Basic Immunology Flashcards
What are the 2 main categories of the immune system?
Innate and adaptive
Explain the differences in
- resonse time
- specificity, memory, response to repeat infection, cellular components and humeral components
Innate: Response hours, limited specificity, no memory, identical response to repeat infection, phagocytes/NKC, complement pathway
Adaptive: réponse days, diverse specificity, efficient memory, in repeat infection much more rapid and vigorous response, T cells/Bcells, antibodies
What are the main types of phagocytes?
- Monocyte/macrophage lineage
- granulocytes (neutrophils, mast cells, basophils and eosinophils
What is the most abundant type of leukocyte?
Neutrophils
How are phagocytes routinely activate?
Attracted to chemokine and activate by cytokines that are secreted by antigen specific T cells
How do NK cells detect tumour cells to virally infected cells?
CD16 receptor (FcyRIII) - attaches to specific antibodies bound to tumour cells/virally infected cells KIRs (killer cell immunoglobulin like receptors) - interacts with MHC class 1 on target cells
Describe the 3 ways in which the complement pathway can be activated (both adaptive & innate.
- Classic pathway (Antigen-antibody complex) adaptive immunity
- Alternative pathway (C3b bind to hydroxyl/amine group on surface of pathogen) Innate
- Lectin pathway (lectin binds to glycoproteins + carbohydrates on surface of pathogens)
Briefly describe the complement pathway
The most abdundant complement C3 is activated by either of the 3 pathways, all coverage as C5-C9 interact to form a membrane attack complex which binds to the membrane of target cells → transmembrane channel salt & water can flow = lysis
Where are B cells developed?
Bone marrow
Briefly describe the activation of B cells
Antigens bind to antibodies on the surface of the naive B cells. They are internalised and complex with MHC class II and returned to the cell surface.
Antigen-specific T cells recognise these and secrete cytokines causing clonal B cell proliferation and differentiate into plasma cells which produce antibodies.
What are the 5 main types of antibodies?
IgM, IgG, IgA, IgE, IgD
What is the basic structure of antibodies?
2 identical light chain
2 Identical heave chains
Differ in size, charges carbohydrate content and amino acid sequence.
Antigen binding fragment (fab) region → antibodies antigen specificity
Fc region → effector function
For IgM describe:
- % of serum immunglobin pool
- Shape
- Role in primary/secondary response?
- Can it cross the placenta?
- what is its effector function
- 5-10%
- pentamer
- 1st antibody in primary response
- Can not cross placenta, 1st antibody the newborn baby produces.
- potent activator of complement pathway due to 4 complement binding pathway
For IgG
- % of serum immunglobin pool
- Role in primary/secondary response?
- Can it cross the placenta?
- what is its effector function
- 70-80%
- predominant in Secondary immune responses not primary
- Can cross into placenta
- Activate complement and bind to phagocytes
For IgA
- % of serum immunglobin pool
- Where is it abundant?
- Role in primary/secondary response?
- Can it cross the placenta?
- what is its effector function
- 10-20%
- Salivia, tears, mucus, breast milk
- Important in secondary immune response
- No but secreted in breast milk important for fetes in first few months of life
- Induce phagocytosis, prevent attachment to mucosal cells
For IgE
- High affinicty for which cells
- what is its effector function
- Mast cells and basophils
- Degranulation release of active mediators, allergic manifestations
How does vaccination improve future secondary responses to infection.
As vaccination expose the immune system in an inocus antigen, this produces primary antibody response and leads to generation of long lived antigen specific memory B cells.
Subsequent expose to same pathogen leads to faster more intense secondary response.
T cells recognise antigens through the T cell receptors, what 2 main types of TCRs have been categorised?
alpha/beta TCRs - 95% circulating T cells
gamma/delta TCRs - T cells in mucosal surfaces (small intestines, pregnant uterus)
Explain the maturation of T cells
Generated in bone marrow
matured in thymus
- negative selection if regonise self antigens
- single positive for CD4 or CD8
mature cells leave thymus and travel to secondary lymphoid tissues
Describe effector function dependant on CD4/8 group
T helper (Th) cell, CD4 + MHC class II cytotoxic T (Tc) cell, CD8 + MHC class I
CD4 positive T cells can be categorised into Th1 and Th2.
What cytokines do they release and what impact does that have on immunity?
Th1 produce IFN-y and IL-2 which activate macrophages and CD8 T cells → cell mediated immunity
Th2 produces IL-4 & IL-5 which activates B cells to produce antibodies → humeral immunity
What are the main categories of cytokines?
Interferons Interleukins Chemokine Growth factors Many overlaps between these groups
Main roles of chemokines
form concentraction gradient along which circulating leucocytes can imgrate towards the stimulus
What are the main groups of Class I MHC.
