Week 1: Introduction to the Immune System Flashcards
A 4-year-old girl presents with lethargy, dyspnoea, fever, and bruising. On examination, she has hepatosplenomegaly. Blood tests showed low Hb.
A chest x-ray shows a mediastinal mass and pleural effusion. A full blood count and cytogenetic analysis was performed. The girl was diagnosed with acute lymphocytic leukaemia (ALL) and chemotherapy was performed.
Given the information provided what is the likely cause of this girl’s lethargy?
Low haemoglobin levels and anaemia leading to lack of oxygen supply
A 4-year-old girl presents with lethargy, dyspnoea, fever, and bruising. On examination, she has hepatosplenomegaly. Blood tests showed low Hb.
A chest x-ray shows a mediastinal mass and pleural effusion. A full blood count and cytogenetic analysis was performed, which showed high calcium. The girl was diagnosed with acute lymphocytic leukaemia (ALL) and chemotherapy was performed.
Suggest possible reasons for the hypercalcemia seen in this patient?
Hypercalcemia may be caused by bony infiltration or ectopic release of a parathormone-like substance.
Name the hormone that is secreted when blood calcium levels are higher than normal? From where is it secreted?
Calcitonin
Thyroid gland acts to stimulate incorporation of calcium into bone
Suggest why chemotherapy may result in hyperkalaemia?
Potassium is at a higher concentration inside cells and thus extensive cell lysis due to chemotherapy can alter the electrolyte balance in the extracellular fluid leading to hyperkalaemia.
Acute lymphocytic leukaemia patients regularly have a chromosomal abnormality called the Philadelphia chromosome. What type of chromosomal abnormality is this and state the karyotype of the cells?
robertsonian translocation t(9;22)(q34;q11)
State the correct order of abundance of cell types in the peripheral blood?
RBCs, platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils
List the mature white blood cells would you not see in a peripheral blood smear?
Macrophage
Mast cell
In Acute lymphocytic leukaemia, which type of hematopoietic cell would you find in the peripheral circulation that you would usually find only in bone marrow?
Lymphoblast. The diagnosis of ALL is made when at least 20% lymphoblasts (WHO classification) are present in the bone marrow and/or peripheral blood.
Bone marrow aspirates or biopsies are usually taken from ALL patients to confirm the diagnosis. What histological stain should be used to visualise the different cell types?
Giemsa or Wright stains
What are the two categories of bone marrow tissue?
There are two categories of bone marrow tissue: ‘red marrow’ (medulla ossium rubra), which consists mainly of hematopoietic tissue, and ‘yellow marrow’ (medulla ossium flava), which is mainly made up of fat cells.
A consultant at the hospital is visited by parents of a 7-year-old patient. The young girl has Fanconi’s anaemia a rare, autosomal recessive disease characterised by aplastic anaemia (bone marrow failure), brittle chromosomes, and the variable presence of skeletal, cardiac, and renal anomalies. The parents understand that definitive treatment of the disorder relies on reconstituting the patient’s bone marrow by transplantation or cord blood donation. They would like to talk about having another baby and using the cord blood to help their daughter.
Which type of bone marrow would be the major component of their daughter’s bone marrow?
There are two categories of bone marrow tissue: ‘red marrow’ (medulla ossium rubra), which consists mainly of hematopoietic tissue, and ‘yellow marrow’ (medulla ossium flava), which is mainly made up of fat cells.
From birth to early adolescence, the majority of our bone marrow is red marrow.
Describe the blood vessel of umbilical cord?
Two umbilical arteries - Deoxygenated blood from fetus to placenta
One umbilical vein- Oxygenated blood from placenta to fetus
A consultant at the hospital is visited by parents of a 7-year-old patient. The young girl has Fanconi’s anaemia a rare, autosomal recessive disease characterised by aplastic anaemia (bone marrow failure), brittle chromosomes, and the variable presence of skeletal, cardiac, and renal anomalies. The parents understand that definitive treatment of the disorder relies on reconstituting the patient’s bone marrow by transplantation or cord blood donation. They would like to talk about having another
baby and using the cord blood to help their daughter.
What cells should be harvested from the cord blood to best treat patients with blood diseases?
Stem cells - Although erythrocytes and leukocytes might be helpful in the short term, it makes more sense to harvest and implant stem cells that can create new erythrocytes and leukocytes.
Describe the process of Haematopoiesis?
Haematopoietic stem cells (HSCs) reside in the medulla of the bone (bone marrow) and have the unique ability to give rise to all of the different mature blood cell types and tissues.
Daughter cells of HSCs (myeloid and lymphoid progenitor cells) can follow any of the other differentiation pathways that lead to the production of one or more specific types of blood cell, but cannot renew themselves.
All blood cells are divided into three lineages.
Erythroid cells are the oxygen carrying red blood cells. Both reticulocytes and erythrocytes are functional and are released into the blood.
Lymphocytes are derived from common lymphoid progenitors. The lymphoid lineage is primarily composed of T-cells and B-cells (types of white blood cells).
