Immunology Flashcards
Neutrophils (granulocyte)
- 40-75% of all white blood cells
- first line of defense against ALL infections
- phagocytize invading organisms and presenting antigens to the immune system
- Have segmented nuclei, cytoplasm is full of pink/purpe intracellular granules
Eosinophils (granulocyte)
- 1-6% of white blood cells
- specifically act against multicellular parasites by dissolving their cell surfaces
- involved in IgE mediated allergic disorders
- have bilobed nuclei and intracelluar granules and stain brick red
Basophils (granulocytes)
- 0-1% of white blood cells
- circulating counterparts of tissue mast cells and are mysterious
- bilobed nucleim dark staining intracellular granules
blood monocytes
- 2-10% of white blood cells
- produced in the bone marrow and travel in the bloodstream to their target tissues and become MACROPHAGES
- roles in phagocytosis, antigen presentation and cytokine production
- large cells, fine ground glass granules and horsehose shaped nuclei
tissue macrophages
- aren’t found on a full blood count
- derived from blood monocytes, which differentiate once they reach their target tissues and express CD14 receptors
- tidy up pathogens or foreign debris
- perform antigen presentation and can activate memory cells
- large cells with horseshoe shaped nuclei
- have pseudopodia
- contain a phagosome
- Kupffer in liver, alveolar in lung, osteoclast in bone, and microglial in neurons
dendritic cells
-main antigen presenting cells of the immune system
-role in activating helper T cells and memory cells
-formed in the bone marrow and circulate in the bloodstream until they reach their target tissues, where they are activated by pathogens and differentiate into mature form
0phagocytose pathogens before migrating to the lymph nodes and present antigens to activate the adaptive immune respone
-have processes braching out
-langerhans cells in skin
lymphocytes
- 20-45% of all white blood cells
- B, T, and NK cells
- B and T make up majority of lymphocyte population
B cells
- 25% of total lymphocyte population
- B cell surface markers: CD19, CD20, CD21, MHC II
- essential for humoral immunity ie antibody mediated response
- plasma cells are mature B cells that secrete antibodies
- memory B cells allow for quicker antibody response to subsequent infections
T Cells
- 70% of total lymphocyte population
- all express CD3 on surface along with TCRs that recognize specific antigens presented in MHC I or II molecule
- Helper T cells (CD4) facilitated activation of immune response and stimulate division and differentiation of various effector cells
- Cytotoxic T cells (CD8) effector T cells, provide cell mediated immunity by targeting and killing infected cells
- Regulatory T cels (CD25 and FOXP3) suppressor T cells, limit immune response to prevent excessive damage to tissues and orgas
- memory T cells (CD62 and CCR7) allow immune system to ount a faster, more effective response
NK cells
- 5% total lymphocyte population
- larger, primitive, with granules
- express CD15 and CD56 and many express CD8
- form part of both the innate and adaptive immune systems
- able to destroy pathogens and infected cells without the need for prior activation by specific antigens
- important in viral immunity and tumor rejection
Very first steps of innate immune system
- Fast: established within about 4 hours
- Non-specific and no memory
- Cellular response by innate immune system, chemical response by cytokines and complement, and initiation of an acute inflammatory response
phagocytes
- innate immune response
- dendritic, blood monocytes, tissue macrohages, and neutrophils
- identify pathogens by recognizing PAMP and PRRs
- internalize and kill dangerous organisms
- present digested protein antigens to MHCs
- MHC restriction prevents immune system fro being activated too easily
- when phagocyte PRRs are exposed to PAMPs, NFKB is activated
- NFKB is a transcription factor which results in the release of proinflammatory cytokines and the initiation of inflammatory response
natural killer cells
- do NOT require activation by specific antigens and are able to respond immediately to pathogen
- all nucleated “self” cells express MHC I to protect from NK cells
- any cells without identifiable MHC I are likely to be destroyed by NK cells, which release toxic granules to induce apoptosis
- MHC I expression often suppressed if cells are infected with viruses or have become cancerous
classical pathway
activated by antibody-antigen complexes (immune complexes) on pathogen surfaces
mannose-binding lectin pathway
activated when mannose-binding lectin binds to the carbohydrate molecule mannose on pathogen surfaces
alternative pathway
C3 reacts directly with pathogen surfaces
C3 convertase
- all three pathways act to generate this enzyme
- claves into C3a and C3b and activates the rest of the cascade
C3a
- mediator of inflammation which augments the inflammatory response
- anaphylotoxins that trigger mast cell degranulation, histamine release, and further inflammation
C3b
- binds to and coats pathogens, making it easier for phagocytes to identify and ingest
- process called opsonisation
- also binds immune complexes to facilitate their removal by the spleen, triggers production of terminal components including C5b
C5b
- innitiates the membrane attack pathway “terminal lytic sequence”
