Microbes Exam 2 Immune systems

Opportunistic Pathogens

Common and not problematic in healthy patients, but found in immunocompromised patients.

Strict Pathogens

Always associated with disease and not found in normal flora. If present, individuals will be infected and ill.

Facultative Pathogens

Able to cause disease in healthy individuals but don’t always. Most found in this group and found in normal flora.

Pathogen Entry into the host 

Pathogens must gain access to the host tissues by penetrating the skin or mucous membranes in order to multiply before disease is caused.

Virulence Factors

Increased pathogenicity, the organisms ability to infect and cause disease. Molecules that increase the degree of pathogenicity.

Gram Negative Virulence

Most produce endotoxin, released when bacteria cells are lysed and has several responses: fever, activation of complement, DIC, decreased peripheral circulation, shock, death

Innate Line of Defense

Hard wired (in your genes and never changes). Structures, chemicals, and processes that work to prevent pathogens from entering the body or stop their process. Skin and mucous membranes of the respiratory, integumentary, digestive, urinary, and reproductive systems

Epidermis in innate immunity

Multiple layers of tightly packed cells that only few pathogens can penetrate. Shedding of dead skin cells removes microorganisms, while epidermal dendritic cells phagocytize pathogens by engulfing them

Dermis in innate immunity

Collagen fibers help skin resist abrasions that could introduce microorganisms

Perspiration in innate immunity 

Salt inhibits growth of pathogens. Antimicrobial peptides act against microorganisms

Sebum in innate immunity

Helps keep skin pliable and less likely to break or tear. Lowers skin pH to level inhibitory to many bacteria

Mucous Membranes in Innate Immunity

Lines all body cavities open to the environment. Composed of Epithelium and Deeper Connective. Produces chemicals that defend against pathogens.

Role of the Lacrimal Apparatus (Tears)

Lysozyme in tears destroys bacteria (targets bacterial cell walls via lysis)

Antimicrobial peptides

Present in skin, mucous membrane, neutrophils (innate immune cells). Act against a variety of microbes - targets foreign, not you.

Body’s Second Line of Defense

Operates when pathogens penetrate the skin or mucous membrane. Composed of cells, antimicrobial chemicals, and processes. Many of these components are contained or originate in the blood

Plasma

Mostly water containing electrolytes, dissolved gases, nutrients, and proteins

Serum

Fluid remaining when all cells and clotting factors are removed

Leukocytes

“White Blood Cells”. Cells and cell fragments in plasma are called formed elements. Three types of formed elements: Erythrocytes, Platelets, Leukocytes.

Erythrocytes

Red blood cells. Carry oxygen and carbon dioxide in the blood

Platelets

Involved in blood clotting. Cell fragments from megakaryocytes - WBC trapped in bone marrow.

Leukocytes

Involved in defending the body against invaders and divide into granulocytes and agranulocyte

Granulocytes 

Contains large granules that stain different colors

Neutrophils and eosinophils

Phagocytize pathogens. Capable of diapedesis - movement via pseudopods.

Lymphocytes

Most involved in adaptive immunity. B cells / T cells.

Natural killer lymphocytes

Most discussed with cancer, mature = macrophages (largest immune cells)

Monocytes

Leave the blood and mature into macrophages. Phagocytic cells that devour foreign objects. 

Phagocytosis

Cells capable of phagocytosis are called phagocytes. Divided into six stages. 

Chemotaxis - phagocytosis

Movement toward the foreign item

Adherence - phagocytosis

Attachment via a receptor (ex. Toll like receptor)

Ingestion - phagocytosis

Endocytosis

Maturation - phagocytosis

Phagosome + lysosome - phagolysosome (functional unit)

Killing - phagocytosis

Via enzymes

Elimination - phagocytosis

Cell engulfs and removes unwanted material, such as dead cells, pathogens, and cellular debris, to maintain tissue health and homeostasis

Phagocytes

Phagosomes fuse with the lysosome to form the phagolysosome - microbes (usually) killed and digested

Oxygen dependent killing

Toxic oxygen compounds generated in the peroxisome (hydrogen peroxide, super oxide anion, hydroxyl radicals, etc). Reactions catalyzed by leukocyte enzymes following a respiratory burst of increased oxygen uptake by the leukocyte. Kills the ingested cell

Killing by eosinophils

Attack parasitic helminths by attaching to their surface. Secrete toxins that weaken or kill the helminth. Eosinophil mitochondrial DNA and proteins from structure that kills some bacteria. 

