive T cells become nonreactive without costimulatory molecule. B cells also become anergic, but tolerance is less complete than in T cells.
What is anergy?
Self-reactive T cells become nonreactive without costimulatory molecule. B cells also become anergic, but tolerance is less complete than in T cells.
What is the effect of bacterial toxins on the immune system?
Superantigens (S. pyogenes and S. aureus)-cross-link the B region of the T-cell receptor to the MHC class II on APCs. Can activate any T cell, leading to massive release of cytokines.
Endotoxins/lipopolysaccharide (gram-negative bacteria)-directly stimulate macrophages by binding to endotoxin receptor CD14; Th cells are not involved.
What is the effect of bacterial toxins on the immune system?
Superantigens (S. pyogenes and S. aureus)-cross-link the B region of the T-cell receptor to the MHC class II on APCs. Can activate any T cell, leading to massive release of cytokines.
Endotoxins/lipopolysaccharide (gram-negative bacteria)-directly stimulate macrophages by binding to endotoxin receptor CD14; Th cells are not involved.
What are the features of passive immunity?
Receiving preformed antibodies
Rapid
Short span of antibodies (half-life= 3 weeks)
IgA in breast milk, antitoxin, humanized
monoclonal antibody
After exposure to Tetanus toxin, Botulinum toxin, HBV, or Rabies virus, patients are given preformed antibodies (passive)-“To Be Healed Rapidly”
What are the features of passive immunity?
Receiving preformed antibodies
Rapid
Short span of antibodies (half-life= 3 weeks)
IgA in breast milk, antitoxin, humanized
monoclonal antibody
After exposure to Tetanus toxin, Botulinum toxin, HBV, or Rabies virus, patients are given preformed antibodies (passive)-“To Be Healed Rapidly”
What are the features of active immunity?
Exposure to foreign antigens
Slow
Long-lasting protection (memory)
Natural infection, vaccines, toxoid
Combined passive and active immunizations can be given in case of hepatitis B or rabies exposure.
What are the features of active immunity?
Exposure to foreign antigens
Slow
Long-lasting protection (memory)
Natural infection, vaccines, toxoid
Combined passive and active immunizations can be given in case of hepatitis B or rabies exposure.
Name the live attenuated vaccines, their mechanism, and their pros and cons
Measles, mumps, polio (Sabin), rubella, varicella, yellow fever.
Microorganism loses its pathogenicity but retains capacity for transient growth within inoculated host. Mainly induces a cellular response.
Pro: induces strong, often life-long immunity.
Con: may revert to virulent form.
Name the live attenuated vaccines, their mechanism, and their pros and cons
Measles, mumps, polio (Sabin), rubella, varicella, yellow fever.
Microorganism loses its pathogenicity but retains capacity for transient growth within inoculated host. Mainly induces a cellular response.
Pro: induces strong, often life-long immunity.
Con: may revert to virulent form.
Name the killed vaccines, their mechanism, and their pros and cons
Cholera, hepatitis A, polio (Salk), rabies.
Pathogen is inactivated by heat or chemicals; maintaining epitope structure on surface antigens is important for immune response. Humoral immunity induced.
Pro: stable and safer than live vaccines.
Con: weaker immune response; booster shots usually required.
Name the killed vaccines, their mechanism, and their pros and cons
Cholera, hepatitis A, polio (Salk), rabies.
Pathogen is inactivated by heat or chemicals; maintaining epitope structure on surface antigens is important for immune response. Humoral immunity induced.
Pro: stable and safer than live vaccines.
Con: weaker immune response; booster shots usually required.
What is the associated disorder for:
Anti-dsDNA, anti-Smith
Antihistone
Anticentromere
SLE
Drug induced lupus
Scleroderma (CREST syndrome)
What is the associated disorder for:
Anti-dsDNA, anti-Smith
Antihistone
Anticentromere
SLE
Drug induced lupus
Scleroderma (CREST syndrome)
What is the associated disorder for:
Anti-Scl-70 (anti-DNA topoisomerase I)
Antimitochondrial
lgA antiendomysial, lgA anti-tissue transglutaminase
Scleroderma (diffuse)
Primary biliary cirrhosis
Celiac
What is the associated disorder for:
Anti-Scl-70 (anti-DNA topoisomerase I)
Antimitochondrial
lgA antiendomysial, lgA anti-tissue transglutaminase
Scleroderma (diffuse)
Primary biliary cirrhosis
Celiac
What are the associated disorders for:
Anti-basement membrane
Anti-desmoglein
Antimicrosomal, antithyroglobulin
Goodpastures
Pemphigus vulgaris
Hashimoto’s thyroiditis
What are the associated disorders for:
Anti-basement membrane
Anti-desmoglein
Antimicrosomal, antithyroglobulin
Goodpastures
Pemphigus vulgaris
Hashimoto’s thyroiditis
What are the associated disorders:
Anti-Jo-1, anti-SRP, anti-Mi-2
Anti-SSA (anti-Ro)
Anti-SSB (anti-La)
Polymyositis, dermatomyositis
Sjogrens
What are the associated disorders:
Anti-Jo-1, anti-SRP, anti-Mi-2
Anti-SSA (anti-Ro)
Anti-SSB (anti-La)
Polymyositis, dermatomyositis
Sjogrens
What are the associated disorders?
Anti-Ul RNP (ribonucleoprotein)
Anti-smooth muscle
Anti-glutamate decarboxylase
MCTD
Autoimmune hepatitis
Type 1 DM
What are the associated disorders?
Anti-Ul RNP (ribonucleoprotein)
Anti-smooth muscle
Anti-glutamate decarboxylase
MCTD
Autoimmune hepatitis
Type 1 DM
What are the associated disorders?
c-ANCA (PR3-ANCA)
p-ANCA (MPO-ANCA)
Wegeners
Microscopic polyangiitis, Churg Strauss
What are the associated disorders?
c-ANCA (PR3-ANCA)
p-ANCA (MPO-ANCA)
Wegeners
Microscopic polyangiitis, Churg Strauss
What are the contraindications to the flu vaccine?
Fluvax vaccine must not be used in children under 5 years.
Anaphylactic hypersensitivity to previous influenza vaccination or to eggs, neomycin, polymyxin B sulfate (antibiotic) or any of the constituents or trace residues of this vaccine.
Immunisation must be postponed in people who have febrile illness or acute infection.
What are the contraindications to the flu vaccine?
Fluvax vaccine must not be used in children under 5 years.
Anaphylactic hypersensitivity to previous influenza vaccination or to eggs, neomycin, polymyxin B sulfate (antibiotic) or any of the constituents or trace residues of this vaccine.
Immunisation must be postponed in people who have febrile illness or acute infection.