- triggers formation of membrane attack complex (MAC)
proinflammatory cytokines
- second key componenet of innate chemical immune response
- mediate acute inflammatory response
- interleukins, tumor necrosis factors, and chemokines
IL-1
causes fever and activates lymphocytes
IL-6
causes fever, stimulates the liver to produce acute phase proteins such as CRP, activates lymphocytes and promotes antibody production
IL-8 (CXCL8)
causes neutrophil chemotaxis
IL-12
activates NK cells and TH1 cells
TNF-alpha
increases vascular permeability to allow immune cells to reach tissues
IL-4, IL-5, IL-13
promote IgE production and eiosonophilic reactions in patients with allergies
IFN gamma
essential in activating cell-mediated immunity in viral infections
IL-10
anti-inflammatory response
inflammatory response
- kick started by innate immune cells, proinflammatory cytokines, and complement
- bridging mechanism to localize and contain the infection in the period of 4-96 hours after onset
features of inflammatory response
- vasodilation and increased blood flow (erythema and warmth)
- increased vascular permeability (allows inflammatory cell infiltrate, causes tissue edema and swelling)
- release of inflammatory mediators (bradykinins and prostaglandins which increase pain sensitivity and cause hyperalgesia)
- neutrophil chemotaxis (neutrophils migrate to the site of infection and begin clean up)
- microvascular coagulation (induced by local tissue damage, acts to confine the infection and prevent spread)
- systemic features ( fever, raised inflammatory markers ie ferratin and CRP; hot flush, sweats, chills, rigors, headache, nausea, myalgia, arhtralgia, fatigue)
- upregulation of costimulatory molecules (MHC II and B7)
Antigen presentation
- adaptive immune system
- dendritic cells laden with digested antigens travel to lymph nodes
- present antigens to naive helper T cells (TH0) within MHC II complexes on cell surface
protective mechanisms during antigen presentation-
- MHC restriction ensure that only antigens presented within the context of MHC complexes are able to trigger the immune response
- to become fully activated by their specific antigen, naive T helper cells require second signal from antigen presenting cell
- dendritic cells provide this in the form of B7 proteins (CD80 or CD86) which bind to CD28 receptors on the T cell surface
- expression of second signal molecules is increased by the presence of the inflammatory response, increasing the likelihood of T cell activation
- combination of right antigen, MHC II, and B7 second signal gives green light for naive T helper cells to get going
- then differentiate into TH1 cells, promote cytotoxi T cells and cell mediated immunity
- or TH2 cells, which promote B cells and humoral immunity
Humoral immunity
specific adaptive immune response activated by TH2 cells, leads to the production of B cells and antibodies
-designed to fight extracellular infections (bacteria, fungi, protozoans, parasitc worms)
antibody molecules
- essentially secreted B cell receptors that provide an antigen-specific action
- Y shaped molecules with complex structure
- 2 large heavy chains - Ig: M, G, A, E, D
- two small light chains - kappa or lambda
- heavy and light chains connected by a disulfide bond
- all four chains consist of constant and variable regions
- base of the antibody binds to complement and phagocytes
- antigens bind to the ends of each arm o the Y structure
IgM
- pentameric structure
- expressed on B cell surfaces and produced early in the immune response
IgG
- monomeric structure
- provides majority of antibody-based immunity
- found mainly in circulating blood and tissues (can cross the placenta)
IgA
- forms dimeric structure once it reaches target tissue
- found in mucosal areas (GI, respiratory and urinary tracts)
- secreted in saliva, tears, breast milk
IgE
- monomeric structure
- binds to allergens and mediates allergic reactions
- provides immunity against multicellular organisms
IgD
- monomeric structure
- found in low levels in the serum
- may interact with basophils and mast cells
variable region structure
- 3 parts: variable, diversity and joining regions
- RAG proteins allow B cells to shuffles these gene segments around during their maturation and recombine them in millions of different ways (VDJ recombination)
maturation of B cells
-when mature B cells are activated by specific antigen, they start to produce IgM antibodies and undergo isotype class switching to produce different types of antibodies adapted for different locations within the body
B cell activation
- prootes somatic hypermutation of variable regions
- slightly different versions of the same specfiic antibody
- clonal selection is the “testing” to find the best match and the ones with the highest possible affinity for antigen are encouraged to proliferate (affinity maturation)
humoral response and antibody production
- dependent upon T helper cells activating B cells
- naive TH0 cells activated by specific antigen –> differentiate into TH2
- TH2 cells locate corresponding B cell counterparts by identifying the correct antigen within the MHC II On B cell surface
- provide B cell with a second signal, CD40 ligand in this case to bind CD40 on B cell surface
- release cytokines such as IL-2, IL-4, and IL-5 which promote B cell development
