Exam 2
Hematopoiesis
Bone marrow / Making WBCs
Primary lymphoid tissue
Bone marrow / thymus
Secondary lymphoid tissues
lymph nodes / spleen
Lysozymes
enzyme in body fluids, break down beta glycosidic bonds in bacterial CW
Natural Defense mechchanisms
Acidic stomach PH
Skin
Lysozymes
Enzymes
Acquired immunity vs Innate immunity
Memory (Acquired)
Ag specific (innate is broad-PAMPs) (Acquired is specific)
Receptors (PRPs - innate)
Receptors (Cells B and T lymphocytes - adaptive)
Humoral- Abs vs complement
Speed (innate is fast acting)
CD4 (TH)
MHC II
Present CD4+ helper cells
CD8 (Tc)
MHC I
CD8+ cytotoxic T cells
Benefits of the immune system
Antibacterial defense
IT benefit of tolerance to non-self Ag
Kidney transplant
IT DEATH receptors Fas and FasL in T cells
Programmed cell death by apoptosis
They can interact on the same T cell or two neighboring T cells
Lymphocytes and Ag
Immunogenic Ag →
Tolerogenic Ag →
Nonimmunogenic Ag →
Activation; proliferation and differentiation
Tolerance
No response
Functions of split-products of complement
C3a
C3b
C4b
C5a
C5b
MAC
Anaphylaxtoxic
Opsonin
Opsonin
Anaphylatoxic and chemotactic for neutrophils
Component of MAC
Final product
C3 convertases Alternative Pathway
C3 convertases Classic Pathway
AP - C3bBb
CP -
Activators of the Classical and Alternative pathways of C
AP
Lipopolysaccharides
Bacterial cell walls
cobra venom
IgA
No need for Ab-Ag complex or IGM for activation
CP
Antigen-IgG complex
IgM
Anti-self B without TH remains inactive
IT
T cell tolerance longevity
IT
Self-Ag lifelong presence induction of self-tolerance
IT
Nonimmunogenic Ag, anergy, no response
IT
CTLA-4 inhibition
IT / CI
Hypersensitivity
Type I
TH2 and class switching → IgE
Mast cell
Preformed mediators - histamine
Delayed made from arachidonic acid
IgE - Eosinophil against parasites
Ameliorating effect of eosinophil
Epinephrine for anaphylaxis type I
Penicillin allergy - IgE mediated; hapten
Hypersensitivity
Type II
Myasthenia gravis - IgG autoAb to acetylcholine receptor
Transient - IgG crossing placenta
Type II mechanism IgG or M to tissue or membrane Ag
Graves disease - AutoAb to TSHR
Rheumatic fever: Antistreptococcal A antibody cross-reacting with cardiac (heart) antigens
Penicillin allergy - IgG mediated; hapten
Hypersensitivity
Type III
Mechanism: Immune complex
Poststreptococcal pyelonephritis
Hypersensitivity
Type IV
Tc, Th-macrophage, cytokine-mediated
Poison ivy- hapten
Contact allergy
Extravasation
Enables WBCs to leave the blood vessels
Its deficiency increases susceptibility to bacterial infections
VLA-4 accessory molecule (integrin) on Tc binds VCAM-1 (receptor) on endothelium
PMNs include mainly neutrophils, eosinophils, basophils, and mast cells
bone marrow
Universal blood donor
O
Universal acceptor
AB
Rh + / - and pregnancy
Important especially in cases of pregnancy where the mother is Rh- and the baby is Rh+. In the second pregnancy the baby will have problems with blood lysis
Neonate tolerance
GI / IT
Xenograft rejection is strongest
Chronic rejection of kidney
Direct recognition of graft Ag
Hyperacute rejection by preformed Abs
GvHR, bone marrow transplant
Cyclosporine A and FK506 treatment. Blocking T cell-cytokine production by inhibiting the activation of the NFAT transport factor
GI
Types of Graft Rejection
Allograft
Autograft
Isograft
Xenograft
Acute
Chronic
hyper acute
GvHR
NK
Innate immunity lymphocytes
Has no Age-specific receptor
Activated by IL2 → LAKi
Surveillance (cancer and viral infected)
B cells
Display BCR
MHC I
MHC II
Mature plasma
Makes antibodies
Cytotoxic T
Cells display TCR
CD8 molecules on their surfaces
Helper T cells
Display TCR
CD4 molecules on their surfaces
All nucleated cells have MHC…
MHC I
(Tc → CD8 → MHC I)
MHC II cells
B cells
Macrophage
