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105 Cards in this Set
- Front
- Back
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What is Immunology?
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They study of the immune system.
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Explain Innate Immunitity.
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Also called non-specific. When structural, cellular, and molecular components are present at birth and do not change in response to exposure to antigens.
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Explain Adaptive Immunity.
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Also called acquired or specific. Uses T Cells and B Cells with help from MHC components. Can change upon exposure to antigens.
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The Innate and Adaptive systems interact to provide....
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protection against foreign substances.
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What is Hematopoietic cell?
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It is a cell that contains stem cells and differentiates into two other cells. The myeloid stem cell and the lymphoid stem cell.
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The myeloid stem cell differentiates into what kind of cells? What do those cells become?
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1. Erythroblast (Red Blood cells)
2. Megakaryoblast (megakaryocyte to platelets) 3. Myoblast (neutrophils, basophils, Eosinophils) 4. Monoblast (monocytes to macrophages & dendritic cells) 5. Putative mast cell precursors (Mast cells) |
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The lymphoid stem cell differentiates into what kind of cells? What do those cells become?
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1. Natural Killers
2. Lymphoblasts (Lymphocytes to T cells & B cells) |
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The Skin is what type of immunity? Explain how it works.
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Innate; it is a physical barrier, but it is also salty, dry, acidic and is continously sloughed off.
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The Dermal cells & sweat glands are what type of immunity? Explain how they work.
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Innate; the dermal cells secrete dermicidins (broad spectrum antimicrobial 40 AA peptides) and sweat glands secrete lysozyme.
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The Mucous membrane is what type of immunity? Explain how it works.
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Innate; Cells that line regions of the body directly exposed to environment. They continuously flush microbes through production of mucous and ciliary action. Mucous contains anti-bacterial peptides and lactoperoxidase (-OSCN, hypothiocyanite. A big microbe killer)
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The digestive system is what type of immunity? Explain how it works.
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Innate; it uses saliva that contains lysozymes (breaks the bond between Nag & Nam), stomach acid kills microbes, ___ferrin (like gastroferring) binds iron, bile & pancreatic secretions inhibit growth of most microbes.
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What is a growth limiting factor for microbes?
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iron
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What are some other Innate systems?
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Urine & tears. They mekae lysozymes. Paneth cells of intestines also make lysozymes.
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Most mucosal systems sequester _____.
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iron (like gastroferrin or lactoferrin)
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What are monocytes?
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circulating cells that penetrate into tissues and differentiate into various types kinds of phagocytic cells.
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What does the brain monocytes differentiate into?
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microglial cells
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What does the lung monocytes differentiate into?
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alveolar macrophages
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What does the spleen monocytes differentiate into?
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splenic macrophages
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What does the lymph node monocytes differentiate into?
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resident and recirculating macrophages
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What does the joint monocytes differentiate into?
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synovial A cells
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What does the bone monocytes differentiate into?
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osteoclasts
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What does the kidney monocytes differentiate into?
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mesangial cells
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What does the liver monocytes differentiate into?
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kupffer cells
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What does the tissue monocytes differentiate into?
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macrophages in the skin
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All macrophage like cells contain _____ that recognize ______.
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special receptors (PRRs, pattern-recognition receptors); pathogen-associated molecular patterns (PAMPs)
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Most PRRs are found on ____ as well as _______. Both types of cells are _____.
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neutrophils, macrophage-like cells; phagocytes.
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____, a specific type of PRR recognize specific PAMPs from ___ & ____.
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TLRs, Toll-Like Receptors; Bacterial and Eukaryotic pathogens.
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When the TLRs bind, they trigger....
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the immune system's master gene regulator NFkB
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TLRs can recognize...
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1. bacterial LPS
2. CpG dinucleotide (non-methylated) from lysed cell DNA 3. flagella 4. zymosan & mannans from yeast |
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What are some of the other receptors?
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1. independent LPS receptors (ensure efficient phagocytosis of gram - microbes).
