l36-l38: immune system

immune system

diffuse collection of cells and organs that are responsible for the ability to resist infection and disease

physical barriers

anatomical and physiological mechanisms created by non-immune cells that prevent entry of foreign organisms and substances

cell-mediated immune responses

innate and adaptive defense responses that rely on white blood cell (WBC) activity

secretions

wash away (and/or destroy) potential pathogens

hair

keep potential hazards away from the skin surface

stratified squamous epithelium

many closely interlocked layers which keep intruders out

mucous membranes

line the digestive, respiratory, urinary, and reproductive tracts

hematopoietic red bone marrow

birthplace of white blood cells

innate responses

nonspecific responses that react to any threat they detect

• present from birth

adaptive responses

specific and powerful responses triggered by exposure to particular antigens

• ‘learned’ over the lifetime

lymphatic system

consists of vessels that move lymph through the body, and tissues that produce of house lymphocytes

lymph

fluid connective tissue that resembles blood, but lacks most of the cells and most of the plasma proteins

non-immune functions of the lymphatic system

1. return of filtered fluid from ISF to plasma

2. transport of digested and absorbed lipids

lymphatic vessels

• have an endothelial wall around a lumen

• larger vessels have a smooth muscle layer and contain valves

• capillaries have blind ends

• typically more permeable along their length

lymphocytes

white blood cells that come from lymphoid stem cells

lymph nodes

encapsulated structures which are connected to lymph vessels and house mature lymphocytes

afferent vessels

where antigens (or WBCs that have detected antigens) enter the lymph node

efferent vessels

where activated lymphocytes that have acquired specific adaptive immune responses leave the lymph node

lymphoid nodules

regions of lymphoid tissue that are typically associated with mucosa

• lack a distinct capsule

• found in areolar tissue within mucous membranes

• density is highest where there are many live pathogens in the lumen

spleen

organ containing large amounts of lymphoid tissue that filters and monitors the blood

• recycles old RBCs in its red pulp

• white pulp are clusters of lymphocytes

acellular soluble factors

secreted molecules which are involved in immune responses

complement

group of plasma proteins that contribute to anti-microbial defenses

• synthesized by the liver and circulate in blood plasma

• when activated, they generate an enzyme cascade that can lead to pathogen death

cytokine

any signalling molecule that is used as part of cell-mediated immune responses

• paracrine or endocrine

• released by immune or non-immune cells

• act on immune or non-immune cells

• enhance or suppress immune responses

immediate response

phase 1 of the innate immune response that is generated by cells and soluble factors already present in the local tissue

induced response

phase 2 of the innate immune response that occurs with the recruitment of WBCs (especially phagocytes) from blood circulation

mast cells

recognize tissue damage and pathogen entry and release signalling molecules

chemokine

cytokine that functions to attract WBCs to move toward it

paracrine factors

signalling molecules released from mast cells that lead to structural and physiological changes in the local tissue

interleukin 1 (IL-1)

can reprogram the hypothalamic set point for temperature, triggering fever

interleukin 6 (IL-6)

can stimulate proliferation of WBCs (especially neutrophils) in red bone marrow

extravasation

recruitment of circulating WBCs involving

1. changes in the endothelial wall - allowing WBCs to stick to it

2. chemotaxis of WBCs into the interstitial space

phagocytic myeloid cells

resolve infection by engulfing and destroying pathogens

neutrophils

very abundant; the main cell type recruited during innate immune responses

eosinophils

mostly phagocytose pathogens that have already been targeted by antibodies

macrophages

can be resident or recruited; involved in innate responses, removal of dead cell debris, and sometimes act as antigen-presenting cells (APC)

pus

mixture of protein-rich fluid and dead leukocytes (mostly neutrophils) at a local site of infection

complement C3a

can initiate an inflammation response, or enhance its magnitude

complement C3b

leads to recruitment of other complement proteins that trigger cell lysis; also binds to bacterial surface and improves the efficiency of phagocytosis

natural killer (NK) cells

perform immune surveillance, locating (and destroying) abnormal self cells

• resolve infection by releasing substances that trigger cell membrane permeability and lysis

abnormal ‘self cell’

body cell that is either infected by a virus or part of a tumor

interferon alpha (IFN-α)

cytokine secreted by NK cells to recognize abnormal cells

tumor necrosis factor alpha (TNF-α)

cytokine released by NK cells which acts as a paracrine signal that can induce apoptosis in tumor cells

interferon gamma (IFN-γ)

cytokine released from NK cells that can act an a chemokine, attracting and stimulating macrophages (and other cells) to the site

antigens

molecules that stimulate an immune response

antigen-presenting cells

prepare and present antigens to lymphocytes

T cells

execute cell-mediated immunity to physically or chemically destroy pathogens and infected cells

B cells

facilitate humoral immunity and produce antibodies that target antigens for destruction

intracellular antigens

undergo processing and presentation through the MHC class I pathway

MHC class I molecules

located on the surface of all nucleated cells

extracellular antigens

are phagocytosed, broken down into smaller peptides, then loaded onto MHC class II molecules for cell surface presentation

MHC class II molecules

are exclusively located on the surface of antigen presenting cells and lymphocytes

T cell receptors

are unique to each lymphocyte; different lymphocytes recognize different antigens

cluster of differentiation (CD) markers

play a role in antigen recognition, intercellular communication, and environment sensing

CD8+ T cells

• when an inactive cell interacts with an MHC class I molecule and recognizes the bound antigen, the T cell becomes primed

• for full activation, it must receive a co-stimulation signal either from the infected cell or from its surroundings

• activation stimulates T cell division and differentiation

cytotoxic T cells (T_c)

directly attack and destroy infected cells by releasing cytotoxins that enter the infected cell and induce cell death

memory T_c cells

inactive T_c cells that remain in secondary lymphoid organs until a later antigen exposure

CD4+ T cells

• inactive cells become primed after binding and recognizing antigens presented by MHC II

• activation requires co-stimulation

• activated cells divide and differentiate

regulatory T cells

suppress immune activation by releasing inhibitory cytokines

helper T cells (T_H)

secrete cytokines that stimulate cell-mediated and antibody-mediated immunity

sensitization

B cell receptors bind antigens, endocytose and load them onto MHC II molecules, and await helper T cell interaction for activation

antibodies

small proteins made by plasma cells

• consists of 2 parallel polypeptide chains: heavy and light

• each chain contains a variable and constant segment

• tips of the variable segments form a unique antigen-binding site

• when the variable segments bind their target antigen, binding sites on the constant segments are accessible and bind complement proteins or innate immune cells

IgG

accounts for 80% of all antibodies and protects against bacteria, bacterial toxins, and viruses

IgA

found in glandular secretions and mucus membranes and prevent pathogens from accessing internal tissues

IgM

the first Ig type to be released during infection and circulates through blood and lymph

IgE

associated with allergic reactions and binds mast cells, eosinophils,and basophils

IgD

located on B cells and binds extracellular antigens during sensitization

resolution

• removal of pro-inflammatory cytokines

• immune cells clear from site of inflammation and undergo apoptosis

post-resolution

• tissue-resident macrophages and dendritic cells return

• influx of regulatory T cells to establish immune suppression