Intro to Immunity Flashcards
Antigens
biochemical components (proteins, carbohydrates, lipids, and nucleic acids) that alert leukocytes to their presence within the body. Leukocytes recognize antigens via antigen receptors displayed on the leukocyte surface
When a leukocyte binds to an antigen via its antigen receptor, the interaction induces the leukocyte to eliminatevantigen by one or more mechanisms:
phagocytosis, cytotoxicity, synthesis of soluble factors
Phagocytosis
ingestion and enzymatic digestion of particulate antigens, e.g.,microbes, allergens, damaged host cells, etc.
Cytotoxicity
induction of lysis and/or apoptosis of microbe-infected host cells, tumor cells, or mismatched tissue grafts
Synthesis of soluble factors
production of antibodies, complement components, defensins, cytokines, and other substances that help eliminate the foreign antigen
How do immunologists separate the immune system?
Innate versus adaptive immunity
Humoral versus cell-mediated immunity
Innate immunity
includes all host defenses that are present and functional at birth, including natural barriers like skin, and leukocytes whose antigen receptors have broad specificity, e.g., phagocytes, granulocytes, NK cells. Complement/CRP/defensins/cytokines, pattern rec receptors, normal flora
broadly identifies groups of antigens, rapid response, no memory, unaffected by vaccination
Adaptive immunity
develops slowly in response to host contact with a specific antigen and includes just four major components: antibodies, B lymphocytes, plasma cells, and T lymphocytes.
very specific, slow response, memory, improved by vaccination
Immunological memory/Clonal Selection Theory
the increase in speed and strength with which B and T lymphocytes respond to an antigen upon re-exposure to that same antigen. Immunological memory can be explained by the Clonal Selection Theory, which states that a given antigen will induce proliferation and differentiation only of those B and T lymphocytes that have receptors specific for that antigen. Some of the responding B and T lymphocytes will develop into memory cellsthat can survive for years within the lymph nodes. Memory cells undergo rapid activation and expansion when they encounter the same antigen againat a later time, resulting in greater numbers of antigen-specific lymphocytes with higher affinity antigen receptors than in previous encounters.
Humoral immunity
mediated by soluble proteins and glycoproteins present in serum and the extracellular tissue fluids. It is most effective against extracellular pathogens rather than pathogens that live inside host cells
Cell-mediated immunity(CMI)
is mediated by “effector cells” that directly kill intracellular and extracellular pathogens, tumors, and damaged host cells by phagocytosis or cytotoxicity.
The most important humoral immune factors are:
Antibodies (immunoglobulins)***–highly antigen-specific glycoproteins produced by B cells and plasma cells
Complement –a series of serum proteins that work together to lyse bacteria and other pathogens
C-reactive protein (CRP) –a general marker for inflammation or infection
Cytokines –soluble proteins that are used for communication between leukocytes
The most important effector cells in CMI are:
Phagocytes that engulf and kill extracellular pathogens using enzymes and reactive oxygen species generated within the phagolysosome. The most efficient phagocytes are neutrophils and monocytes/macrophages.
Granulocytes that release enzymes and reactive oxygen species from granules to kill extracellular pathogens. The most efficient granulocytes are neutrophils, eosinophils, and basophils.
Cytotoxic cells that release enzymes and use receptors on their surfaces to induce apoptosis in infected host cells or tumors. The most important cytotoxic cells are natural killer cells (NK cells) and cytotoxic/cytolytic T cells (Tc cells).
Antibody, complement component C3b, and CRP are opsonins. Opsonins are….
substances that coat bacteria and other particulate antigens to aid their recognition and ingestion by phagocytes. Many bacteria have capsules that protect them from phagocytosis. However, when the capsules become coated by opsonins, the capsules no longer provide protection against phagocytosis.
Leukocytes
White blood cells that carry out the functions of the immune system. They develop by the process of hematopoiesis from self-renewing hematopoietic stem cells in the bone marrow.
CD34 and Stem cell antigen-1 (SCA-1)
these markers are used clinically to enrich stem cells for transplantation and immune reconstitution
The two major lineages of leukocytes arising from hematopoietic stem cells are
myeloid and lymphoid
Lymphoid Cells
B lymphocytes
T lymphocytes
Natural killer (NK) cells
Myeloid Cells
Erythrocytes –oxygen transport to tissues
Platelets (from megakaryocytes) –blood clotting and inflammation
Granulocytes (neutrophils, basophils, eosinophils)
Phagocytes (neutrophils, monocytes/macrophages)
Antigen-presenting cells (dendritic cells, monocyte lineage)
Erythropoietin (EPO)
Reverse anemia (especially in renal failure) by restoring erythrocytes/RBCs
Granulocyte colony-stimulating factor (G-CSF)
Filgrastim
Recovery of bone marrow (PMNs)
Granulocyte-monocyte colony-stimulating factor (GM-CSF)
Sargomastim
Recovery of bone marrow (PMNs, monocytes, macrophages)
IL-11
Oprelvekin
Reverse thrombocytopenia (platelets)
Thrombopoietin
TPO
Reverse thrombocytopenia (platelets)
Mucosa-associated lymphoid tissue (MALT; secondary lymphoid tissue)
The MALT responds primarily to antigens that enter the body through mucosal surfaces. B lymphocytes in the MALT produce mainly secretory IgA, an antibody class that resists digestive enzymes found in the gut and other mucosal tissues.