2. lipotechoic acid receptors (ensures efficient phagocytosis of gram + microbes). 3. peptidoglycan receptors (ensures efficient phagocytosis of gram + microbes). |
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All receptors (including TLRs) trigger...
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phagocytosis of a pathogen.
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What are opsonins?
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Fc regions on IgG or IgM antibodies or complement protein C3b.
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Receptors for opsonins are _____ and cause...
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abundant; efficient phagotcytosis of opsonin-covered pathogens.
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Explain how phagocytes kill pathogens.
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1. The bound pathogen is internalized in a phagosome that fuses with lysosomes to create a phagolysosome.
2. The Phagolysosome contain enzymes that form ROIs (Reactive oxygen), RNIs (Reactive nitrogen), and digestive enzymes. 3. Digested debris is released, but only macrophages present antigen. |
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Very high levels of ROIs (Reactive oxygen intermediates) are made within.....
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phagolysosomes that then kill microbes that are ingested.
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NO synthase makes ____ from ___.
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NO (Nitric Oxide) from Arg
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NADPH oxidase forms _____ from _____.
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super oxide anions (2O2-) + H+ NADP+; NADPH + 2O2
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Super oxide dismutase makes ____ from _____.
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hydrogen peroxide (H2O2) +O2; 2O2- + 2H+
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Myeloperoxidase makes _____ from _____.
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Hypochlorous acid (HOCl) + OH+; Hydrogen peroxide (H2O2) + Cl-
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Peroxidase makes ____ from ______.
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1. Singlet Oxygen (1O2) + Cl- + H2O; ClO- + Hydrogen peroxide (H2O2).
2. Hydroxyl radical (2OH-) + O2; O2- + H2O2 |
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Neutrophils (PMNs) are very short lived because...
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they make so many enzymes and RNIs that there is collateral damage. They end up self-destructing. They are very abundant, but have to be continuously made.
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Are macrophages short-lived or survive a long time?
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They survive to activate rest immune system.
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Antimicrobial cationic peptides are made by ______ and work by ______.
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a variety of host cells; binding to and damaging bacterial cytoplasmic membranes or other cell structures.
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What are the three classifications of antimicrobial cationic peptides?
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1. cathelicidin (do not contain cysteine)
2. Defensins (contain large amounts of ARG + CYS) 3. Histatin (contains lost of HIS) |
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Bacteriocins (example _______) are made by _______. They are made to _____.
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colicins; resident microbes; kill other species of microbes.
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What is complement?
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a multi-component system (> 30 serum proteins) of proteins that circulate in dormant states until activated. (made by the liver & other places)
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What are the three pathways leading to the C3 convertase
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1. Classical pathway - Antigen:antibody complexes
2. MB-Lectin Pathway - Mannose-Binding lectin binds mannose on pathogen surfaces. 3. Alternative Pathway - Pathogen surfaces. |
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After getting to C3 convertase, what are the three possibilites?
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1. Inflammatory mediators (C3a, C5a, a's)
2. Opsinins (C3b) 3. Formation of membrane attack complexes (MACs, madse from C3bs) |
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Explain the Classical Pathway
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Gets activated after you get an antibody response. Takes a week to get a good antibody response. You have to have antibodies bound to the surface of the pathogen. It will then bind to C1 and cleave to other Cs (C1q, C1r, C1s) then to C4 and C2.
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How do you make C3 convertase when an antibody is sitting on the surface of the microbila cell?
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Classical Pathway
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Explain the MB-lectin Pathway
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Binds to mannose residues on the pathogen's surface. It binds to MASP-1, MASP-2 (MBL associated). End up with C4 or C2. SP stands for serine proteases.
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Explain the alternate pathway?
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It's called alternate because a different C3 convertase is made. Things like LPS are on the pathogen surface can bind to C3 components. C3 by itself can cleave to C3a & C3b. So in the presence of Factor B & D, C3b can be made into C3 convertase.
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When C3a and C5a are made from C3 convertase, what is it used for?
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It goes away and circulates. These are potent pro-inflammatorys, chemotaxins. Neutrophils will follow a concentration of C5a to the source of the infection.
