Overview of Immune Responses Flashcards
What is the immune system comprised of?
Cells and molecules which collectively mediate an immune response
What is immunity?
It is a defense mechanism that provides protection from infectious diseases
What can also elicit an immune response?
Noninfectious foreign substances called antigens (Ags)
What can cause collateral damage?
An immune response against microbes can cause tissue injury (immunopathology)
What happens if immune system goes against self Ags?
autoimmune response
What are antigens?
Substances which induce an immune response
What are types of antigens?
Proteins, carbs, lipids, nucleic acids
What do microbes have that can be recognized by the immune system?
many different antigens
What can antigens contain a number of?
Different antigenic determinants to which individual antibodies or T cell responses are made
What is the smallest unit of antigenic determinant to which an antibody can be made?
About three to six amino acids or five to six sugar residues long
What are all large molecules?
Multideterminant-have multiple epitopes
What do antibodies bind to?
Conformational antigenic determinants which depend on folding of the molecule
What do T cell receptors recognize?
Linear amino acid sequences
What are Ags that can stimulate an immune response called?
Immunogens
All Immunogens are antigens but _______
Not all antigens are immunogens
What can bind to Ab’s or TCR’s but they cannot initiate an immune response?
Haptens
What is the first line of defense against infection?
Innate immune system
How does the innate immune system work?
Works rapidly, gives rise to the acute inflammatory response, and has some specificity for microbes, but NO memory
What takes longer to develop, is highly specific, remembers what microbe it has encountered previously (memory)?
Adaptive immune system
What exists even before infection and are poised to respond rapidly to infections?
Innate immunity
What are other names for innate immunity?
Natural or native immunity
What does native immunity react to?
products of microbes and injured cells
How does native immunity respond to repeated exposures?
In the same way everytime
What does native immunity recognize?
Recognizes common antigens belonging to groups of related microbes
What does native immunity not distinguish?
Fine differences between microbes
What are principal components of innate immunity?
Physical and chemical barriers (skin, mucosal epit, antimicrobial molec)
Phagocytic cells (neutrophils, macrophages), dendritic cells, and natural killer cells and other innate lymphoid cells
Blood proteins, including the complement system and other mediators of inflammation
What are the components of adaptive immunity?
Cellular and chemical barriers - lymphocytes, antibodies at epithelial surfaces
Blood proteins - antibodies, cytokines
Cells - B and T lymphocytes
In addition to inflammation, the innate immune system is also called what?
“decision-making stage” of an immune response
Before providing instructions to adaptive immunity, what does the innate immunity evaluate?
It evaluates the invader in the context of intracellular vs extracellular microbes and then passes on the info
How do cells communicate?
Direct cell-to-cell contact and interactions involving cytokines and chmokines
What are cytokines?
Large group of small secreted proteins with diverse structures and functions, which regulate and coordinate many activities of the cells of innate and adaptive immunity
What does each cell express for several cytokines?
A set of specific signaling receptors
What are the functions of cytokines?
Growth and differentiation of all immune cells, activation of effector function of lymphocytes and phagocytes
What are chemokines?
Large subset of structurally related cytokines that regulate cell migration and movement
What are the two major types of lymphocytes?
B and T cells
What are critical to the development of specific immunity?
Interactions between T and B cells as well as between T cells and APCs
Where do T cells mature? What doe they give rise to?
Under the influence of the thymus. On stimulation by Ag, they give rise to cellular immunity
Where do B cells mature? What do they give rise to?
Be cells mature mainly under the influence of bone marrow and give rise to humoral immunity.
What are soluble molecules in the immune system
Immunoglobulins
Who is the father of humoral immunity?
Paul Ehrlich
What did Paul Ehrlich do?
Postulated that immune cells use receptors
Coined the term antibodies
Model for the function of B cells
Humoral theory of immunity
What is humoral adaptive immunity?
Immunity mediated by antibodies (Abs) in the blood and mucosal secretions which are produced by cells called B lymphocytes
What do Antidbodies do?
