Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
66 Cards in this Set
- Front
- Back
|
What happens shortly after entry in the thymus to T cells? |
They rearrange their TCR genes in the thymus? |
|
|
Why are thymic epithelial cells important? |
Found in the thymus and naturally express MHC class I and class II. These are self MHC molecules, i.e. the MHC type the individual has |
|
|
What are double positive T cells and how do they arise in the thymus? |
T cells start off as double negative T cells- do not have CD4 or CD8 on their surfaceShortly after entering the thymus they recombine their TCR genes (via VDJ recombination) and start to express a TCR. They switch on both the genes for CD4 and CD8 - double positive T cells. Double positive T cells can recognise both MHC class I and class II. |
|
|
What is the default pathway for double positive T cells in the thymus? |
Apoptosis |
|
|
What happens in positive selection of T cells in the thymus? |
T cells that can bind to self-MHC on the thymic epithelial cells are rescued, those that do not bind are neglected- apoptosis by negletc. |
|
|
What is the default pathway of positively selected T cells? |
Survival |
|
|
What happens in the thymus in central tolerance once the double positive T cells have been selected for? |
Double positive cells that interact well with MHC class II become CD4+ T cells & those that interact well with MHC class I become CD8+ T cells. I.e. they become single positive T cells. Negative selection now takes place |
|
|
What happens during negative selection of T cells in the thymus during central tolerance? |
Apoptosis is induced in any T cells with high affinity for: - Self-MHC regardless of the peptide- - Self MHC that carry self-peptides Results in a pool of T cells that have a weak affinity to self MHC that are single positive |
|
|
What is AIRE? |
Autoimmune regulator. Is a transcription factor in the thymus that switches on expression of tissue restricted antigens so that T cells which have a high affintiy for self-peptides that are only produced in certain tissues/organs are negatively selected out in the thymus, i.e. AIRE makes antigens that would not normally be present in the thymus or can travel there (via circulation) |
|
|
What happens in the peripheral tolerance? |
prevents harm from any self-reactive cells that escape deletion in the primary lymphoid organ. (this can be due to not all self-antigens being present in the primary lymphoid organs). Occurs outside of the bone marrow or thymus. This is done by signalling apoptosis or clonal anergy |
|
|
What is clonal anergy? |
|
|
|
What do natural T reg cells have and how do they work? |
Foxp3 (TF in the nucleus) expressed as the T cells are developed in the thymus so they become T reg cells in the thymus and supress unwanted immune responses Have CD25 which is a IL-2 receptor <-- mops up Il-2 in the local environment so that none is left to stimulate other T cells & B cells |
|
|
What do induced Treg cells have and how do they work? |
Foxp3 not expressed in the thymus, but subsequent to encountering an antigen in the periphery, switch on the gene for the transcription factor and express Foxp3 CD25 expressed after activation after encountering an antigen |
|
|
What are the 4 phases of wound healing? |
1) Haemostasis 2) Inflammatory 3) Proliferative 4) Remodelling |
|
|
What is an autoimmune disease? |
Immune attack on body's own components (i.e. against self (auto) antigen) causing an immune pathology. Autoimmune disease results from a breakdown in immunological tolerance |
|
|
What is molecular mimicry? |
Ab produced against antigen when we get an infection, but there are structures on our own cells that are similar to the structure of the antigen. These Ab can react with our human cells - cross reactivity |
|
|
What happens in rheumatic fever? |
Following infection of Group A streptococci, B-cells respond to microbial antigens that cross-reacts with self-muscle antigens Rheumatic fever tends to be transient, when infection clears, autoimmune severity fails |
|
|
What is Hashimoto's thyroiditis?
