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173 Cards in this Set
- Front
- Back
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Where are naive lymphocytes found?
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in circulation, lymph nodes, spleen
Where they have never encountered an antigen |
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Where are activated lymphocytes found?
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At the peripheral site of infection where they have encountered an antigen
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Antigen
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Part of the pathogen that you immune system can recognize
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Types of immune responses
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Antigen specific
Antigen non-specific |
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What are the advantages/disadvantages of Antigen Specific immune responses?
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Advantage:
Can differentiate between foreign and self (response will not attach host cell) Disadvantage: Response is slower (5 days) |
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Which immune cells recognize foreign antigens
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Only B and T lymphocytes
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T-Lymphocytes
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Type Types: Alpha-Beta and Delta-Gamma?
AB cells -CD4 effector cells -CD8 cytotoxic cells -determines what type of pathogen the T--cell will recognize (intra vs extra cellular) DG cells -live in tissues -Involved in periapical lesions -Look like T-cells in the blood but dendritic cells in the tissues |
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B-Lymphocytes
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Two Types: Conventional cells and CD5 cells
Cells secrete antibodies that will recognize foreign antigens Conventional cells -majority of cells CD5 cells -Minority of cells -Live in tissues -Work faster than Conventional B-cells |
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What is the advantage/disadvantage of Antigen Non-Specific Immune Response
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Advantage:
Response is faster Disadvantage: Cannot differentiate between foreign and self (may also attack host cells) |
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What type of cells perform Antigen Non-Specific Immune Response
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Phagocytes (monocytes, macrophages, dendritic cells)
Granulocytes (PMN/neutrophils, basophils, eosinophils, mast cells) Natural Killer Cells (relative of T-cell) |
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Which cells are the first to arrive at the site of bacterial infection?
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Neutrophils/PMN (granulocyte)
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Types of Lymph Organs
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Primary Organs - where cells develop
Secondary Organ - where cells spend most of their life |
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Primary Organs
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Where cells develop
Includes: Bone Marrow Thymus Start from a common progenitor int he bone marrow T-cells leave bone marrow and migrate into thymus to mature while other cells remain in bone marrow |
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Secondary Organ
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Where the cells spend most of their life. Function to unite T-cells and B-cells with stuff from periphery
Includes: Bone Marrow Spleen Tonsils & adenoids Lymph Nodes & Vessels Bronchus (BALT, MALT) Gut (GALT, MALT) Urogenital lymphoid tissue, Peyer's patch |
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Function of lymph vessels
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Drains fluid from peripheral tissues into the lymph nodes
Pathogens travel with lymph vessels into nearest lymph node where you immune system can respond |
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How do cells enter and exit the thymus
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There is NO lymphatic vessels so cells enter/exit via blood circulation
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Structure of Thymus Gland
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Dense cortex
Less dense medulla No lymphatic vessels No reticular fibers |
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Involution of Thymus Gland
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Beings at puberty
Most of the glandular tissue is replaced with fat T-cells no longer develop fast therefore lifespan is very long 90% of T-cells are present when you hit puberty Death of T-cells cannot be replaced |
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Cells of the Thymus Gland
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Thymocytes - becomes T-cells
Dendritic cells - support the thymocyte as they develop Hassall's Corpuscles - unique only to thymus (unknown function) Macrophages |
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Dendritic cells
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AKA Reticular Epithelial cells
Support the thymocyte cells in the Thymus develop into T-cells |
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Thmocytes
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Cells of the Thymus gland that eventually become T-cells
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Function of Lymph Nodes
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Work horses of immune system
Unite B and T-cells with pathogens coming in from the periphery |
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Structure of Lymph Nodes
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High endothelial venules in the cortex
Dense cortex Less dense medulla with cellular cords and empty sinuses Has afferent and efferent lymphatic vessels |
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Afferent Lymphatic Vessels
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Drain peripheral pathogens into the nearest lymph nodes
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Efferent Lymphatic Vessels
