Term
|
Definition
-congenital failure of thymus to develop
-absence of circulating T-cells and increased number of infections |
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Term
|
Definition
-normally occurs with age-
-thymus is largest at puberty |
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Term
|
Definition
-connective tissue cells of an organ, like bone marrow, that have a support role
-B-cell require cytokines secreted by stromal cells |
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Term
|
Definition
Mucosal Assoicated Lymphoid Tissue:
-appendix, Peyer's patcehs, tonsils
-T and B-cells, plasma cells, and macrophages
-poised to encounter antigens crossing mucosa |
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Term
|
Definition
-Yolk Sac to Liver to Spleen to Bone Marrow
-initiates from Pluripotent Hematopoietic Stem Cells (PHSC) whcih represent only 1-2% of bone marrow |
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Term
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Definition
| -when the bone marrow is replaced by collagenous connective tissue (scar tissue) |
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Term
| Derivatives of Common Lymphoid Progenitors |
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Definition
| B, T, Plasma, Effector T, NK Cells |
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Term
| Derivatives of Myeloid Progenitor Cells |
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Definition
| Neutrophils, Eosinophils, Basophils, Monocytes, Dendritic Cells, Mast Cells, Marcrophages |
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Term
| Derivatives of Erythroid Progenitors |
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Definition
-Megakaryocytes- give rise to platelets and Erythroblasts
-Erythroblasts give rise to RBC's |
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Term
| Clinical Relevance of Stem Cells |
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Definition
-for bone marrow transplant, MHC must be carefully matched to avoid Graft vs. Host Disease- GVHD (rejection)
-used in gene therapy for SCID (Severe Combined Immunodeficiency) and ADA Deficiency (Adenosine Deaminase Deficiency) |
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Term
| What can be used to recognize CD markers? |
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Definition
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Term
| What CD marker is found on all T-cells? |
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Definition
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Term
| What CD marker is found on Macrophages? |
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Definition
|
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Term
| What CD markers are found on NK cells? |
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Definition
|
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Term
| What CD markers are found on B-cells? |
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Definition
|
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Term
| What CD markers are found on Stem Cells? |
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Definition
|
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Term
| What percentage of blood composition is composed of Neutrophils? |
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Definition
|
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Term
| What percentage of blood composition is composed of Lymphocytes? |
|
Definition
|
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Term
| What percentage of blood composition is composed of Monocytes? |
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Definition
|
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Term
| What percentage of blood composition is composed of Eosinophils? |
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Definition
|
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Term
| What percentage of blood composition is composed of Basophils? |
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Definition
|
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Term
| Name 3 types of Mononuclear Cells : |
|
Definition
-Macrophages
-Granulocytes
-Dendritic Cells |
|
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Term
| Name 4 types of Granulocytes: |
|
Definition
| Neutrophils, Eosinophils, Basophils, Mast Cells |
|
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Term
| What co-factor is required for the T-cell receptor to recognize antigen? |
|
Definition
| T-Cells only recognize antigen in association with MHC (HLA) |
