Pathology: immunity Flashcards
Natural immunity
- primitive, nonspecific from of immunity
- inherited NOT dependent on previous exposure to foreign substances
- Includes various mechanical factors such as skin or ciliated cells in the mucosa of the nose or bronchus in lung
- Includes phagocytic cells such as macrophages and polymorphonutriphil cell (PMNs)
- Includes NK (natural killer) cells
- includes protective proteins found in tissues and plasma
- complement
- properdin - plasma protein that activates the alternate complement pathway
- Lysozyme - protein found in tears, nasal and intestinal secretions, bactericidal
What is immunity
Protection from diseases, especially infectious diseases
Two kinds of immunity
Natural immunity- born with it /innate
Acquired immunity- develops with exposure
Acquired immunity
-complex system of reactions that evolve in response to foreign matter
-based on specific responses stimulated by substances known as antigens
-Antigen - any chemical substance that can elicit a specific immune response
-Based on the ability of the body’s immune system to
1. distinguish self from non-self and
2. generate an immunologic memory
3. Mount an integrated reaction of various cells
Acquired immunity relies on immunocompetance - the body’s ability to mount an appropriate immune response
Cells of immune system
Derived from stems cells in the bone marrow
- Lymphocytes - T Lymphocytes (T cells), T helper cells (CD4+ cells, marker for cell type), T suppressor/cytotoxic cells (CD8+ cells, killing bacteria), B lymphocytes (B cells)
- Plasma cells (releases histamine)
Lymphocytes - Primary lymphoid organs
- small cells with a round nucleus and very little cytoplasm
- Derived from bone marrow stem cells which give rise to two types of cells
- The first type migrates to the thymus and matures into T lymphocytes
- The second type stays in the bone marrow and matures into B lymphocytes
- The bone marrow and thymus are called primary lymphoid organs
Lymphocytes -secondary organs
- From primary lymphoid organs, the T and B Lymphocytes enter the blood circulation and colonize secondary lymphoid organs.
- The most prominent secondary lymphid organs include spleen and lymph nodes
- Also include GI tract and bronchial mucosa (mucosa-associated lymphoid tissue - MALT)
- T Lymphocytes and B lymphocytes have very distinct functions but difficult to distinguish them morphologically
T Lymphocytes (T cells)
Lymphocytes that have matured in the thymus
- Account for two thirds of all lymphocytes in the blood
- also found in the lymph nodes and spleen
- include T helper cells (CD4+ cells) and T suppressor/cytotoxic cells (CD8+ cells)
- Common to all T cells is the surface T-cell receptor (TCR) which is linked to a protein called CD3
- T cells use TCR for recognition of antigens
- TCR-CD3 complex is essential for activity of T cells
Natural killer (NK) cells
T Cells that do not express TCR - CD3 Complex
Mediate innate immune reactions and are not involved in T cell and B cell mediated immune reaction
Their function is to react against virus-infected cells and to kill tumour and foreign cells without previous sensitization
T Helper (CD4+) cells
participate in the immune response to antigens, helping B cells produce antibodies
Express CD4 on their surface
Secrete cytokines (signaling molecule) including interleukins
Classified as TH1 or TH2 depending on which cytokines they produce
TH 1(T helper CD4+ 1) cells
Make interleukin 2 (IL-2) and interferon-gamma (IFN) which stimulate macrophages to become phagocytic and mediate the formation of granulomas
TH 2 (T Helper CD4+ 2) cells
make IL4, IL5, IL13 which are important for secretion of IgE and other immunoglobulins and activation of eosinophils
T suppressor/cytotoxic (CD8+) cells
- Suppress unwanted antibody production
- Mediate killing of virus-infected or tumour cells (recognized by body as foreign)
- express CD8 on their surface
CD4+/CD8+
CD4 and CD8 are used as markers for T lymphocytes and for the counting of T helper and T supressor/cytotoxic cells in blood
-normal ratio of CD4(helper)/CD8(killer) is 2:1
B lymphocytes
- Lymphocytes that differentiates into antibody-producing plasma cells when stimulated by antigens
- an antibody is a protein produced by plasma cells in response to stimulation by an antigen
- antibodies are produced to help fight against antigens
Plasma cells
Fully differentiated descendants of B lymphocytes
Oval shape and eccentrically located round nucleus
Cytoplasm contains an abundance of ribosomes and RER (Rough endoplasmic reticulum)
RER is the site of synthesis of antibodies, the primary secretory products of plasma cells
Antibodies
Proteins of the immunoglobulin class that are secreted by plasma cells
Each antibody is made up of about 110 amino acids
Includes IgA, IgD, IgE, IgG, IgM
IgM
Composed of five basic units
-functions to neutralize microorganisms
-The largest immunoglobulin
-Their first immunoglobulin to appear after immunization
-natural antibody against blood group ABO antigens
-complement activator
Mega - most largest!