Killing by natural killer (NK) lymphocytes

Secrete toxins onto surface of virally infected cells and tumors. Differentiate normal body cells because they have membrane proteins similar to the NK cells.

Killing by neutrophils - granulocyte function

Can destroy microbes without phagocytosis by producing chemicals that kill nearby invaders (attracted by f-met). Generate extracellular fibers called neutrophil extracellular traps (NETs) that bind to and kill bacteria

Inflammation

Nonspecific response to tissue damage from various causes. Characterized by redness, heat, swelling, and pain. Two types. 

Acute Inflammation

Develops quickly and is short lived, typically beneficial, and is important in the second line of defense. Dilation and increased permeability of the blood vessels, which allows immune cells to the area to do tissue repairs.

Chronic Inflammation

Long lasting and the damage caused to tissues can cause disease (rheumatoid arthritis).

Fever 

Results when pyrogens trigger the hypothalamus to increase the body’s core temperature

Outcomes of fever

• Enhances effects of interferons 

• Inhibits growth of some microbes because body proteins tie up irons ions needed by bacteria

• May enhance the activities of phagocytes, cells of specific immunity, and the process of tissue repair

Leukocytes

White Blood Cells. Cells with antimicrobial properties found in blood and lymph

Lymph

Fluid that drains from tissues into the lymphatic capillaries, then enters the lymphatic system and filters through the lymph nodes. Lymph nodes filter the lymphs to detect pathogens

Spleen

Filters the blood to detect pathogens

Non-specific killing

Used to kill any pathogen - no specificity (innate function: has no memory function, responds to non-human).

Lysosomes function to kill

Lysozyme - breaks down peptidoglycan

Toll like receptors (TLRs)

Integral membrane proteins produced by phagocytic cells. Bind pathogen-associated molecular patterns (PAMPs). Initiate defensive responses

Interferons

Protein molecules released by host cells to nonspecifically inhibit the spread of viral infections. Causes many symptoms associated with viral infections.

Adaptive Immunity

The body’s ability to recognize and defend itself against distinct invaders and their products - it is a learned response during your lifetime. And with each exposure, the response improves.

Five attributes of adaptive immunity

Specificity, Inducibility, Clonality, Unresponsiveness to self, Memory

Two main types of lymphocytes

1. B lymphocytes (B cells): antibody factories that mature in the bone marrow.

2. T lymphocytes (T cells): mature in the thymus.

 Two types of adaptive immune responses

1. Cell-mediated immune responses (T cell-only mediated responses)

2. Antibody immune responses (B cell with the help of TH2)

Antigens

Molecules the body recognizes as foreign and worthy of attack. Recognized by three-dimensional regions called epitopes or antigenic determinants on surfaces of antigens

B Cells and Antibodies

Antigen-presenting cells (APC), to show foreign items to TH cells. A small percentage of B cells circulate in the blood, but their major function is the production and secretion of antibodies (proteins). Primarily fight extracellular pathogens

Specificity of the B cell receptor (BCR)

Each B lymphocyte has multiple copies of its B cell receptor, all recognize single epitope

Specificity and antibody structure

Antibodies are immunoglobulins similar to BCRs. Secreted by activated B cells and called plasma cells. (B cells can turn into TH2 (memory cells) or plasma cells (antibody factories).

Antibody function

Binding sites are like a lock and key. Function in several ways, such as: Activation of complement and inflammation, Neutralization, Opsonization, and Aggulation.

Complement

Innate system to target and lyse foreign cells, but has pathway dependent on antibodies

IgM Antibody

The first antibody produced by a naive B cell (has never seen its epitope). Never has seen its epitope and is free floating with 2 binding sites.

