CLS 251 UNIT 1 STUDY GUIDE

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what is innate immunity/natural immunity?

a nonspecific/nonadaptive response that is characterized by its ability to resist infection by the body’s built-in defense mechanism → reacts in a short time frame to infective challenge and is less vigorous (not as potent/immunogenic) and effective than adaptive immunity

consists of an external defense system and an internal defense system

what is involved in the internal defense system in innate immunity?

• pathogen-recognition receptors

• acute-phase reactons (markers of inflammation and sometimes referred to as cytokines)

• inflammation

• phagocytosis

• NK cells

what is the innate immune system?

defenses against infection that immediately act when a host is attacked by a pathogen and is composed of two system that work to promote phagocytosis

• external defense system → anatomical barriers designed to keep microorganisms from entering the body & composed of physical, chemical, and biological barriers that work together to prevent infection from entering the body

• internal defense system → includes cellular responses that recognize specific molecular components of pathogens

how is the skin an external defense system?

a physical barrier with secretions that discourage microorganism growth and contains:

• epidermis → tightly packed epithelial cells coated in keratin

• dermis → connective tissue with blood vessels, hair follicles, sebaceous glands, sweat glands, and WBCs

• lactic acid and fatty acids → maintains the pH of the skin at ~5.6

• psoriasin → small protein produced by skin cells that have antibacterial effects

how is the respiratory tract an external defense system?

mucous secretions block bacteria from adhering to epithelial cells (engulfs the pathogeb → coughing/sneezing moves pathogens out of the tract

how is urine an external defense system?

helps remove potential pathogens from the genitourinary tract

how is the digestive tract an external defense system?

the stomach’s hydrochloric acid keeps the pH of the stomach as low as 1 which prohibits microorganism growth and normal flora (microbiota) helps keep pathogens from establishing themselves in these areas

what are pathogen-recognition receptors (PRRs) in the innate immune system?

recognizes molecules unique to infectious organisms which are pathogen-associated molecular patterns (PAMPs) on microorganisms… encoded by host’s DNA to sense extracellular infection and when bound to a pathogen, phagocytic cells (monocytes and macrophages) are activated

where are pathogen-recognition receptors (PRRs) found on?

• macrophages and dendritic cells

• neutrophils

• eosinophils

• monocytes

• mast cells

• T cells

• epithelial cells

what are acute-phase reactants in the innate immune system?

soluble factors that are found in serum and increases rapidly in response to infection, injury, or tissue trauma (like cardiac arrest but is not specific like troponin is)… facilitates contact between microbes and phagocytic cells and will mop up and recycle the important proteins after phagocytosis

what are the 7 acute-phase reactants?

• C-reactive protein

• serum amyloid A

• alpha1-antitrypsin (enzyme in the lungs)

• fibrinogen

• haptoglobin

• ceruloplasmin

• complement C3

what is adaptive immunity?

a type of resistance that is characterized by specificity for each individual pathogen, or microbial agent, and the ability to remember a prior exposure → has a delayed response of 5-7 days but is more vigorous and effective than natural immunity

Involves T and B lymphocytes (memory cells) & increases response to a pathogen upon repeated exposure but it lasts longer

what are leukocytes?

cells of the innate immune system that are found in the peripheral blood (circulating blood) that plays a key role in both innate and adaptive immunity (5 types of WBCs)

what is diapedesis?

the movement/passage of WBCs and other cells, primarily monocytes, out of the vascular system through gaps between cells comprising the vessel walls into the tissues (cells are “flush” together and there are small gaps in-between them)

what is chemotaxis?

movement of a cell or organism in a direction corresponding to a gradient of increasing or decreasing concentration of a particular substance like chemical agents or signals (calls cells to a specific location)

what are phagocytic cells?

macrophages in tissues and monocytes in blood which playa role in initiating and regulating innate and adaptive immune responses

what are the innate immune functions of phagocytic cells?

• microbial killing

• anti-tumor activity

• intracellular parasite eradication

• phagocytosis

• secretion of cell mediators

• play a role in both innate and adaptive immunity

• antigen processing cells (APCs)

what are mast cells?

plays a role in allergic reactions and can also function as APCs… can also enhance and suppress the adaptive immune response

resembles basophils but come from a different lineage (darker in color)

what are dendritic cells?

the most effective APC in the body and the most potent phagocytic cell and is covered with long membranous extensions that resemble nerve cell dendrites

defined as cells with a stellate (star) morphology that can effectively present antigens on MHC molecules and activate naive T cells

what are dendritic cells, monocytes, and macrophages members of?

they are members of the mononuclear phagocyte system (MPS) which exhibit multiple functions during immune responses

what are lymphocytes?

