pcs unit 3 - immune system

immune system

a distributed set of cells that fight disease in the blood, lump fluid, tissues, and organs throughout the body; a system of physiological defense that…

• distinguishes self vs non-self

• removes/makes harmless foreign substances

• destroys cancerous cells

innate immune responses

defend against foreign substances without having to recognize their specific identities

adaptive immune responses

depend on the immune system recognizing specific pathogens; usually needs to be introduced to the pathogen before (i.e., getting sick or vaccination)

leukocytes

white blood cells

macrophages

natural killer cells (NKs)

neutrophils

lymphocytes

B and T cells

categories of innate defenses

• physical barriers

• phagocytes

• natural killer cells

• complement system

• immune system

physical barriers

keep hazardous organisms and materials outside the body

ex: multilayered skin, hair, mucus linings, stomach acid, and antimicrobial chemicals (lysozomes)

phagocytes

cells that engulf pathogens and cellular debris

ex: macrophages and neutrophils

natural killer cells (NKs)

perform immune surveillance by recognizing and destroying cancer cells and virally infected cells by lysing the cells

complement system

a set of at least 30 proteins circulating in the plasma that assist in the destruction of pathogens

• can recruit phagocytes (e.g., neutrophils and macrophages)

• activates the membrane attack complex (MAC)

steps of inflammation

1. a number of types of cells, including epithelial cells and leukocytes, release signaling molecules that

   1. increase capillary permeability → endothelial cells contract, widening spaces (intercellular clefts) between them to increase protein and leukocyte delivery to the injured area

   2. dilate local arterioles → increase blood flow to the areas, increasing the delivery of proteins and WBCs (edema)

2. phagocytes such as neutrophils and macrophages, move out of the blood (across the endothelium of capillaries) to enter the inflamed area

   1. chemotaxis

3. killing the pathogen

   1. engulfment (then destruction) by a phagocyte cell, like neutrophils

   2. complement system

4. tissue repair

chemotaxis

directed, multistage migration of WBCs from the blood to an injury site in response to a chemical stimulus

C3B

one of the complement proteins; interacts with the pathogen membrane and marks it for destruction via phagocytosis or MAC

membrane attack complex (MAC)

a complex of complement proteins that embeds in the membrane of the pathogen and pokes holes in it

patten recognition receptors (PRRs)

transmembrane proteins on neutrophils that recognize molecular patterns commonly found in potential pathogens

complement receptor-1 (CR1)

binds to C3B and blocks the complement system

natural killer cells (NKs)

use a combination of activation and inhibitory receptors

• activating receptors → send an activating signal, telling NKs to kill cells

• inhibitory receptors → send an inhibitory signal, telling NKs not to kill cells

• when both are present, cell destruction depends on how much of the activation receptor vs inhibitory receptor is present

lymphocytes

key cells in adaptive immune response; originate in the bone marrow, and can be found in the lymphatic system and the blood

• B cells → plasma cells, memory B cells

• helper T cells

• cytotoxic T cells

lymphatic system

vessels that drain interstitial fluid into the veins

term and blood vessels are where most B and T cells reside

antigens

any kind of marker (typically proteins/sugars) that the immune system can recognize to generate an adaptive immune system; the key to specify in adaptive immune response

• exist on viruses, bacteria, allergens, parasites, proteins, tumor cells (non-self), and normal cells (self) in our own bodies

B cells

express one antigen receptor (which can be secreted as an antibody) which recognizes one antigen

antigen binding to receptors cause division → creates plasma cells and memory term

antigen presentation is a second function

a type of immunoglobulin

immunoglobulin

multi-subunit proteins with a vairable region

plasma cells

secrete antibodies

memory B cells

store antigen receptors for future immune responses

antibodies

secreted by memory B cells

the Fc (stem) portion interacts with antigen receptor molecules on phagocytes, stimulating phagocytosis of pathogens

also activate the complement system

helper T cells

bind to antigens complexed with MHC Class II

specific to one antigen

require co-stimuli to fully activate and secrete signals that

• activate themselves (autocrine signaling)