IgG
Smallest immunoglobulin
-The most abundant
-produced in small amount on initial immunization, but production is boosted on re-exposure to antigen
-can cross placenta
-act as opsonin (opsonization…coats bacteria and make them taste better and facilitates their phagocytosis)
SMALL GOURMET
IgA
Found in mucosal secretions (tears, nasal secretions), milk, intestinal contents
Ace it, 1st line of defense!
IgE
Secreted by plasma cells in tissue
- Locally attached to mast cells - secrete histamine
- Mediates allergic reactions such as hay fever or asthma
- present in trace amounts in serum
IgD
Found exclusively on B cells
-cell membrane bound
-participates in antigenic activation of B cells
-Is not released into serum or body fluids
DOMINANT IN B CELLS
Antibody production
Begins with contact between an antigen and the cells of the immune system
- Any substance identified by the body as foreign may serve as an antigen and elicit an immune response
- To elicit antibody production, the antigen must bind to the B-lymphocyte antigen receptor complex
- B cells can internalize the antigen and function as antigen -presenting cells (APCs) by presenting internalized antigen to T cells
- antibody production requires the support of T helper cells
Major Histocompatibility Complex (MHC)
All processed antigens are presented to T cells in the context of the major histocompatibility complex (MHC)
- Proteins presented on the surface of antigen presenting cells (APCs)
- T helper cell produces cytokines
- Cytokines transform the B cell into a plasma cell
- Plasma cell produces antibodies
Ag-Ab reaction
Ag are multivalent (more than one binding site or epitope)
- Ag and Ab bind to form complexes
- Complexes enlarge util phagocytosed in spleen/liver by fixed macrophages
- smaller complexes may bind on RBCs/Endothelial cells
- AgAb complexes binding on RBCs cause clumping known as agglutination (clumping of RBCs and their separation from serum)
- If the Ag-Ab complexes activate complement cascade then RBC lysis (hemolysis) occurs
Hypersensitivity reactions
AKA allergic disorders
-an abnormal immune response to exogenous antigen or a reaction to endogenous auto-antigens (auto-immune disorders)
Hypersensitivity 4 types
- Type I Anaphylactic type reaction (IgE)
- Type II- Cytotoxic Ab-mediated reaction (Ig G)
- Type III-Immune complex-mediated reaction
- Type IV-Cell medicated, delayed-type reaction
Type I Hypersensitivity
Mediated by IgE and mast cells or basophils
- IgE produced by plasma cells sensitized to foreign proteins (e.g. pollen)
- Re-exposure leads to antigen-antibody complex on mast cells triggering release of vasoactive granules (histamine)
- Release is instantaneous - increased vascular permeability, edema, eosinophilia
Type I Hypersensitivity pathology
Atopic dermatitis (eczema)
Anaphylactic shock
Bronchial asthma
Atopic dermatitis (eczema)
Type I hypersensitivity Typically disease of childhood Chronic skin irritation Genetic predisposition Associated with hyperproduction of IgE in response to potential environmental allergens Generally improves with age
Bronchial asthma
Type I hypersensitivity
Several forms and not always immunologically mediated
-coughing and wheezing associated with constriction of bronchi and overproduction of mucous by bronchial glands
Anaphylactic shock
Type I hypersensitivity
Life threatening, severe, systemic response to an allergen to which the body was previously sensitized
-marked by a massive release of histamine and other vasoactive substances into the circulation
-symptoms include circulatory collapse, wheezing, pulmonary edema, fainting
Type II hypersensitivity
