Immunology Final Objectives PDF

Autoimmune (on last test but wanted to review some of it because the lecture was virtual → wont be tested too much on the final) - Big take away: failure of immune response occurs in the porifiery → after T cells have been selected in thymus and released → they get confused once they get...

Autoimmune (on last test but wanted to review some of it because the lecture was virtual → wont be tested too much on the final) - Big take away: failure of immune response occurs in the porifiery → after T cells have been selected in thymus and released → they get confused once they get out and see pathogens and might attack a pathogen that looks similar to self tissue, or get over stimulated by antigens that T cells in area of cytokines get stimulated that shouldnt be Lecture 25 – Immunodeficiency 1. Differentiate clinical signs associated with deficiencies of the innate immune system from deficiencies in the adaptive immune system Innate Immune system deficiencies: worried about lck of this - Non cellular (complement) - Cellular (neutrophils, monocytes, macrophages, and dendritic cells) Complement deficiency: non cellular - Vital role in clearance of extracellular bacteria - Group of brittney spaniels bred to study muscle disease had an unknown C3 deficiency - Developed bacteria infections and renal disease - Rarely seen in practice - See C1 and C4 deficiencies in humans → develop lupus - CD18 is a complement receptor too, so deficiency in CD18 affects bacterial opsonzation - Diagnosis: - Determine protein levels of complement components - Total hemolytic complement assay - Would be seen at a young age - Treatment: supportive antimicrobials Neutrophils (Cellular deficiency): - Typically found in circulation  - Functions: - Migrate areas of inflammation - Phagocytize bacteria - Kill bacteria Adaptive immune deficiencies: predominantly B cell and T cell dysfunction - B cell deficiency → The most common abnormality that we see if animals and patients are B cells that arent able to make one of the heavy chains, like IGA deficiency - Only the one antibody subtype that is not made, so the patients usually do quite well but will get random infections (especially bc IgA is a mucosal protector) - One of the best ways to see if a patient has B cells and T cellsis with flow cytometry - Side scatter is how complex they are (do they have granules, nucleus?) - Forward scatter is how large they are - Have reference intervals for these in dogs to see if they are decreased - T cell deficiency → big problem because T cell stimulation is needed for antibody production, so even if the B cells are there, their not being stimulated by the T cells to form antibodies - Defects in all the T cells and immunoglobulins too - So recurrent bacterial, viral, and fungal infections 2. Identify specific diseases associated with each of the following: complement proteins, neutrophils, B cells, T cells Neutrophil deficiency → 1. Unable to leave bloodstream → Can get messed up if unable to leave blood vessels and go into the tissues (CLAD and BLAD) missing CD18 on surface or CD18 abnormal so it doesnt bind to endothelium to allow neutrophils to get out - High neut count because they are stuck in blood, but dont see them in tissue where they should be  2. Not functioning in the tissue → Neutrophils can also get messed up if there phagocytizing abilities and ROS function poorly (essentially there granulocytes) - Harder to diagnose because things become more chronic - Neutrophils get out but arent function so macrophages get released as secondary defense → results in granulomas - Failure to kill pathogens (CGD, higashi disease, myeloperoxidase deficiency) 3. Not enough neutrophils → neutropenia syndromes are pretty severe - Cyclic neutropenia in collies you can have neutrophils one day and none the next (due to defect in bone marrow production) → very susceptible to bacteria infection with no neutrophils like pneuominia Canine leukocyte adhesion deficiency: cellular deficiency - PCR test available - Multiple testing/breeding programs incidence of disease - Treatment with stem cell therapy - CLAD like disease observed in mixed breeds likely not genetic but alteration in receptor expression - Bovine can get it too Common variable immunodeficiency in horses: CVID - If all B cells are gone → then will have much more severe disease and these occur mostly in horses as common variable immunodeficiency - No B cells means no antibodies - No antibodies means high rate of infection (both bacterial, viral, and fungal) - Happens at birth in horses, but wont see disease onset until after maternal antibodies have worn off so see around 4 to 5 months of age 3. Know which type of immunodeficiency is the most common in veterinary patients Secondary immunodeficiencies: the most common immunodeficiency we are going to see - Adult animals - May not respond well to vaccines, but may not need them because of age - Associated with pathological or physiological change - Age related decline (normal) - Any patient with Chronic disease, stress, malnutrition (dont have to be old) - Doesnt have energy to put into fighting pathogens and generating immune response - Medical immune suppression → prednisone or chemotherapy - Makes them susceptible to other diseases and therapeutics can kill neutrophils in bone marrow 4. Understand the different genetic causes of SCID Severe combined immunodeficiency disorder (SCID): found in several veterinary species and the genetic causes differ in said species Essentially lack B cell and T cells - Autosomal reccesive disorder - Genetic → - arabian horses can not rearrange VDJ segments in T cell and B cell receptor → very severe infections very young - Dogs (bassets) IL-2 receptor not functioning and it is needed to respond to IL2 which causes proliferation of T cells (which is why they dont have B cell and T cell function at all) → can also see in young age once material antibodies where off (6-8 weeks) - Caused by defect of DNA dependent protein kinase activity (DNA-PK) - DNA-PK: involved in T and B cell receptor gene rearrangement (VDJ) - Not protected by vaccination Lecture 26 – Grafts 1. Define four different types of grafts 1. Autograft: animals’ own tissue, no rejection 2. Syngeneic graft: genetically identical animals’ tissue, no rejection 3. Xenograft: graft from a different species, rejection - Ex: pig organ to a human 4. Allogeneic graft: unrelated animals of same species, rejection 2. Outline the differences in immune response to different types of grafts Xenograft rejection: - mostly an antibody response against foreign carbohydrates - Antibodies bind graft endothelial cells - Activate complement and clotting cascades Allogeneic graft rejection: - Alloreactive response - Mostly a T cell response against “foreign” MHC class 1 molecules - Minor histocompatibility antigens also plays a role - Can be blocked with immunosuppresive drugs - Usually have to be on these meds for life - Direct: Donor APCs leave the graft and travel in blood to activate recipient T cells - Indirect: recipient APCs present graft antigens to recipient T cells - Antibodies develop after T cell activation occurs Chronic graft rejection: - Graft half life