IgG Antibody 

Most common and longest-lasting antibody - found in blood

IgA Antibody 

Associated with body secretions - mucous, breast milk

IgE

Involved in response to parasitic infections and allergies

IgD

Exact function is not known

T Cells

Produced in the red bone marrow and mature in the thymus. Circulate in the lymph and blood. Migrate to the lymph nodes, spleen, and Peyer’s patches. Are lymphocytes.

T cell receptors (TCRs)

Can’t become activated - only through antigen binding, activation is a 2 step process. Only bind epitopes associated with an MHC protein. Act primarily against cells that harbor intracellular pathogens - TH1 facilitated defense.

Cytotoxic T lymphocyte (TC)

Directly kills other cell when activated MHC1 of infected cell or TH1. CD8+ protein on cell surface

Helper T lymphocyte (TH)

Helps regulate B cells and cytotoxic T cells (TH2). Includes type 1 and type 2 helper T cells (TH1). Controls system of adaptive immunity. CD4+ is the protein on cell surface.

Regulatory T lymphocyte (TR)

Represses adaptive immune responses, CD4

Clonal Deletion

Vital that immune responses not be directed against autoantigens. Body eliminates self-reactive lymphocytes. Lymphocytes that react to autoantigens undergo 2 rounds of apoptosis.

Clonal Deletion “+” regulation

If cells respond to something they are eliminated

Clonal Deletion “-” selection

If cells respond to autoantigens they are eliminated

Immune response cytokines: signaling molecules

Soluble (float in blood) regulatory proteins that act as intercellular signal between cells. Cytokines are secreted by various leukocytes.

Cytokine network

For activated cells to be called to the area or told to act. Complex web of signals among cells of the immune system

Interleukins (ILs)

Signal among leukocytes

Interferons (IFNs)

Antiviral proteins that may act as cytokines, paracrine signaling in viral infections

Growth factors

Proteins that stimulate stem cells to divide

Tumor necrosis factor (TNF)

Secreted by macrophages and T cells to kill tumor cells and regulate immune responses and inflammation

Chemokines

Chemotactic cytokines that signal leukocytes to move

Complement activation

Classic Pathway or Alternative Pathway. Activation results in lysis of foreign cell and indirectly triggers inflammation and fever.

 Major Histocompatibility Complex (MHC)

Major histocompatibility antigens are glycoproteins found in the membranes of most cells of vertebrate animals. If there’s no MHC, no T cells will respond. Two classes of MHC proteins.

MHC class I

All nucleated cells - display infection with the cells. Present on all cells except red blood cells

MHC class II

APS (antigen presenting cells) “Show” Th cells the problem. Present on antigen-presenting cells and include B cells, macrophages, and dendritic cells.

Cell Mediated Immune Responses

Respond to intracellular pathogens and abnormal body cells. Common intracellular pathogens are viruses.

Activation of Cytoxin T cell clones and their functions

Adaptive immune responses initiated in lymphoid organs. Steps involved in activation or cytotoxic T cells:

• Antigen presentation 

• Helper T cell differentiation: TH1 or TH2 

• Clonal expansion 

• Self-stimulation: autocrine

Memory T Cells

Immediately functional upon subsequent contacts with epitope MHC complex specific to its TCR - no Th needed. Memory response is more effective than the primary. 

T Cell Regulation

Regulation needed to prevent T cell response to autoantigens. T cells require additional signals from an antigen-presenting cell (APC). Interaction of the T cell and antigen-presenting cell stimulates the T cell to respond to the antigen

Plasma cells - Humoral Immunity 

Majority of cells produced during B cell proliferation. Only secrete antibody molecules complementary to the specific antigen. Short lived cells that die within a few days of activation

Memory B cells and the establishment of Immunological Memory

• Produced by B cell proliferation but do not secrete antibodies 

• Have BCRs complementary to the epitope that triggered their production

• Long lived cells that persist in the lymphoid tissue 

• Initiates antibody production if antigen is encountered again