Examples of MALT
- Gut-associated lymphoid tissues (GALT): lines intestinal tract
- Bronchus-associated lymphoid tissue (BALT): lines respiratory tract
- Genito-urinary tract-associated lymphoid tissue (GU-ALT)
- Specific tissues include the lamina propria, tonsils, adenoids, appendix, and Peyer’s patches. Peyer’s patches are loose clusters of lymphoid tissue in the small intestine. M cellsare epithelial cells overlying Peyer’s patches specialized for transcytosis of antigens from the lumen to subepithelial T cells.
White Pulp of spleen
comprises the lymphocyte-rich regions of the spleen. It contains:
T cells arranged in a periarteriolar lymphoid sheath (PALS)around a central arteriole
B cell-rich follicles(some containing germinal centers) occupying the space between the PALS and the marginal sinus
A marginal zone at the outer boundary of the white pulp. The marginal zone contains specialized macrophages and additional B cells
Red Pulp of Spleen
contains plasma cells, resident macrophages, erythrocytes, platelets, granulocytes and lymphocytes. Its main function is hemocatheresis, the destruction of aged platelets and erythrocytes. Iron recycled from erythrocytes is stored here.
Spleen
responds primarily to blood-borne antigens. It is the major organ where antibodies are synthesized and released into circulation. Asplenic persons are highly susceptible to infection by encapsulated bacteria, e.g. Streptococcus pneumoniae, Haemophilus influenzae, Neisseria and Salmonella spp. This is because antibodies are needed as opsonins to neutralize the anti-phagocytic property of bacterial capsules. The spleen is located in the upper left quadrant of the abdomen.
Medulla (of the lymph node)
Medullary cords contain closely packed lymphocytes and plasma cells
Medullary sinuses contain macrophages
Medullary sinuses communicate with the efferent lymphatics
Paracortex of Lymph node (T cell area)
Lymphocytes in the blood enter the paracortex region of the lymph node through specialized post-capillary venules called high endothelial venules (HEVs)
HEVs contain specialized cuboidal cells that express adhesion molecules in high density
These adhesion molecules allow lymphocytes to bind tightly to the venule wall, and then extravasate from the venule to enter the node
The paracortex becomes greatly enlarged during extreme cellular immune responses. The paracortex is poorly developed in DiGeorge syndrome because affected individuals produce no/few T cells
Cortex of Lymph Node (B cell area)
Primary folliclesin the cortex contain naïve B cells that have never contacted antigen
Secondary folliclesin the cortex contain germinal centerscomposed of B cells undergoing mitosis in response to antigen stimulation
Lymph nodes (secondary lymphoid organs)
respond primarily to antigens entering through the skin and subcutaneous tissues. The functions of lymph nodes and the lymphatic system include:
- Isolation of infectious agents and cellular debris from the body
- Surveillance and filtration of the lymph by macrophages
- Storage and activation of B and T cells
- Antibody production by B cells
- Maintenance of interstitial fluid pressure and volume by returning excess water and dissolved substances from the interstitial fluid to the circulation
- many afferent vessels but only 1 efferent
T cell education is the process by which
self-reactive T cells are eliminated and is essential for avoiding autoimmune diseases. T cell education takes place in the cortex and medulla of the thymus.
Thymus (a primary lymphoid organ)
encapsulated organ that develops from the epithelium of the third and fourth pharyngeal (branchial) pouches. It is a bilobed structure that reaches its maximum size at puberty and then atrophies with age. THIS IS WHERE T CELL EDUCATION AKA REGULATION OCCURS
DiGeorge Syndrome
Persons with a chromosome 22 deletion(22q11.2) are born with little or no thymus. These patients are highly susceptible to viral infections and cancer because they have few or no functional T cells.
