Immunology

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primary lymphoid tissues

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sites of lymphocyte formation

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B cells

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form in bone marrow

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T cells

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form in bone marrow but mature in thymus

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secondary lymphoid tissues

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sites of activation by antigen and initiation of immune response

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lymph nodes

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contains WBC that filter antigen out of lymph

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spleen

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filters antigens out of blood

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tonsils, mucosal tissues, and secretory glands

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part of the secondary lymphoid tissues

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lymph

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fluid derived from blood that collects in intercelluar spaces, then moves into lymph ducts that eventually join together in one large vessel: thoracic duct, which returns lymph to subclavian vein back to blood system.

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innate immune response

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non specific, found in in/vertebrates

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physical barriers (innate)

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skin, mucosal, epithelia

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chemical defenses (innate)

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acid secretion, lysozyme

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lysozyme

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enzyme that attacks bacterial cell walls

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physiological defense (innate)

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vomit, fever, inflammation

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histamine release

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increased vascular permeability allowing influx of fluids, molecules, and cells that contribute to response

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cellular defenses (innate)

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phagocytosis, natural killer cells, and production of:

1. interferons and other anti-microbials
2. complement proteins
3. defensins

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interferons

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kill viruses and activate surrounding cells to kill too

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anti-microbials

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type of cytokine

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complement proteins

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attract phagocytes, activate imflammation, and lyse cells

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defensins

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peptides that are toxic to pathogens; insert themselves to membrane to destroy

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induction of innate response

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toll-like receptors on WBC recognize conserved microbial components

binding of pathogen to toll-like receptor triggers signal transduction pathways that activate mediators, wihich activate:

phagocytosis of pathogen
transcription factors (NF-kB) that activate innate and inflammatory responses by inducing expression of cytokines

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cytokines

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protein hormones of immune system

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adaptive immune response

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unique to vertebrates

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4 key features of adaptive response

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specificity, diversity, memory, and self vs. non-self discrimination

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2 main types of adaptive responses

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1. humoral response

2. cell-mediated responses

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Humoral response (adaptive)

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helper T cells help activate B cells

antigen activation of B cells --> differentiate into plasma cells that produce antibodies

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Cell-mediated responses (adaptive)

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antigen-activated cytotoxic T cells kill altered self cells that express foreign antigens

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Antibody proteins (Ab) (syn)

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Immunoglobulins (Ig) (syn)

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Structure of Ab/Ig

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tetramer of two identical heavy and two identical light chains

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N-term of heavy and light chains

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are variable and create antigen-binding sites

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C-term of heavy and light chains

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constant region

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2 types of constant light chains

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Kappa or Lambda

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5 types of constant heavy chains that determine class of antibodies

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Gamma, Mu, Delta, Alpha, and Epsilon

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Gamma Heavy chain

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IgG, monomer, free in blood plasma; involved in primary and secondary responses

Bind to Fc receptors on macrophages to promote phagocytosis of antigen

Cross placenta to immunize fetus

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Mu Heavy chain

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IgM, pentamer, surface of B cell and free in blood plasma; antigen receptor on B cell; first antibodies released by B cells during primary response

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Delta Heavy chain

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IgD, dimer, surface of B cell; found in mature B cells --> important for B cell activation

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Alpha Heavy chain

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IgA, monomer; secretions: saliva, tears, milk, blood; protects mucosal surfaces

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Epsilon Heavy chain

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IgE, monomer; secreted by plasma cells in skin and lining tissues; antigen binding triggers mast cells and basophils to release histamine

Allergies

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Secretory IgA

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contains an extra chain: the secretory component

can get across epithelial cell barriers

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How secretory IgA gets acros epithelial cell barriers

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IgA binds poly-IG receptors on basel (outside of gut) side of epithelium --> triggering receptor-mediated endocytosis of IgA-poly-Ig complex

Endocytic vesicles travel through epithelial cell and fuse with apical/lumenal surface (inside)

in lumen, receptor is cleaved releasing secretory IgA

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IgE is responsible for what response?

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Allergic ones

Mast cells and basophils have receptors for IgE, and secretory granules containing histamine

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How does IgE work in allergic responses?

