Lecture 1-cells, Organs Flashcards
What is immunity?
Recognition of and reaction to foreign agents
What are foreign agents?
Pathogens
Host cells that infected, necrotic, neoplastic
Allergens, chemicals
Mismatched tissue or blood.
Foreign agents are composed of antigens which can be: proteins, carbohydrates (strong antigens-make good vaccines), nuclei acids ne lipids (weak antigens)
What are the mechanisms used by leukocytes to destroy antigens?
Phagocytosis-Ingestion and digestion of antigen particles
Cytotoxicity- induction of apoptosis in tumors, tissue grafts and infected host cells
Synthesis of soluble factors- antibodies, complement, cytokines, aid in the elimination of antigens
What are the branches of immunity?
Innate Vs adaptative
Humoral VS cell mediated
What are the characteristics of innate immunity?
Natural, native Present and functional at birth Rapid response (within minutes) Discriminate between self and non self Low specificity No memory Not enhanced by vaccination
What are the components of innate immunity?
Natural barriers (skin, mucus, ph extremes, sneezing)
Phagocytes, granulocytes, natural killer cells
Soluble mediators(complement, CRP, cytokines)
Pattern recognition receptors
Normal flora microbes
What are the characteristics of adaptive immunity?
Acquired Induced by antigen contact Slow response (take days) Able to discriminate between self and non self Highly specific Memory Enhanced by vaccination
What are the components of the adaptive immunity?
B lymphocytes, plasma cells
Antibodies/immunoglobulins
T lymphocytes
What is the mechanism of clinal selection?
Antigen is specific to one type of T or B cells
Contact of antigen with matched receptor cells causes proliferation of that cell
From one cell we have thousand of cells for that antigen
proliferation is followed by differentiation
Differentiation gives rise to cells secreting specific antibody for the antigen and memory cells
Memory cells reside in spleen and lymph nodes and can be used for further production of antibodies
What are the characteristics of humoral immunity?
Most effective against extracellular bacteria
Antibody (immunoglobulin) is the most common
But includes:
Complement-pathogen lysis
C-reactive protein (CRP)-activates complement, general marker of infection and inflammation
What are the characteristics of the cell mediated immunity (CMI)?
Effective against intracellular and extracellular pathogens, tumors, damaged host cells
Can be :
Phagocytes-monocytes, neutrophils, eosinophils, macrophages
Granulocytes- neutrophils, eosinophils, mast cells, basophils
Cytotoxic cells-NK cells, Tc cells–> apoptosis of targets
What is opsonization?
Humoral immunity and CMI work together
Opsonins are ( antibody, complement and CRP) are substances that coat the capsule of bacteria to facilitate phagocytosis
Opsonins neutralize anti phagocytic property of bacterial capsules
What is hematopoiesis?
Formation of red blood cells, leukocytes and platelets from multipotent stem cells
Formation of 2 major lineages
Myeloid
Lymphoid
What is the mechanism of formation of the lymphoid lineage cells?
Stem cell under the influence of IL-7 gives the common lymphoid progenitor (CLP)
CLP gives B lymphocytes, natural killer cells and in the thymus T lymphocytes
T lymphocytes can further differentiate into T helper cells and cytotoxic T cells
What is the mechanism of the formation of the myeloid lineage cells?
Stem cell differentiates into common myeloid progenitor (CMP)
CMP+erythropoietin gives erythropoietin CFU which differentiates into erythrocytes
CMP+IL-3, GM-CSF+ thrombopoietin(IL-11) gives megakaryocyte which gives platelets
CMP+IL-3, GM-CSF gives basophil CFU which differentiates into basophils
CMP+IL-3, GM-CSF+Il-5 gives eosinophil CFU which differentiates into eosinophils
CMP+IL-3+GM-CSF gives granulocyte-monocyte CFU
G-M/CFU+G-CSF (filgrastim) gives neutrophils
G-M/CFU +M-CSF gives monocytes
What a re some clinical uses of CSF and ILs?
