Immune System Ontogeny & Neonatal Immunology PDF

Immune System Ontogeny & Neonatal Immunology Animal Systems and Professional Life 1 VETS10018 Dr Katja Klein Lecturer in Endemic, Enzootic and Emerging Infectious Diseases [email protected] ...

Immune System Ontogeny & Neonatal Immunology Animal Systems and Professional Life 1 VETS10018 Dr Katja Klein Lecturer in Endemic, Enzootic and Emerging Infectious Diseases [email protected]  Intended Learning Outcomes 1. Describe the four different types of placentas found in animal species. 2. Outline differences between transfer of maternally derived immunity between the different types of placentas. 3. Discuss how passive transfer of maternal immunity interferes with vaccination of young animals. 4. Describe the clinical indications of immunodeficiency. 5. Summarise the pathophysiology of neonatal isoerythrolysis (NI) in foals and identify other species in which this condition may occur. THE DIFFERENT TYPES OF PLACENTAS FOUND IN ANIMAL SPECIES The classification of placenta according to how many cell layers separate the maternal and fetal circulation Horses Ruminants Dogs Primates Pigs Cats Rodents Rabbits Figure: Roberts et al 2016, Reproduct  PASSIVE TRANSFER OF IMMUNITY *THE TRANSFER OF ANTIBODIES FROM ONE INDIVIDUAL TO ANOTHER* *Ig = Immunoglobulin (another term for antibody)*  DEPENDS ON TYPE OF PLACENTATION  HUMAN AND PRIMATE Haemochorial Placentation Born with serum IgG as adult level IgM Maternal IgG Fetal IgA Maternal Trophoblast blood (IgG can pass through this barrier)  DOG AND CAT Endotheliochorial Placentation Small amount IgG (5-10% adult level) passes Maternal IgG Fetal Contact of maternal endothelium and Trophoblast trophoblast  RUMINANT Synepitheliochorial Placentation Trophoblast cells fuse with uterine epithelial cells No Ig transfer possible Maternal Fetal Contact of maternal endothelium, uterine connective tissue, uterine Trophoblast epithelium and trophoblast (syndesmochorial: trophoblast invades the uterine connective tissue)  HORSE AND PIG Epitheliochorial Placentation No Ig transfer possible Maternal Fetal Contact of maternal endothelium, uterine Trophoblast connective tissue, uterine epithelium and trophoblast  BREAK POINT Four different types of placenta according to how many cell layers separate the maternal and fetal circulation. Different types of placenta impact the degree to which antibodies can move from the maternal to the foetal circulation.  COMPOSITION OF COLOSTRUM AND MILK  32-212 mg/ml COLOSTRUM Serum IgG/M/A Local IgA/M serum local MILK Serum IgG/A 0.72 mg/ml Local IgG/M/A Leyton et al 2007, Anal Bioanal Chem G M RUMINANT MILK NON-RUMINANT MILK  BREAK POINT Colostrum contains substantially more antibody than milk. Colostrum is important for the newborn, particularly in those born without maternal derived antibodies in their circulation. Different classes of antibodies (IgG, IgA, IgM). Species differences in terms of subclasses of antibody. ABSORPTION OF COLOSTRUM Gut permeability is increased from 6 – 24 hours Colostral protein protected by: Low proteolytic activity in gut IgA secretory component Colostral trypsin inhibitors Other things absorbed from colostrum: Absorbed but non-functional Complement IgG IgM IgA Some absorption Maternal Passive transfer CMI lymphocytes  lacteal FcRn on enterocyte IgG IgM IgA Some loss via capillary neonatal glomeruli (permeable 24hr) CIRCULATION Transient Peak serum Ig 12-24hr proteinuria HORSE & PIG RUMINANT IgG/M IgG/M IgA IgA absorb & re-excrete  BREAK POINT From roughly 6 to 24 hours after birth the permeability of the gut is increased. Protein within the colostrum is protected by various mechanisms. Other things can be absorbed from colostrum (complement, lymphocytes). Enterocytes express FcRn, which facilitates the absorption of antibody. Differences in terms of the way in which antibodies from the colostrum are passing across the gut surface. NEONATAL VACCINATION  Colostral Ig inhibits development of neonatal immune response until maternal Ig is catabolised. Neonates cannot respond to vaccine until this has occurred. Repeat vaccination of neonates accounts for variability in colostral intake and catabolism.  