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B and T-cells exit this pathway to go out to the peripheral site of infection to defend against those pathogens
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Diapedesis
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Movement of cells from periphery into the lymph nodes
Facilitated by the puffy, big spaces within lymph nodes |
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Cells present in Lymph Nodes
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B-cells - Live in cortex
T-cells - live in paracortex Dendritic cells & Macrophages - live in follicles and paracortex Reticular cells with fibers |
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B-cells in Lymph Nodes
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Live in the outer cortex of Lymph Nodes
Unactivated B-cells are in primary follicle Activated B-cells are in secondary follicle |
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T-cells in Lymph Nodes
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Live in paracortex, the zone in between the outer cortex and the inner medulla
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Structure of Spleen
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Consists of red pulp and white pulp
Red pulp functions as a filter to clean out old RBC and debris White pulp functions as a lymph node only during systemic infection Cords have reticular cells Sinuses have reticular fibers Blood infections can be cleared out through the spleen since it doesn't go through lymph nodes |
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Red Pulp
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Most of the structure of the spleen
Less dense Stains red Lots of RBCs and macrophages Functions as a filter to clean out old RBC and debris from the immune response |
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White pulp
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Area of Spleen organized in areas surrounding capillaries
More dense Stains blue Lots of WBCs, macrophages, and dendritic cells Function like a lymph node only in the event of a systemic infection. |
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Which organs are encapsulated and have septa?
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Spleen, thymus and lymph nodes
(Tonsils are variable) |
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Which organs have cortex and medulla?
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Thymus
Lymph nodes (Spleen and Tonsils do not) |
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Which organs have sinuses and cords?
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Spleen
Lymph nodes (Thymus and Tonsils do not) |
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Cells of the Spleen
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B-cells - found in follicular and germinal regions in white pulp
T-cells - found in Periarteriolar Lymphatic Sheath (PALS) of white pulp macrophages - in both white and red pulp Dendritic cells - in white pulp only |
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Why do you need antibiotics for surgery but not for exfoliation/extraction of teeth?
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Enclosed environments like your gut don't have the same full-blast immunity
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Function of Tonsils
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They are a reservoir for bacteria
Act like lymph nodes to maintain contact between bacteria and functional memory immune cells The reservoir of bacteria can also contribute to re-populating the pathogens that cause periodontal disease |
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Types of Tonsils
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Palatine
Pharyngeal Lingual |
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Palatine Tonsils
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Bilateral (2)
Located in oropharynx Stratified Squamous Epi Partial thick capsule 10-20 crypts/tonsil Crypts hold aerobic and anaerobic bacteria |
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Pharyngeal Tonsil
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AKA Adenoid (when inflamed)
1 Located in nasopharynx Startified Squamous Epi - less epithelium Partial thin capsule No crypts, but has folds Lots of Lymphocytes |
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Which tonsil does not have crypts
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Pharyngeal
It has folds |
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Lingual tonsil
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Numerous
Located at root of tongue Stratified squamous epi No capsule 1 crypt per tonsil |
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Which tonsil does not have a capsule
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Lingual tonsils
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Which tonsil has numerous crypts
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Palatine tonsils - 10-20 per tonsil
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Associated Lymphoid Tissues
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Discrete lymph tissues that exist in any area that is exposed to the outside environment
Absent in the stomach (stomach acid takes care of it) Absent in skin (outer keratin layer provides barrier) B-ALT G-ALT M-ALT |
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BALT
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Associated lymphoid tissue int he respiratory tract
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GALT
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Associated lymphoid tissue in the GI tract
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MALT
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Associated lymphoid tissue in the mucosa
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M-Cell
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Cell of MALT/GALT
no known function Takes in all kinds of particles Forms tight junctions with surrounding enterocytes (intestinal absorptive cell) Food particles get transported through M-cell and induces tolerance to food Polio, shingella, salmonella causes food poisoning by invading M-cells and entering through tight junctions into enterocytes Houses B and T-cells to fight pathogens |
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Which organ do WBC NOT travel to?