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Term
| What type of antigen do CD4+ cells recognize, and in conjunction with what class of MHC? |
|
Definition
| CD4+ recognize EXOGENOUS antigen in conjunction with Class II MHC |
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Term
| What type of antigen do CD8+ cells recognize, and in conjunction with what class of MHC? |
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Definition
| CD8+ cells recognize ENDOGENOUS antigen in conjunction with Class I MHC |
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Term
| Which type of T-cells directly recognize and kill target cells? |
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Definition
|
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Term
|
Definition
-Autosomal Recessive absence of NK cells
-increased incidence of lymphomas because NK cells typically act as cytotoxins against a wide array of tumors |
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Term
|
Definition
-They develop in the bone marrow, enter the blood to mature, circulate for about 8 hours and then migrate to tissue and differentiate
-MACROPHAGES TAKE UP ANTIGEN AND KILL IT |
|
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Term
| Name 3 important qualities of ACTIVATED macrophages: |
|
Definition
-increased phagocytotic activity
-increased ability to activate TH cells
-express higher level of Class II MHC on the cell surface |
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Term
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Definition
| In response to infection, the bone marrow releases a bunch of neutrophils- leukocytosis is synonymous with a RAISED WBC COUNT |
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Term
| What cells are the first at the site of inflammation? |
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Definition
| NEUTROPHILS ARE ALWAYS FIRST TO ARRIVE |
|
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Term
| What is the major role of eosinophils? |
|
Definition
| Kill Parasites- secretion of eosinophilic granules results in damage to the parasite membrane |
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Term
| What activates basophils and what do they release? |
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Definition
| Basophils are activated by IgE and release pharmacologically active substances within their granules |
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Term
| What are the two most important proteins that dendritic cells express? |
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Definition
| High levels of Class II MHC and B7 |
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Term
| What is the major role of dendritic cells? |
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Definition
| These are the BEST antigen presenting cells- they present antigen to T-cells in lymphoid tissue |
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Term
| Where will you find Interdigitating Dendritic Cells? |
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Definition
| T-cell zones of secondary lymph tissue; thymic medulla |
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Term
| Where will you find Follicular Dendritic Cells, and what do they do? |
|
Definition
-Follicles of lymph nodes
-these are not antigen presenting cells; rather they function in the formation of memory B-cells by binding to circulating antibody-antigen complexes-
-THESE ARE RETAINED FOR A LONG TIME (Weeks-years) |
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Term
| Name 3 epithelial barriers to infection that are part of the Innate Immunity: |
|
Definition
-mechanical- flow of air, mucus movement by cilia
-chemical- fatty acids, low pH, enzymes like pepsin, lysozyme
-microbiological- friendly normal flora |
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Term
| Name 4 types of Phagocytes: |
|
Definition
| Neutrophils, Macrophages, Eosinophils and Basophils (to a lesser extent) |
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Term
| What are the major types of receptors that can be found on macrophages? |
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Definition
| Toll Receptors, CR3 and CR4 complement receptors, CD14 LPS receptor (for bacterial lipopolysaccharide) |
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Term
| What are the major types of receptors that can be found on neutrophils? |
|
Definition
| Toll Receptors, CR3 and CR4 complement receptors, F-met peptides receptor (for n-Formylmethionone, a bacterial amino acid) |
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Term
| Name 5 functions of the Complement system: |
|
Definition
-opsonization
