Chapter 29,30,31-Immunology

Whole blood is composed of plasma, a liquid containing proteins ,other solutes and suspended cells.

Outside the body, plasma forms an insoluble clot. Plasma remains liquid only when an anticoagulant (anticlotting agent) is added.

After clotting, the remaining fluid, called serum, contains no cells or clotting proteins. Serum does, however, contain a high concentration of other proteins, including soluble antibody proteins, and is widely used in immunological investigations.

The Innate Immune Response
Not antibody mediated

Innate immunity is mediated by phagocytes.

Phagocytes recognize pathogen-associated molecular patterns (PAMPs) via a family of membrane-bound pattern-recognition molecules (PRMs)

Cytokines participate in cellular signals

Leukocytes
A variety of leukocytes participate in immune responses. Be able to name and recognize. Neutrophils, Eosinophils, Basophils, Monocytes/Macrophages, Lymphocytes

Phagocytosis-Ingestion and killing of invader by phagocytic cells (neutrophil)

Inflammation, Fever, and Septic Shock
Inflammation is characterized by pain, swelling (edema), redness (erythema), and heat. The inflammatory response is a normal and generally desirable outcome of an immune response.
Uncontrolled systemic inflammation, called septic shock, can lead to serious illness and death.

Adaptive Immune Response
In adaptive immunity, nonspecific phagocytes present antigen to specific T cells, triggering the production of effector T cells and antibodies. Immune T cells and antibodies react directly or indirectly to neutralize or destroy the antigen.
The adaptive immune response is characterized by

Specificity for the antigen
Memory-the ability to respond more vigorously when reexposed to the same antigen
Tolerance- the ability to discriminate self antigens from nonself antigens

B Cell Receptor (BCR)
B lymphocytes have multiple copies of a BCR type
BCR is identical to that of the secreted antibody for that particular cell
The randomly generated antibody variable region determines the BCR (not in response to antigens)
Each BCR is complementary to one antigen

Specific-Adaptive Immunity
Cell-mediated immunity leads to killing of pathogen-infected cells through recognition of pathogen antigens found on infected host cells.
Humoral immunity –killing of cells by antibodies and complement

Immunogens
Immunogens are foreign molecules that induce an immune response. Molecular size, complexity, and physical form are intrinsic properties of immunogens.
Antigens are molecules recognized by antibodies or by T-cell receptors (TCRs).

Presentation of Antigen to T Lymphocytes
T cells recognize antigens presented by antigen-presenting cells (APCs) or by pathogen-infected cells.
At the molecular level, TCRs bind peptide antigens presented by major histocompatibility complex (MHC) proteins. Class I MHC proteins are found on the surfaces of all nucleated cells.
Class II MHC proteins are found only on the surface of B lymphocytes, macrophages, and dendritic cells, all of which are APCs

Cytokines
These molecular interactions stimulate T cells to kill antigen-bearing cells or to produce cell-stimulating proteins known as cytokines.


Natural Killer Cells
Natural killer (NK) cells use the same effectors to kill virus-infected cells and tumors. However, NK cells do not require stimulation, nor do they exhibit memory. NK cells respond in the absence of MHC proteins.

T-Helper Cells: Activating the Immune Response
TH1 and TH2 cells play pivotal roles in cell-mediated and antibody-mediated immune responses.
Following the initial antigen exposure, each antigen-stimulated B cell multiplies and differentiates to form both antibody-secreting plasma cells and memory cells . TH1 inflammatory and TH2 helper cells each stimulate effector cells through the action of cytokines.

Antibody
The amino-terminal region is a variable domain, meaning that the amino acid sequence in this structural region differs in each different antibody.

The antigen-binding site is formed by the interaction of variable regions of heavy and light chains

Antibody Production
Antibody production is initiated by antigen contact with an antigen-specific B cell that processes the antigen and presents it to an antigen-specific TH2 cell.

The activated TH2 cell then signals the antigen-specific B cell to produce antibody.


Plasma Cells
Plasma cells are relatively short-lived (less than 1 week), but produce and secrete large amounts of IgM antibody in this primary antibody response.

Memory B Cells
The memory B cells generated by the initial exposure to antigen may live for years. If reexposure to the immunizing antigen occurs at a later time, memory cells need no T-cell activation; they quickly transform to plasma cells and begin producing IgG.

Secondary Antibody Response
Upon reexposure, the antibody titer rises rapidly to a level 10–100 times greater than the titer achieved following the first exposure. This rise in antibody titer is referred to as the secondary antibody response.

Complement, Antibodies, and Pathogen Destruction-Know complement and alternate pathways

Passive Immunity
Occurs naturally during pregnancy
IgG from mother crosses placenta
Infers protection to the baby
Occurs naturally as result of breast feeding
IgA antibodies in breast milk given to child
Artificial passive immunity involves transfer of antibodies produced by another person or animal
Can be used to prevent disease before or after likely exposure

Vaccines and Immunization
Attenuated vaccines
Weakened form of pathogen
Generally unable to cause disease
Strain replicates in vaccine recipient
Causes infection with undetectable or mild symptoms
Results in long lasting immunity

Vaccines and Immunization
Inactivated vaccines
Unable to replicate in vaccinated individual
Retains immunogenicity of infectious agent
Immunogenic not pathogenic
Inactivated vaccines fall into two categories
Whole agents
Contain killed organisms of inactivated virus
Fragments
Portions of organisms or agents including toxins proteins and cell wall components

Hypersensitivity Reactions
Hypersensitivity results when foreign antigens induce cellular or antibody immune responses, leading to host tissue damage.

Type I-IgE allergic response
Type II-Cytotoxic-complement and antibodies
Type III-Immune Complexes
Type IV-Cell-mediated-Delayed response

Type II (Cytotoxic) Hypersensitivity
Results when cells are destroyed by an immune response, often due to the combined activities of complement and antibodies
Component of many autoimmune diseases
2 examples
Destruction of blood cells following an incompatible blood transfusion
Destruction of fetal red blood cells in hemolytic disease of the newborn


Type III (Immune-Complex Mediated) Hypersensitivity
Due to the formation of antigen-antibody complexes, also called immune-complexes
Can cause systemic or localized reactions
Systemic
Systemic lupus erythematosus
Rhematoid arthritis
Localized
Hypersensitivity pneumonitis
Glomerulonephritis

Type IV Hypersensitivity

Type IV hypersensitivity, or delayed-type hypersensitivity (DTH), is cell-mediated hypersensitivity characterized by tissue damage due to inflammatory responses produced by TH1 inflammatory cells.

Autoimmune Diseases
Body usually recognizes self antigens
Destroys cells that would destroy self
Malfunction in immune recognition basis for autoimmunity
Autoimmune diseases may result from reactions to antigens that are similar to MHC self antigens
Autoimmunity may occur after tissue injury
Self antigens released from injured organ
Autoantibodies form and interact with injured tissues