What is the length of the protein it can present to CD8 positive T cells.
HLA A/B/C/E/F
8-9 amino acids
What are the main groups of Class II MHC.
What is the length of the protein it can present to CD4 positive T cells.
HLA-DR, HLA-DQ, HLA-DP
15-24 amino acids
Describe the terms: Autograft Isograft Allograft Xenograft
Autograft: one part of body to another on same individual
Isograft: transfered betwee genetically identical indvidual
Allogrft genetically different, same species
xenograft different species
Describe graft vs host diease
The grat initiates a rejection response again recipient
Immune competent T cells from graft recognise MHC or minor histocompatibility as forming and initateimmune response against the host.
How to prevent graft vs host
careful match of HLA groups
removal of all T cells from the graft
effective immunosuppression
Describe 3 main types of graft vs host
Hyeracute (mins to hours) natrually occurring antibodies
Acute rejection (days to weeks) donor leukocytes migrate out of graft and initiate primary immune response - Type IV hypersensitivity
Chronic months-years: occlusion of blood vessels, macrophage infiltration and smooth muscle proliferation
Explain main features of type 1 hypersensitivity reaction and examples
- Allergen + IgE activate mast cells which release histamine
- Once mast cells are sensitised on repeat exposures → explosive release of histamine/leukotriene
e.g.: Allergic asthma, anaphylaxis
Explain main features of type 2 hypersensitivity reaction and examples
IgM + IgG antibodies bind to antigens on cells or extracellular material.
Generally cytotoxic
tissue specific
e.g Haemolytic anaemia (RBCs), good pastures (glomerula membrane) graves TSK receptor, myasthenia graves
Explain main features of type 3 hypersensitivity reaction and examples
Failure to clear immune complexes, which travel in the blood and are deposited (kindey, joints) - where they activate the complement pathway, attract granulocytes
Examples Lupus RA viral hepatitis farmers lung/ pigeon fanciers lung post strep gloemrular neuritis
Explain main features of type 4 hypersensitivity reaction and examples
Localised inflammatory reaction caused by T cells at site of antigen, develops over 24-72 hours.
Foreign: Nickle
Autoimmun: IBD, MS, T1DM, hasimatos
GVHD
What are the 2 immunological interfaces of pregnancy?
- Extravillous cytotrophoblst which invades into decide - tissue/tissue
- Surface if the chorionic villus (syncytotrphoblast) and maternal blood (gas + nutrient exchange - tissue/blood
extended 2: syncytiotrophoblast in maternal circulation
Which class of MHC does the extravillous cytotrophoblast express?
MHC class 1 ONLY HLA-C/E/G (not A/B) no MHC class II
Which class of MHC does the syncytiotrophoblast express?
Neither MHC class 1 or 2
What maternal immune cells are found at the interactive between invasive extravillous cytrotrophoblast
T cells, macrogphafes, dendritic cells
No B cells
Decidual NK cells (70%) - not cytotoxic, produces cytokines/chemokines/angigenic factors
What is unique about HLA-G
Very little polymorphism (4 alleys) maternal & paternal likely to be identical and therefore unlike to induce an alloreactive maternal T response during pregnancy
Does not induce immune response but instead implantation, trophoblast invasion and placentation
What is the difference of the immune response between the fetal leukocytes that entre the maternal bloods vs extravillous cytotrophoblast/syncytiotrophoblast?
Fetal leucocytes express HLA-A HLA-B HLA-C can simulate antoboud mediated and cell mediated immunity
Explain the process of haemolytic diease of the newborn
RHD- mother has RHD +ve baby. Fetal blood enters maternal circulation, mother produced Anti RhD antibodies + memory B cells post partum. No clinical significant until 2nd pregnancy with Rhesus +ve baby.
IgG crosses placental barrier and damages fetal RBCS → fetal anaemia, impaired platelet function and dysfunction of liver and spleen
How is the maturation of CD+ve into Th1 & Th2 changed in pregnancy?
Placenta produces Th2 promoting cytokines (IL4 &IL10) + progesterone which inhibitors Th1 response.
Bais to T2 immunity (humoral rather than cellular. Product paternal DNA
Affect of shift of T1 on
- RA
- Herpes/malria
- Lupus
- RA is Th1 mediated - temoprary remission
- Exacerbation of intracellular disease herpes & malaria
- Worsening of LUPUS (Th2 mediated)
What is the incidence of antiphopholipid syndrome in the obstetric population?
What is the risk of fetal mortality?
2-5%
85-95%
Consider antiphospholpid if high rates of miscarriage and blood clots