B cells (circulating humoral immunity), T cells (cellular immunity), and NK cells (cell responsible for apotosis) that represent between 20% and 40% of the circulating WBCs

virgin B cells are found in the spleen and most of the lymphocytes in circulation are T cells… mature antibody producing B cells (MPCs) are found in the lymph nodes

what are the two primary lymphoid organs and what do they do?

bone marrow

• one of the largest tissues in the body that fills the core of all long flat bones → main source of HSCs which develop into blood cells

thymus

• small, flat, bilobed organ found in the thorax and is the location for maturation of T lymphocytes

what do the secondary lymphoid organs function as?

functions as potential sites for contact with foreign antigens and increase the proability of an immune response

what are the secondary lymphoid organs?

• spleen

• lymph nodes

• mucosal-associated lymphoid tissue (MALT)

• cutaneous-associated lymphoid tissue (CALT)

  • T cells, monocytes, macrophages, and dendritic cells found on skin

whats the purpose of the red pulp and white pulp in the spleen?

red pulp

• destroys old RBCs (cellular components after destruction is filtered by the liver) and is the splenic tissue that makes up more than one-half of the total volume

white pulp

• contains lymphoid tissue arranged around arterioles in a periarteriolar lymphoid sheath containing T cells and comprises about 20% of the total weight of the spleen

what is contained in the primary follicles in the spleen?

B cells not yet stimulated by antigens, virgin B cells (naïve B cells), unassigned B cells

when B cells activate, they differentiate into plasma cells

what are lymph nodes?

central collecting points for lymph fluid that are located in groups, and each group drains a specific area of your body → lymphocytes and any foreign antigens enter nodes via afferent lymphatic vessels

lymph nodes can swell when the body is fighting off an infection, so the site of the swollen lymph nodes may help identify the underlying cause

what do the secondary follicles consist of and what do they do?

contains antigen-stimulated proliferating B cells & is the location where transformation of B cells take place → forms plasma cells and memory cells when exposed to an antigen

what is muscosal associated lymphoid tissue or MALT?

a main port of entry for foreign antigens with numerous macrophages and lymphocytes present → found on mucosal surfaces of the GI, respiratory, and urogenital tracts

what is the cardinal signs and symptoms of inflammation?

• redness (erythema) (rubor)

• swelling (edema) (tumor)

• heat (calor)

• pain (dolor)

body’s overall reaction to injury or invasion by an infectious agent

what is the process of inflammation?

1. the resident macrophages and mast cells at the site of inflammation will release chemokines that will cause vasodilation and induce selectins

2. selectins will then loosely bind circulating leukocytes and cause them to roll along the vascular wall

3. chemokine-induced integrins on the leukocytes bind firmly to the endothelial cells

4. integrins enable the leukocytes to crawl between endothelial cells, which is diapedesis

5. leukocytes then follow the chemokine concentration gradient to the site of infection which is chemotaxis

what cells are most involved in phagocytosis?

• neutrophils

• monocytes

• macrophages

• dendritic cells

what are NK cells?

recognizes any damaged cell and can eliminate it without any prior exposure to it which gives the immune system time to activate adaptive response of specific T and B cells

stimulated by exposure to cytokines, and when activated, additional cytokines and colony-stimulating factors are produced

what do NK (natural killer) cells provide a first line of defense against?

cells that are virally infections, cells that are infected with other intracellular pathogens, and tumor cells

influences innate and adaptive immunity

what are the functions of mature CD4 and CD8 T cells, and what types of antigens do they respond to?

CD4 T helper cells

• helps B cells produce antibodies → responds to exogenous antigens (bacteria) → MHC 2

CD8 cytotoxic T cells

• kills infected/abnormal target cells using perforins and granzymes→ responds to endogenous antigens → MHC 1

what are T regulatory (Treg) cells and what do they do?

are a CD4 and CD25 T-cell population that suppresses the immune response to self-antigens & secrete inhibitory cytokines (proteins that help put cells into action) to inhibit proliferation of other T-cell populations

Treg = “regulates/restrains” the immune response → protects against self-attack.

what are the 3 main stages of B-cell differentiation?