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Thymus
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Which organ is never involved in the immune response
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Thymys b/c the cells there are not yet mature to fight pathogens
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Why doesn't the thymus gland have lymphatic vessels
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Because there's no point in sending pathogens to immature T-cells that can't handle them
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Homing
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Cells tend to go to the place where they got activated
Homing is controlled by cell surface proteins |
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Which organs have lymphoid follicles
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Lymph Node
Spleen Tonsils (Thymus does not) |
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Which organ does NOT have a cortex and medulla
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Spleen
Tonsils |
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Which organ does NOT have Lymphoid follicle
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Thymus
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Which organ does NOT have cords and sinuses
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Thymus
Tonsils |
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Which organ does NOT have a capsule
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Tonsils (variable)
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Which organs have a hilum
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Lymph Node
Spleen (Thymus and Tonsils do not) |
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Which organs do NOT have a hilum
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Thymus
Tonsils |
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Which organs have B-cells
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Lymph nodes - Follicles in outer cortex
Spleen - Peripheral white pulp Tonsils - Follicles |
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Which organ does NOT have B-cells
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Thymus
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Which organ has T-cells
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Thymus - whole organ
Lymph Node - Inner Cortex (paracortex) Spleen - Periarterial Lymphatic Sheathe Tonsils - between follicles |
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Which organ does NOT have T-cells areas
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All organs do
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What is the unique structure for Thymus
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Epithelial cells/Hassall's corpuscles
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What is the unique structure for Lymph Nodes
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Afferent lymphatics
Follicles adjacent to capsule |
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What is the unique structure for Spleen
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Central arteriole
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What is the unique structure for Tonsils
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Follicles adjacent to epithelium
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Antigen Non-Specific Cells
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Kill by eating or releasing killer granules
Ex: phagocytes, granulocytes, natural killer cells |
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IL-1
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Macrophage Cytokine
Activates vascular epi Increase access of effector cells Activates naive T-lymphocytes Causes local tissue destruction Produces fever Upregulates IL-6 |
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IL-6
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Macrophage Cytokine
Upregulates antibody production Increases lymphocyte production Assists in B-cell activation Produces fever |
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TNF-a
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Macrophage Cytokine
Activates vascular epi Shuts down venous return to increase fluid draining to lymph nodes (causes shock) Produces fever Mobilizes ROS metabolites Activates neutrophils (with IL8) Activates dendritic cells |
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IL-8
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Macrophage Cytokine
A chemokine Steers other immune cells to the site of antigenic challenge Activates neutrophils (with TNGa) |
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IL-12
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Macrophage Cytokine
Activates NK cells Causes differentiation to TH1 T-cells |
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IFa/IFb
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Macrophage Cytokine
Inhibits protein synthesis Inhibits DNA replication in virus-infected cells Increases MHC class I expression and antigen presentation in all cells Activates NK cells against virus |
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IF-gamma
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TH1 Effector T-cell cytokine
Induces respiratory burst enzymes to generate activated destructuve macrophages Increases activated CD8 T-cell activity Increases activated NK cell activity Causes B-cells to swtich to IgG Isotype |
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IL-2
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TH1 Effector T-cell cytokine
T-cell growth factor leading to clonal proliferation when activated by dendritic cell costimulation Induces apoptosis in effector T-cells |
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LT
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TH1 Effector T-cell cytokine
Inhibits B-cells Kills T-cells Activates macrophages Activated PMN Kills tumor cells |
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FasL
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TH1 Effector T-cell cytokine
Induces apoptosis in Fas bearing cells |
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Complement
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Proteins found in serum that are usually inactive and when activated can go into 2 different pathways
-classical (antibody activated) and alternative (self activated) |
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Classical Complement Pathway
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Antibody binds to specific antigen on pathogen surface
Antibody activation Involves 9 complement serum proteins |
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Alternative Complement Pathway
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Pathogen surface creates local environment conducive to complement protein activation
Self activation Involves 8 complement serum proteins |
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What are the first cell responders to infection?