• activate nearby B cells, cytotoxic T cells, and NK cells (paracrine signaling)

cytotoxic T cells

activated by antigen complexed with MHC Class I molecules

specific to one antigen

require signals from helper T cells for activation

MHC Class II

not antigen-specific

made by a macrophages, B cells, and other antigen-presenting cells

bind to Helper T cells

MHC Class I

not antigen-specific

expressed by all cells so cytotoxic T cells can target the destruction of any cell

DNA recombination

occurs in B cell receptors and T cell receptors

occurs during development for DNA coding antibodies/receptors

results in the coding of different versions of proteins to produce enormous diversity → allows cells to respond to different types of antigens

second exposure

bigger and faster than the first (peak response 7-10 days vs 2-5 days) due to more antibody production

immunological memory is mediated by memory T and B cells

after an infection

• most activated lymphocytes undergo apoptosis

• antibodies can last for days to months

• memory B cells remain, some helper T cells and cytotoxic T cells also remain as memory cells

active immunity

resistance to a pathogen that occurs because of exposure to a pathogen or vaccination, causing an adaptive immune response

passive immunity

resistance to a pathogen that occurs because of direct transfer of antibodies from one individual to another

occurs during gestation, breastfeeding, and as therapy

encounter and antigen recognition (step 1 of adaptive response)

each lymphocyte expresses one type of surface receptor that could recognize an antigen

if the surface receptor binds an antigen, that is “recognition”

lymphocyte activation (step 2 of adaptive response)

binding of antigen activates lymphocytes, causing multiple rounds of cell division, clonal expansion, and stimulating their function in coordinating attack/immune memory

coordinate attack (step 3 of adaptive response)

antibodies target pathogens for destruction by macrophages and the complement system

cytotoxic T cells kill our cells presenting antigen with the MHC Class I molecule (most often virally infected cells)

helper T cells supply signals that participate in the activation of other immune cells

passing the infection (step 4 of adaptive response)

once the pathogen is destroyed, most activated lymphocytes undergo apoptosis

antibodies and memory B and T cells mean that we respond more quickly and robustly to the next infection

immune tolerance

the development of the prevention of lymphocytes from attacking our own cells

includes central and peripheral term

central tolerance

development of tolerance in the organs where developing B and T cells mature by clonal deletion

B cells mature in the bone marrow, T cells mature in the thymus (lymph organ above the heart)

clonal deletion in B cells

process of apoptosis when immature B cells with strongly reactive receptors to antigens encounter a wide range of self-antigens during maturation in the bone marrow

clonal deletion in T cells

process of apoptosis when immature Helper T cells and Cytotoxic T cells with strongly reactive receptors to antigens encounter a wide range of self-antigens during maturation in the bone marrow

mediated by TECs

thymic epithelial cells (TECs)

express both MHC Class I and II molecules and present antigens to both immature Helper T and Cytotoxic T cells

peripheral tolerance

recognition of specific antigens by Regulatory T cells to inactivate T cells

mediated by Regulatory T cells

regulatory T cells

central role occurs outside of the thymus and bone marrow

can recognize self antigen complexed with MHC Class I and II proteins

target both autoreactive Cytotoxic T cells and Helper T cells for inactivation

autoimmune disease

occurs when the immune system attacks antigens on our own cells

ex: multiple sclerosis (attacks myelin in the CNS), type 1 diabetes mellitus (attacks beta islet cells in the pancreas)

common pathways of autoimmune diseases

1. failure in clonal deletion and/or inactivation of autoreactive lymphocytes

   1. low number or low activity of TECs or Regulatory T cells

2. exposure to pathogens containing antigens very similar to our own proteins can lead to cross-reactivity

innate vs adaptive immune responses

innate → rapid (hours, requires chemotaxis), non-specific, no immunological memory

adaptive → longer (days, requires clonal expansion), specific, has immunological memory

interaction of innate and immune responses

antibodies direct phagocytes and the complement system to pathogens

macrophages present antigens to helper T cells

Helper T cells supply signals that help activate NK cells

B and T cells arrive via chemotaxis to sites of inflammation