Immunology Flashcards
Primary vs Secondary Lymphoid Organs
Central vs Peripheral Lymphoid Organs
Primary lymphoid organs = sites of B and T cell maturation
- thymus, bone marrow
- fetal liver
- in birds: bursa of Fabricius
- in humans: thymus and bone marrow
Secondary lymphoid organs = in which further differentiation of lymphocytes occurs
Central Lymphoid Organs: Bone marrow, thymus
Peripheral Lymphoid Organs: Spleen, lymph nodes, tonsils
Lymphocytes Maturation
All lymphocytes derive from stem cells in the bone marrow
Initially immuno-incompetent
Stem cells destined to become B lymphocytes remain in the bone marrow as they mature, while T cells migrate to thymus to undergo further growth
Mature B and T lymphocytes exit primary lymphoid organs and transported via bloodstream to secondary lymphoid organs, where become activated by contact with foreign materials (antigens)
Lymphoid progenitor cells (3)
Hematopoietic stem cells (precursors): immature cells that develop into all types of blood cells
Myeloid progenitor cells: descendants of stem cells differentiate into specialized cell types
Natural killer cells: recognize general signals of immune stress such as inflammation
B vs T cells
B and T cells recognize foreign antigens via hypervariable B cell and T cell receptors (BCRs and TCRs)
B cells: recognize free, unprocessed antigens
T cells: recognize antigens within a complex of cell surface proteins on the surface of antigen-presenting cells
T-cells –mature in thymus, effector T-cells
B-cells –mature in bone marrow, differentiate into antibody-secreting plasma cells
T cell Receptors (TCRs)
made up of 2 polypeptide chains (α &β)-compose 1 antigen binding cite
T cell receptor structure is maintained by a disulfide bond linking the 2 chains together
Types of T cells (4)
Cytotoxic T cells = Killer T cells: target cancer, virally infected, or damaged cells
Helper T cells: 3⁄4 of total T-cells, help B cells by releasing cytokines
AIDS patients, inactivated or destroyed T helper cells which leaves body unprotected against infectious disease
Memory T cells: have extended lifetime and help to recognize antigens to which they were previously exposed
Suppressor T cells: block actions of some other types of lymphocytes to keep immune system from becoming over-active
Role of Killer T cells
Secretes hole-forming proteins, called perforins, that punch round holes in membrane causing fluid to rapidly flow into cell
Release cytotoxic substance directly into attacked cell
Role of Helper T cells
Stim growth and proliferation of cytotoxic and suppressor T-cells
Stim growth and differentiation of B-cells to form plasma cells and antibodies
Activate macrophages
B cell receptors (BCRs)
made up of 4 peptides (2 light & 2 heavy chains) comprise 2 antigen-binding regions immunoglobulin (Ig)
Heavy chains can be IgG, IgA, IgM, IgD, or IgE isotypes
IgM=largest antibody, 1st antibody to appear in response to initial exposure to an antigen
B cells activated in two ways:
• T cell-dependent activation – helper T cells recognize the antigen-MHC complex then deliver activating signals to B cell= clonal expansion= produce IgM= IgG
• T cell-independent activation –B cell receptor bind with antigen= produce (IgM)
Effector B cells vs Memory B cells
Effector B cells (aka plasma cells): produce antibodies
• Antibodies work as alarms to target invading agents for destruction by other immune agents like macrophages
Memory B cells: help immune system respond more quickly to future invasions by the same agent
First Line of Defense (non-specific & local)
Physical & chemical barriers include:
• Skin (physical = keratin) & (chemical = acidity and sebum (oily secretion of the sebaceous glands) have bacteriostatic effect)
• Mucous membranes (sweat, tears, stomach acid, saliva, urine flow, vaginal secretions, urine flow)
Mucous membrane secretions:
• gastric secretions contain HCl and proteolytic enzymes
• acidic vaginal secretions are bacteriostatic
• mucus traps microorganisms
Exocrine secretions:
• saliva, tears, and perspiration contain lysozyme (bacteriostatic agents)
Second Line of Defense (non-specific & local)
Includes: 1) Antimicrobial substances (such as cathelicidins), 2) Natural killer cells, 3) Phagocytes, 4) Inflammation, 5) Fever
Macrophages: have lysosomes which contain lysozyme +low pH
Natural Killer (NK) cells: look for foreign cells, MHC proteins - If MHC pr NOT present, NK cells release deadly cocktail of enzymes and chemicals
Inflammation: non-specific response triggered when tissues are injured (or infected)
• Prevent spread of toxic/harmful agent (infection)
• Eliminate cell debris and noxious agent
• Prepare the tissue for repair
***Chemicals of Inflammation (4)
Histamine: released by basophils and mast cells
o promotes vasodilation, increased capillary permeability of capillaries to WBC/pr
Kinins: plasma protein kininogen activated by enzymes from lysosomes → kinin-induce pain