Myelocytes, which include granulocytes, megakaryocytes and macrophages and are derived from common myeloid progenitors, are involved in innate immunity, adaptive immunity, and blood clotting.
Aplastic anaemia causes pancytopenia, a deficiency of all three blood cell types. Name the three types?
Red blood cells (anaemia), white blood cells (leukopenia), and platelets (thrombocytopenia).
What is the probability of a naturally conceived child would also have Fanconi’s anaemia, an autosomal recessive disease?
25%
two broad categories of immunity
Innate immunity – the mechanisms have evolved to be ready to react before an infection occurs. The innate immune system provides the first and some of the second line of defences.
Adaptive immunity – The system is stimulated by microbes and the mechanisms ‘adapt’ to this stimulus to build an immune response.
Cells of innate immune system
epithelial cells mast cells phagocytes dendritic cells NK cells complement system
Cels of adaptive immunity
B lymphocytes > plasma cells and antibodies
T lymphocytes > effector T cells
Describe the first and second line of defence of the innate immune system.
First - These are a combination of physical and chemical barriers that prevent all types of foreign agents from penetrating the outer layer of the body. No specific foreign agent is targeted at this level.
Second - Leukocytes (white blood cells)
Leukocytes are derived from…
Leukocytes derived from pluripotent stem cells in the bone marrow protect
five types of leukocytes
neutrophils, eosinophils, basophils, lymphocytes, and monocytes
Two major classifications of leukocytes
Granulocytes (with granules). Granulocytes are mainly involved in non-specific responses. The granules contain a rich blend of killer molecules and metabolic pathways that can generate low pH and oxidizing agents. Release of the granules to the extracellular environment will be highly lethal to pathogens but also to surrounding tissue.
Agranulocytes (without granules). Agranulocytes can play a role in both specific and non-specific immune responses.
Classify the 5 leucocytes into granulocytes vs. agranulocutes
Granulocytes: neutrophils, eosinophils, basinophils
Agranulocutes - lymphocytes, monocytes
Main function associated with neutrophils
Granulocyte
Phagocytes (engulf and destroy bacteria)
Neutrophils are the dominant cells of acute inflammation but their short life span means they do not provide prolonged defence.
Main function associated with eosinophils
Granulocyte
Kills parasitic worms, destroys antigen-antibody complexes
Eosinophils are relatively rare in peripheral blood under normal conditions but can increase rapidly in patients with large parasites or allergic reactions
Main function associated with basinophils
Granulocyte
Releases heparin (anti-coagulant) and histamine.
Basophils and Mast cells can act as antigen presenting cells and also have specialised granules and receptors that are important in specialised antibody reactions and parasite defence.
Main function associated with monocytes
Agranulocytes. Phagocytosis. Monocytes are the chief phagocytes. They circulate in the blood for 1–2 days before entering body tissues to become macrophages.
Polymorphonuclear leukocytes is another name for which leukocute
neutrophil
The most common leukocyte in the circulating blood and is the final arbiter in most inflammatory reactions is which leukocyte?
neutrophils
The production of neutrophils is
stimulated by ______.
cytokines.
Function of Mast cells
Mast cells are bone marrow derived cells that have many cytoplasmic granules. They can be activated as part of the innate immune system when microbial products bind to TLRs or the adaptive immune system by antibody
dependent mechanisms. The granules of the mast cells contain vasoactive amines e.g. histamines that cause vasodilation and capillary permeability as well as proteolytic enzymes that kill the bacteria. The mast cells can also secrete cytokines to stimulate inflammation.
What are mast cells derived from?
Mast cells are bone marrow derived cells that have many cytoplasmic granules.
The monocyte is a circulating and can develop into two types of cell:
Dendritic cells antigen-presenting cells which are able to mark out cells that need to be destroyed by lymphocytes.
Macrophages, phagocyte cells.
Describe the life cycle of monocytes
Monocytes are produced in the bone marrow and then enter the blood. After a few hours in the blood, monocytes migrate to tissues (such as spleen, liver, lungs, and bone marrow tissue), where they mature into macrophages.
Which cell type are the sentinel cells of the immune system that activates the adaptive system?
Dendritic cells (DC)
Dendritic cells (DC) are the sentinel cells of the immune system and the critical cell that activates the adaptive system. These bone marrow derived cells are present in all tissues and continuously sample the environment for danger. Dendritic cells are activated by recognizing pathogen structures (much more to follow).
The key features of dendritic cells are:
Located in key places to capture antigens
They express many receptors for capturing and responding to microbes e.g. Toll like receptors and lectins.
They produce numerous cytokines to initiate inflammation and stimulate the adaptive immune responses.
When the immune system has been activated by a microbe, the dendritic cells move to the T-cell zones of the lymphoid organs so they can present to the T cells.
Dendritic cells express high levels of MHC needed to present antigens to activate T cells.
Which cell type expresses many receptors for capturing and responding to microbes e.g. Toll like receptors and lectins?
Dendritic cells
Dendritic cells (DC) are the sentinel cells of the immune system and the critical cell that activates the adaptive system.