-chemoattraction (chemotaxis)
-release of anaphylatoxins
-direct lysis of bacterial cells
-CLEARANCE OF IMMUNE COMPLEXES |
|
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Term
|
Definition
an enhancement to phagocytosis that BRINGS FOOD TO THE MACROPHAGE
-makes the macrophages job much easier |
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Term
|
Definition
-best and most potent
-produces reactive oxygen intermediates that are very unstable and very toxic
-UTILIZES NADPH OXIDASE to convert NADPH into these radicals |
|
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Term
| What is the consequence of a deficiency in NADPH Oxidase? |
|
Definition
-Chronic Granulomatous Disease
-phagocytes can't kill stuff, so it builds up
-leads to recurrent infections |
|
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Term
| What are the products of the Respiratory Burst, and what do they do? |
|
Definition
-Hydrogen peroxide, hypochlorous acid, and nitric oxide
-they kill pathogens |
|
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Term
| Oxygen Independent Killing |
|
Definition
-weak, like a BB gun-
-uses inducible nitric oxide synthetase (iNOS) to make nitric oxide in phagocytic and non-phagocytic cells |
|
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Term
| Elements of Oxygen Independent Killing: |
|
Definition
-Cathepsin G- protease that kills and digests engulfed pathogens
-Lactoferrin- antimicrobial
-Lysozyme- breaks down cell walls
-Defensins- punch holes in things |
|
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Term
| What cytokines are secreted by macrophages? |
|
Definition
| IL-1β, TNF-α, IL-6, CXCL8, IL-12, IL-8 |
|
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Term
| What is rolling adhesion? |
|
Definition
-macrophages activate endothelial cells with cytokines-
-selectins are expressed (P, then E)
-carbohydrate ligands on leukocytes bind to selectins on inner wall of the vessel (like velcro)
-leukocytes SLOW DOWN and roll along inner surface of vessel |
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Term
| What type of carbohydrates do neutrophils communicate with on WBC's? |
|
Definition
| Sialyl Lewis Carbohydrates |
|
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Term
| What are the 4 steps of Leukocyte Extravasation? |
|
Definition
-Chemoattraction by IL-1β, TNF-α
-Rolling adhesion
-Tight Adhesion
-Transmigration |
|
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Term
| What is point of Leukocyte Extravasation? |
|
Definition
| To get WBC's from the blood into the infected tissue |
|
|
Term
| What is the important integrin in tight adhesion of leukocytes? |
|
Definition
| ICAM-1 on the vascular endothelium, which binds to LFA-1 on leukocytes along with CR3 |
|
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Term
|
Definition
|
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Term
| What initiates Chemotaxis? |
|
Definition
Macrophages release cytokines after phagocytosis:
-C5a, a chunk of complement, that increases WBCs
-IL-8 and IL-1- attract neutrophils and Leukocytes (IL-1)
-Leukotrienes, Histamine, and PG |
|
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Term
| What do IL-1, IL-8 and, TNF-α act on? |
|
Definition
STIMULATE INFLAMMATION:
-liver- activate complement opsonization
-bone marrow epithelium- mobilize neutrophils for phagocytosis
-hypothalamus- increase body temperature
-fat and muscle- mobilize energy to increase temperature
-Dendritic Cells- TNF-α stimulates migration of dendritic cells to lymph nodes where they mature and initiate adaptive immunity |
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Term
| What produces IFN-α and what does it do? |
|
Definition
| Produced by LEUKOCYTES- inhibits viral replication |
|
|
Term
| What produces IFN-β and what does it do? |
|
Definition
| Produced by FIBROBLASTS- inhibits viral replication |
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Term
| What is the general function of interferons? |
|
Definition
-Interferons degrade mRNA and inhibit protein synthesis
-they are not viral specific
-Interferon is produced by viral infected cells and protects neighboring cells via IFN receptors
-Interferons increase MHC Class I expression and antigen presentation in ALL CELLS
-Interferon activates NK cells to kill virally infected cells |
|
|
Term
| What has to bind to cause apoptosis? |
|
Definition
| FasL on NK cells binds to Fas on target cells and causes apoptosis |
|
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Term
| What is the purpose of the inhibitory receptor on NK cells? |
|
Definition
-if it binds to MHC Class I on the target cell, the cell is spared