Lymphokines: released by lymphocytes –enhance inflammation, and immune response
Prostaglandins: induce vasodilation and symptoms of inflammation
Stages of Inflammation
- Cell injury –Causes: mechanical trauma, thermal trauma (heat/cold), chemicals, microbes, hypoxia (deficiency of oxygen), autoimmunity
- Vascular response
Characterized by: vasodilation (increases blood flow) =hyperemia & erythemia (increase capillary permeability) =fluid accumulates at site of infection & albumin released keep fluid in bloodstream=maintenance of appropriate edema - Cellular response
Diapedesis: of leukocytes out of circulatory system and towards site of tissue damage/infection
Chemotaxins: attraction of macrophages and neutrophils to site of cell injury
Phagocytes: (neutrophils and macrophages) engulf pathogens and secrete cytotoxic chemicals
First Signs of Inflammation
Redness (rubor/erythema): capillary dilation=hyperemia (increase blood flow to the area)
Heat (hyperemia): localized heat (more blood to surface)
Swelling (tumor): hyperemia=increase tissue permeability exudation of albumin (& fibrinogen)
Pain: stim of nerve endings by edema
Inflammation chemicals: bradykinin stim pain receptor by pressure exerted by edema
Impaired function (if a joint is involved)
Edema: joint stiffness
Third Line of Defense (specific, has memory)
Types of Immunity (2)
Cell-mediated immunity
• T cells directly attack invading antigens
• Driven by activated T lymphocytes
Antibody-mediated immunity (humoral immunity)
• B cells transform into plasma (larger than B cells) or memory cells, circulate in the blood & lymph
• Secrete antibodies or immunoglobulin
Antigen vs Antibody
Antigen: any material that can stim immune response (production of antibodies)
EX: Proteins/carbs on cell membrane of
bacteria, viruses, parasites, transplanted tissues
Antibody (immunoglobulin/gamma globulin):
Protein produced in response to an antigen
Neutralizes only the antigen against which it was developed
Structure: Y-shaped pr molecule w 2 arms, arms contain antigen-binding sites
Primary Immune Response
Occurs when in contact w antigen for 1st time
Response begins 3-6 days following exposure
Antibody level peak at 7-10 days of exposure, level fall within 28 days till it becomes undetectable
Responding cells: naïve B cells and T cells
Large amount of IgM and small amount of IgG
Few antibodies produced (weaker than secondary response)
Secondary Immune Response
Occurs when in contacts w antigen for the 2nd and subsequent times
Faster (onset occurs within hrs, and antibody levele reaches its peaks in 3-5 days)
More antibodies (100-1000x more)
More prolonged (antibody level tends to remain high for longer time for weeks/months)
Responding cells: memory cells
Large amount of IgG, small amount of IgM, IgA, IgE
Clonal Selection Theory of Immunity
process proposed to explain how a single B or T cell that recognizes an antigen that enters the body is selected from the pre-existing cell pool of differing antigen specificities and then reproduced to generate a clonal cell population that eliminates the antigen.
If antigen is part of the surface of a virus or bacterium, then the antibody labels that organism as foreign (“not-self”). The organism is then ingested by phagocytic cells and degraded
T cell co-receptors
Naïve T cells need to be activated by two signals:
1. Signal from T-cell receptor (TCR): TCR recognizes small part of antigen (called peptide), this ensures the specificity of the response; only T cells that recognise this antigen will be activated
2. Signal 2 (co-stimulatory signal) provided by costimulatory molecules, which are induced by antigen presenting cells (APC) cutting antigen into small peptides for presentation in a complex with MHC protein
T-cells recognize only antigens bound to MHC
***More EX of co stimulators
CD80 on APC cells & CD28 on T cell –inhibit T-cell activation –called co-inhibitors (CTLA-4 and PD-1)
• These molecules only expressed on T cells that have already been activated
• Stim of these induced co-inhibitory receptors contribute to balanced immune response
• Defects in co-inhibitory receptors lead to unusual immune responses, such as lymphoproliferation and autoimmunity
B cell co-receptors
- Specific B-cell receptor (BCR–immunoglubulin molecule attached to membrane of B cell) recognizes the antigen in native form
- Co-stimulation of B cells is achieved by CD40 ligand is expressed by CD40 helper T cells
As B cells can also present peptides to T cells, dialogue between T & B cells allows continuous B-cell proliferation and activation =lead to their differentiation into mature plasmocytes = produce high affinity antibodies against the antigen
Adaptive Immune Response
• Antibodies
• Life-long protection
Specificity (specific antibodies/TCRs)
Ability to distinguish self from non-self
Ability to respond to enormous diversity of non-self molecules
Immunological memory
Third line of defense