Dendritic cell
(TH → CD4 → MHC II)
Basophil & Mast cell
Degredultation with IgE
Release histamine and other effectors
Type I hypersensitivity
Eosinophil
Anti-parasitic
Neutrophils
Part innate immunity
major phagocyte
Most common WBC
Opsonization and its relation to phagocytosis
Innate immunity opsonins
C3b, C4b (complement)
CRP produced by hepatocytes
Opsonization and its relation to phagocytosis
Adaptive immunity opsonin
Opsonin: IgG
Harmful effects of the immune system
Graft rejection
Autoimmune diseases
Immunodeficiencies
hypersensitivity or allergic reactions
Benefit effects of the immune system
Immunization and defense against infectious disease
Cancer detection and management
Another benefit fo immunology application: organ transplantation and blood transfusion
Innate VS Adaptive
Innate
Specificity: For structures shared by classes of microbes (molecular patterns) which are different microbes, identical mannose receptors
Receptors: Encoded in germline, limited diversity. Which are like Toll-like receptors, N-formyl methionyl receptor, Mannose receptor. Receptors are PRRS
No memory of prior exposure
Adaptive
For structural detail of microbial, molecules (antigens) may recognize non microbial antigens. which are different microbes, distinct microbes
Receptors: encoded by genes produced by somatic recombination fo gene segments, greater diversity. which are Ig, TCR. Receptors are B-cell (BCR) and T-cell (TCR) for antigen
Memory of prior exposure
Humoral adaptive immunity, IgG, and its producing cell, and cell-mediated adaptive immunity (Tc, T helper)
During the antigen recognition Naive IgM+, IgD+ of B-cell attacking microbe it would activate B lymphocyte of clonal expansion and produce IgG and cells that would be Humoral response
During cell mediation it uses CD4+ effector T-cells (TH1 cells) to activate macrophages and kill ingested microbes and also inflammation. Also CD8+ T cells (CTLs) recognize microbial antigens in the cytoplasm of infected cells and killing
Blood type A can take…
Blood type A can give…
A O
A AB
Blood type B can take…
blood type B can give…
B O
B AB
Blood type AB can take…
Blood type AB can give…
All
AB
Blood type O can take…
Blood type O can give…
O
all
Opsonins In Innate immunity
(complement- C3B)
Abs may cause disease by opsonizing cells for phagocytosis
Opsonins in Adaptive immunity
IgG
Opsonized microbes by IgG the binding of opsonized microbes to phagocyte Fc receptors, Fc receptors signals activated phagocytes, killing of ingested microbes
CRP
C - Reactive protein
Made in liver, secreted in increased amounts with 6 hours of acute inflammatory stimulus, where the plasma level can double every 8 reaching a peak of 50 hours
Only condition that interferes with CRP is severe hepatocellular impairment
Chemotaxis
Attracting cells to site of high concentration of a chemical
C5a (promotes inflammation)
IFN-a & IFN-b is produced by what cell
Macrophage
IFN-Y is produced by what cell
T cell
Ultimate end product of complement
MAC
Neutrophil
Help attract second wave of leukocytes called mononuclear phagocytes
Hereditary angioedema
C1 inhibitor deficiency
treatement- epinephrine
Acquired angioedema
C1 inhibitor auto-Ab
Immunoglobin produced by plasma (B cells)
IgA
IgG
IgM
IgE
IgD
T-dependent antigens
peptides
only Ags for T cells
class-switching of Abs
memory B cells
require APC
recognizes protein antigens
long term immunity
IgG is produced by class switching
memory cells
T-Independent antigens
recognized by B cells
without APC
no memory
no t cell recognition
no long term immunity
only IgM is produced
no memory cells
Functions of Abs
IgA: Breast feeding, secretory protection/ mucosal
IgE: antiparasitic activity
IgG: opsonin, neonatal immunity, feedback inhibition, IgG-Ag complex activate C