Which cell type are located in key places to capture antigens, under the epithelia and in the interstitial of all tissues?
Dendritic cells
Dendritic cells (DC) are the sentinel cells of the immune system and the critical cell that activates the adaptive system.
Which cells of the innate immune system, when activated, move to the T-cell zones of the lymphoid organs so
they can present to the T cells?
Dendritic cells
Dendritic cells (DC) are the sentinel cells of the immune system and the critical cell that activates the adaptive system.
Which cells of the innate immune system express high levels of MHC needed to present antigens to activate T cells.
Dendritic cells
Dendritic cells (DC) are the sentinel cells of the immune system and the critical cell that activates the adaptive system.
Which cells of the innate immune system phagocytose
microbes and protein antigens to process the antigens and present the fragments to T cells?
These cells are also effector cells in cell mediated and humoral immunity.
Macrophages
Which cell type is activated by T cells to enhance their
ability to kill ingested microbes?
Macrophages
Which cells type phagocytoses microbes that are opsonised by IgG or C3b?
Macrophages
4 types of T cells
Helper T cells
Cytotoxic or killer T cells
Regulatory T cells (Suppressor T cells)
Memory T cells
Function of Helper T cells
Helper T cells detect infection and get the other cells of the immune system ready for battle. The cells migrate to the site of infection and promote phagocytosis by macrophages. Helper T cells also tell B cells to produce antibodies; highly specialized proteins that help defend the body against infection
Function of Cytotoxic or killer T cells
Cytotoxic, or killer T cells migrate to the site of infection to destroy antigens /infected cells.
Function of Regulatory T cells (Suppressor T cells)
Regulatory T cells (Suppressor T cells) halt the response when it is excessive or if the infection has been dealt and so tell the immune system to stop fighting.
Function of Memory T cells
Memory T cells recognise the original antigen if it invades again and remember how to defeat an infection and can respond rapidly if the same infection reoccurs.
Which cell type detect infection and get the other cells of the immune system ready for battle?
Hint: These cells migrate to the site of infection and
promote phagocytosis by macrophages. They also tell B cells to produce antibodies;.
Helper T cells
Which cell type migrate to the site of infection to destroy
antigens /infected cells?
Killer T cells
Which cell type halts the immune response when it is
excessive or if the infection has been dealt and so tell the immune system to stop fighting?
Regulatory T cells
Which cell type recognises an original antigen if it invades again and remembers how to defeat an infection?
Hint: this cell can respond rapidly if the same infection reoccurs
Memory T cells
How do B cells respond when they encounter disease-causing substances?
they respond by maturing into plasma cells which produce antibodies.
What are antibodies?
Antibodies are highly specialized proteins in the blood also known as immunoglobulins. Antibodies attach themselves to foreign invaders and mark them for destruction.
Antibodies make pathogens easier to kill by alerting the immune system that the germs need to be destroyed.
Role of IgM
IgM antibodies are the first to respond. They offer important protection during the early days of infection. These antibodies tend to stay in the bloodstream where they aid in killing bacteria
Which type of antibodies are the first to respond?
IgM
They offer important protection during the early days of infection. These antibodies tend to stay in the bloodstream where they aid in killing bacteria
Which type of antibodies stay in the bloodstream where they aid in killing bacteria?
IgM
Role of IgA
IgA antibodies are secreted in body fluids such as tears, saliva, and mucus. They protect against infection in the respiratory tract and intestines. These antibodies can pass from mothers to new-borns through breast milk.
Which type of antibodies are secreted in body fluids such as tears, saliva, and mucus?
IgA
Which type of antibodies protect against infection in the respiratory tract and intestines?
IgA
IgA antibodies are secreted in body fluids such as tears, saliva, and mucus. They protect against infection in the respiratory tract and intestines. These antibodies can pass from mothers to new-borns through breast milk.
Which type of antibodies can pass from mothers to new-borns through breast milk?
IgA
IgA antibodies are secreted in body fluids such as tears, saliva, and mucus. They protect against infection in the respiratory tract and intestines. These antibodies can pass from mothers to new-borns through breast milk.
Role of IgD antibodies
IgD antibodies may be present on the surface of B cells but their function is not fully understood at this time.
Which type of antibodies may be present on the surface of B cells but their function is not fully understood at this time
IgD
Role of IgG antibodies
IgG antibodies are formed in large quantities and work in the blood and tissues of the body. They bind to pathogens so that the immune cells have an easier time destroying them. IgG antibodies can pass from a mother to her unborn baby through the placenta.
Which type of antibodies bind to pathogens so that the immune cells have an easier time destroying them?
IgG
IgG antibodies are formed in large quantities and work in the blood and tissues of the body. They bind to pathogens so that the immune cells have an easier time destroying them. IgG antibodies can pass from a mother to her unborn baby through the placenta.
Which type of antibodies can pass from a mother to her unborn baby through the placenta?
IgG
IgG antibodies are formed in large quantities and work in the blood and tissues of the body. They bind to pathogens so that the immune cells have an easier time destroying them. IgG antibodies can pass from a mother to her unborn baby through the placenta.
