Immunology Flashcards
Hemopoietic Cell Origins
Stem Cells: All blood cells arise in the bone marrow from stem cells - undifferentiated bone marrow cells that self-renew
Hemopoietic Cell Origins
At division two daughter cells are produced; one daughter cell matures into the various blood cells after passing through a series of steps; the second daughter cell become the new stem cell
Types of blood cells:
Leukocytes (white blood cells)
Erythrocytes (red blood cells)
Thrombocytes or platelets (which are fragments of a precursor cell - the megakaryocyte)
Myeloid progenitors
Develop into cells of the Innate Immune system. Monocytes/Macrophages; Neutrophils; Eosinophils; Basophils/Mast cells. Leukemia involving these cell lines are known as acute/chronic myelocytic leukemia
Lymphoid progenitors
Develop into lymphocytes, member of the adaptive immune system. Leukemia involving these cells lines are referred to as acute/chronic lymphocytic leukemia
“Blast”
A very immature blood cells –when observed in a peripheral blood smear, or increased numbers in a bone marrow aspirate - reflects a leukemic state
Immune cells are sometime classified by the presences or absences of large granules in their cytoplasm
Granulocytes: Neutrophils, eosinophils, basophils/mast cells
Agranulocytes: Lymphocytes and Monocytes
Cytokines
Diverse and potent chemical messengers produced primarily by the cells of the immune system. Cytokines function as hormone like signals between cells of the immune system. They are the chief communication signals of the T cell. Cytokine binding to specific receptors on target cells results in recruitment of other cells to the battle field, promotion cell activation, encouragement of cell growth, and direction of cellular traffic. There are a great number of known (and likely a greater number of undiscovered) cytokines.
Commonly known cytokines:
The Interferon family
The Interleukin family
Tissue necrosis factor (TNF)
Growth factors
- Granulocyte Colony Stimulating Factor (GCSF)
- Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)
Lymphokines
Are cytokines secreted by T and B cells (lymphocytes)
Monokines
Are cytokines secreted by Monocytes and macrophages
Interleukins
Messenger between leukocytes (WBC’s)
Chemokines
Cytokines that attract specific cells to an area. They are release at the site of infection/injury and call other cells to the area
Although we emphasize the cytokine role in immune system communication, it is important to keep in mind their roles in influencing local area dynamics (increased capillary permeability, vaso dilatation etc.) and systemic influences, (fever, influencing prostaglandins, etc.)
Although we emphasize the cytokine role in immune system communication, it is important to keep in mind their roles in influencing local area dynamics (increased capillary permeability, vaso dilatation etc.) and systemic influences, (fever, influencing prostaglandins, etc.)
Physical Barriers
The first line of defense
o Skin covers about 2 square meter
o Mucous membranes covers about 400 square meters
o The structure of skin and mucous membrane are physical impediments to invasion. Additionally these structures secrete substances producing an inhospitable environment for microbes. (ex. low pH, mucous, fatty acids, etc.)
Innate Immune System
The second line of defense; Nonspecific in focus and “Always on” - ready to protect us from invasion. Generally composed of: o Macrophages o Neutrophils o Natural Killer Cells o Eosinophils o Basophils o Mast Cells o The Complement System
The Adaptive Immune System
The third level of defense
o Defends against specific invaders – Edward Jenner and his work with the small pox vaccine in 1790 is a classic example of an adaptive immune response
o Composed of Lymphocytes
T Cells
(Thymus derived lymphocytes) subdivided into:
- T helper cells (aka. Th, CD4 cells)
- Cytotoxic Lymphocytes or Killer T cells (CD8 cells)
- Regulatory T cells
B Cells
(aka. Bursa or Bone marrow derived lymphocytes)
- When a B cell is activated and producing antibodies it is often referred to as a Plasma cell.
Macrophages
Long lived cells which are very active phagocytes ingesting microorganism and cellular debris.
Macrophages
First exiting the bone marrow and circulating in the blood are called Monocytes. They slip between the endothelial lining of capillaries into tissues where they mature into macrophages.