IgM: B-cell receptor; complement activation; pentermaieric, indicates acute infection
IgD: B-cell receptor, IgM receptor
Structure of Abs
2 H chains and 2 L chains
variable domain
CH determines class
Papain digest a Fab + Fc
Polyclonal Ab vs Monoclonal Ab
Polyclonal-
produced by many clones, a mixture
have affinity
no avidity
Monoclonal-
secreted by single clone
produced in hybridoma
has the same affinity
no avidit
Compare Ab and TCR
Both as membrane receptors
Both specific
Ab has effector function
TCR no effector function
Ab recognize proteins, polysacc., lipids, and epitopes(linear and 3-dimensional)
TCR recognize complex, epitopes(linear), peptides only with APC
With MHC: MHC I to CD8 & MHC II to CD4
TCR require cross-linking
Microbes Evasion of humoral immunity:
Resistance of phagocytosis
Encapsulated bacteria: Streptococcus pneumonia, haemophilus influenzae
Inhibit of complement activation
bacteria
Antigenic variation
Influence virus
HIV
E-coil
Neisseria gonorrhoeae
Leprosy and immunity
Cell-mediated immunity necessary for defense against intracellular infection and cancer
Caused by mycobacterium
Two forms of disease
Tuberculoid leprosy-mild
Lepromatous leprosy- severe
Vaccines
Conjugated vaccines, a heamoplilus influenze type B
Live attenuated virus a sabin polia vaccine
Subunit antigen vaccine a tetanus toxoid, diphtheria
Synthetic vaccine a hepatitis recombinant
Killed bacteria BCG TB
Autoimmune / hypersensitivity mechanisms
Type 1
IgE, mast cells; bee, wasp stings, hay fever, penicillin allergy
Autoimmune / hypersensitivity mechanisms
Type 2
IgG or M against self Aga activates complement, inflammation
Graves disease
Myasthenia gravis
Transient MG because IgG crosses the placenta to the fetus
Rheumatic Fever, antibodies against group a streptococci cross-react with cardiac tissue
Autoimmune / hypersensitivity mechanisms
Type 3: Hypersensitivity
Immune complex with Abs other than IgG
Ag-Ab complexes induce an inflammatory response in tissue
In persistent bacteria and viral infections, immune complexes may be deposited in the organs such as kidneys and result in damage
Autoimmune / hypersensitivity mechanisms
Type 4
Delayed because it starts hours or days after contact with Ag and lasts for days
DTH is the prime defense against intracellular bacteria and fungi
Acute Desensitization
This involves administration of very small amounts of Ag at 15 minutes intervals. Few Ag-IgE complexes are formed, so mediator release is so low that it cannot give major allergic reaction
Chronic Desensitization
Involves in long-term weekly administration of Ah to the sensitive patient. This leads to the production of IgG-blocking Ag in the serum, which can prevent subsequent Ag from reaching the IgE on mast cells
Ankylosing spondylitis and B27: 90 risk
Ankylosing spondylitis progressive deformity due to ankylosing spondylitis over a period of 26 years
Individuals who have the HLA-B27 allele are 90 to 100 times more likely to develop the disease ankylosing spondylitis than B27-negative individuals
Congenital Immunodeficiency
Adenosine deaminase ADA
ADA or PnPn deficiency to accumulation of toxic metabolites in lymphocytes, deficiency prevents maturation
Congenital Immunodeficiency
Autosomal SCID
Severe combined immunodeficiency caused by ADA and PNP and RAG
Decreased T and B cells: reduced serum Ig
Congenital Immunodeficiency
X linked SCID
Signaling IL-2Ry chain. Interferes with Pro-T →Pre-T-cell
Markedly decreased T cells: normal or increased B cells: reduced serum Ig
Cytokine receptor common y chain gene mutations, detective T cell maturation due to lack II-7 signals
Prevention of B cell and T cell Maturation
B cell prevention maturation
X-linked agammaglobulinemia: Block in maturation beyond pre-B cells, because of mutation in B cell tyrosine kinase