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Dendritic cells- always lie in tissue
Macrophages |
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C3b
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Keeps bacterial load in check during the next 5 days as adaptive immune response kicks in
It Opsonizes bacteria to facilitate recognition and phagocytosis by neutrophils Transports RBC to spleen for filtration Activated B-cells |
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Anaphylotoxins
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Fragments of complement serum proteins (C2a, C3a, C4a, C5a)
C5a > C3a > C4a > C2a in effectiveness Recruit neutrophils and macrophages by activating expression of LFA-1 and CXCL-8 receptors on WBCs Alter vascular epi making them leaky allowing WBC to migrate out of blood vessels into site of infection |
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How to fight off viruses?
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Interferon a and B (IFa, IFb) - produced by infected hold cell to disrupt viral replication
Natural killer cells |
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Interferon A and B
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Produced by an infected host cell to disrupt viral replication
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Natural killer cells
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Looks for absence of MHC-1 on cells that have been removed from viruses and kills those virally-infected host cells
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What complement initiates the polymerization of the Membrane Attack Complex
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C5b
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What complement pokes a hole in the bacterial membrane
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When C8 binds to C5b-C6-C7
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What complement forms a cylindrical pore in the bacterial cell membrane causing the bacteria to explode and die?
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When 10-15 units of C9 binds to C5b-C6-C7-C8
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Order of important/effectiveness of anaphylotoxin A-pieces
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C5a > C3a > C4a > C2a
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Glomerulonephritis
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When the spleen cannot filter out antibody-antigen complexs on RBC
They end up getting trapped in the glomerular capillary beds |
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Deficiency in which complements cause disease?
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Deficiencies C3b and C5a are associated with severe diseases
Anything further down in complement is not crucial to survival |
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C1 Inhibitor
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Soluble factor
indiscriminately inactivates complement on both the bacteria and host cell to turn off complement cascade Takes away C1 to prevent cleavage of C4 and C2 |
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C4 binding protein
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Soluble Factor
indiscriminately inactivates complement on both the bacteria and host cell to turn off complement cascade Dissociates C2a |
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Factor H
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Soluble Factor
indiscriminately inactivates complement on both the bacteria and host cell to turn off complement cascade Type of C3 Convertase Inhibitor Inactivates C3b in the Alternative Pathway |
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Factor I
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Soluble Factor
indiscriminately inactivates complement on both the bacteria and host cell to turn off complement cascade Type of C3 Convertase Inhibitor Inactivates C3b in the Alternative pathways and Inactivates C4b in the Classical Pathway |
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Soluble Factors
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indiscriminately inactivates complement on both the bacteria and host cell to turn off complement cascade
Includes: C1 Inhibitor C4 binding protein Factor H Factor I |
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Membrane Bound Factors
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Specifically inactivates complement only on the host cells
Includes: DAF MCP Cd=59 |
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DAF
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Membrane-bound Factor
Specifically inactivates complement only on the host cells Dissociates Factor-Bb to inhibitor the formation of C3 Convertase in the Alternate Pathway Makes it ok for C3 to spontaneously cleave without hurting your host cells |
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MCP
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Membrane-bound Factor
Specifically inactivates complement only on the hold cells Dissociates Factor-Bb to inhibitor the formation of C3 Convertase in the Alternate Pathway Makes it ok for C3 to spontaneously cleave without hurting your host cells |
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Cd-59
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Membrane-Bound Factor
Specifically inactivates complement only on host cells Prevents the formation of C9 pore structures |
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How do WBC travel through vessels?