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When C3b is made from C3 convertase, whatis it used for?
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When a lot of C3b is made it helps the immune system because there are lots of C3b receptors on the neutrophils and macrophages. This makes lots of opsinins.
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When C5b is made from C3 convertase, whatis it used for?
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When it is made on the surface, it recruits 6,7,8 & 9 to make a membrane attack complex. It is used for lysing. It is used for immediate killing/lysing the Gram negative cells.
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All complement pathways lead to the formation of.....
What is the composition of them? |
Membrane attack complexes (MACs). C5b, C6, C7, C8, & lots of C9s.
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What happens during the formation of MAC?
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holes form in the bacterial membranes, which leads to the lysing of Gram negative cells. It is not effective at lysing Gram positive pathogens. In both Gram positive and negative, it leads to production of C3b (opsinin) being made on the surface of the microbes.
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What is opsinization?
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When C3b and Fc receptors on phagocytes help ingestion of pathogens covered with IgG, IgM, or C3b
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IgG, IgM, and C3b are called ____.
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opsinins
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A phagocytic cell that has _____ is more effective with ingesting pathogens.
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receptors for both C3b and Fc
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When are opsinins effective?
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when they are bound to either bacteria (Gram negative or positive) or eukaryotic microbes.
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What is the order of effectiveness for opsinins?
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Antibody receptors < Fc receptors < Antibody + Fc receptors (100x more effective).
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Components of the adaptive immunity.
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1. B Cells - Antibodies.
2. T Cells - T Cell receptors 3. MHC (Major histocompatibility complex) 4. Macrophage-like cells |
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The adaptive immune system is comprised mostly of _____.
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lymphocytes.
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Explain the production of B Cells.
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B Cells are produced in the bone marrow from Lymphocyte stem cells. It then produces a plasma cell or memory B cell.
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Explain the production of T Cells.
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T Cells are produced in the Thymus from Lymphocyte stem cells. It then produces the T helper cell, cytotoxic T lymphocyte, & memory T cell.
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What is the function of B cells?
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To produce antibodies (immunoglobulins) to mark foreign antigens for destruction by phagotcytic cells or neutralize antigen (or toxin).
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Regions of the antigen that make contact with the Imunoglobulin are called....
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antigenic determinants or epitopes
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If the antigen is a protein, how big is it?
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10-15 AA
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What happens when antibodies bind to antigens?
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the antibody undergoes an confromational changes that activate effector functions (like binding to the macrophages, etc.)
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Explain the parts of an antibody.
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2 identical heavy chains, 2 identical light chains. Both chains contain variable and constant regions (variable being at the end). The variable regions from one heavy and one light chaincombine to form the antigen binding site.
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Fc regions are responsible for .....
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special effector functions (like complement fixation, & opsonization); these are activated after the antigen is bound.
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Explain how a light chain is formed.
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There are 2 light chain loci (kappan and lambda). They contain genes that rearrange to bring a single variable region next to one of several J regions.
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In the light chain there are __ segments that recombine; ____ VL genes and ____ JL genes. Which means you can get a total of ______ combinations.
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2;
400; >6 2400 |
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In the heavy chains __ segments recomine; ___ VH, __ DH, and __ JH. Total combinations of ___.
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4;
200, >20, 6; 24,000 |
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What is the first Ig heavy chain rearrangement and how does it occur?
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IgM; It uses Cµ constant gene and it is initally a membrane protein.
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In the formation of heavy chain, later other constant regions are used by.....
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further rearrangements to replace Cµ with other C genes.
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___ total possible heavy + light chain antibodies. ___ of these circulate.
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10^13; 10^8.
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Each T Cell receptor is composed of ____. Each chain has....
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2 chains; alpha & beta.
constant and variable regions made by recombinations analogous to Ig genes. |
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Variable regions of the alpha & beta chains.....
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combine to form antigen binding pockets.
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T Cells with functional TCRs mature in the thymus into several types:
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TH0 - Helper cells comprised of CD4+
CTLs - Cytotoxic T lymphocytes comprised of CD8+; These then circulate through the body. |
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Any cell with a TCR that binds to a self-antigen is _____.