Recognize microbial antigens, neutralize the infectivity of the microbes, and target microbes for elimination by various effector mechanisms.
What is the principal defense mechanism against extracellular microbes?
Humoral adaptive immunity because of antibodies
Who is the father of cell-mediated immunity?
Elie Metchnikoff
What did Elie Metchnikoff discover?
Stated that host cells are the principal mediators of immunity
Phagocytes
Nobel prize 1908
When did the cellular theory of immunity become firmly re-established?
When resistance could be transferred with cells but not with serum
What is the specificity of cell-mediated immunity due to?
T cells which often function with phagocytes to eliminate microbes
What does cell-mediated immunity defend against?
Intracellular microbes such as viruses and some bacteria where they are inaccessible to circulating antibodies
What is the function of cell-mediated immunity?
Destruction of microbes residing in phagocytes or the killing of infected cells to eliminate reservoirs of infection
What contributes to eradication of extracellular microbes by helping B cells make effective antibodies?
T helper cells
What activates macrophages to kill phagocytized microbes?
T helper cells
What directly destroys infected cells?
Cytotoxic T cells
What happens when an Ag is introduced into an individual?
Lymphocytes with receptors for this Ag seek out and bind it and are triggered to proliferate and differentiate, giving rise to clones of cells specific for the Ag
What is the clonal selection hypothesis?
Explains how the immune system could respond to a large number and variety of Ags
Who came up with the clonal selection hypothesis?
Suggested by Dr. Jerne and further by Dr. Burnet
According to the clonal hypothesis, when do Ag-specific clones develop?
Before and independent of exposure to Ag
What is a clone?
Lymphocyte of one specificity and its progeny
What is a characteristic of the immune system involving clones?
A very large number of clones is generated during the maturation of lymphocytes, thus maximizing the potential for recognizing diverse microbes
What happens once an Ag selects a preexisting clone of specific lymphocyte? What does the same principle also apply to?
Proliferation and differentiation of that clone is stimulated. Also applies to T lymphocytes
Compared to the primary adaptive immune response, how fast is the secondary response to the same antigen?
Secondary is more rapid and larger than the primary response because of memory
What happens during contraction phase?
Expanded lymphocyte clones die and homeostasis is restored. A few become memory cells
What are more effective in combating microbes than naive lymphocytes?
Memory cells because they are more numerous than naive cells specific for the Ag and respond faster and more effectively than do naive cells
What is an important goal of vaccination?
Generation of memory cells
Who is the father of immunology?
Dr. Pasteur who developed the principle of vaccination and contributed to the foundation of immunology
The concept of protective immunity dated back to when?
Ancient Chinese custom of making children resistant to smallpox by having them inhale powders made from skin lesions of patients recovering from the disease. Edward Jenner later successfully vaccinated against smallpox
What is active immunity?
Conferred by a host response to a microbe or microbial Ags
(vaccine or infection)
Goal is to create lymphocytes with specificity and memory to pathogen
What is passive immunity?
Conferred by adoptive transfer of antibodies or T lymphocytes specific for the microbe.
Provides resistance to infection and are specific for microbial Ags but no memory.
Example-mothers immunity passed onto child but does not remain
Role of B lymphocytes:
Recognize soluble Ags and develop into Ab-secreting cells
Role of T helper cells
Recognize ags on the surfaces of Ag presenting cells and secrete cytokines, which stimulate different mechanisms of immunity and inflammation
Role of cytotoxic T cells
Recognize Ags on infected cells and kill these cells
Role of regulatory T cells:
Suppress and prevent immune responses to self antigens for example
What is the primary function of phagocytes
To ingest and destroy microbes and get rid of damaged tissues
What are types of phagocytes?
Neutrophils and macrophages
What are the steps of functional responses of phagocytes?
- Recruitment of cells to the sites of infection
- Recognition of and activation by microbes
- Ingestion of the microbes by the process of phagocytosis
- Destruction of ingested microbes
What do activated phagocytes secret?
Cytokines to promote or regulate immune responses
What are neutrophils also called?