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Rolling adhesion
Tight binding Diapedesis - Cells get sucked through between endothelial cells out of blood vessels Migration |
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Rolling Adhesion
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Weak binding between endothelial Selectin molecules and WBC S-Lex receptors allows the WBC to roll along with the force of blood flow
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Tight binding
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CXCL-8 and ICAM-1 on the endothelium surface induces a change in the endothelium that allows stronger bonds so that the WBC is stopped and can no longer roll
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Diapedesis
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WBC gets sucked through between endothelial cells out of the blood vessel
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Migration
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WBC follows the CXCL-8 gradient being secreted at the site of infection
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How do neutrophils, macrophages, dendritic cells recognize bacteria once at the site of infection?
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They have receptors that can recognize things specific to bacteria like:
Endotoxin Mannose n-formylmethionine FC-receptors complement |
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Once macrophages recognize bacteria at the site of infection, what do they do?
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They secrete cytokines that function to:
activate innate immune response activate adaptive immune response |
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Dendritic cells
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Immature in the tissues until activated by TNF-a
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How are antigens presented to T-cells
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Foreign antigens are presented on Major Histocompatibility Complex (MHC)/ Human Leukocyte Antigen (HLA) docking proteins on the surface of dendritic cells
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MHC
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Major Histocompatibility Complex
Same as Human Leukocyte Antigen (HLA) They are proteins on the surface of dendritic cells that recognize foreign antigens |
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CD4 T-cells
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Looks for extracellular (bacterial) peptides on HLA-2 docking proteins
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CD8 T-cells
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Looks for intracellular (viral) peptides on HLA-1 docking proteins
Lyse the host cell via apoptosis Virus gets killed too because it lives inside the lysed host cell |
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HLA-1
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AKA MHC-1
Human Leukocyte Antigen-1 protein made by most nucleated host cells (except RBC-no nuclei and neurons) Composed of heavy and light chains Activates only CD8 T-cells Acquires peptides in ER Heavy chains binds to CD8 co-receptors |
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HLA-2
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AKA MHC-2
Human Leukocyte Antigen-2 protein made by antigen presenting host cells (APC) only Ex: Dendritic cells, B-cells, macrophages Composed of alpha and beta chains Activates only CD4 T-cells Acquires peptides in vesicles Beta chain binds to CD4 co-receptors |
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what is binding specificity of the T-cell receptor determined by?
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T-cell receptor does not determine binding to HLA-1 or HLA-2
Binding specificity is determined by CD4 and CD8 co-receptors |
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Which cells make MHC/HLA-1 proteins?
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Most nucleated host cells
Except RBC - they dont have nuclei Except Neurons - you don't want to be killing these cells because they can't regenerate |
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Which cells do not make MHC/HLA-1 proteins?
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RBC because no nuclei
Neurons because you don't want to be killing these cells |
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Which cells make MHC/HLA-2 proteins?
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Made only by antigen presenting host cells (APCs)
Ex: Dendritic cells B-cells Macrophages |
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What is the only APC that presents antigens to activate CD4 and CD8 T-cells
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Dendritic cells
Both B-cells and Macrophages present antigens only to activate itself |
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MHC/HLA-1 Protein Synthesis
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Makes heavy and light chains by getting building blocks from pool of degraded peptides in ER
If healthy, the proteins will be self peptide If virally infected, the proteins will be viral peptides HLA-1 gets transported through cell in Golgi vesicle to be exocytosed on to host cell membrane surface HLA-1 can now bind to CD8 T cell receptors on the cell membrane |
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MHC/HLA-2 Protein Synthesis
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Dendritic cell must first bring bacteria inside through phagocytosis
Bacterium gets degraded into peptide segments Invariant chain chaperone protein prevents HLA-2 from getting peptides from ER and instead signals it to find a phagosome to acquire bacterial peptides If healthy, CLIP segment remains attached to HLA-2 blocking acquisition of vesicle peptides If bacterially infected, HLA-dm removes CLIP allowing HLA-2 to acquire peptides in veiscles HLA-2 then gets exocytosed and can now bind to CD4 receptors on dendritic cell membrane |
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CLIP
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Segment that remains attached to HLA-2, preventing acquition of vesicle peptides to form, unless the dendritic cell is bacterially infected
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MHC/HLA-dm
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Removes CLIP segment for HLA-2 allowing it to assemble using peptides in vesicles
Only removes CLIP when bacterially infected |
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Invariant Chain
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Chaperone protein in APC cells that prevents HLA-2 from acquiring peptides in the ER
Signals to HLA-2 to go find a phagosome where it may be able to acquire its bacterial peptides |
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How is antigen recognition maximized
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Polygenism - HLA1-A, HLA1-B, HLA1-C, etc
Polymorphism - HLA1-AA, HLA1-Aa, HLA1-aa Multiplication - peptide binding groove binding number different peptides 60,000 possible peptides can be recognized by B-cells and T-cells This is how MHC/HLA polymorphism and polygenism ensures that T-cells can recognize any possible antigen on any kind of foreign invaders |
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How are MHC/HLA peptide binding grooves able to recognize and bind so many different peptides?
