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MMG Specific Defenses


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What triggers specific immune responses in the body?
What forms can antigens take?
-bacterial cell walls
How do antigens enter the body?
-breaks in the skin (and mucous membranes)
-direct injection (as with a bite or needle)
-organ transplants (and skin grafts)
What does the lymphatic system do?
-to screen the tissues of the body for foriegn antigens
What do lymphatic vessels do?
-form a one-way system that conducts lymph from local tissues and returns it to the circulatory system
What is lymph?
-liquid with similar composition to blood plasma that arises from fluid leaked from blood vessels into surrounding tissues
Where do lymphoid cells develop?
-stem cells
-red bone marrow
What designates B and T lymphocytes?
-glycoprotein found on surface
ie: CD4, CD8
Where do B cells mature?
T cells?
B=bone marrow
Where are B-cells found?
-spleen, lymph nodes, red bone marrow, and Peyer's Patches
*small percentage circulating in blood
What is the major function of B cells?
-secrete antibodies such as immunoglobulins
What is the humoral immune response?
-body fluid immunity (such as lymph and blood)
What are antigen-binding sites?
-complementary to antigenic determinants (epitopes)
-form strong, noncovalent interactions
-Hydrogen bonds and other attractions may also be involved
What are 6 antibody functions?
-activation of complement
-stimulation of inflammation
-antibody-dependent cell mediated cytotoxicity
What is agglutination?
-each antibody has 2 antigen binding sites
-binding of multiple antibodies can lead to clumping or agglutination
What is neutralization?
-binding to toxin or cell, thereby blocking active sites or adherence to target cells
What is opsonization?
-AKA enhanced phagocytosis
-phagocytes have receptors that recognize parts of antibodies
-coating of antigen with antibodies
What is antibody-dependent cell mediated cytotoxicity?
-attachment of antibody to target cell leads to lysis by non-specific immune cell
What does antibody classification depend on?
-type of foreign antigen
-portal of entry
-antibody function needed
What are 5 antibodies?
What is the function of IgG?
-complement activation, agglutination, opsonization, and neurtralization
-crosses placenta to protect fetus
-85% in serum
What is IgM?
-complement activation, agglutination, and neutralization
What is IgA?
-Agglutination and neutralization
What is IgE?
-Triggers release of histamines from basophil mast cells
What is IgD?
What antibody is the only non-monomer (pentamer)?
How about a dimer?
-IgA (also a monomer)
What is a B-cell receptor (BCR)?
-antibody molecule that remains attached to cytoplasmic membrane of B cells
-complementary to only one antigenic determinant
Where are T-cells found?
-circulate in lymph and blood
-migrate to lymph nodes, spleen, and Peyer's patches
How do T-cells work?
-in a cell-mediated immune response (no antibody secretion, act directly on:)
-endogenous invaders
-many of the body's cells that harbor intracellular pathogens
-abnormal host cells that produce abnormal surface proteins (cancer cells)
What are the three types of T-cells?
-Cytotoxic T cells
-2 Types of helper T cells
Describe Cytotoxic C cells (Tc)?
-contain hundreds of T cell receptors (TCR)
-distinguished by the CD8 cell-surface glycoprotein
-directly kills
What do Tc cells kill directly?
-cells infected with viruses and other intracellular pathogens
-abnormal cells, such as cancer cells
What distinquishes Helper T cells (TH)?
-CD4 cell-surface glycoprotein (this is what HIV binds to)
What is the function of Helper T cells?
-help regulate the activities of B cells and cytotoxic T cells during an immune response
-secrete various soluble protein messengers, called cytokines, that determine which immune response will be activated
What are the two types of helper T cells?
-Type 1 (TH1)
-Type 2(TH2)
What do Type 1 helper T cell do?
-assist cytotoxic T cells
-express cytokine reveptor CCR5- plays a role in binding of HIV!!
What do Type 2 helper T cells do?
-Activate B cells to make and secrete antibodies
-have cytokine receptors CCR3 and CCR4
What are cytokines?
-soluble regulatory polypeptides that act as intercellular signals when released from certain body cells
What is the cytokine network?
-the complex web of signals among all the cell types of teh immune system
What are 5 types of cytokines?