-if there is no MHC Class I for the NK cell to bind to, apoptosis is initiated by the activating receptor on the NK cell |
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|
Term
| What is the end result of complement activation? |
|
Definition
|
|
Term
|
Definition
-if lacking, patients are prone to successive severe infections
-C3b fragments bond covalently to pathogen (COMPLEMENT FIXATION) and tag the pathogen for destruction by phagocytes
-soluble C3a is a chemoattractant to recruit effector cells to the site of infection |
|
|
Term
| What is a quick and dirty summary of the 3 pathways to complement activation? |
|
Definition
-Classical- adaptive and antibody dependent- REQUIRES IgG and IgM
"GM is a classic
-Alternative- Innate- no antibodies needed- SPONTANEOUS LYSIS OF C3
-Lectin- almost irrelevant- lectin binds to mannose on pathogen surface |
|
|
Term
| What is the end result of all 3 complement pathways? |
|
Definition
| It's the same for all 3: Inflammatory cells are recruited, pathogens are opsonized, pathogen membranes are perforated and the pathogens die |
|
|
Term
| How is complement activated in the classical pathway? |
|
Definition
-C1 binds to IgG or IgM, or
-Activated C1 cleaves C4 into C4a and C4b
-C4b binds to pathogen surface
-the activated C1 also cleaves C2 into C2a and C2b
-C2a binds to C4b on the surface of the pathogen, and builds the enzyme needed to cleave C3
-C3b sticks to complex, C3a is a chemoattractant |
|
|
Term
| What happens after C3 is cleaved? |
|
Definition
-C5 lands on the C1-C4 clump and cleaves, initiating the MAC
-the MAC uses C6,C7, C8, and C9 to poke holes in the pathogen lipid bilayer |
|
|
Term
| What do we call the smaller proteins (usually "a" fragments") that result from complement activation? |
|
Definition
|
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Term
|
Definition
| Molecules that act as binding enhancers for phagocytosis |
|
|
Term
| What happens if complement cannot clear immune complexes? |
|
Definition
| HYPERSENSITIVITY REACTIONS |
|
|
Term
| What are the two most important opsonins? |
|
Definition
|
|
Term
| What part of the neutrophil binds to what part of the antibody? |
|
Definition
Fc receptor on the neutrophil binds to Fc part of the antibody
**remember that it is the Fc, or CONSTANT, region of the Ab that is biologically active** |
|
|
Term
| What type of hypersensitivity reaction is triggered by immune complexes? |
|
Definition
| TYPE III HYPERSENSITIVITY REACTIONS |
|
|
Term
| How are immune complexes cleared? |
|
Definition
| They bind to CR1 receptors on RBC's and are taken to the liver and spleen to be removed by professional phagocytes |
|
|
Term
| What immune system issue causes lupus? |
|
Definition
| Inability to clear immune complexes |
|
|
Term
| What do C3a and C5a actually do? |
|
Definition
-C5a is a major chemoattractant for inflammation that recruits cells to infection
-the presence of both causes vascular permeability to increase
-the presence of these anaphylatoxins stimulates phagocytosis |
|
|
Term
| What part of the complement cascade forms the MAC? |
|
Definition
|
|
Term
| What are the only types of infections that the MAC can fight? |
|
Definition
-Gonorrhea or
-Bacterial Meningitis
(Caused by Neisseria) |
|
|
Term
| What should you immediately think of if a patient presents with recurrent Neisseria infections? |
|
Definition
| Problem with complement/MAC- |
|
|
Term
| What is unique about Neisseria that allows the MAC to work on it? |
|
Definition
-it is coated in Lipooligosaccaride, which is not very bulky
**gram-positive bacteria have super thick cell walls, so MAC doesn't work
**gram-negative bacteria have LPS so complement can't get in and MAC doesn't work |
|
|
Term
| How can complement be turned off? |
|
Definition
| C1INH (C1 inhibitor)- inhibits activated C1 and kills the pathway |
|
|
Term
| What happens if the classical complement pathway gets messed up? |
|
Definition
-C1,C4,and C2 don't work
-increase number of immune complex diseases
-INCREASE IN PYROGENIC BACTERIAL INFECTIONS |
|
|
Term
| What happens if the alternative complement pathway gets messed up? |
|
Definition
-Factor B and properdin don't work right
-Increase in Neisserial infections |
|
|
Term
| If C3 is missing or doesn't work right, we get: |
|
Definition
-Recurrent bacterial infections
-IMMUNE COMPLEX DISEASE (because C3 helps clear immune complexes) |
|
|
Term
| What happens if C5-C9 gets messed up? |
|
Definition
NO MAC
RECURRENT NEISSERIAL INFECTIONS |
|
|
Term
| What happens if C1-INH doesn't work? |
|
Definition
HEREDITARY ANGIOEDEMA- overuse of C1,C4, and C2-
EDEMA AT MUCOSAL SURFACES |
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