|
Anti-thyroid autoantibodies against thyroperoxidase and thryoglobulin Organ specific autoimmune disease |
|
|
How can you test for Hashimoto's thyroiditis? |
Thyroglobulin can be tested with the patient's serum, an Ag-Ab reaction can be seen if the serum has autoAb for thyroglobulin. The autoAb can form large immune complexes with thyroglobulin, forming a precipitate |
|
|
What is myasthenia Gravis? |
Organ specific autoimmune disease AutoAb to Ach receptors block transmission of nerve impulses at motor end plate junction. Transient autoimmune disease can be found in new-born babies of mothers with myasthenia gravis due to transplacental IgG autoAb transfer |
|
|
What is Grave's disease? |
Organ specific autoimmune disease AutoAb against thyroid-stimulating hormone (TSH) receptor- type V hypersensitivity |
|
|
What is type I diabetes? |
Organ specific autoimmune disease Tissue damage of beta cells in the Islets of Langerhans - Type IV hypersensitivity |
|
|
What is systemic lupus erythematosus (SLE)? |
-non organ specific autoimmune disease - Antinuclear Ab Ab bind with Ag and form immune complexes - trapped in cetain locations leading to the site of dominant pathology Butterfly rash where capillaries in the cheeks of the face are trapping immune complexes, and activation of complement causing a rash |
|
|
What is rheumatoid arthritis? |
Non-organ specific autoimmune disease Rheumatoid factors (AutoAb to the Fc region of IgG) is deposited in the joints leading to chronic inflammatory response - destruction of joint tissue |
|
|
What are the mechanisms of autoimmune diseases? |
1) Cross-reactive antigens (molecular mimicry) 2) Aberrant expression of MHC class II molecules 3) Polyclonal activation 4) Release of sequestered antigens |
|
|
What is aberrant expression of MHC Class II molecules? |
Cytokines can lead to aberrant expression of MHC class II on cells which are not professional APCs which can then activate Th cells
a) Hashimoto's disease - thyroid epithelial cells b) Type I diabetes - pancreatic cells |
|
|
What is polyclonal activation? |
Anergic B cells often recognises self-antigens in normal individuals but are inactivated. Non-specific polyclonal activation of B cells activates production of clones irrespective of antigen specificity. This induces Ab against many different antigens, including autoantigens a) Epstein-Barr virus can activate many different specificities of B cells |
|
|
What is the release of sequestered antigens? |
Antigens hidden from the immune system (eye, testes, brain) which immune cells are not tolerant to are exposed by trauma to these organs |
|
|
What is Type 1 hypersensitivity? |
= IgE mediated mast cell degranulation e.g. asthma, eczema, hayfever |
|
|
What happens in Type 1 IgE mediated mast cell degranulation? |
Most of IgE in body is bound to mast cells in tissue via FcER1 receptors (sensitises it) because more stabilised like this (& so low serum conc) Antigen binds to IgE. IgE-antigen complex cross links FcER1 --> causes signalling into cell --> mast cell degranulates, releasing inflammatory mediators (e.g. histamine, serotonin) found in granules |
|
|
What is the role of class switching in type 1 hypersensitivities? |
Class switching is required to produce the IgE Ab in the first place. Il-4 & IL-13 promotes class switching to IgE. (class switching is inhibited by IFN gamma from Th1 cells) |
|
|
What is type 2 hypersensitivity?
|
cytotoxic antibody against cell surface antigens e.g. HDN, transfusion, transplant rejection |
|
|
What happens in type 2 cytotoxic Ab against cell surface antigens hypersensitivities? |
Ab are present in body which are specific for our own antigens. These Ab lead to cytotoxic action by: - ADCC by K cells (attacks Ab coated target cells) - Activating complement & MAC <-- cell death - Activating complement & enhancing phagocytosis <-- of Ab coated target cells |
|
|
What happens in HDN? |
|
|
|
What happens in type 3 immune complex mediated hypersensitivity? |
Immune complexes which fail to be cleared by immune cells accumulate --> activates complement via classical pathway with subsequent recruitment of neutrophils by C5a --> inflammation (due to mast cell degranulation by C3a) |
|
|
What are some examples of type 3 hypersensitivity? |
SLE Rheumatoid arthritis Post-streptococcal glomerulonephritis |
|
|
What happens in type 4 delayed type hypersensitivity? |
Interaction of antigen with T cells induces proliferation & cytokine release- does not involve Ab. Macrophage present antigen on their surface associated with MHC class II, Th recognise - causes cell mediated response e.g. M tuberculosis, contact dermatitis to nickel, poison Ivy |
|
|
Describe how M tuberculosis can be an example of type 4 delayed type hypersensitivity |
M. tuberculosis is engulfed by macrophages after being identified as foreign, but is able to escape phagocytosis and remain inside of the macrophage. After several weeks, immune system ramps up & there is recruitment of monocytes to the area --> causes harmful local tissue damage & inflammation |
|
|
What is Type V hypersensitivity? |
=Stimulatory Differentiates from type 2 Stimulatory Ab against cell surface receptors (i.e. hormone receptors) which activate the receptor by acting as an agonist e.g. Grave's disease - affects thyroid gland |
|
|
What happens in Grave's disease? |
Type V hypersensitivity
AutoAb against TSHR which act like TSH and bind to TSHR and trigger the receptor Feedback loop is disrupted leading to hyperthyroidism |
|
|
Give 2 examples of innate hypersensitivity reactions |
1) Staphylococcus aureus or Streptococcus pyogenes that provoke toxic shock syndrome involving excessive release of TNF, Il-1 and Il-6 2) Acute respiratory distress syndrome associated with gram negative bacteria. LPS endotoxin provokes a massive invasion of the lung by neutrophils |
|
|
What are transplantation antigens? |
Aka alloantigens = Antigens on transplanted cells recognised as foreign by the immune system Include the ABO blood group antigens The strongest transplantation antigens are highly pormorphic |
|
|
What is a host-vs-graft rejection? |
Recipient cells attack the graft (tissue) |
|
|
What is the difference between a first set rejection and a second set rejection? |
First set rejection = primary immune response, new Ab need to me made Second set rejection= secondary immune response, rapid, because memory is present from previous transplantation attempt i.e when foreign graft inserted into host for 1st time, memory cells are produced and so second time graft inserted there will be a much faster rejection |
|
|
What is a graft-vs-host rejection? |
When the graft has HLA-incompatible T cells, these can must immune response against the host tissue, leading to life threatening GVH disease. Particular problem is in bone marrow transplant - immune cells within the bone marrow can attack the recipient. |
|
|
How can the risk of graft-vs-host rejection be reduced? |
By removing the T lymphocytes prior to transplantation & using the immunosuppressive drugs |
|
|
What happens in the hyperacute rejection reaction? |
Takes minutes Pre-exisiting Ab bind to blood vessel endothelium in graft--> complement activated, neutrophils recruited, platelet aggregation & blood clotting. Pre-existing Ab due to either blood group incompatibility or pre-sensitisation to Class I MHC through blood transfusion Rare as methods are made to match the graft to the host |
|
|
What happens in the acute rejection reaction? |
Takes several days Lymphocytes are activated - Tc cells attack the donor cells expressing foreign MHC. Helper T cells & B cells collaborate in production of Ab to alloantigens |
|
|
What happens in the chronic rejection reaction?