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eliminated
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What are MHC cells and what do they do?
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these molecules are found on all cells and they help the immune system to focus on foreign invaders (viruses, microbes, cancer, etc.)
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MCH cells bind to _____ and present them ____.
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peptides located within the cell; on the surface.
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What are Class I MCH?
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single peptide with three domains; peptides come from the ER, and are only antigenic in virally infected/cancerous cells; they are found on all nucelated cells; they are responsible for graft rejection.
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What are Class II MCH?
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loaded with peptides from the phagolysosome (usually antigenic); MCH Class II proteins are found only on antigen-presenting cells of immune system (macrophage-like cells, B-cells).
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MCH molecules are ____ and each co-expresses....
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polymorphic; 6 different molecules/pairs (in Class I), 3 from each parent.
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What are the steps in antibody response (APC to TH0 steps)?
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1. Phagocytosis by macrophage-like cells
2. Antigen presentation on Class II MHC molecules and debris expelled. 3. TH0 cells bind via interactions of T-cell and APC: TC receptor binds to antigen, CD4 binds to MHC II, & CD28 binds to B7. 4. TH0 cells are then activated to proliferate and differentiate into TH1, TH2 and other types, all with the same TC receptor as the original TH0. (memory cells are produced too). |
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What are the steps in antibody response (TH2 & B Cell steps)?
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1. B-Cell phagosomes are formed after surface IgM (from B Cells) bind to extracellular debris from macrophage-like cells, and is internalized.
2. B Cells are APCs that load antigens from phagolysosomes. 3. TH2 cells interact with B cells; TC receptor binds with antigen, MCH II binds to CD4. This activates B Cell proliferation and differentiation. 4. IL factors 4,5,10,13 are produced. |
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What does APC stand for?
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Antigen-presenting cells.
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Interactions of macrophages, B & T Cells all occur ....
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in the lymphnodes
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What happens after B Cell activation?
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They secrete IgM and divide.
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What is a class switch?
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When some B Cell progeny further rearrange genes to make new classes of Heavy chains.
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What are memory B Cells?
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long lived; have surface Immunoglobulin and will immediately secrete antibody after future encounters with the antigen.
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IgGs and IgMs _____ and bind to ____.
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fix complement; Fc receptors on phagocytic cells
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IgAs are found where? how are they used?
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in secretions; when they bind to the foreign invader, they cover up the ability for the foreign invaders to bind to the cell
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What do IgEs do?
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they mediate allergic responses.
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All classes of Igs...
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deactivate toxins and inhibit pathogen binding.
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How does the activation of CTLs occur?
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1. 2 encounters with the antigen mus occur: a) TH0 cell interacts with APC, making TH1. b) TH1 interacts with APC to produce cytokines that pre-activate CTLs.
2. CTLs then circulate to find host cells with cognate antigen. They then kill the infected cell. |
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Binding of an activated CTL requires...
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CD8-MHC I binding and TC receptor-antigen binding.
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What are the three ways that CTLs can kill transformed or infected cells?
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1. Secreting perforins - perforins lyse the cell directly.
2. Secreting granzymes - this triggers apoptosis oh host cells. 3. Secreting - CD95L-CD95 - CD95/FAS is a common cell surface molecule; CD95/FASL in microvesicles trigger apoptosis. |
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What is the fast way to activate CTLs?
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Dendritic cells. They are able to directly activate CTLs via antigen-presenting on MHC class I molecules (no TH1 involved).
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What are dendritic cells?
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super antigen presenting cells that are derived from 2 seperate lineages (myeloid and lymphoid).
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What are ctyokines?
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soluble proteins made and released by one cellthat act as signaling molecules.
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Four types of cytokines and what they act as.
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1. Chemokines - act as chemotaxins
2. Hematopoeitins - growth factors 3. Interlukins - act as growth factors, differentiation factors. Lots of them. Made by monocytes & lymphocytes. 4. Tumor Necrosis Factor - promote inflammation, fever & shock. |