-interleukins (ILs)
-interferons (IFNs)
-growth factors
-tumor necrosis factors (TNFs)
What do interleukins do?
-signal among leukocytes (27 to date)
-antiviral proteins that may act as cytokines
What do growth factors do as cytokines?
-proteins that stumulate stem cells to divide, maintaining an adequate supply of leukocytes
What are Tumor necrosis factors?
-secreted by macrophages and T cells to kill tumor cells and regulate immune responses and inflammation
What are chemokines?
-signal leukocytes to go to a site of inflammation or infection and stimulate other leukocytes
What are MHC antigens?
-glycoproteins found in the membranes of most cells of vertebrate animals
When were MHC antigens first identified?
Why are they important?
-first identified in graft patients
-important in determining the compatibility of tissues in successful grafting
What is the function of MHC antigens?
-to hold and position antigenic determinants for presentation to T cells
Where do antigens bind to the MHC?
-antigen-binding groove
What are the two classes of MHC proteins?
-MHC class I; found in most membranes
-MHC class II; only found on B cells and antigen-presenting cells (macrophages, leukocytes, monocytes)
What are exogenous antigens?
-extracellular pathogens such as bacteria, fungi, protozoa
What does APC do?
-internalizes the invading pathogen and enxymatically digests it into smaller antigenic fragments which are contained within a phagolysosome
What happens to the phagolysosome after pathogen is digested?
-fuses with a vesicle containing MHCII molecules
What happens to each fragment from the phagolysosome?
-binds to the antigen-binding groove of a complementary MHCII molecule
What happens to the vesicle once it fuses with phagolysosome
-vesicle inserts the MHCII-antigen complex into the cytoplasmic membrane so the antigen is presented on the outside of the cell
What are endogenous antigens?
-intracellular pathogens such as viruses and bacteria
What happens in endogenous antigen processing?
-intracellular pathogens also digested and each fragment binds to a MHCI molecule (in ER membrane)
-membrane packaged into vesicle by Golgi body which is inserted into cytoplasmic membrane so antigen is displayed on cell's surface
How does the body respond to exogenous pathogens?
-by mounting humoral immune responses
What is the first step in humoral immune responses?
-APC presents antigen to complementary Th cell
-CD4 binds to MHC II protein, stabilizing the TCR-antigen interaction
What is the second step in humoral immune responses?
-TH cell differenetiates into a TH2 cell, cuased by IL-1 secreted by APC
What is the third step in humoral immune responses?
-TH2 cell binds to B cell that contains a BCR complementary to antigen (clonal selection)
What is the fourth step in humoral immune responses?
-the B cell MHCII binds to CD4 of TH2 cell, which leads to IL-4 secretion
-then activation of B cell proliferation into plasma cells, which produce antibodies, and memory B cells
What do Cytotoxic T cells respond to?
-intracellular pathogens (viruses, intracellular bacteria) and abnormal body cells
What is the first step in the TC cell-mediated immune response?
-viral-encoded antigens are presented via MHC I complex
What is step two in the Tc cell mediated immune response?
-TCR and CD8 of Tc cell bind to MHC I-antigen complex
What is step three in teh Tc cell mediated immune response?
-either perforin-granzyme pathway or CD95 pathway is activated, leading to induction of enzymes that cause apoptosis (programmed cell death)
How are T cells regulated?
-cell-mediated immune response must be regulated to prevent T cells from responding to autoantigens
-T cells require additional signals from APC to an immunological synapse to stimulate the T cell response to the antigen
What are 6 ways microbes can evade immune systems?
-LPS modifications (O antigen)
-Enzymes that degrade C5a
-Surviving phagocytosis
-Antigenic variation
How do capsules help microbes evade detection from the immune system?
-prevents complement activation and phagocytic killing:
1) C3bBb formation on surface inhibited
2) phagocyte receptors can't reach
3) nonimmunogenic; no opsonization for phagocytes
What are the two ways LPS modifications work?
-different side chains prevent complement activation
-different side chain lengths prevent MAC formation
How do proteases help in immune system evading?
-specifically degrade antibodies
What is used for enzymes that degrade C5a in immune system evading?
-phagocyte chemoattractant

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