chapter 24

first line of defense against infection

non-specific natural barriers which restrict entry of pathogen (“innate resistance”)

second line of defense against infection

innate non-specific immune defenses provide rapid local response to pathogen after it has entered host

examples: fever, phagocytes (macrophages and neutrophils), inflammation, interferon

third line of defense against infection

antigen-specific immune responses, specifically target and attack invaders that get past first two lines of defense

examples: antibodies and lymphocytes

innate immunity

2nd line, phagocytes are primary effector cells, general response to broad range of pathogens, no immune memory after exposure, rapid response within hours

more on innate immunity

nonspecific immunity and non inducible (preexisting) ability to recognize and destroy an individual pathogen or its products

• does not require previous exposure to a pathogen or its products

• involves recognition of common pathogen-associated molecular patterns (PAMPs) on pathogens (as well as the PRRs, PAMP recognition receptors, like TLRs)

• mediated by phagocytes

adaptive immunity

adaptive immunity = 3rd line, lymphocytes are primary effector cells, focused attack on specific pathogen, antibodies (from plasma cells) and cytotoxic T cells help clear specific infection, postexposure immunity by B and T memory cells ins common, response requires days

more on adaptive immunity

acquired ability to recognize and destroy a particular pathogen or its products

• dependent on previous exposure to the pathogen or its products for large number of cells/receptors

• directed toward an individual molecular component of the pathogen (antigen)

tell me about primary and secondary immune response

following first antigen exposure, a primary adaptive immune response occurs

stimulation of specialized antigen-reactive immune leukocytes (lymphocytes: T and B cells)

each lymphocyte produces a unique protein that interacts with a single antigen

• T cells: TCRs

• B cells: BCRs = antibodies or immunoglobulins (igs)

T cells can recognize antigen only when…

presented on self proteins called major histocompatibility complex (MHC) proteins

how does adaptive immunity begin?

with interactions of immune T cells with antigens on infected cells (MHC1) or as APC (MHC2)

T lymphocyte subsets

1. T-cytotoxic (Tc) cells (CD8 cells)

2. T-helper (Th) cells (CD4 cells)

3. Th1 cells

4. Th2 cells

CD8 cells

• recognize antigen presented by MHC1 protein on an infected cell

• kill antigen-bearing target cells directly

CD4 cells

• interact with peptide-MHC2 complexes on the surface of antigen-presenting cells

• act through cytokines to promote immune reactions

Th1 cells

initiate inflammation and immunity by activating macrophages

Th2 cells

stimulate antigen-reactive B cells to produce antibodies

leukocytes

nucleated white blood cells

lymphocytes

specialized leukocytes involved exclusively in adaptive immune response

1. B cells = originate and mature in bone marrow

2. T cells = originate in bone marrow, mature in thymus

primary lymphoid organs

bone marrow and thymus where Bs and Ts develop

secondary lymphoid organs

where Bs and Ts are activated » sites where antigens interact with antigen-presenting phagocytes and lymphocytes to generate an adaptive response (made of lymph nodes, MALT, and spleen)

cytokines/chemokines

proteins that are messages for immune cells

lymph

fluid similar to blood that contains nucleated cells and proteins but not RBCs

stem cells

common precursor cells with the ability to renew and differentiate

the whole blood is composed of…

cells and plasma (liquid with proteins and solutes)

serum

remaining fluid after clotting (when taken outside the body); no cells or clotting proteins but does contain antibodies and other proteins

pluripotent stem cells

can make any cell of organism, NOT placenta

totipotent stem cells

can make ANY cell including placenta

multipotent stem cells

can make multiple types of cells

describe the lymphatic system

a separate “circulatory” system that drains lymph fluid from extravascular tissues

what percentage of blood cells are leukocytes?

0.1%: and this includes phagocytes and lymphocytes

what happens in capillary beds?

leukocytes and solutes pass from blood into the lymphatic system

lymph nodes contain…

high concentrations of lymphocytes and phagocytes » high B cells and T cells so that there’s a higher probability of “bumping into each other”

mucosa-associated lymphoid tissue (MALT)

contains lymphocytes and phagocytes » interacts with antigens and microorganisms from gut, respiratory tract, other mucous membranes

what does the white pulp of spleen also contain?

lymphocytes and phagocytes which filters the blood

myeloid cells (derived from myeloid precursor cell)

1. antigen-presenting cells (APCs) engulf (phagocytose), process, and present antigens to lymphocytes

   1. monocytes, macrophages, dendritic cells, B cells

   2. mast cells phagocytose, but are not APCs

2. granulocytes contain toxins or enzymes that are released to kill target cells

   1. neutrophils (can phagocytose too), basophils, eosinophils, mast cells

if B cell does not bump into right antigen…

then phages and dendritic cells need to spring into action

what are antibodies/immunoglobulins?

soluble proteins made by B cells in response to exposure to non self antigens

why do B cells display antibodies on their cell surfaces that directly interact with antigens?

to cause B cells to ingest pathogen via phagocytosis » B cells then produce many pathogen-derived peptide antigens that are presented to antigen specific Th2 cells

do Th2 cells interact directly with the pathogen?

no, but they stimulate other cells (antigen-reactive B cells)

what do activated B cells differentiate into?

plasma cells that produce soluble antibodies (primary antibody response) detectable ~5 days after exposure (peak ~2 weeks)

subsequent exposure to the same antigen induces memory (secondary antibody response)

how are different classes of antibodies distinguished from one another?

by their amino acid sequence

igM and igG are found…

in blood (primary response consists mostly of IBM and secondary is large amounts of igG)

igA is found…

in blood and in high concentrations of secretions from mucous membranes (lungs, gut, breast milk)

igE is found…

attached to mast cells and is involved in parasite immunity and allergies

igD is found…

on surface of B cell (the B cell receptor)

functions of antibodies

• can bind to pathogens (block adhesion)

• can bind to toxins and inactivate the toxin: “neutralization”

• provide targets for interaction with proteins of the complement system, resulting in destruction of antigens through lysis or opsonization

describe complement system

igM or igG bind to pathogen and recruit complement protein

1. form pore in pathogen membrane (gram positive relatively resistant to this)

2. induce phagocytosis (C3 receptor or FcR receptor on phagocytes bind C3 protein of complement or antibody C region)

inflammation

both innate and adaptive immune response can cause it; nonspecific reaction to noxious stimuli

• redness, swelling, pain, and heat localized at site of infection

in the context of inflammation, what are the molecular mediators?

proteins called cytokines and chemokines

describe effective inflammatory response

• isolates and limits tissue damage, destroying damaged cells and pathogens » can result in considerable damage to healthy tissue

• PRRs on macrophages and other tissue cells at site bind pathogen PAMPs; activates local cells to produce and release mediators including cytokines/chemokines; bind receptors on cells like neutrophils

which are the first to arrive at infection?

neutrophils, attracted to site by interleukins (pro inflammatory cytokines) released by local macrophages, release more chemokines when activated to recruit more neutrophils

what do cytokines do to the body as a whole?

increase vascular permeability and blood flow, causing swelling (edema), reddening (erythema) and local heating associated with inflammation

in some cases when inflammation fails to localize pathogen…

pathogen becomes systemic and can lead to septic shock » life-threatening

serious consequences of systemic inflammatory reactions

1. uncontrollable fever

2. extremely low BP and severe edema

3. death in up to 30% of individuals from the septic shock

give the spiel on superantigens

proteins capable of eliciting a strong response because they activate more T cells than normal immune response

• produced by many viruses and bacteria that interact with TCRs

• super antigen-activated T cells may produce systemic diseases characterized by systemic inflammatory reactions