Dendritic cells
Is the general name of tissue macrophages. Tissue macrophages often have particular names associated with particular tissues: lung -alveolar macrophages; liver - Kupffer cells; central nervous system – microglia; Macrophages are abundant in the lining of lymph nodes and spleen, epidermis and mucous membranes –esp. anal, vaginal, and oral areas. Some are fixed to the tissues, other are “wandering macrophages”
Macrophages
o Actively seek invaders and scavenges for “garbage”
o Sequence: Phagocytosis – “to eat”
Bacterium outside macrophage, Macrophage engulfs bacterium in a phagosome, Phagosome taken inside the macrophage, Phagosome fuses with a lysosomes, Enzymes in lysosomes digest bacterium
Macrophages
Once the macrophage phagocytizes a cell, it transports some of the invader’s proteins to its surface to show and stimulate other immune cell. Macrophages are important Antigen Presenting Cells (APC)
Macrophages
After battling with bacteria, macrophages give off cytokines that are important mediators of the inflammatory response
Neutrophils
An aggressive phagocyte
Neutrophils
Aka. Polymorphonuclearcytes (“polys”); polymorphonuclear neutrophils (PMN); segmented neutrophils (mature neutrophils); “bands” (neutrophils without segmentation, a reflection that they are very recently produced).
Neutrophils
o Short lived (3-5 days). Depends on glycogen stores for energy
o Very active phagocytes
o Comprise 70% of WBC in blood – we normally see 70% polys on a peripheral smear blood count with 1-2% bands forms
o The presences of an increased percentage of “bands” in a blood smear indicates a ramping up of the immune response to bacterial infection and is referred to as a “Shift to the left”
o PMN’s are attracted to cytokines such as TNF, interleukin 1 produced by macrophages and others
o They do not function as antigen presenting cells
Natural Killer Cells
o Difficult to study ( they are lymphocyte like and difficult to differentiate from B and T cell to study )
o Once NK cells exit the vessels and are in tissue, they are very versatile -they can kill tumor cells, virus-infected cells, bacteria, virus, fungi, and parasites; they kill infected cells by instructing them to commit suicide. (apoptosis)
o Given NK cell’s power /versatility a two signal system is needed for control – a balance between “kill’ and “don’t kill” signals determines whether a NK cell will destroy a target cell
o NK cells recognize and attack cells lacking “self” markers. (If the cell does not have normal “this is me” antigens, NKC will kill the cell without prompting from other immune sources. (This is a different from cytotoxic lymphocytes who have similar functions, but require prompting from other immune system cells)
o Some NK cells function as cytokines factories
Eosinophils
o Granule containing cells which circulate in low levels in the blood stream. Important in allergic phenomena and particularly important in combating parasites
Basophils and their cousin, the Mast cells
o Stationed primarily in the tissues. Contain granules loaded with histamine, leukotrienes and other allergy related chemicals. Very important in allergic phenomena.
o If a parasite invades tissue, mast cell attempt to neutralize the invader by dumping their contents onto them
Pattern-Recognition Receptors
Cells of the innate immune system are able to bind to antigens using inherited pattern-recognition receptors. These receptors are encoded in the germ line of each person and are passed from generation to generation. As our species evolved, receptors for pathogen associated molecular patterns developed via natural selection to be specific to certain characteristics of broad classes of infectious organisms. Receptors to bacterial cell wall lipopolysaccharides and peptidoglycans, bacterial DNA, dsRNA and many other substances are present on our immune cells
The Complement System
o Composed of approximately twenty different proteins that work together to destroy invaders and signal other immune system components that an attack is on. These are proteins produced primarily by the liver and present in high concentrations in blood and tissues. C3 is the most abundant compliment protein.
o A spontaneous and very fast system
Activation of complement (the functioning of compliment) may result in:
o Opsonization of the invader
o Chemo-attraction of other killing cells
o Lyses of the cell /virus: Activation of the complement cascade result in the production of a “membrane attack complex” which opens up a hole in the surface of the bacterium/virus killing it.
Compliment activation may occur by several pathways:
o “Classic” pathway – depends on the presences of antibody-antigen complexes for activation of compliment
o Alternative pathway – C3 will attach to any “unprotected” cells, resulting in a cascade of compliment activation (destroying any unprotected surface). Stated a second way, any cell surface that is not “protected” will be attacked by compliment. Protected cells have certain proteins on their surfaces (ex. DAF –decay acceleration factor; CD59-protectin) that control compliment activation. Human cells are covered with protective substances which keep the positive feedback loop of complement activation from gaining a foothold and taking off.
o Lectin Activation Pathway –Patterns of carbohydrates and fats on the surface of common pathogens (bacteria, fungi) activate mannose binding lectin (MBL -produced in the liver) which in turn actives the complement cascade.