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Anchor Residues - specific hydrophobic AA at specific locations on the peptide
MHC/HLA-1 has anchor residues at the ends MHC/HLA-2 has anchor residues in the middle |
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T-cell Receptor
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Specific for both allele and the peptide
Both must be a correct match in order to activate the T-cell |
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Which cells perform antigen processing and presentation
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Dendritic cells
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How do B-cells get activated?
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1. B-cell antibody receptors bind to antigens on dendritic cell
2. Receptor mediated endocytosis causes B-cell to phagocytose the bacteria and produce HLA-2 3. B-cell leaves primary follicle (outer cortex) of lymph node looking for T-cell in paracortex of lymph node 4. B-cell presents its antigen peptide to a receptor on the TH2/CD4 cell 5. CD-40 ligand on activated TH2/CD4 cell binds to CD-40 receptor on unactivated B-cells 6. TH2/CD4 cell cytokines bind to B-cell receptors 7. B-cell returns back to primary follicle and undergoes clonal proliferation in the secondary follicle (outer cortex) 8. daughter B-cells under somatic hypermutation resulting in variability in antibody binding capabilities 9. Undergo further rounds of proliferation and hypermutations to produce progressively stronger affinities 10. Strongest daughter B-cells differentiate into Plasma cells to produce antibodies at the site of infection 11. At the end of infection, some daughter B-cells differentiate into Memory Cells to keep you protected for life 12. Isotype switching of IL4 to IgE, and IL-10 to IgA |
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Antibody
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Antigen specific receptor of B-cells
They can recognize almost any stucture such as proteins, lipids, carbs, etc, on the bacterium (T-cells can only recognize proteins presented on MHC cells) |
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IgM
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COMPLEMENT ACTIVATION
Activates complement by binding bacterium First kind of antibody to be secreted |
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IgE
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MAST CELL SENSITIZATION
Mast cells have high affinity receptors for IgE Causes mast cells to release all its granules Leads to allergic/asthma symptoms - coughing, sneezing, itching etch Not found free in serum - always bound to mast, basophils, eosinophils |
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IgD
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B-CELL ACTIVATION
Only function is to activate B-cell Does not get secreted into serum |
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Which isotypes do Naive B-cells have
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IgM and IgD
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Which isotypes do Activated B-cells have
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Isotype switching occurs in daughter B-cells and only happens after B-cell is activated
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Clonal deletion
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Form of tolerance
If B-cell makes receptor that recognizes self, the B-cell will die by apoptosis |
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Anergy
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Form of tolerance
If B-cell receptor binds to a soluble antigen, the B-cell will become anergic (permanently deactivated) |
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Central Tolerance
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When tolerance occurs in the thymus or bone marrow (developmental organs)
Like clonal deletion or anergy |
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Peripheral tolerance
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When B-cells are anergized (deactivated)
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Maturation
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If there is no self-reaction, mature, but naive B-cells will have IgD and IgM on its cell surface and migrates into circulation to flow from lymph nodes to spleen.