Erythropoietin (Epoetin, EPO)- Reverse anemia, restore RBCs especially in renal failure
G-CSF (Filgrastim)- Recovery of bone marrow, restore PMNs
GM-CSF (Sargramostim)-Recovery of bone marrow, restore PMNs, monocytes and macrophages
Interleukin 11 (oprelvekin)-Reverce thrombocytopenia, restore platelets
Thrombopoietin (TPO)- Reverse thrombocytopenia, restore platelets
What are the markers and cell function of B lymphocytes?
CD markers: CD19, CD 20, CD21
Function: antibody secretion-humoral immunity
What is the marker common to all T lymphocytes?
CD 3
What are the markers and function of T helper cells?
CD3, CD4
Function: cytokines secretion
What are the markers and function of the T regulatory cells (Treg)?
CD3, CD4, CD 25
Function: prevent autoimmunity
What are the markers and function of cytotoxic T cells (Tc)?
CD3, CD8
Functions: Killing of infected or neoplastic cells, rejection of grafts
What a re the markers and functions of natural killer cells (NK)?
CD16, CD56
Functions: killing of infected or neoplastic cells, rejection of grafts
What are the markers and functions of Natural Killer T cells (NKT)?
CD3, CD16, CD56 plus TCR and NK1.1
Function: prevent infection through gut
What are the functions of the innate lymphoid cells (ILCs)?
Protection and inflammation of mucosa
What are the characteristic of B lymphocytes?
Develop in bone marrow (humans), bursa (birds)
In infant they are produced in the bone marrow and liver
Function in humoral immunity
Produce antibodies (immunoglobulins/Ig)-toxin and microbe neutralization, opsonization and complement activation
Differentiate into plasma cells or memory B cells
What are the characteristics of T lymphocytes?
Mature in thymus
All express TCR (specificity) and CD3 (signal transduction)
Differentiate into T helper cells, cytotoxic T cells and T regulatory
What are the subdivisions of the T helper cellls?
TH1- promote cell mediated immunity
TH2-promote antibody synthesis by B cells (allergies)
TH17- promote clearance of extracellular bacteria and fungi, contribute to asthma and autoimmunity
What are the characteristics of the Natural Killer cells?
Only cells off the lymphoid lineage that are from the innate immunity
Kill infected and neoplastic host cells
Collaborates with IgG during antibody dependent cel mediated cytotoxicity (ADCC)
What are the characteristics of the mononuclear phagocytes?
Horseshoe-shaped nucleus
Circulating monocytes
Dendritic cells
Tissue fixed macrophages-line for years and comprise the reticuloendothelial system (RES)
RES is a filtering system for antigen removal from blood and lymph
Function in phagocytosis, antigen processing and presentation
What are the types of mononuclear phagocytes?
Kupffer cells in the liver Alveolar macrophages in the lung Splenic macrophages Peritoneal macrophages Microglial cells in the brain Osteoclasts in the bone Mesangial cells in the kidneys Synovial A cells in the joints
What are the steps of phagocytosis?
Chemotaxis(migration) of macrophage toward bacterial f-met-leu-phe
Adherence to microbe aided by opsonins
Extension of pseudopodium to form phagosome
Fusion of phagosome and lysosomes to form phagolysosome
Digestion-lysozyme( also found in tears, saliva, sweat genitourinary secretions) breaks down peptidoglycan in bacterial cell wall
Respiratory burst-ROS damage protein, DNA
What are the steps of antigen processing and presentation?
Processing-destruction of antigen in phagolysosome
Presentation
antigen fragments paired up with MHC
Complex transported to macrophage surface and presented to T cell
T cell can’t see antigen unless presented along with MHC by APC
What are the characteristics of the dendritic cells?
Related to macrophages Found under epithelia,in most organs Langerhans cells in skin Most efficient APC Activate naive T cells
What are the characteristics of the polymorphomuclear granulocytes ?
Short-lived
Bilobes or multilobed nucleus
Granules contain enzymes (lysozyme, others) and lactoferrin harmful to microbes
Produce ROS
What are the components of the polymorphonuclear granulocytes?
