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Immune System (IS)

• Can be divided into two parts and is responsible for defense against foreign entities
• The second part keeps abnormal damaged cells from causing havoc
• Responds against damaged red blood cells (RBCs) or diseased cells like tumors in the host body

Innate or Natural Immunity

• Functions as the primary line of defense
• Represents an early stage in evolutionary development
• Nonspecific in its response
• Present at birth
• Immediately available for defense
• Can involve physical, biochemical, or mechanical defense mechanisms, or a combination thereof
• Mechanism does not alter on repeated exposure to any specific antigen

Acquired or Adaptive Immunity

• Supplements the protection provided by innate immunity
• Represents a later stage in evolutionary development, only seen in vertebrates
• Specific, specialized and is acquired by contact with a specific foreign substance
• Initial contact with a foreign substance triggers the synthesis of specialized antibody proteins
• The end result is reactivity to that particular foreign substance
• Contains memory
• The Response improves with each successive encounter with the same pathogen
• Remembers the infectious agent and can prevent it from causing disease later
• Body acquires immunity to withstand and resist subsequent exposure to the same foreign substance

Cellular and Humoral Components of the Immune System

• Cellular components are mediated by macrophages, T-cells and dendritic cells
• Lymphokines communicate between cellular systems that include cytokines and chemokines
• Humoral components include antibody and complement components found in plasma, saliva, and other secretions
• The function of the antibody is to bind to foreign molecules called antigen
• Antigen-Antibody complex formation inactivates the antigen; this elicits a number of complicated effects that result in the destruction of the antigen and the cell to which it is bound -- this reaction is called serology

Innate and Acquired Immunity

• Work to prevent infection and damaged cells from destroying the host in two ways:
  • Innate system: less complicated, primitive, primary defense, non-specific, is natural, and immediately available
    • Includes physical barriers like intact skin, mucosal membranes, cilia, and the cough reflex
    • Biochemical secretions like sweat, tears, saliva, mucus, and the low pH of the vagina and stomach
    • Mechanism does not alter on repeated exposure to any specific antigen
    • Phagocytic cells include mononuclear cells (monocytes in plasma and macrophages in tissues), polymorph nuclear cells (neutrophils, basophils and eosinophils), and natural killer (NK) cells
    • Recognizes host cells infected with a virus/bacteria or abnormal “tumor” cell before acquired immune response: secretes very potent “interferon” cytokines
• Humoral Immunity: Cytokines have some function, works to help regulate the immune response in specificity, intensity and duration
• Interferon Destroys virally infected cells, helps stop rapid progression, interleukin acts as signaling between leukocytes to divide/increase
• Complement- alternate pathway via recognition of polysaccharides and liposaccharides on the surfaces of bacteria and tumor cells
• Acute Inflammatory Reaction is imitated by any type of tissue damage which elicit an inflammatory response by increasing blood flow/permeable vessels at that site and activating heat-shock proteins to maintain healing process
• Liver produces inflammatory proteins in acute phase: C reactive protein, fibrinogen and amyloid protein

Acquired or Adaptive Immunity

• Major defense of IS, depends on innate immunity
• Develops by adapting to and destroying now complex pathogens
• Specific to recognize new pathogens
• Uses antibodies which have memory and provide defense for repeat pathogens: third line of defense

Lymphocytes

• T-lymphocytes mature in the thymus and make cytokines while destroying virally infected host cells
• B-lymphocytes mature in the bone marrow when stimulated and secrete antibodies
• NK cells play a role in immune protection against viruses
• Dendritic cells present in many tissues and systems and are responsible for antigen presenting
• Macrophages process antigens
• Cells have markers that can distinguish between them, called the Cluster of Differentiation (CD)
• The IS has adapted to recognize many different antigens with a specific antibody
• The IS activates host cells to recognize the antigen and multiply to a great number (progenition)
• Clones attack the same antigen
• If antigen is recognized by different cells, the cells make colonies and produce many different antibodies for different epitopes for the antigen.