If B-cell does not find antigen, it dies |
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CD5 B-cell
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AKA B1 B-cells
Small part of total B-cell population (majority is Conventional B-cells) Lives in tissues Does NOT need T-cell activation Secretes IgM antibodies which activates classical and alternative complement Recognizes bacterial carbs |
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How are T-cell receptors made
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Gene arrangements and nucleotide splicing occurs in the thymus cortex
It maximizes diversity in receptor recognition abilities T-cell receptors that cannot bind to HLA receives no CD3 survival signals and causes T-cell to die via apoptosis T-cell receptor that can bind to HLA receives CD3 survival signal |
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Positive Selection during T-cell Development
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T-cell needs to demonstrate that it can bind well enough to HLA molecules and peptides which will give it a survival signal from CD3
T-cell will receive survival signal if it can recognize self peptides High affinity will prevent apoptosis Type of HLA that T-cell receptor binds determines if that T-cell becomes CD4 or CD8 cell |
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Negative Selection during T-cell Development
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T-cell needs to demonstrate that it won't bind to HLA too well
Don't want T-cell to bind too tightly to host peptides and kill the host Test to see if T-cell Receptor binds too tightly to self protein High avidity (the sum of strength of binding molecules to one another) induces apoptosis Negative selection induces apoptosis |
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Type I diabetes and Positive/Negative Selection
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They don't do positive and negative selection very well
Therefore some T-cells will attack islets of Langerhans decreasing production of insulin |
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How are dendritic cells so good at activating T-cells
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They have evolved so that they can be infected by all types of viruses (that means dendritic cells can put viral peptides on HLA-1)
They can secrete IFa and IFb to prevent viral replication and consequential destruction of itself They have a shuttle mechanism to transport degraded viral peptides into vesicles (allowing Dendritic cells to put viral peptides on HLA-2) Therefore can activate both CD8 T-cells (HLA1) and CD4 T-cells (HLA2) Can secrete DC-CK to recruit both types of T-cells |
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DC-CK
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Dendritic Cell Chemokine
Secreted by activated dendritic cells that have arrived at the lymph node Recruits both types of T-cells |
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How do T-cells get activated?
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1. dendritic cells are still immature in the tissues
2. During infection, TNFa is secreted by macrophages signalling dendritic cells to diapedesis out of blood vessels 3. Dendritic cells become activated in the paracortex of lymphnodes allowing them to secrete DC-CK and present HLA molecules 4. Naive T-cells cruise lymph nodes and are activated by antigens present on dendritic cells 5. T-cell LFA-1 binds to dendritic ICAM-1 to allow T-cell to roll along surface of dendritic cell to scope out correct HLA-peptide 6. If there is a match, T-cell stays in lymph node to get activated via phosphorylation signals (CD3 and co-stimulatory signal) 7. If both signals given successfully, T-cell secretes IL-2, and causes clonal proliferation |
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What are the phosphorylation signals that get T-cells activated in the lymph node?
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1st signal - CD3
Changes conformation to allow tight binding 2nd signal - co-stimulation Dendritic cell binds to T-cells CD-28. Causes T-cells to secrete IL2 leading to clonal proliferation creating 10,000 daughter T-cells |
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What occurs if there is no co-stimulatory signals produced by the APC cells
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T-cell gets anergized to prevent host cell destruction
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TH1 cells
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Type of CD4 T-cell
Leaves the lymph node to drive adaptive immune response at the site of infection |
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TH2 cells
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Type of CD4 T-cell
Stays in lymph node to activate B-cells so that you can produce antibodies |
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How does the body separate naive B/T cells from Activated B/T cells fro the site of infection?