|
Months to years Multiple immune mechanisms or recurrence of the original disease Major problem of graft rejection |
|
|
What is the order of importance of HLA classes for matching in preventing graft rejection?
|
HLA-DR most important, followed by HLA-B and then HLA-A |
|
|
What determines the severity of graft rejection? |
By the number of genetic differences in the MHC molecules between the donor and recipient |
|
|
What chromosome is human MHC encoded on? |
Chromosome 6, except the beta chain of MHC Class I |
|
|
What are the MHC Class I genes and what are the MHC class II genes? |
Class I - A, B, C (present peptides from inside cell) Class II - DP, DQ, DR (present antigens from outside of cell to Th cells which then stimulate B cells) |
|
|
What are the three main immunosuppressive drugs? |
Tacrolimus, cyclosporine & rapamycin |
|
|
What do tacrolimus & cyclosporine do? |
Immunosuppressive drugs Inhibit cytokines, block signal being sent from TCR to nucleus, preventing IL2 transcription Il-2 required for T cell & B cell growth |
|
|
What does rapamycin do? |
Immunosuppressive drug Blocks signalling through the IL-2 receptor IL-2 required for T cell & B cell growth |
|
|
What are primary immunodeficiences? |
Result from defects in either innate or adaptive immunity Is rare Result of an inherited genetic defect |
|
|
What is chronic granulomatous disease? |
Primary immunodeficiency (PID) affecting innate immune response NADPH oxidase defect affects phagocytic cells & so intracellular bacterial killing affected. |
|
|
What does NADPH oxidase consist of and how does it contribute to PID? |
Consists of a group of 6 molecules which form a complex taking up molecular oxygen & produce reacive oxygen intermediates - toxic to MO 5 are coded on autosome, gp91pfox is coded on the x chromosome- male more likely to have PID Any one of these molecules can be mutated & leads a spectrum of severity of PID depending on the location of the mutation |
|
|
What is leukocyte adhesion deficiency? |
Beta2integrin defect affecting neutrophils & monocytes. PID affecting innate immune response |
|
|
Give some examples of primary immunodeficiencies affecting B cells |
- Selective IgA deficiency: B & T cells fail to develop or function normally - X-linked hyper IgM syndrome: CD40L or CD40 defect. CD40L on T cell interacting with CD40 on B cell is essential to class switch B cells. Lack of this leads to accumulation of IgM as Ab cannot class switch - X linked agammaglobulinaemia - Bruton's tyrosine kinase (Btk) defect- lack of gamma globulins-Ig- no mature Ab-secreting B cells produced |
|
|
Give some examples of primary immunodeficiencies affecting T cells |
-Wiskott Aldrich syndrome: WASP defect- mutation on WASP gene on X chromosome --> defect in cytoskeletal organsation, particularly in lymphocytes & NK cells - DiGeorge Syndrome- TBX1 gene defect. Thymus development depends on TBX1 gene, if mutated, there may be a complete of partial lack of thymus |
|
|
What is severe combined immunodeficiency (SCID)? |
PID affecting B & T cells γc, RAG, ADA, PNP defect No functional T cells γc is a component of Il-2,-4-7-9-15-21 receptors Mutation in RAG means no recombination of TCR or BCR genes |
|
|
What are secondary immunodeficiencies? |
Results of external agents or breakdown in body systems with then affect the immune system. More common than primary ID |
|
|
What factors can cause Secondary ID? |
Malnutrition Loss of cellular/humoral component Lymphangiectasisa- proteins, esp Ab lost into urine in nephrotic syndrome Tumours Cytotoxic drugs/irradiation - damage immune cells Infections such as malaria - inhibit development of immune responses, e.g HIV causes AIDs Other diseases such as diabetes are associated with infection |
|
|
How are immunodeficiencies treated? |
Antibiotics Passive gammaglobulins for Ab deficiencies Cell replacement Foetal liver & thymus grafts (has rejection risks) Gene therapy |