Polymorphonuclear leukocytes because their nucleus is segmented into three to five connected lobules
What are the most abundant population of circulating white blood cells that are 12 to 15 um in diameter?
Neutrophils
What mediates the earliest phases of inflammatory reactions?
Neutrophils
Where are neutrophils produced and where do they arise from?
In the bone marrow. They arise from precursors that also give rise to mononuclear phagocytes
What is the production of neutrophils stimulated by?
Cytokine called granulocyte colony-stimulating factor
How many neutrophils are produced a day in an adult?
10^11
How long do neutrophils circulate in the blood?
Four hours or a few days
After entering tissues, how long do neutrophils function?
for 1 to 2 days and then they die
How are specific granules in neutrophils stained?
With neutral dyes (neutrophiles) but not with eosin or basic dyes
What are azurophilic granules?
Lysosomes that contain enzymes and other microbicidal substances. (Elastase, myeloperoxidase, cathepsin, acid hydrolases) Found in neutrophils
How do neutrophils respond to microbes of small sizes?
Bind and internalize the cells via phagocytosis. The microbes are sequestered in phagosomes that fuse with asurophilic granuels. The production of ROS and the release of enzymes (i.e elastase) into the phagosome contribute to killing the microbes
How do neutrophils respond to microbes that are large?
Cannot internalize them, so azurophilic granules are free to deliver their contents into the nucleus instead, which triggers chromatin decondensation and the release of NETs. NETs contribute to the immobilization and killing of extracellular microbes, but at the cost of some tissue damage
Describe the formation of NET
It is a rapid, active process occurring in minutes that has been suggested to be mediated by a cell death-dependent process referred to as NETosis.
What is NET?
NETs are composed of DNA and histones and are decorated by proteins from primary granules and secondary granules
In addition to the nucleus, what can also serve as a source of DNA for NET formation?
Mitochondria
Mast cells, basophils, and eosinophils play roles in what type of immunity?
Innate and adaptive immunity responses
What protects against helminths and reactions that cause allergic diseases?
Mast cells, basophils, and eosinophils
What common feature do Mast cells, basophils and eosinophils share?
Cytoplasmic granules filled with various inflammatory and antimicrobial mediators
What are cytoplasmic granules in mast cells filled with? What are they stained with?
Histamine and other mediators. Stained purple with giemsa
What shows the characteristic blue granules stained with Giemsa?
Blood basophil
What contains basic proteins which are stained red with acidic dye eosin?
Eosinophil granules
What are common sites of mast cells?
Sites that are exposed to the external environment such as the skin
What are mast cells found in close proximity to?
Blood vessels, where they can regulate vascular premeability and effector-cell recruitment
How do mast cells communicate?
Although they do not have direct cell to cell contact with local cell populations, they can modulate the behavior of these and other neighboring effector cells through the release of mediators
What are the two types of mononuclear phagocytes?
Circulating monocytes and resident tissue macrophages
What are many tissues populated with?
Long-lived resident macrophages witch assume specialized phenotypes depending on the organ
What is the lineage of macrophages?
Arise from committed precursor cells in the bone marrow, driven by monocyte/macrophage colony stimulating factor
Mature monocytes enter the blood circulation and then migrate into tissues, where they further mature into macrophages, especially during inflammation
What are the special types of macrophages the differentiate from the fetus and yolk sac?
Microglial cells: brain
Kuppfer cells: liver
Alveolar macrophage: lung
Sinusoidal macrophages: spleen
What process is important for the eradication of microbes that are ingested by the phagocytes but resist killing?
Microphages present Ags to helper T cells at the sites of infection that leads to T cell activation and production of cytokines that further activate the microphages
What do dendritic cells arise from?
A common precursor cell of the myeloid lineage in the bone marrow.
What do dendritic cells further differentiate into?
Subsets, the major ones being classical DCs and plasmacytoid DCs
What do inflammatory DCs arise from?
Monocytes in inflamed tissues
Where are Langerhans cells located and where do they develop from?
In the skin and appears early in life and may develop from embryonic precursors