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Activated cells switch their receptors from Selectin to become Integrin
Activated endothelium switch their molecules from Adressins to become Adhesin in response IL2 Naive T-cells cannot leave circulation because they have L-Selectin receptors that can only bind to S-Lex on un-activated endothelium Activated T-cells are forced to site of infection because they have VLA-4 receptors that can only bind to VCAM on activated endothelium |
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Activation of macrophages
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Macrophages cannot degrade bacteria to their fullest killing potential until TH1/CD4 cells leave the lymph node
TH1 cells receptor binds to Macrophage's HLA2 TH1 cell's CD40 ligand binds to macrophages CD40 receptor (coactivation) TH1 cell secretes IF-gamma that binds to macrophages IF-gamma receptor Macrophage can now effectively degrade and can secrete ROS to kill un-eaten bacteria |
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Granuloma
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Formation of a wall of T-cells to try to isolate the un-eaten bacteria.
This occurs when there is no activation of macrophages Ex; Tuberculosis |
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Tuberculosis
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Wall of lymph tissue forms around the alveoli and interferes with breathing
macrophages cannot effectively lyse TB bacterium do to resistant coating and the T-cell has to surround the un-eaten bacteria |
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Foamy Macrophages
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Activated macrophages that have eventually exhausted their degrading capabilities and come to the end of their life
Ends is apoptosis |
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Apoptosis of Macrophages
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Occurs when they become Foamy
TH1 FAS-ligand binds to macrophages FAS-receptor to induce apoptosis Cell membrane dissolves last Everything inside the macrophage degrades before cell membrane explodes |
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IF-gamma
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Main TH1 cytokine
Coordinates all the activities involved in fighting an extracellular infection Macrophages are coactivated w/ CD40-ligan NK cells are made more efficient CD8 T-cells are made more efficient B-cells switch isotypes to IgG giving NK and macrophages their targets Epithelial cells upregulate HLA-1 production and HL2 expession |
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NK cells
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are not antigen-specific because they don't have antigen receptors. They can only recognize antigens when bound to IgG antibodies
Only need IL-12 to get activated (IL-12 secreted by macrophage) Also secrete IF-gamma keeping TH1 and macrophage activity up and makes CD8 cells more effective in fighting intracellular infections |
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How do effector CD8 T-cells kill cells that have been intra-cellularly infected?
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Two ways:
Perforin and Granzyme causes infected cell to go through Capase Pathway leading to apoptosis and FAS-Ligand (apoptosis) |
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Perforin
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Secreted by CD8 T-cells
Forms a pore structure in the infected cell |
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Granzymes
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Secreted by CD8 T-cells
Enters the infected cell |
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FAS-ligand
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Macrophage presents its peptide to HLA-1 to the activated CD8 T-cell
T-cells FAS-ligand binds to macrophages FAS-receptor leading to apoptosis |
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What drives shutting off an immune response?
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The decrease in the amount of Antigens present in the body
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IgG
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NEUTRALIZATION, OPSONIZATION & TARGETED KILLING
Neutralization: Actively transported into extracellular spaces Competes against pathogens for their binding site Cannot stop bacterial replication Opsonization: Bacteria gets coated to allow for easier phagocytosis by macrophages/neutrophils Targeted Killing: IgG binds to bacterium allowing NK cells to recognize bacteria |
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IgA
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NEUTRALIZATION
Can be pumped across epithelial cells into lumen spaces Primary antibody in saliva, sweat, tears, gut Competes against pathogens for their binding site Cannot stop bacterial replication |
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Fc receptors
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Located on the cells that can bind to IgG
IgG - can only recognize the antibody after the antibody has bound to an antigen IgE - Can recognize the antibody even when the antibody is unbound to an antigen |
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B-cell tests
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If B-cell can bind to cell surface self-antigens --> apoptosis
If B-cell can bind to soluble free self-antigens --> anergic If B-cell cannot bind to any self-antigen --> B-cell migrates out of the bone marrow and enters peripheral circulation |