Immune Memory

• Acquired when lymphocytes recognize antigens from previous encounters
• Some lymphocyte cells remain in the circulation for rapid immune response for repeated pathogens

B-Cells

• Responsible for producing antibody
• Bind to antigen by antibody secreted from plasma cell “mature B-cell" or directly contact pathogen when antibody is membrane-bound
• T cells function to recognize antigens of the host cell that are recognized by the Major histocompatibility Complex (MHC), a cell membrane-protein produced by MHC genes (MH) that determine the humor leukocyte antigen (HLA) on cells
• MHC Class 1 genes code for the HLA-A, HLA-B and HLA-C; MHC Class 2 genes code HLA-DR, HLA-DQ and HLA-DC
• T-cells produce immune mediating substance “cytokines” by TH1 or TH2 to stimulate B-cells/macrophages and TC cells Killing cells that contain foreign antigen and interact with MHC Class I and by receiving help from TH cells then destroy tumor cells, infected cells and grafts tissue

Antigen Presenting Cells (APCs)

• Consist of macrophages - neutrophils; some B-cells
• Dendritic present in the skin, Nervous tissue
• Lymph nodes, spleen, intestines, liver, thymus bone
• All can phagocytize the foreign antigen

Immune System Organs

• Primary lymphoid organs are the thymus and bone marrow where cells differentiate and mature
• Secondary lymphoid organs are lymph nodes and spleen, with associated tissue/mucosa, where cells interact with each other and antigen.

Immune Maturation

• Immune responses usually take days to months; including a latency or window period where antigen is not detected and antibody not produced

Immunoglobulins

• Response to an antigen can occur when T and B cells are very active initiate the primary Antibody which is IgM
• Secondary responses make IgG -- after the antigen is cleared, memory cells are stored in the host, causing repeated exposure to Quantitative IgG antibodies
• Hematopoietic stem cells, “Pluripotent hematopoietic progenitors" or "CD34 + cells”
• Myeloid Pathway: monocytes form to macrophages: MPS polymorph nuclear cells (PMNs neutrophils, eosinophils and basophils); also erythrocytes and platelets
• Lymphoid lineage: T cells divided to T(H) T Helper TH1 and TH2, B cells and NK cells
• FC receptor and complement receptor (CD16) CR1 are used by phagocytes during opsonization. -PMNs have FC receptors (CD16) CR1 (CD35), C5a receptors and CR3 (CD1lb).
• Eosinophils play critical role in allergic reaction and inflammation in parasitic infection
• Basophils and mast possess high-affinity FC immunoglobulin and allergic reaction/release of localized histamine B-cells possess complement receptor CD35 and CD21, FE receptors for IgG and CD19, CD20 and CD21 markers
• NK cells are “third population” referred as large granular lymphocytes and possess CD56/CD16: able to lyse via the process known as antibody-dependent cell mediated cytotoxicity (ADCC) through FC receptor

Soluble Protein Cytokines

• Functions as mediators of immune response
• Lymphocytes --> lymphocytes, and Monokines --> monocytes /macrophages
• Function to regulate growth/mobility/differentiation of leukocytes
• Major Cytokine Classes: Inteleukin/Tumor necrosis Factor/colony stimulating Factor
• Act by binding to specific cell receptors as attractant molecules: interact between cells such as immunoglobulin/ compliment protein

System Genetics

• Not all reciepients make antibodies to transfused RBCs
• Depends on the individual, high/low responders -- During early development
• B-cells form antibodies/switch isotypes as antibodies: isotype reacts with the temperature phases
• MHC Class type I are founded on a nucleated cell; role is in T-cell function: MHC Class II are found on APCs
• Immunosupression can cause decrease in immune responsiveness. as well as too little immunoglobulin: T- cells become susceptible: IS organ fails

Immunoglobulin Complex

• Proteins by plasma can neutralize toxicity in the body; classified to the structures of the heavy chains IgG, IgA, IgE, IgD, IgM
• IG Structure: two ident. light chains bound together by covalent disulfide
• Linked by heavy chain (hinge region) constant and variable region: The papain will split at the hinge- Fc receptors and PLACENTA TRANSFER
• B-Immunoglobin

Characteristics of Significance

• IgG, IgM + IgA: react at 37 C w/ IgG
• ABO antibodies are IgM; response in intestinal flora/pollen grains- Produce IgM at 22 to 24 degrees -- monomer-polymer with the J joining chain.
• Can be cleaved from B-2 mercaptoethanol by thiol reducing
• IgG is more significant as HDY antibody class/ bonds with the gamma chains with more sub-units than bonds

Antibody inherited Variations

• Isotype: IgG/IgM/ IgA
• Allotype: Variation in consistent region
• Idiotype: antigen-binding specificity

Antigen-Antibody

Macrophages have receptors on cell membrane to the IgG molecule NK/ Neutrophils and the mature B cells