Re-exposure results in HS reaction/disease i.e. autoimmune diseases
Type II hypersensitivity pathologies
Goodpasture’syndrome
Hemolytic anemia
Graves Disease
Myasthenia Gravis
Good pasture’s syndrome
Type II Hypersensitivity
- Autoimmunity of collagen type IV
- Renal and pulmonary pathologic damage
Hemolytic anemia
Type II Hypersensitivity
- acute hemolytic reaction-transfusion of mismatched blood
- systemic Lupus Erythematosus (SLE) - RBC autoimmunity
Graves Disease
Type II Hypersensitivity
Form of hyperthyroidism in women with antibodies to thyroid-stimulating hormome (TSH) receptor resulting in overproduction of thyroid hormones
Myasthenia Gravis
Type II Hypersensitivity
-Severe muscle weakness resulting from antibodies to acetylcholine receptor of striated muscles
Prevents binding causing progressive weakness even paralysis
Type III Hypersensitivity
Meadiated by immune complexes between Ag and appropriated Ab
- systemic reaction: Ab-Ag complexes in circulation
- Localized reaction: complexes in tissues
- Immune complexes are filtered through basement membranes of glomeruli/anterior eye chamber/brain choroid plexus/pericardium/lung
- trapped complexes activate complement, attract PMNs (polymorphneutriphils) and result in acute inflammation characterized by fibrinoid necrosis
Type III Hypersensitivity pathologies
Systematic Lupus Erythematosus (SLE)
Post-streptococcal glomerulonephritis
Polyarteritis nodusa
Systematic Lupus Erythematosus
Type III hypersensitivity
Post-streptococcal glomerulonephritis
Acute renal disease following upper respiratory tract infection
Antibodies to streptococcal antigen stuck on glomerular basement membrane - complement mediated inflammation
Polyarteritis nodusa
Type III hypersensitivity Localized immune complexes Occurs in various forms of vasculitis Damaged vessels thrombose and occlude Arterial occlusion causes infarcts and ischemic symptoms
Type IV Hypersensitivity
AKA cell mediated or delayed type immune reaction
Involves T-lymphocytes and macrophages
-Aggregate and form granulomas at injurysite
-macrophages or langerhan’s cells of epidermis function as APCs
-Process Ag-complex and present to T lymphocytes
-T helper cells are exposed to Ag complex
-This forms immune memory-important for subsequent exposure
-Occurs in response to complex Ag of M. tuberculosis, Mycobacterium leprae and various fungi
-Accounts for granulomas developing in response to tumours and idiopathic granulomatous diseases: sarcoidosis
-Most common clinical form: contact dermatitis i.e. gold, rubber gloves, poison ivy
Transplantation
Solid tissue transplant.graft will only “take” if donor and recipient are immunologically similar enough to avoid rejection
Immunosuppressive drugs used to facilitate acceptance of transplants
Types of Transplantation
Autografts - self donor - skin, hair blood vessels
Isografts - Idential twins
Homografts/allografts - same species not genetically identical
Xenografts - Transplants between different species
Blood transfusion
Type of transplant
Because RBC in greater number than WBCs, success depends on matching RBCs
Major blood surface antigens lead to formation of four groups with specific antibodies
Blood transfusion reaction
Transfusion reaction e.g. if blood group of A donor is infused into B group, the recipient’s blood antibodies will hemolyze donor’s RBCs
Leads to chills, shivering, fever and eventually shock
Rh Factor Incompatibility
Rh+ people express certain antigens on their RBCs
If mother is Rh- and 1st child is Rh+, mother may create Rh antibodies during delivery
If 2nd child is Rh+, antibodies will destroy fetal RBCs
Preventable by immunizing mother against Rh immediately following first delivery