Neutrophils- killed extracellular bacteria-Phagocytosis and inflammation (60-%)-receptors for IgG
Eosinophils-killed worms (helminths)- participate in immediate hypersensitivity reactions -Receptors for IgE
Basophils-Killed worms-Participate in immediate hypersensitivity reactions , good source of histamine- receptors for IgE
Mast cells-killed worms-participate in immediate hypersensitivity reactions, major source of histamine-receptors for IgE, tissue fixed, long lived
What are the characteristics of megakaryocytic lineage?
Megakaryocyte: Large cell with lobulated nucleus Gives rise to platelets/thrombocytes Platelet: Anucleate Blood cl;outing and inflammation
What is the normal count of WBC?
Total WBC should be between 4800-10,800 per microliters
What are the characteristics of lymphoid organs and tissues?
Sites of lymphocyte maturation, differentiation, proliferation
Can be 2 types
Primary
Secondary
What are the general characteristics of primary lymphoid organs?
Antigen receptors are first expressed here
consist of :
Bone marrow-where B cells begin surface immunoglobin expression
Thymus where T cell begins TCR expression
What are the general characteristics of secondary lymphoid organs?
B and T cells respond to antigens here (clonal selection)
consist of:
Lymph nodes
Spleen-site of most antibodies production
MALT-adenoids, tonsils, Peyer’s patches, appendix, BALT
What are the characteristics of bone marrow?
Site of hematopoiesis
Stem cells express CD34 and Stem Cells antigen 1 (SCA-1) used to harvest stem cells for immmune reconstitution
Stromae cells secrete cytokines that drive differentiation
Site of B cell maturation
What are the steps in B cells maturation?
Stem cell gives Pro B Pro B gives Pre B Pre B gives immature B Immature B gives Mature B Mature B differentiate into memory B cell or plasma cell
What are the characteristics of Thymus?
Site of T cell maturation
Develops from 3rd and 4th pharyngeal pouches
Reaches max size at puberty
Atrophies with age
What is DiGeorge syndrome?
Defect associated with thymus
Little/no thymus
Few/no T cells–>heightened susceptibility to viruses and cancer
22q11.2 microdeletion
Deficient parathyroids–>hypocalcemic tetany
Deformed ears, facial anomalies
Heart and kidney defects
What are the steps in T cell development in the thymus?
In the subscapsular region: Double negative thymocytes Neither CD4 or CD8 present In the cortex: Double positive thymocytes Both CD4 and CD8 present In the medulla: Single positive T cells-Either CD4 or CD8 present, both TCR and CD3 present Hassall's corpuscles-Function in dendritic cell and /or Treg maturation
What are the characteristics of lymph nodes?
Respond to antigens entering through skin or subcutaneous tissues
Encapsulated clusters
Function :
in survey of lymph by macrophages
storage/activation of B and T lymphocytes
Antibody production
Constant circulation of lymphocytes between lymph nodes, tissues, lymph and blood
What is the structure of the lymph node?
Cortex (B cells)
Paracortex (T cells)
Medulla
What is the characteristic of the cortex?
Primary follicles- naive B cells
Secondary follicles-germinal centers contain dividing B cells
No/few secondary follicles in patients with B cell deficiencies
What are the characteristics of paracortex?
Poorly developed in DiGeorge syndrome
HEVs facilitate entry of lymphocytes from blood into node
Enlarged during cellular immune responses
What are the characteristics of Medulla?
Cords contain lymphocytes and plasma cells
Sinuses contain macrophages, drain into efferent lymphatics
What are the characteristics of the spleen?
Responds to blood-borne antigens Major site of antibody synthesis Asplenic persons are susceptible to encapsulated bacteria like (strep pneumonia, H.influenza, Neisseria meningitis) Red pulp-hemocathereis White pulp- Lymphocytes
What are the characteristics of splenic white pulp?
PALS-T cells surround a central arteriole
B cells rich follicles-primary and secondary germinal centers
What are the characteristics of MALT?
Respond to antigens entering through mucosal surfaces B cells produce secretory IgA 50% of bodys lymphoid tissue GALT(Gut) BALT(Bronchus) GU-ALT(Genito-urinary) Peyers patches of small intestine Tonsils, adenoids, appendix, mesenteric lymph nodes etc.
What are the M cells?
Unique to Peyers patches
Epithelial cells that mediate transcyotosis of antigens from lumen to subepithelial T cells