• development of mature immunocompetent B cells

• activation of B cells by antigen

• differentiation of activated B cells into antibody-producing plasma cells

develop → activate → plasma → antibodies

what are the stages of the antigen-independent phase of B-cell differentiation?

pro-B cell → pre-B cell → immature B cell → mature B cell

this phase occurs before the B cell encounters its antigen

what are pro-B cells?

develops from rearrangement of genes that code for heavy and light chains of antibody molecules and is made specific for certain antigens by variable regions → must successfully rearrange one set of heavy-chain genes to become pre-B cells

what are the 2 main types of mature B cells, and where are they found?

marginal B cells

• remains in spleen & responds quickly to bloodborne pathogens

follicular B cells

• migrates to the lymph nodes and other secondary organs and recirculates

what happens when mature B cells encounter their specific antigen?

has IgM and IgD on their surface which provides an activating signal to B cells when there is contact with an antigen → when the B cell is stimulated, the antigen-dependent phase is entered which forms memory cells (can last for decase) and antibody-secreting plasma cells

what are plasma cells?

a differentiated B cell which has a lot of cytoplasmic immunoglobulin but little or no surface immunoglobulin that produces antibodies and found in peripheral lymphoid organs and bone marrow

what are the main markers and functions of B cells?

has CD19, MHC class 2, and surface immunoglobulins → their antigen specificity develops as they mature and MHC 2 allows B cells to interact with CD4 T helper cells, which helps B cells produce antibodies

how do T cells initiate the adaptive immune response?

APCs are activated during the innate immune response and present antigens to T cells (activates adaptive immune response) → T cells will circulate throughout the bloodstream, lymph nodes, and secondary lymphoid tissue looking for antigens

APC finds antigen → T cell recognizes it → adaptive response starts

how are lymphocytes identified in the laboratory, and why is this important?

identified in the laboratory through flow cytometry using monoclonal antibodies → identifies and separates lymphocytes into subsets (like T and B cells)… helps diagnose malignancies, immunodeficiency diseases (like Chediak Higashi) and AIDS

how do age and overall health affect the immune response?

• neonates: immune system is not fully developed → weaker response

• older adults: decreased response to antigen stimulation

• pooor health: malnutrition, fatigue, and stress can weaken the immune response

how do route, dose, and genetics affect the immune response?

• route: IV, intradermal, subcutaneous, and oral can affect the response

• dose: generally larger dose → stronger response, but very large doses → tolerance

• genetics: inherited predisposition affects immune responsiveness

what two major traits determine whether a substance is a strong immunogen?

size

• must be at least 10,000 daltons to be recognized

• the most effective immunogens are at least 100,000 daltons

foreignness

• the more different/foreign the substance is from the body, the stronger its ability to trigger an immune response

bigger + more foreign = more immunogenic

what are the two types of epitopes?

linear

• sequential → amino acids are next to each other in sequence on the same chain

conformational

• has folding of one or more chains which allows amino acids from different segments to come into close proximity

epitope is a specific portion of an immunogen recognized by the immune system

what is a hapten?

a small, nonimmunogenic substance that creates new antigenic determinants when combined with a carrier and can react with the antibody, even without being complexed to a carrier molecule (meaning it can react with the antibody on its own)

what happens when haptens bind to its carrier?

when bound, haptens help form the lattice needed for precipitation and agglutination reactions

what are adjuvants?

substances that are added to immunogens/vaccines to make immunization more effective

how do adjuvants enhance the immune response?

• targets/activates APCs

  • important to the adaptive immune response

• protects immunogens from degradation

• allows a longer response time that attracts more immune cells to the injection site

• used to accelerate immune response and increase duration of protective immunity

adjuvant = boosts the vaccine

what are autoantigens?

belongs to the host and does not usually evoke an immune response → if a immune response occurs, an autoimmune condition is likely

what are alloantigens?

from other members of host species (such as in transplantation and blood transfusion)

what are heteroantigens?

from other species, such as animals, plants, or microorganisms

what are heterophile antigens?

exists in plants or animals but are identical to or closely related in structure so that antibody to one will cross-react with antigen of the other

ex. antigen from pneumococci bacteria cross-reacting with type B blood group antigen

what are the functions of major histocompatibility complex (MHC) molecules?

presents antigen fragments on the cell surface for recognition by T cells, and helps the immune system distinguish self from foreign… also helps determine whether transplanted tissue/organs are accepted or rejected

what is the MHC 1 molecule and what is it associated with?

found on all nucleated cells and are glycoprotein dimers made up of two noncovalently linked polypeptides & is associated with cellular immunity and CD8 T cells… also differs in levels of expression:

• highest on lymphocytes and myeloid cells

• lowest or undetectable on liver hepatocytes, neural cells, muscle cells, and spermatozoa

what is the MHC 2 molecule and what is included?

found primarily on APCs and includes B lymphs, monocytes, macrophages, dendritic cells, and thymic epithelium

what does MHC class 1 present, and which T cells does it interact with?

presents peptides from inside the cell (like viral peptides) to CD8 T cells, leading to cytotoxic killing of the target cell

inside → MHC 1 → CD8 → kill

what does MHC class 2 present, and which T cells does it interact with?

presents peptides from outside the cell (like pathogen-derived antigens) to CD4 T helper cells, which help stimulate an antigen-specific antibody response