NEONATAL VACCINATION (Maternal antibody) Vaccination at 8, 12 & 16 wks to ensure that all are able to respond  BREAK POINT Absorbed antibody from the colostrum, inhibits the development of the neonates own immune response until maternal antibody is catabolised. Neonates cannot respond to vaccine until maternal antibody is catabolised below a certain level. Repeated vaccination of neonates accounts for variations in colostral intake and its breakdown. DISORDERS OF THE NEONATAL IMMUNE SYSTEM  FAILURE OF COLOSTRAL TRANSFER Symptoms: Leads to enteric, respiratory disease or septicaemia Possible Causes: Premature birth and no colostrum Premature lactation with loss colostrum Poor quality colostrum Failure to suckle Failure to absorb  ADEQUATE COLOSTRAL TRANSFER? Determine serum Ig concentration after 24 hours of life Equine IgG Radial Immunodiffusion test kit Snap™ Foal IgG Idexx  BREAK POINT There are different causes why you might get failure of colostral transfer which can lead to various symptoms. Colostrum is really important in animal species with no transfer of antibody across the placenta (e.g. horse). IMMUNODEFICIENCY  IMMUNODEFICIENCY PRIMARY congenital, inherited Rare ~16 weeks of age SECONDARY acquired secondary to drugs, infectious, metabolic, neoplastic or inflammatory disease common  Numbers refer to stages at which genetic defects can occur > determines the severity of disease  CLINICAL INDICATIONS OF IMMUNODEFICIENCY chronic, recurrent infection in young, littermate animals infection at multiple sites failure to respond to standard antimicrobials infection with unusual agents Horses and dogs Dogs: ~30 immunodeficiency diseases (breed associated) Weimaraner Immunodeficiency Syndrome CLAD IgG deficiency Canine Leukocyte Adhesion Deficiency (Irish Setters) Congenital immunodeficiency in cats is rare  BREAK POINT Immunodeficiencies are usually classified as: Primary immunodeficiencies: genetic cause – rare. Secondary immunodeficiencies: acquired secondary to something else (e.g. drugs, infection,…) – more common. Indicators for immunodeficiency: recurrent infections or chronic infections in individual animals. failure to respond to standard treatments. infection with unusual pathogens. Dogs have a range of different immunodeficiencies (breed dependent). NEONATAL ISOERYTHROLYSIS  NEONATAL ISOERYTHROLYSIS (NI) Isoimmune haemolytic anaemia Colostrum contains antibodies to neonate’s erythrocytes Dam sensitised to sire erythrocyte antigens or Dam has spontaneously arising antibody that cross- reacts with sire erythrocytes Given incompatible Sensitised to foal Transfusion with Q+A+ cells at first Q+A+ blood parturition Q-A- mare Q+A+ stallion Anti-Q/A in colostrum HAEMOLYTIC CRISIS IN FOAL  FELINE BLOOD GROUPS blood groups A, B and AB all type B cats have high titred anti-A type A cats sometimes have low titred anti-B  NEONATAL ISOERYTHROLYSIS Occurs when A or AB kittens born to type B queens with colostral anti-A type B more prevalent in Birman, Rex, BSH, Abyssinian, Persian, Somali rare in dog - sensitised DEA 1- bitch mated to DEA 1+ dog  NEONATAL ISOERYTHROLYSIS IN KITTENS Subclinical disease but may develop tail tip necrosis 1-3 weeks post-partum Severe haemolytic anaemia (Coombs positive) jaundice haemoglobinuria weakness, lethargy reluctance to suckle death within first few days of life  PREVENTION AND TREATMENT OF FELINE NEONATAL ISOERYTHROLYSIS Prevent at-risk mating by blood typing sire and dam Determine level of anti-A in dam serum before birth by titrating against sire RBC Prevent susceptible kittens access to colostrum for 24 hr after birth Type A foster queen Colostrum replacement with type A cat serum  BREAK POINT Neonatal Isoerythrolysis: Presence of antibodies in the colostrum against the neonates' erythrocytes (red blood cells). Two reasons for antibodies in colostrum specific to neonate’s erythrocyts: 1. Dam’s immune system has been exposed to the red blood cell antigens of the sire and in being exposed they have mounted an immune response against these antigens. 2. Dam has spontaneously arising antibody that can cross react with sire erythrocytes.