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1.) Sensitization: initial exposure to antigen --> B cells produce IgE

2.) IgE binds to receptors on basophils/mast cells --> release histamine and other substances

3.) Later response: IgE already bound to mast cell/basophil. When antigen binds, mast cell/basophil releases histamine --> allergic response, important for anti-parasite immunity.

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what cells are involved in the humoral immune response?

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B cells and helper T cells

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(Hummoral response)

Step 1: ___ takes up antigen by phagocytosis and degrades antigen in _____

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macrophage; lysosome

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(Hummoral response)

Step 2: Macrophage releases interleukin-1 (cytokine) to activate ___

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T_h cells

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(Hummoral response)

Step 3: A ___ protein binds antigen fragment in lysosome and brings to macrophage cell surface, where ____ on helper T Cell recognizes antigen fragment. T_h co-receptor ___ also binds MHC II protein to enhance activation

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MHC II; T cell receptor; CD4

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(Hummoral response)

Step 4: Result of TCR binding antigen fragment is release of ___ by T cell that causess self-activation

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cytokines

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(Hummoral response)

Step 5: T_h cells proliferates to form ___ T_h cells and ___ T_h cells

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effector; memory

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(Hummoral response)

Step 6: Binding of antigen to specific ____ receptor on B Cells triggers endocytosis, degradation, and display of processed antigen on B cell surface by _____

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IgM; MHC II

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(Hummoral response)

Step 7: _____ releases cytokines to activate B cell proliferation

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Helper T Cells

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(Hummoral Response)

Step 8: __ recognizes antigenic fragments on ____

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T_h cell; B cell surface

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(Hummoral Response)

Step 9: B cells proliferate and differentiate into ___ or ___. Heavy chain switching (to IgG, IgA, IgD or IgE) can occur at this stage

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plasma cells; memory cells

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(Humoral response)

Step 10: ___ cells produce and release ____

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plasma cells; soluble antibodies

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MHC II involved in ____ response

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humoral

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MHC I involved in ____ response

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cell-mediated (cytotoxic)

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Cytotoxic T cells (T_c)

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kill self-cells containing foreign antigens

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(Cell-mediated response)
Step 1: viral proteins are made in infected cell and degraded in cytosol are picked up by ___ proteins and brought to cell surface

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MHC I

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(Cell-mediated response)

Step 2: T cell receptor on ____ cytotoxic T cell recognizes antigenic fragment bound to MHC I protein on infected cell surface. T_c co-receptor ___ also binds MHC I and enhances activation

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immature; CD8

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(Cell-mediated response)

Step 3: T_c cell proliferates to form __ T_c and ___ T_c cells

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effector; memory

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(Cell-mediated response)

Step 4: effector T_c cells recognize antigenic fragments on ___

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infected cells

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(Cell-mediated response)

Step 5: T cells release ____ and other proteins

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perforin

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(Cell-mediated response)

Step 6: perforin causes ___ of infected cell before ___ can multiply

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apoptosis; viruses

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Gene rearrangements

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account for diversity and specificity of Igs and T-cell receptors

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Gene rearrangement details

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1. germline cells contain many V, D, and J genes

2. when cell commits to B/T cell lineage, gene rearrangements occur in ___ region to result in random combo of V, D, and J gene segments

-- Occurs in Ig V_l (V and J genes) and V_h (V, D, and J genes) during B cell developement

-- Occurs in TCR (V, D, and J genes) during T cell development

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variable

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(Property of TCR or Antibodies?)
Anitgenic determinants are all peptides

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TCR

(Ab can response to whole Ag as well)

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(Property of TCR or Antibodies?)

Can be expressed as a secreted protein

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Ab

(TCR just on membrane)

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(Property of TCR or Antibodies?)

Can be expressed as a membrane protein

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BOTH

(IgM = membrane protein)

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(Property of TCR or Antibodies?)

Recognition of antigens causes cells to divide and differentiate into effector and memory cells

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BOTH

(B cell will form plasma and memory)

(T_h and T_c)

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(Property of TCR or Antibodies?)

Can trigger phagocytosis/endocytosis of bound pathogens

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Ab

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(Property of TCR or Antibodies?)

Recognizes conserved (general feature) components of pathogens

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NONE

(will be recognized by toll-like)

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(Property of TCR or Antibodies?)

Is encoded by V, D, J, and C segments

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BOTH

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(Property of TCR or Antibodies?)

cells of a clone can undergo heavy chain switching

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Ab