Process of T cell development
- cell produced in bone marrow
- cell travels to thymus: called double-negative thymocytes (have no CD molecules)
- cell in cortex develops both CD4 and CD8 becoming a double-positive thymocyte
- cell in medulla loses expression of one CD and becomes single positive cell
Primary Lymphoid Organs
bone marrow
thymus
Secondary Lymphoid Organs
spleen, lymph nodes, MALT
Bone Marrow
where B cells begin expression of surface immunoglobulin molecules
Megakaryocyte
large cell with a lobulated nucleus found in the bone marrow that gives rise to platelets (thrombocytes)
Platelets/thrombocytes
are anucleate cells that promote blood clotting and inflammation. They bind to collagen exposed on damaged endothelial cells, forming microthrombi.
complete blood count (CBC)
reveal whether a patient has a normal absolute number of circulating white blood cells (WBC). The typical range in adults is 4500-10,800 WBCs/mcL
Leukocytosis
higher than normal WBC count
indicates infection, inflammation, leukemia, or trauma
Neutrophil
purple
EC bacteria
live 2-3 days in circulation die in tissues
IgG receptors
Eosinophil
red
worms
hypersensitivity, IgE
Basophil
purple-black
worms
hypersensitivity, histamine, IgE
Mast Cell
purple
worms
hypersensitivity, histamine, IgE
List the polymorphonuclear Granulocytes
Neutrophil, Eosinophil, Basophil, Mast Cell
Polymorphonuclear (PMN) granulocytes
short-lived cells that contain a multi-lobed nucleus and granules rich in enzymes (e.g.,lysozyme) and other substances (e.g.,lactoferrin) that are harmful to microorganisms. Granulocytes also produce reactive oxygen species.
Dendritic cells
related to macrophages and are found under the epithelia and in most organs. In the skin, they are called Langerhans cells. Dendritic cells are the most efficient antigen-presenting cells (APCs). They are necessary for activating naïve T cells (T cells that have never before encountered antigen).
Monocytes and macrophages (mononuclear phagocytes)
- Circulating monocytes develop into tissue-fixed macrophages
- The reticuloendothelial system (RES) is a network of tissue-fixed macrophages that remove foreign substances from the bloodstream and lymph
- 10-18 μm diameter, horseshoe-shaped nucleus, long-lived
- Functions are phagocytosis, antigen processing, andantigen presentation
Example of Monocytes/macrophages of the mononuclear lineage: Kuppfer Alveolar macros/dust cells Splenic macros Peritoneal Macros Microglial cells Osteoclasts Mesangial cells Synovial A cells
liver lung spleen peritoneal brain bones kidneys joints
Phagocytosis
recptor ligand interaction initiated
macro pseudopods engulf bacterium/form phagosome
phagosome fuses with lysosome=phagolysosome
lysozymes destroy PDG of bacterial cell wall and ROS damage pt and DNA
end of bacteria
Antigen processing
destruction of bacteria within a phagolysosome
Peptides specific to the destroyed bacteria are paired up with MHC, transported to cell surface, and used for T cell (antigen) presentation. Now cell is called APC
Natural killer (NK) cells
part of the innate immune system.
eliminate infected host cells (especially virus-infected cells) and tumor cells, so they are very similar to Tc cells in this regard.
NK cells work most efficiently when the CD16 molecules on the NK cell surface bind to IgG-coated target cells. This collaboration between NK cells and IgG is called antibody-dependent cell-mediated cytotoxicity (ADCC). (Also CD56)
B lymphocytes
develop in the bone marrow of humans and the Bursa of Fabricius of birds. They can differentiate into short-lived plasma cells that secrete high quantities of antibodies (immunoglobulins) or into long-lived memory cells that express surface immunoglobulin (sIg). The main function of B cells is to mediate humoral immunity.
The antibodies they produce can:
Neutralize toxins and microorganisms
Opsonize microbes for phagocytosis
Activate complement, leading to microbe lysis
T lymphocytes
mature in the thymus. The T cell receptor (TCR) for antigen binds mainly to protein antigens. A TCR-associated accessory molecule, CD3, mediates signal tranduction to the T cell nucleus, thus activating the cell after antigen engagement. Activated T cells secrete cytokines or become highly cytotoxic toward infected host cells or cancer cells.
Helper T, Regulatory T, Cytotoxic T
Helper T cell (TH)
all are CD4+ (also CD3)
immunity by cytokine secretion
TH1:works with macrophages, NK cells and Tc cells to promote cell-mediated immunity
TH2:stimulates antibody production by B cells to promote immunity against worms and allergens
TH17:aidsclearance of extracellular bacteria and fungi
Regulatory T Cells (Treg)
all are CD4+, CD25+ (CD3)
Regulates the functions of macrophages, NK cells, and other T cell subsets
Helps prevent autoimmunity via cytokine secretion
Cytotoxic T (Tc) cell
all are CD8+ (CD3)
Kills infected (especially virus-infected) and neoplastic host cells (tumors)
Involved in rejection of mis-matched tissue grafts
B Lymphocyte (markers and function)
CD19, CD20, CD21(and surface immunoglobulin, sIg)
antibody secretion - humoral immunity
All T lymphocytes have what markers
CD3 and TCR