• The complement system have functions to have Immune response

Role of Immune System

• Lysis Bacteria/cells
• Assist Phagocytosis Peptide: split fragments
• The activation processes need the molecules of C1-C9
• The alternate needs B and other protein factors- the activation occurs by antigen binding

Classical Pathway

• Activated by antigen-binding molecules with Ig-1
• Alternate, activated by polysaccharides and lipopolysaccharides on the surfaces of target cells. Bacteria/Parasites - third pathway needs lectin protein activated by attaching/producing proteins as by activation by molecules needing to binding
• The Membrane Attack Complex-after connecting with small pores of the cell to destroy subsequent the death of the cells binding the antibodies when cells are binding each other needs at least another factor on RBC surfaces Lewis bodies can activate other complement

Antigens Formation

• Immunogen can initate more of the molecular wt. More rigorous immune responses less soluble immune responses chemicals --
• --Polyclonal antibodies
• ---Monoclonal antibodies
• Reagent antibodies - test results.

Occurrence;

• Serum from those who have antigens for the test and for pregnancy.
• The reagent needs anitbodies -- can detect the body with routine groups.
• Autobidies produce to test if are self antigens - Antigen antibody reactions of the force

Body Test

• Hydrogen bonds force with a molecule charge wate/amino acids-Antibody affinities specific with relative affinity and reactivity.
• Body strength depends on immune suppression / malnutrition --- inheritance/ age

Immunoglobulin detection

Plasma

• Preferred for DAT studies * Complement activates 4C or 50 degrees.
• Traditional Methods

Aggulation

• Centrifuge for time
• Antibodies

Methods using antibodies that recognize substances

• Hemolysis
• Ph levels need to be adjusted/IgM type cells - enhanced cell that will reduce cell from separating/bind

Cells react more close to the body

• AHG cell reagent to be tested with the molecules ---reduction to joining those cell and the surface antigens

Cloning to multiply the antibodies

monoclonal cells against the clone batches -- flow - quantify / measure the cells to light. separate the antibody and determine their positivity

Test types

• Cell detection
• Cross matching, binding
• affinity to cells with protein markers
• The IS causes responses.

Hypersensitivity

• Is inflamm. to anti gen- with the help of the T cells with the other molecules like gamma and cell death

• Anaphylaxis- involves histamine.

• Immune System Characteristics

• Very complex and old, interacts with system, maintained w. IS.

• --Removal or protection

• Innate-Nonspecific and adaptive

• The two majors for the immune responses includes humoral -antibodies by lymphocytes

• *-Diversity / Uniqueness

• *-Recognition/ specificity.

Factors:

• Antibodies/ T cell receptors

• Memory and tolerance responses.

• There are Cell Lymphocytes-T /N and helper cells with CD factors/ cytotoxic and specific markers binding to cells/ release when stimmed

• Lymphocytes have CD markers and are able to kill

• 5-15 % B antibodies made with receptors and differentiate and create cells.

• The cells help with producing cell membranes and clone, the cell response is an immune response as orginal and produce molecules

Pathways that are initiated:

_Classical anti - body for process _Alternative bacteria/factors _ Interferon binding molecules.

• There are RBC membranes by the subtypes and allotypes reflected by the light chains
• Cells have to show that it is determine to have a response such like in antigens like proteins and glycolipids with a good immune response
• --The region can show if reactions are from: antibody to cell and mono and poly sensitivity- IgM and IgG and rarely-

IgA activity

• (warm or cold reactive or both)- and cells
• Selected T and B cells can remain dormant and later respond more rigorously upon second exposure of a previously recognised antigen
• Immune responses against the host are either removed or down regulated
• There are three types of lymphocytes: T cells, B cells and NK cells
• T cells (or lymphocytes) have the TCR, which is usually associated with the CD3 complex. T cells require APCs to respond to antigens. There are two well-characterized subpopulations of T cells distinguished by CD markers, T helper (TH, CD4-positive) and T cytotoxic (Tc, CD8-positive) lymphocytes
• In laboratory testing, T cells can be distinguished from B cells by their ability to bind sheep erythrocytes (called the CD2 marker) as well as specific markers TH lymphocytes:
• Has CD4 markers within the cell membranes
• Provides in B cell to stimmulate the immune responses- released in responses to antibodies markers
• Has T cell C8 and eliminates target cell with or without cytotoxic
• Recognize antigenns with one configuration from the three stimmed B cells differenciate by producing B-cell molecules.