Ig heavy chain deletions: Chromosomal deletion at 14q32 (Ig heavy chain locus)
T cell prevention maturation
Anomalous development of 3rd and 4th branchial pouches, leading to thymic hypoplasia
Chronic granulomatous disease, phagocyte defect
Defection production of reactive oxygen intermediates by phagocytes
Mutations in genes encoding components of the phagocyte oxidase enzyme, most often cytochrome b558
Acquired ID Secondary
HIV entering T helper through CD4
Human immunodeficiency virus infection mechanism is depletion of CD4+ helper T cells
Protein malnutrition
Protein-calorie malnutrition is metabolic derangements inhibit lymphocyte maturation and function
Hypersensitivity: Allergen definition
Type 1
Type 2
Type 3
Type 4
Type 1
TH2 and class switching a IgE
Mast cell
preformed mediators- histamine
IgE- Eosinophils against parasites
Penicillin allergy-IgE mediated: hapten
Type 2
Myasthenia gravis-IgG autoAb to acetylcholine receptor
Transient- IgG crossing placenta
Type 2 mechanism IgG or M to tissue or membrane
Graves diseases
Rheumatic Fever
Penicillin allergy-IgG mediated; hapten
Type 3
Mechanisms: immune complex
Poststreptococcal pyelonephritis
Type 4
Tc, TH-macrophage, cytokine-mediated
Poison ivy-hapten
Contact allergy
Tolerance
The acquisition of a specific non responsiveness to a molecule recognize by the immune system as nonself
Tolerance Disadvantages
Tolerance to certain foreign antigens that cause diseases such as bacterial infections
Tolerance to some self-antigens associated with cancer
Tolerance Advantages
Self-tolerance is essential for the function of the immune system
Tolerance to foreign tissue grafts
Gene therapy
Control of damaging immune responses such as: Hypersensitivity and autoimmune diseases
Graft rejection/acceptance depending on donor-recipient compatibility
Graft vs. Host Reaction
Bone marrow
Donor immunocompetent
recipient incompentent
Both in compatible
Graft rejection/acceptance depending on donor-recipient compatibility
Chronic
Kidney transplant failure years after success
Blood vessel narrowing results of accumulation of WBC and fibroblasts
Chronic DTH reaction in vessel wall, intimal smooth muscle cell proliferation vessel occlusion
Graft rejection/acceptance depending on donor-recipient compatibility
Acute
Cell-mediated, newly activated
Inflammation
Blood supply stop
CD8+ T lymphocytes reactive with alloantigens on graft endothelial cells
Graft rejection/acceptance depending on donor-recipient compatibility
Hyperacute rejection
Preformed Ab
Inflammation
Complement activation
Prevent vascularization blood supply stop
Cancer
Mechanisms of immune evasion
Tumor evasion of the immune system by MHC I downregulation
Cancer
NK surveillance for cancer
cytokines (IFNs, TNF, IL-2, IL12) increase the tumoricidal capacity of NK cells
IL-2 activated NK cells are called lymphokine-activated killer (LAK) cells
Cancer
Magic bullet treatment of cancer with monoclonal Ab + toxin
Monoclonal antibodies as magic bullets when conjugated with toxins or radionuclides to target tumor cells or antigens on malignant fibroblasts
Markers
CEA / Colon cancer marker
CEA is a type of tumor marker made by cancer cells or by normal cells in response to cancer in the body, at high level CEA can be sign of certain types of cancers
Markers
CALLA
Is an antigen associated with childhood leukemia
Markers
Alpha-fetoprotein / hepatocellular carcinoma
PSA / Prostate
GM1 monosialoganglioside / pancreatic carcinoma
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Autoimmunity induction by cross reaction with foreign antigens
Recognition of allogeneic MHC molecules
In which T cell is specific for a self MHC molecule
Forgein peptide complexes are also allogeneic